The ascent of dinosaurs in the Triassic is an exemplary evolutionary radiation, but the earliest phase of dinosaur history remains poorly understood. Body fossils of close dinosaur relatives are rare, but indicate that the dinosaur stem lineage (Dinosauromorpha) originated by the latest Anisian (ca 242-244 Ma). Here, we report footprints from the Early-Middle Triassic of Poland, stratigraphically well constrained and identified using a conservative synapomorphy-based approach, which shifts the origin of the dinosaur stem lineage back to the Early Olenekian (ca 249-251 Ma), approximately 5-9 Myr earlier than indicated by body fossils, earlier than demonstrated by previous footprint records, and just a few million years after the Permian/Triassic mass extinction (252.3 Ma). Dinosauromorph tracks are rare in all Polish assemblages, suggesting that these animals were minor faunal components. The oldest tracks are quadrupedal, a morphology uncommon among the earliest dinosauromorph body fossils, but bipedality and moderately large body size had arisen by the Early Anisian (ca 246 Ma). Integrating trace fossils and body fossils demonstrates that the rise of dinosaurs was a drawn-out affair, perhaps initiated during recovery from the Permo-Triassic extinction. PMID:20926435
Brusatte, Stephen L; Nied?wiedzki, Grzegorz; Butler, Richard J
The ascent of dinosaurs in the Triassic is an exemplary evolutionary radiation, but the earliest phase of dinosaur history remains poorly understood. Body fossils of close dinosaur relatives are rare, but indicate that the dinosaur stem lineage (Dinosauromorpha) originated by the latest Anisian (ca 242–244 Ma). Here, we report footprints from the Early–Middle Triassic of Poland, stratigraphically well constrained and identified using a conservative synapomorphy-based approach, which shifts the origin of the dinosaur stem lineage back to the Early Olenekian (ca 249–251 Ma), approximately 5–9 Myr earlier than indicated by body fossils, earlier than demonstrated by previous footprint records, and just a few million years after the Permian/Triassic mass extinction (252.3 Ma). Dinosauromorph tracks are rare in all Polish assemblages, suggesting that these animals were minor faunal components. The oldest tracks are quadrupedal, a morphology uncommon among the earliest dinosauromorph body fossils, but bipedality and moderately large body size had arisen by the Early Anisian (ca 246 Ma). Integrating trace fossils and body fossils demonstrates that the rise of dinosaurs was a drawn-out affair, perhaps initiated during recovery from the Permo-Triassic extinction.
Brusatte, Stephen L.; Niedzwiedzki, Grzegorz; Butler, Richard J.
Large-scale adaptive radiations might explain the runaway success of a minority of extant vertebrate clades. This hypothesis predicts, among other things, rapid rates of morphological evolution during the early history of major groups, as lineages invade disparate ecological niches. However, few studies of adaptive radiation have included deep time data, so the links between extant diversity and major extinct radiations are unclear. The intensively studied Mesozoic dinosaur record provides a model system for such investigation, representing an ecologically diverse group that dominated terrestrial ecosystems for 170 million years. Furthermore, with 10,000 species, extant dinosaurs (birds) are the most speciose living tetrapod clade. We assembled composite trees of 614-622 Mesozoic dinosaurs/birds, and a comprehensive body mass dataset using the scaling relationship of limb bone robustness. Maximum-likelihood modelling and the node height test reveal rapid evolutionary rates and a predominance of rapid shifts among size classes in early (Triassic) dinosaurs. This indicates an early burst niche-filling pattern and contrasts with previous studies that favoured gradualistic rates. Subsequently, rates declined in most lineages, which rarely exploited new ecological niches. However, feathered maniraptoran dinosaurs (including Mesozoic birds) sustained rapid evolution from at least the Middle Jurassic, suggesting that these taxa evaded the effects of niche saturation. This indicates that a long evolutionary history of continuing ecological innovation paved the way for a second great radiation of dinosaurs, in birds. We therefore demonstrate links between the predominantly extinct deep time adaptive radiation of non-avian dinosaurs and the phenomenal diversification of birds, via continuing rapid rates of evolution along the phylogenetic stem lineage. This raises the possibility that the uneven distribution of biodiversity results not just from large-scale extrapolation of the process of adaptive radiation in a few extant clades, but also from the maintenance of evolvability on vast time scales across the history of life, in key lineages. PMID:24802911
Benson, Roger B J; Campione, Nicolás E; Carrano, Matthew T; Mannion, Philip D; Sullivan, Corwin; Upchurch, Paul; Evans, David C
Large-scale adaptive radiations might explain the runaway success of a minority of extant vertebrate clades. This hypothesis predicts, among other things, rapid rates of morphological evolution during the early history of major groups, as lineages invade disparate ecological niches. However, few studies of adaptive radiation have included deep time data, so the links between extant diversity and major extinct radiations are unclear. The intensively studied Mesozoic dinosaur record provides a model system for such investigation, representing an ecologically diverse group that dominated terrestrial ecosystems for 170 million years. Furthermore, with 10,000 species, extant dinosaurs (birds) are the most speciose living tetrapod clade. We assembled composite trees of 614–622 Mesozoic dinosaurs/birds, and a comprehensive body mass dataset using the scaling relationship of limb bone robustness. Maximum-likelihood modelling and the node height test reveal rapid evolutionary rates and a predominance of rapid shifts among size classes in early (Triassic) dinosaurs. This indicates an early burst niche-filling pattern and contrasts with previous studies that favoured gradualistic rates. Subsequently, rates declined in most lineages, which rarely exploited new ecological niches. However, feathered maniraptoran dinosaurs (including Mesozoic birds) sustained rapid evolution from at least the Middle Jurassic, suggesting that these taxa evaded the effects of niche saturation. This indicates that a long evolutionary history of continuing ecological innovation paved the way for a second great radiation of dinosaurs, in birds. We therefore demonstrate links between the predominantly extinct deep time adaptive radiation of non-avian dinosaurs and the phenomenal diversification of birds, via continuing rapid rates of evolution along the phylogenetic stem lineage. This raises the possibility that the uneven distribution of biodiversity results not just from large-scale extrapolation of the process of adaptive radiation in a few extant clades, but also from the maintenance of evolvability on vast time scales across the history of life, in key lineages.
Benson, Roger B. J.; Campione, Nicolas E.; Carrano, Matthew T.; Mannion, Philip D.; Sullivan, Corwin; Upchurch, Paul; Evans, David C.
This is a series of experiments about dinosaurs and paleontology that was designed for use in the second grade. Each activity gives the needed materials, what to do, and what to think about. All are designed so the student uses everyday, inexpensive materials and they reinforce information that has already been taught. The Teacher's Notes provide the purpose of the activity, preparation, and notes.
Candelora, D. M.; Program, The H.
Lineage tracing involves labeling cells to track their subsequent behavior within the normal tissue environment. The advent of genetic lineage tracing and cell proliferation assays, together with high resolution three-dimensional (3D) imaging and quantitative methods to infer cell behavior from lineage-tracing data, has transformed our understanding of murine epidermal stem and progenitor cells. Here, we review recent insights that reveal how a progenitor cell population maintains interfollicular epidermis, whereas stem cells, quiescent under homeostatic conditions, are mobilized in response to wounding. We discuss progress in understanding how the various stem cell populations of the hair follicle sustain this complex and highly dynamic structure, and recent analysis of stem cells in sweat and sebaceous glands. The extent to which insights from mouse studies can be applied to human epidermis is also considered. PMID:24384814
Alcolea, Maria P; Jones, Philip H
This is a four day lesson plan that high school students grade 10-12 in the Child Care course can use to evaluate and then create their own lesson plan. This lesson plan also includes an example field trip. It can also be used for the high school students to experience teaching the preschool school children a unit on dinosaurs. At the end of reviewing this lesson plan students will be able to identify the components of this lesson plan and identify which DAP learning experience was used in each activity. After analyzing this lesson plan and identifying all the parts students will then be able to create their own lesson plan , picking a theme of their own. If used for students to teach the unit to preschoolers they will be able to present the lesson plan with all requirements met, and then better understand them to then create their own. Dinosaurs NOTE: For students who may have a disability preventing them from typing their lesson plan you could use the following assistive technology which allows them to speak into the computer and the computer types it up for them. A great source for this is: Dragon naturally speaking. Also you could ...
The present invention relates to methods of modulating epithelial stem cell lineage by regulating the expression of Lef1 or a BMP inhibitor and/or the stability of beta-catenin or the expression of a Wnt; regulating the expression or activity of GATA-3; o...
C. Jamora C. Kaufman E. Fuchs K. Kobielak
Adhesion of stem cells - like most cells - is not just a membrane phenomenon. Most tissue cells need to adhere to a ``solid'' for viability, and over the last decade it has become increasingly clear that the physical ``elasticity'' of that solid is literally ``felt'' by cells. Here we show that Mesenchymal Stem Cells (MSCs) specify lineage and commit to phenotypes with extreme sensitivity to the elasticity typical of tissues . In serum only media, soft matrices that mimic brain appear neurogenic, stiffer matrices that mimic muscle are myogenic, and comparatively rigid matrices that mimic collagenous bone prove osteogenic. Inhibition of nonmuscle myosin II activity blocks all elasticity directed lineage specification, which indicates that the cytoskeleton pulls on matrix through adhesive attachments. Results have significant implications for `therapeutic' stem cells and have motivated development of a proteomic-scale method to identify mechano-responsive protein structures  as well as deeper physical studies of matrix physics  and growth factor pathways . [4pt]  A. Engler, et al. Matrix elasticity directs stem cell lineage specification. Cell (2006).[0pt]  C.P. Johnson, et al. Forced unfolding of proteins within cells. Science (2007).[0pt]  A.E.X. Brown, et al. Multiscale mechanics of fibrin polymer: Gel stretching with protein unfolding and loss of water. Science (2009).[0pt]  D.E. Discher, et al. Growth factors, matrices, and forces combine and control stem cells. Science (2009).
In all animals, germline cells differentiate in intimate contact with somatic cells and interactions between germline and soma are particularly important for germline development and function. In the male gonad of Drosophila melanogaster, the developing germline cells are enclosed by somatic cyst cells. The cyst cells are derived from cyst stem cells (CySCs) of somatic origin and codifferentiate with the germline cells. The fast generation cycle and the genetic tractability of Drosophila has made the Drosophila testis an excellent model for studying both the roles of somatic cells in guiding germline development and the interdependence of two separate stem cell lineages. This review focuses on our current understanding of CySC specification, CySC self-renewing divisions, cyst cell differentiation, and soma-germline interactions. Many of the mechanisms guiding these processes in Drosophila testes are similarly essential for the development and function of tissues in other organisms, most importantly for gametogenesis in mammals.
Zoller, Richard; Schulz, Cordula
Livers are comprised of maturational lineages of cells beginning extrahepatically in the hepato-pancreatic common duct near the duodenum and intrahepatically in zone 1 by the portal triads. The extrahepatic stem cell niches are the peribiliary glands deep within the walls of the bile ducts; those intrahepatically are the canals of Hering in postnatal livers and that derive from ductal plates in fetal livers. Intrahepatically, there are at least 8 maturational lineage stages from the stem cells in zone 1 (periportal), through the midacinar region (zone 2), to the most mature cells and apoptotic cells found pericentrally in zone 3. Those found in the biliary tree are still being defined. Parenchymal cells are closely associated with lineages of mesenchymal cells, and their maturation is coordinated. Each lineage stage consists of parenchymal and mesenchymal cell partners distinguishable by their morphology, ploidy, antigens, biochemical traits, gene expression, and ability to divide. They are governed by changes in chromatin (e.g. methylation), gradients of paracrine signals (soluble factors and insoluble extracellular matrix components), mechanical forces, and feedback loop signals derived from late lineage cells. Feedback loop signals, secreted by late lineage stage cells into bile, flow back to the periportal area and regulate the stem cells and other early lineage stage cells, in mechanisms dictating the size of the liver mass. Recognition of maturational lineage biology and its regulation by these multiple mechanisms offers new understandings of liver biology, pathologies, and strategies for regenerative medicine.
Turner, Rachael; Lozoya, Oswaldo; Wang, Yunfang; Cardinale, Vincenzo; Gaudio, Eugenio; Alpini, Gianfranco; Mendel, Gemma; Wauthier, Eliane; Barbier, Claire; Alvaro, Domenico; Reid, Lola M.
Stem cells that adopt distinct lineages cannot be distinguished based on traditional cell shape. This study reports that higher-order variations in cell shape and cytoskeletal organization that occur within hours of stimulation forecast the lineage commitment fates of human mesenchymal stem cells (hMSCs). The unique approach captures numerous early (24 h), quantitative features of actin fluororeporter shapes, intensities, textures, and spatial distributions (collectively termed morphometric descriptors). The large number of descriptors are reduced into “combinations” through which distinct subpopulations of cells featuring unique combinations are identified. We demonstrate that hMSCs cultured on fibronectin-treated glass substrates under environments permissive to bone lineage induction could be readily discerned within the first 24 h from those cultured in basal- or fat-inductive conditions by such cytoskeletal feature groupings. We extend the utility of this approach to forecast osteogenic stem cell lineage fates across a series of synthetic polymeric materials of diverse physicochemical properties. Within the first 24 h following stem cell seeding, we could successfully “profile” the substrate responsiveness prospectively in terms of the degree of bone versus nonbone predisposition. The morphometric methodology also provided insights into how substrates may modulate the pace of osteogenic lineage specification. Cells on glass substrates deficient in fibronectin showed a similar divergence of lineage fates, but delayed beyond 48 h. In summary, this high-content imaging and single cell modeling approach offers a framework to elucidate and manipulate determinants of stem cell behaviors, as well as to screen stem cell lineage modulating materials and environments.
Treiser, Matthew D.; Yang, Eric H.; Gordonov, Simon; Cohen, Daniel M.; Androulakis, Ioannis P.; Kohn, Joachim; Chen, Christopher S.; Moghe, Prabhas V.
The initial period of mammalian embryonic development is primarily devoted to cell commitment to the pluri-potent lineage, as well as to the formation of extraembryonic tissues essential for embryo survival in utero. This phase of development is also characterized by extensive morphological transitions. Cells within the preimplantation embryo exhibit extraordinary cell plasticity and adaptation in response to experimental manipulation, highlighting the use of a regulative developmental strategy rather than a predetermined one resulting from the non-uniform distribution of maternal information in the cytoplasm. Consequently, early mammalian development represents a useful model to study how the three primary cell lineages; the epiblast, primitive endoderm (also referred to as the hypoblast) and trophoblast, emerge from a totipotent single cell, the zygote. In this review, we will discuss how the isolation and genetic manipulation of murine stem cells representing each of these three lineages has contributed to our understanding of the molecular basis of early developmental events.
Artus, Jerome; Hadjantonakis, Anna-Katerina
Many lineage-specific genes are poised and silenced in stem cells. Upon differentiation, genes that are related to self-renewal and alternative lineages are stably silenced. CpG methylation at proximal promoters and PRC2-mediated H3K27me3 play a role in silencing genes temporarily or permanently, with or without coexistence of active epigenetic marks, respectively. Interestingly, DNA methylation on neuronal genes that is distal to transcription start site enable transcription activation owing to its ability to repel PRC2-mediated inhibition. In addition, DNA demethylase Tet proteins play a role in regulation of changes in DNA methylation and related H3K27me3 during differentiation. Collectively, a complex epigenetic network formed by H3K4me3, histone acetylation/deacetylation, H3K27me3 and DNA methylation/demethylation act together to regulate stem cell self-renewal and differentiation.
Coskun, Volkan; Tsoa, Rosemarie; Sun, Yi E
Background During implantation the blastocyst trophectoderm attaches to the endometrial epithelium and continues to differentiate into all trophoblast subtypes, which are the major components of a placenta. Aberrant trophoblast proliferation and differentiation are associated with placental diseases. However, due to ethical and practical issues, there is almost no available cell or tissue source to study the molecular mechanism of human trophoblast differentiation, which further becomes a barrier to the study of the pathogenesis of trophoblast-associated diseases of pregnancy. In this study, our goal was to generate a proof-of-concept model for deriving trophoblast lineage cells from induced pluripotency stem (iPS) cells from human fibroblasts. In future studies the generation of trophoblast lineage cells from iPS cells established from patient’s placenta will be extremely useful for studying the pathogenesis of individual trophoblast-associated diseases and for drug testing. Methods and Results Combining iPS cell technology with BMP4 induction, we derived trophoblast lineage cells from human iPS cells. The gene expression profile of these trophoblast lineage cells was distinct from fibroblasts and iPS cells. These cells expressed markers of human trophoblasts. Furthermore, when these cells were differentiated they exhibited invasive capacity and placental hormone secretive capacity, suggesting extravillous trophoblasts and syncytiotrophoblasts. Conclusion Trophoblast lineage cells can be successfully derived from human iPS cells, which provide a proof-of-concept tool to recapitulate pathogenesis of patient placental trophoblasts in vitro.
Chen, Ying; Wang, Kai; Chandramouli, Gadisetti V.R.; Knott, Jason G.; Leach, Richard
Highlights: •Epithelial-like phenotype of trophoblast lineage cells derived from human iPS cells. •Trophoblast lineage cells derived from human iPS cells exhibit trophoblast function. •Trophoblasts from iPS cells provides a proof-of-concept in regenerative medicine. -- Abstract: Background: During implantation, the blastocyst trophectoderm attaches to the endometrial epithelium and continues to differentiate into all trophoblast subtypes, which are the major components of a placenta. Aberrant trophoblast proliferation and differentiation are associated with placental diseases. However, due to ethical and practical issues, there is almost no available cell or tissue source to study the molecular mechanism of human trophoblast differentiation, which further becomes a barrier to the study of the pathogenesis of trophoblast-associated diseases of pregnancy. In this study, our goal was to generate a proof-of-concept model for deriving trophoblast lineage cells from induced pluripotency stem (iPS) cells from human fibroblasts. In future studies the generation of trophoblast lineage cells from iPS cells established from patient’s placenta will be extremely useful for studying the pathogenesis of individual trophoblast-associated diseases and for drug testing. Methods and results: Combining iPS cell technology with BMP4 induction, we derived trophoblast lineage cells from human iPS cells. The gene expression profile of these trophoblast lineage cells was distinct from fibroblasts and iPS cells. These cells expressed markers of human trophoblasts. Furthermore, when these cells were differentiated they exhibited invasive capacity and placental hormone secretive capacity, suggesting extravillous trophoblasts and syncytiotrophoblasts. Conclusion: Trophoblast lineage cells can be successfully derived from human iPS cells, which provide a proof-of-concept tool to recapitulate pathogenesis of patient placental trophoblasts in vitro.
Chen, Ying, E-mail: firstname.lastname@example.org [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, 333 Bostwick NE, Grand Rapids, MI 49503 (United States)] [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, 333 Bostwick NE, Grand Rapids, MI 49503 (United States); Wang, Kai; Chandramouli, Gadisetti V.R. [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, 333 Bostwick NE, Grand Rapids, MI 49503 (United States)] [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, 333 Bostwick NE, Grand Rapids, MI 49503 (United States); Knott, Jason G. [Developmental Epigenetics Laboratory, Department of Animal Science, Michigan State University (United States)] [Developmental Epigenetics Laboratory, Department of Animal Science, Michigan State University (United States); Leach, Richard, E-mail: Richard.email@example.com [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, 333 Bostwick NE, Grand Rapids, MI 49503 (United States) [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, 333 Bostwick NE, Grand Rapids, MI 49503 (United States); Department of Obstetrics, Gynecology and Women’s Health, Spectrum Health Medical Group (United States)
Bones adapt to accommodate the physical forces they experience through changes in architecture and mass. Stem cells differentiate into bone-forming osteoblasts, and mechanical stimulation is involved in this process. Various studies have applied controlled mechanical stimulation to stem cells and investigated the effects on osteogenic lineage commitment. These studies demonstrate that physical stimuli can induce osteogenic lineage commitment. Tension, fluid shear stress, substrate material properties, and cell shape are all factors that influence osteogenic differentiation. In particular, the level of tension is important. Also, rigid substrates with stiffness similar to collagenous bone induce osteogenic differentiation, while softer substrates induce other lineages. Finally, cells allowed to adhere over a larger area are able to differentiate towards the osteogenic lineage while cells adhering to a smaller area are restricted to the adipogenic lineage. Stem cells are able to sense their mechanical environments through various mechanosensors, including the cytoskeleton, focal adhesions, and primary cilia. The cytoskeleton provides a structural frame for the cell, and myosin interacts with actin to generate cytoskeletal tension, which is important for mechanically induced osteogenesis of stem cells. Adapter proteins link the cytoskeleton to integrins, which attach the cell to the substrate, forming a focal adhesion. A variety of signaling proteins are also associated with focal adhesions. Forces are transmitted to the substrate at these sites, and an intact focal adhesion is important for mechanically induced osteogenesis. The primary cilium is a single, immotile, antenna-like structure that extends from the cell into the extracellular space. It has emerged as an important signaling center, acting as a microdomain to facilitate biochemical signaling. Mechanotransduction is the process by which physical stimuli are converted into biochemical responses. When potential mechanosensors are disrupted, the activities of components of mechanotransduction pathways are also inhibited, preventing mechanically induced osteogenesis. Calcium, mitogen-activated protein kinase/extracellular signal-regulated kinase, Wnt, Yes-associated protein/transcriptional coactivator with PDZ-binding motif and RhoA/Rho kinase signaling are some of the mechanotransduction pathways proposed to be important. In this review, types of mechanical stimuli, mechanosensors, and key pathways involved in mechanically induced osteogenesis of stem cells are discussed.
Human pluripotent stem cells have the unique properties of being able to proliferate indefinitely in their undifferentiated state and to differentiate into any somatic cell type. These cells are thus posited to be extremely useful for furthering our understanding of both normal and abnormal human development, providing a human cell preparation that can be used to screen for new reagents or therapeutic agents, and generating large numbers of differentiated cells that can be used for transplantation purposes. Critical among the applications for the latter are diseases and injuries of the nervous system, medical approaches to which have been, to date, primarily palliative in nature. Differentiation of human pluripotent stem cells into cells of the neural lineage, therefore, has become a central focus of a number of laboratories. This has resulted in the description in the literature of several dozen methods for neural cell differentiation from human pluripotent stem cells. Among these are methods for the generation of such divergent neural cells as dopaminergic neurons, retinal neurons, ventral motoneurons, and oligodendroglial progenitors. In this review, we attempt to fully describe most of these methods, breaking them down into five basic subdivisions: 1) starting material, 2) induction of loss of pluripotency, 3) neural induction, 4) neural maintenance and expansion, and 5) neuronal/glial differentiation. We also show data supporting the concept that undifferentiated human pluripotent stem cells appear to have an innate neural differentiation potential. In addition, we evaluate data comparing and contrasting neural stem cells differentiated from human pluripotent stem cells with those derived directly from the human brain.
Schwartz, Philip H.; Brick, David J.; Stover, Alexander E.; Loring, Jeanne F.; Muller, Franz Josef
When paleontologists unearthed the ancient dinosaur Tawa hallae, they knew it was different--and remarkably well preserved. What they did not know is that the animal has an intriguing lineage, one that answers questions about the earliest evolution of dinosaurs.
Transcription factors critical for normal hematopoietic stem cell functions are frequently mutated in acute leukemia leading to an aberrant re-programming of normal hematopoietic progenitor/stem cells into leukemic stem cells. Among them, re-arrangements of the mixed lineage leukemia gene (MLL), including chimeric fusion, partial tandem duplication (PTD), amplification and internal exonic deletion, represent one of the most common recurring oncogenic events and associate with very poor prognosis in human leukemias. Extensive research on wild type MLL and MLL-fusions has significant advanced our knowledge about their functions in normal and malignant hematopoiesis, which also provides a framework for the underlying pathogenic role of MLL re-arrangements in human leukemias. In contrast, research progress on MLL-PTD, MLL amplification and internal exonic deletion remains stagnant, in particular for the last two abnormalities where mouse model is not yet available. In this article, we will review the key features of both wild-type and re-arranged MLL proteins with particular focuses on MLL-PTD and MLL amplification for their roles in normal and malignant hematopoiesis. PMID:23598978
Yip, Bon Ham; So, Chi Wai Eric
Background & objectives: Mesencymal stem cells (MSCs) derived from foetal tissues present a multipotent progenitor cell source for application in tissue engineering and regenerative medicine. The present study was carried out to derive foetal mesenchymal stem cells from ovine source and analyze their differentiation to osteogenic linage to serve as an animal model to predict human applications. Methods: Isolation and culture of sheep foetal bone marrow cells were done and uniform clonally derived MSC population was collected. The cells were characterized using cytochemical, immunophenotyping, biochemical and molecular analyses. The cells with defined characteristics were differentiated into osteogenic lineages and analysis for differentiated cell types was done. The cells were analyzed for cell surface marker expression and the gene expression in undifferentiated and differentiated osteoblast was checked by reverse transcriptase PCR (RT PCR) analysis and confirmed by sequencing using genetic analyzer. Results: Ovine foetal samples were processed to obtain mononuclear (MNC) cells which on culture showed spindle morphology, a characteristic oval body with the flattened ends. MSC population CD45-/CD14- was cultured by limiting dilution to arrive at uniform spindle morphology cells and colony forming units. The cells were shown to be positive for surface markers such as CD44, CD54, integrin?1, and intracellular collagen type I/III and fibronectin. The osteogenically induced MSCs were analyzed for alkaline phosphatase (ALP) activity and mineral deposition. The undifferentiated MSCs expressed RAB3B, candidate marker for stemness in MSCs. The osteogenically induced and uninduced MSCs expressed collagen type I and MMP13 gene in osteogenic induced cells. Interpretation & conclusions: The protocol for isolation of ovine foetal bone marrow derived MSCs was simple to perform, and the cultural method of obtaining pure spindle morphology cells was established. Criteria proposed for defining MSCs by this study includes the cell adherence to culture plates, specific surface protein profiles and differentiation to osteogenic lineage. The MSCs and osteogenic differentiated cells in this ovine animal model may serve as a large source for stem cell applications in regenerative medical therapies.
Gowri, A. Mangala; Kavitha, G.; Rajasundari, M.; Fathima, S. Mubeen; Kumar, T.M.A. Senthil; Raj, G. Dhinakar
In this article, the authors describe how they capitalized on their first-grade students' love of dinosaurs by hosting a fun-filled Dinosaur Day in their classroom. On Dinosaur Day, students rotated through four dinosaur-related learning stations that integrated science content with art, language arts, math, and history in a fun and time-efficient…
Nakamura, Sandra; Baptiste, H. Prentice
Prevailing wisdom holds that hematopoietic stem cells (HSCs) are predominantly quiescent. Although HSC cycle status has long been the subject of scrutiny, virtually all marrow stem cell research has been based on studies of highly purified HSCs. Here we explored the cell cycle status of marrow stem cells in un-separated whole bone marrow (WBM). We show that a large number of long-term multi-lineage engraftable stem cells within WBM are in S/G2/M phase. Using bromodeoxyuridine, we show rapid transit through the cell cycle of a previously defined relatively dormant purified stem cell, the long-term HSC (LT-HSC; Lineage(-)/c-kit(+)/Sca-1(+)/Flk-2(-)). Actively cycling marrow stem cells have continually changing phenotype with cell cycle transit, likely rendering them difficult to purify to homogeneity. Indeed, as WBM contains actively cycling stem cells, and highly purified stem cells engraft predominantly while quiescent, it follows that the population of cycling marrow stem cells within WBM are lost during purification. Our studies indicate that both the discarded lineage-positive and lineage-negative marrow cells in a stem cell separation contain cycling stem cells. We propose that future work should encompass this larger population of cycling stem cells that is poorly represented in current studies solely focused on purified stem cell populations. PMID:23989430
Goldberg, L R; Dooner, M S; Johnson, K W; Papa, E F; Pereira, M G; Del Tatto, M; Adler, D M; Aliotta, J M; Quesenberry, P J
Following nuclear transfer (NT), the most stringent measure of extensive donor cell reprogramming is development into viable offspring. This is referred to as cloning efficiency and quantified as the proportion of cloned embryos transferred into surrogate mothers that survive into adulthood. Cloning efficiency depends on the ability of the enucleated recipient cell to carry out the reprogramming reactions ('reprogramming ability') and the ability of the nuclear donor cell to be reprogrammed ('reprogrammability'). It has been postulated that reprogrammability of the somatic donor cell epigenome is inversely proportional to its differentiation status. In order to test this hypothesis, reprogrammability was compared between undifferentiated stem cells and their differentiated isogenic progeny. In the mouse, cells of divergent differentiation status from the neuronal, haematopoietic and skin epithelial lineage were tested. In cattle and deer, skeletal muscle and antler cells, respectively, were used as donors. No conclusive correlation between differentiation status and cloning efficiency was found, indicating that somatic donor cell type may not be the limiting factor for cloning success. This may reflect technical limitations of the NT-induced reprogramming assay. Alternatively, differentiation status and reprogrammability may be unrelated, making all cells equally difficult to reprogramme once they have left the ground state of pluripotency. PMID:19152749
Isolated, mammalian, adult bone marrow-derived, lineage negative hematopoietic stem cell populations (Lin(sup -) HSCs) contain endothelial progenitor cells (EPCs) capable of rescuing retinal blood vessels and neuronal networks in the eye. Preferably at le...
A. Otani K. Da Silva M. Friedlander S. H. Moreno
Cells of the early mammalian embryo, including pluripotent embryonic stem (ES) cells and primordial germ cells (PGCs), are epigenetically dynamic and heterogeneous. During early development, this heterogeneity of epigenetic states is associated with stochastic expression of lineage-determining transcription factors that establish an intimate crosstalk with epigenetic modifiers. Lineage-specific epigenetic modification of crucial transcription factor loci (for example, methylation of the
Wendy Dean; Myriam Hemberger; Wolf Reik
Embryonic (ES) and epiblast (EpiSC) stem cells are pluripotent but committed to an embryonic lineage fate. Conversely, trophoblast (TS) and extraembryonic endoderm (XEN) stem cells contribute predominantly to tissues of the placenta and yolk sac, respectively. Here we show that each of these four stem cell types is defined by a unique DNA methylation profile. Despite their distinct developmental origin, TS and XEN cells share key epigenomic hallmarks, chiefly characterized by robust DNA methylation of embryo-specific developmental regulators, as well as a subordinate role of 5-hydroxymethylation. We also observe a substantial methylation reinforcement of pre-existing epigenetic repressive marks that specifically occurs in extraembryonic stem cells compared to in vivo tissue, presumably due to continued high Dnmt3b expression levels. These differences establish a major epigenetic barrier between the embryonic and extraembryonic stem cell types. In addition, epigenetic lineage boundaries also separate the two extraembryonic stem cell types by mutual repression of key lineage-specific transcription factors. Thus, global DNA methylation patterns are a defining feature of each stem cell type that underpin lineage commitment and differentiative potency of early embryo-derived stem cells. Our detailed methylation profiles identify a cohort of developmentally regulated sequence elements, such as orphan CpG islands, that will be most valuable to uncover novel transcriptional regulators and pivotal "gatekeeper" genes in pluripotency and lineage differentiation. PMID:23034951
Senner, Claire E; Krueger, Felix; Oxley, David; Andrews, Simon; Hemberger, Myriam
In this activity, learners explore why animals, specifically dinosaurs, live in families. Learners examine Dinosphere scenes (drawing of dinosaurs in groups) and sort the scenes by reasons the animals are living in groups. Then, learners glue together geometric shapes to create dinosaurs interacting in groups and families. This activity is featured on page 26 of the "Dinosphere" unit of study for K-2 learners.
Crosslin, Rick; Fortney, Mary; Indianapolis, The C.
Zoom Dinosaurs is a comprehensive on-line hypertext book about dinosaurs. It is designed for students of all ages and levels of comprehension. An easy-to-use structure allows readers to start at a basic level on each topic, then progress to more advanced information as desired simply by clicking on links. The site contains handouts, dinosaur myths, etymologies, evolution, coloring pages, non-dinosaur creatures, activities, and links for more information. Each dinosaur page contains information on size, anatomy, body features, behavior, life span, diet, intelligence, classification, discovery of its fossils, and a diagram.
Along with the tri-lineage of bone, cartilage and fat, human mesenchymal stem cells (hMSCs) retain neural lineage potential. Multiple factors have been described that influence lineage fate of hMSCs including the extracellular microenvironment or niche. The niche includes the extracellular matrix (ECM) providing structural composition, as well as other associated proteins and growth factors, which collectively influence hMSC stemness and lineage specification. As such, lineage specific differentiation of MSCs is mediated through interactions including cell-cell and cell-matrix, as well as through specific signalling pathways triggering downstream events. Proteoglycans (PGs) are ubiquitous within this microenvironment and can be localised to the cell surface or embedded within the ECM. In addition, the heparan sulfate (HS) and chondroitin sulfate (CS) families of PGs interact directly with a number of growth factors, signalling pathways and ECM components including FGFs, Wnts and fibronectin. With evidence supporting a role for HSPGs and CSPGs in the specification of hMSCs down the osteogenic, chondrogenic and adipogenic lineages, along with the localisation of PGs in development and regeneration, it is conceivable that these important proteins may also play a role in the differentiation of hMSCs toward the neuronal lineage. Here we summarise the current literature and highlight the potential for HSPG directed neural lineage fate specification in hMSCs, which may provide a new model for brain damage repair. PMID:24509075
Okolicsanyi, Rachel K; Griffiths, Lyn R; Haupt, Larisa M
Are you searching for images of dinosaurs? If so, then set your sights on David Goldman's website of dinosaur illustrations. Mr. Goldman, a dinosaur aficionado, has created a nicely organized site connecting visitors to an impressive online network of dinosaur artwork. The website hosts a diverse and extensive collection of dinosaurs including the Allosaurus, Hadrosaur, Oviraptor, Pteranodon, and over course the iconic Tyrannosaurus Rex. Dinosaur illustrations can be located by alphabetic index, or by using the site's search engine. Illustration listings are accompanied by small, hyperlinked preview images that connect to the illustration's Internet source. The website also links to a collection of Panoramas, prehistoric animal images, and paleontology book reviews appearing in _Prehistoric Times_.
Until recently, dinosaurs were looked upon as sluggish, dim-witted beasts dragging their tails in the swamps. With the commercialization of Jurassic Park, students today have a different view of dinosaur life, but what they may not understand is the process used by scientists to revise their interpretation of the fossil record. The purpose of this unit is to have students understand how the scientific method is used to study the life history of dinosaurs. Using readings, video productions, and resources available from museums of paleontology, students are challenged to think of how we can best interpret the fossil record as it pertains to dinosaurs. Students investigate themes in dinosaur evolution, anatomy, physiology, and behavior, as well as ideas regarding the formulation of their own hypotheses pertaining to dinosaur life, and they are further challenged to describe the ways in which they would obtain evidence to support their ideas.
BEGIN:VCARD VERSION:2.1 FN:Mark Stefanski N:Stefanski;Mark ORG:Marin Academy REV:2005-04-14 END:VCARD
This lesson plan will help students learn that discoveries about dinosaurs have a long history and that each paleontologist adds his or her work to a body of fossil evidence used to support theories about dinosaurs. In it, students will use the internet to explore the discovery of fossils and dinosaurs. The website includes the lesson plan, extensions, guidelines for evaluation, and MCREL standards alignment.
To better understand the transcrip- tional program that accompanies orderly lineage- specific hematopoietic differentiation, we analyzed expression changes during the lineage-specific dif- ferentiation of human hematopoietic stem cells (HSC; CD34\\/CD38-\\/CD33-); HSC and multipo- tent myeloid progenitors (MMP; CD34\\/CD38-\\/ CD33) were isolated from the bone marrow of healthy individuals by MACS. CD34 cells in semi- solid culture were stimulated with the
Xiao-Ling Liu; Jin-Yun Yuan; Jun-Wu Zhang; Xin-Hua Zhang; Rong-Xin Wang
This colorful, informative and cluttered site is "a comprehensive on-line hypertext book about dinosaurs" by Enchanted Learning Software. Designed for students "of all ages and levels of comprehension," Zoom Dinosaurs is most appropriate for the K-12 level. Topics are presented at a basic level (e.g., All About Dinosaurs, Anatomy & Behavior, Mesozoic Era), but by clicking on hyperlinked text, users may progress to more advanced information. Classroom activities include dinosaur-related word games, quizzes, art projects, and fossil record/geologic timeline activities. A selection of links connects curious users to additional K-12 educational sites.
Werner syndrome (WS) patients exhibit premature aging predominantly in mesenchyme-derived tissues, but not in neural lineages, a consequence of telomere dysfunction and accelerated senescence. The cause of this lineage-specific aging remains unknown. Here, we document that reprogramming of WS fibroblasts to pluripotency elongated telomere length and prevented telomere dysfunction. To obtain mechanistic insight into the origin of tissue-specific aging, we differentiated iPSCs to mesenchymal stem cells (MSCs) and neural stem/progenitor cells (NPCs). We observed recurrence of premature senescence associated with accelerated telomere attrition and defective synthesis of the lagging strand telomeres in MSCs, but not in NPCs. We postulate this "aging" discrepancy is regulated by telomerase. Expression of hTERT or p53 knockdown ameliorated the accelerated aging phenotypein MSC, whereas inhibition of telomerase sensitized NPCs to DNA damage. Our findings unveil a role for telomerase in the protection of accelerated aging in a specific lineage of stem cells. PMID:24749076
Cheung, Hoi-Hung; Liu, Xiaozhuo; Canterel-Thouennon, Lucile; Li, Lu; Edmonson, Catherine; Rennert, Owen M
The present invention provides methods to promote the differentiation of pluripotent stem cells. In particular, the present invention provides an improved method for the formation of pancreatic endoderm, pancreatic hormone expressing cells and pancreatic hormone secreting cells. The present invention also provides methods to promote the differentiation of pluripotent stem cells without the use of a feeder cell layer.
The advent of reprogramming and its impact on stem cell biology has renewed interest in lineage restriction in mammalian embryos, the source of embryonic (ES), epiblast (EpiSC), trophoblast (TS), and extraembryonic endoderm (XEN) stem cell lineages. Isolation of specific cell types during stem cell differentiation and reprogramming, and also directly from embryos, is a major technical challenge because few cell-surface proteins are known that can distinguish each cell type. We provide a large-scale proteomic resource of cell-surface proteins for the four embryo-derived stem cell lines. We validated 27 antibodies against lineage-specific cell-surface markers, which enabled investigation of specific cell populations during ES-EpiSC reprogramming and ES-to-XEN differentiation. Identified markers also allowed prospective isolation and characterization of viable lineage progenitors from blastocysts by flow cytometry. These results provide a comprehensive stem cell proteomic resource and enable new approaches to interrogate the mechanisms that regulate cell fate specification. PMID:22424930
Rugg-Gunn, Peter J; Cox, Brian J; Lanner, Fredrik; Sharma, Parveen; Ignatchenko, Vladimir; McDonald, Angela C H; Garner, Jodi; Gramolini, Anthony O; Rossant, Janet; Kislinger, Thomas
Summary The advent of reprogramming and its impact on stem cell biology has renewed interest in lineage restriction in mammalian embryos, the source of embryonic (ES), epiblast (EpiSC), trophoblast (TS), and extraembryonic endoderm (XEN) stem cell lineages. Isolation of specific cell types during stem cell differentiation and reprogramming, and also directly from embryos, is a major technical challenge because few cell-surface proteins are known that can distinguish each cell type. We provide a large-scale proteomic resource of cell-surface proteins for the four embryo-derived stem cell lines. We validated 27 antibodies against lineage-specific cell-surface markers, which enabled investigation of specific cell populations during ES-EpiSC reprogramming and ES-to-XEN differentiation. Identified markers also allowed prospective isolation and characterization of viable lineage progenitors from blastocysts by flow cytometry. These results provide a comprehensive stem cell proteomic resource and enable new approaches to interrogate the mechanisms that regulate cell fate specification.
Rugg-Gunn, Peter J.; Cox, Brian J.; Lanner, Fredrik; Sharma, Parveen; Ignatchenko, Vladimir; McDonald, Angela C.H.; Garner, Jodi; Gramolini, Anthony O.; Rossant, Janet; Kislinger, Thomas
On Dinosaur Day, first-grade students rotated through four dinosaur-related learning stations that integrated science content with art, language arts, math, and history in a fun and time-efficient manner. The event drew parents, teachers, and students together as they helped each other discuss, write, draw, measure, mix, and record at each learning station.
Baptiste, H. P.; Nakamura, Sandra
In this activity about dinosaurs and survival, learners use scrap materials to create a miniature dinosaur habitat that includes a food source, water source, and shelter. This resource includes definitions of key words (habitat, carnivores, herbivores, omnivores, extinct) as well as discussion questions to further learning.
Recent discoveries have highlighted the dramatic evolutionary transformation of massive, ground-dwelling theropod dinosaurs into light, volant birds. Here, we apply Bayesian approaches (originally developed for inferring geographic spread and rates of molecular evolution in viruses) in a different context: to infer size changes and rates of anatomical innovation (across up to 1549 skeletal characters) in fossils. These approaches identify two drivers underlying the dinosaur-bird transition. The theropod lineage directly ancestral to birds undergoes sustained miniaturization across 50 million years and at least 12 consecutive branches (internodes) and evolves skeletal adaptations four times faster than other dinosaurs. The distinct, prolonged phase of miniaturization along the bird stem would have facilitated the evolution of many novelties associated with small body size, such as reorientation of body mass, increased aerial ability, and paedomorphic skulls with reduced snouts but enlarged eyes and brains. PMID:25082702
Lee, Michael S Y; Cau, Andrea; Naish, Darren; Dyke, Gareth J
Thermogenic (beige and brown) adipocytes protect animals against obesity and metabolic disease. However, little is known about the mechanisms that commit stem cells toward different adipocyte lineages. We show here that p107 is a master regulator of adipocyte lineage fates, its suppression required for commitment of stem cells to the brown-type fate. p107 is strictly expressed in the stem cell compartment of white adipose tissue depots and completely absent in brown adipose tissue. Remarkably, p107-deficient stem cells uniformly give rise to brown-type adipocytes in vitro and in vivo. Furthermore, brown fat programming of mesenchymal stem cells by PRDM-BF1-RIZ1 homologous domain containing 16 (Prdm16) was associated with a dramatic reduction of p107 levels. Indeed, Prdm16 directly suppressed p107 transcription via promoter binding. Notably, the sustained expression of p107 blocked the ability of Prdm16 to induce brown fat genes. These findings demonstrate that p107 expression in stem cells commits cells to the white versus brown adipose lineage. PMID:24449206
De Sousa, Martina; Porras, Deanna P; Perry, Christopher G R; Seale, Patrick; Scimè, Anthony
This protocol and the accompanying software program called LEVER enable quantitative automated analysis of phase contrast time-lapse images of cultured neural stem cells. Images are captured at 5 min. intervals over a period of 5 to 15 days as the cells proliferate and differentiate. LEVER automatically segments, tracks and generates lineage trees of the stem cells from the image sequence. In addition to generating lineage trees capturing the population dynamics of clonal development, LEVER extracts quantitative phenotypic measurements of cell location, shape, movement, and size. When available, the system can include biomolecular markers imaged using fluorescence. It then displays the results to the user for highly efficient inspection and editing to correct any errors in the segmentation, tracking or lineaging. In order to enable high-throughput inspection, LEVER incorporates features for rapid identification of errors, and learning from user-supplied corrections to automatically identify and correct related errors.
Winter, Mark; Wait, Eric; Roysam, Badri; Goderie, Susan; Ali, Rania Ahmed Naguib; Kokovay, Erzsebet; Temple, Sally; Cohen, Andrew R.
SUMMARY Epigenetic mechanisms have been proposed to play crucial roles in mammalian development, but their precise functions are only partially understood. To investigate epigenetic regulation of embryonic development, we differentiated human embryonic stem cells into mesendoderm, neural progenitor cells, trophoblast-like cells, and mesenchymal stem cells, and systematically characterized DNA methylation, chromatin modifications, and the transcriptome in each lineage. We found that promoters that are active in early developmental stages tend to be CG rich and mainly engage H3K27me3 upon silencing in non-expressing lineages. By contrast, promoters for genes expressed preferentially at later stages are often CG poor and primarily employ DNA methylation upon repression. Interestingly, the early developmental regulatory genes are often located in large genomic domains that are generally devoid of DNA methylation in most lineages, which we termed DNA methylation valleys (DMVs). Our results suggest that distinct epigenetic mechanisms regulate early and late stages of ES cell differentiation.
Xie, Wei; Schultz, Matthew D.; Lister, Ryan; Hou, Zhonggang; Rajagopal, Nisha; Ray, Pradipta; Whitaker, John W.; Tian, Shulan; Hawkins, R. David; Leung, Danny; Yang, Hongbo; Wang, Tao; Lee, Ah Young; Swanson, Scott A.; Zhang, Jiuchun; Zhu, Yun; Kim, Audrey; Nery, Joseph R.; Urich, Mark A.; Kuan, Samantha; Yen, Chia-an; Klugman, Sarit; Yu, Pengzhi; Suknuntha, Kran; Propson, Nicholas E.; Chen, Huaming; Edsall, Lee E.; Wagner, Ulrich; Li, Yan; Ye, Zhen; Kulkarni, Ashwinikumar; Xuan, Zhenyu; Chung, Wen-Yu; Chi, Neil C.; Antosiewicz-Bourget, Jessica E.; Slukvin, Igor; Stewart, Ron; Zhang, Michael Q.; Wang, Wei; Thomson, James A.; Ecker, Joseph R.; Ren, Bing
Members of the SWI/SNF chromatin-remodeling complex are among the most frequently mutated genes in human cancer, but how they suppress tumorigenesis is currently unclear. Here, we use Drosophila neuroblasts to demonstrate that the SWI/SNF component Osa (ARID1) prevents tumorigenesis by ensuring correct lineage progression in stem cell lineages. We show that Osa induces a transcriptional program in the transit-amplifying population that initiates temporal patterning, limits self-renewal, and prevents dedifferentiation. We identify the Prdm protein Hamlet as a key component of this program. Hamlet is directly induced by Osa and regulates the progression of progenitors through distinct transcriptional states to limit the number of transit-amplifying divisions. Our data provide a mechanistic explanation for the widespread tumor suppressor activity of SWI/SNF. Because the Hamlet homologs Evi1 and Prdm16 are frequently mutated in cancer, this mechanism could well be conserved in human stem cell lineages. PAPERCLIP: PMID:24630726
Eroglu, Elif; Burkard, Thomas R; Jiang, Yanrui; Saini, Nidhi; Homem, Catarina C F; Reichert, Heinrich; Knoblich, Juergen A
The Museum of Western Colorado's Dinosaur Journey Museum in Fruita, Colorado is located in the heart of dinosaur country. The Museum features exhibits and information about dinosaurs of western Colorado, eastern Utah and surrounding areas. There are robotic displays of Dilophosaurus, Stegosaurus, Apatosaurus, Triceratops, Utahraptor, T-Rex, and exhibits include real bones plus cast skeletons of Camarasaurus, Camptosaurus, Stegosaurus, Allosaurus, Velociraptor, Othnielia and the rare Mymoorapelta. There is a monthly newsletter available online with information on interpretive hikes and tours, an Extinct Animal of the Month, and the latest information on paleontological finds in the area.
Background The mechanisms responsible for the maintenance of pluripotency in human embryonic stem cells, and those that drive their commitment into particular differentiation lineages, are poorly understood. In fact, even our knowledge of the phenotype of hESC is limited, because the immunological and molecular criteria presently used to define this phenotype describe the properties of a heterogeneous population of cells. Results We used a novel approach combining immunological and transcriptional analysis (immunotranscriptional profiling) to compare gene expression in hESC populations at very early stages of differentiation. Immunotranscriptional profiling enabled us to identify novel markers of stem cells and their differentiated progeny, as well as novel potential regulators of hESC commitment and differentiation. The data show clearly that genes associated with the pluripotent state are downregulated in a coordinated fashion, and that they are co-expressed with lineage specific transcription factors in a continuum during the early stages of stem cell differentiation. Conclusion These findings, that show that maintenance of pluripotency and lineage commitment are dynamic, interactive processes in hESC cultures, have important practical implications for propagation and directed differentiation of these cells, and for the interpretation of mechanistic studies of hESC renewal and commitment. Since embryonic stem cells at defined stages of commitment can be isolated in large numbers by immunological means, they provide a powerful model for studying molecular genetics of stem cell commitment in the embryo.
Laslett, Andrew L; Grimmond, Sean; Gardiner, Brooke; Stamp, Lincon; Lin, Adelia; Hawes, Susan M; Wormald, Sam; Nikolic-Paterson, David; Haylock, David; Pera, Martin F
Adult stem cells have an enormous potential for clinical use in regenerative medicine that avoids many of the drawbacks characteristic of embryonic stem cells and induced pluripotent stem cells. In this context, easily obtainable human adipose-derived stem cells offer an interesting option for future strategies in regenerative medicine. However, little is known about their repertoire of differentiation capacities, how closely they resemble the target primary tissues, and the potential safety issues associated with their use. DNA methylation is one of the most widely recognized epigenetic factors involved in cellular identity, prompting us to consider how the analyses of 27,578 CpG sites in the genome of these cells under different conditions reflect their different natural history. We show that human adipose-derived stem cells generate myogenic and osteogenic lineages that share much of the DNA methylation landscape characteristic of primary myocytes and osteocytes. Most important, adult stem cells and in vitro-generated myocytes and osteocytes display a significantly different DNA methylome from that observed in transformed cells from these tissue types, such as rhabdomyosarcoma and osteosarcoma. These results suggest that the plasticity of the DNA methylation patterns plays an important role in lineage commitment of adult stem cells and that it could be used for clinical purposes as a biomarker of efficient and safely differentiated cells. PMID:23031258
Berdasco, María; Melguizo, Consolación; Prados, Jose; Gómez, Antonio; Alaminos, Miguel; Pujana, Miguel A; Lopez, Miguel; Setien, Fernando; Ortiz, Raul; Zafra, Inma; Aranega, Antonia; Esteller, Manel
\\u000a In the face of extraordinary advances in the prevention, diagnosis, and treatment of human diseases, devastating cardiopulmonary\\u000a diseases continue to deprive people of health. Research in developmental biology has led to the discovery of stem cells, which\\u000a provide a platform to understand the basic mechanism of those diseases and give a hope for potential clinical applications.\\u000a Three main types of
Andriana Margariti; Lingfang Zeng; Qingbo Xu
The propensity of stem cells to specify and commit to a particular lineage program is guided by dynamic biophysical and biochemical signals that are temporally regulated. However, most in vitro studies rely on "snapshots" of cell state under static conditions. Here we asked whether changing the biophysical aspects of the substrate could modulate the degree of mesenchymal stem cell (MSC) lineage specification. We chose to explore two diverse differentiation outcomes: MSC osteogenesis and trans-differentiation to neuron-like cells. MSCs were cultured on soft (~0.5?kPa) or stiff (~40?kPa) hydrogels followed by transfer to gels of the opposite stiffness. MSCs on soft gels express elevated neurogenesis markers while MSCs on stiff substrates express elevated osteogenesis markers. Transfer of MSCs from soft to stiff or stiff to soft substrates led to a switch in lineage specification. However, MSCs transferred from stiff to soft substrates maintained elevated osteogenesis markers, suggesting a degree of irreversible activation. Transferring MSCs to micropatterned substrates reveal geometric cues that further modulate lineage reversal. Taken together, this study demonstrates that MSCs remain susceptible to the biophysical properties of the extracellular matrix-even after several weeks of culture-and can redirect lineage specification in response to changes in the microenvironment. PMID:24898422
Lee, Junmin; Abdeen, Amr A; Kilian, Kristopher A
The propensity of stem cells to specify and commit to a particular lineage program is guided by dynamic biophysical and biochemical signals that are temporally regulated. However, most in vitro studies rely on “snapshots” of cell state under static conditions. Here we asked whether changing the biophysical aspects of the substrate could modulate the degree of mesenchymal stem cell (MSC) lineage specification. We chose to explore two diverse differentiation outcomes: MSC osteogenesis and trans-differentiation to neuron-like cells. MSCs were cultured on soft (~0.5?kPa) or stiff (~40?kPa) hydrogels followed by transfer to gels of the opposite stiffness. MSCs on soft gels express elevated neurogenesis markers while MSCs on stiff substrates express elevated osteogenesis markers. Transfer of MSCs from soft to stiff or stiff to soft substrates led to a switch in lineage specification. However, MSCs transferred from stiff to soft substrates maintained elevated osteogenesis markers, suggesting a degree of irreversible activation. Transferring MSCs to micropatterned substrates reveal geometric cues that further modulate lineage reversal. Taken together, this study demonstrates that MSCs remain susceptible to the biophysical properties of the extracellular matrix—even after several weeks of culture—and can redirect lineage specification in response to changes in the microenvironment.
Lee, Junmin; Abdeen, Amr A.; Kilian, Kristopher A.
In this classroom activity, middle school students learn what kinds of information can be gained by studying teeth. The activity opens with background information for teachers about dinosaur teeth. Working in small groups, students examine their own teeth; hypothesize about how incisors, canine teeth, and molars are used; and test their hypotheses with carrots. The activity concludes with a student worksheet that challenges them to identify the uses of different dinosaur teeth.
Lactation is a process associated with mammals, yet a number of birds feed their newly hatched young on secretions analogous to the milk of mammals. These secretions are produced from various sections (crop organ, oesophageal lining and proventriculus) of the upper digestive tract and possess similar levels of fat and protein, as well as added carotenoids, antibodies and, in the case of pigeons and doves, epidermal growth factor. Parental care in avian species has been proposed to originate from dinosaurs. This study examines the possibility that some dinosaurs used secretory feeding to increase the rate of growth of their young, estimated to be similar to that of present day birds and mammals. Dinosaur 'lactation' could also have facilitated immune responses as well as extending parental protection as a result of feeding newly hatched young in nest environments. While the arguments for dinosaur lactation are somewhat generic, a case study for lactation in herbivorous site-nesting dinosaurs is presented. It is proposes that secretory feeding could have been used to bridge the gap between hatching and establishment of the normal diet in some dinosaurs. PMID:23325856
Else, Paul L
In this activity, learners rotate through several learning and play stations to explore dinosaurs and paleontologists. At these stations, learners use sand and dinosaur bone replicas to create a dig site and make observations, read several dinosaur books and complete dinosaur puzzles, role play as dinosaur hunters as they explore online dinosaur sites, create a dinosaur romp, listen to dinosaur music, and use clay or play dough to make dinosaurs and dinosaur tracks. This activity is featured on page 9 of the "Dinosphere" unit of study for K-2 learners.
Crosslin, Rick; Fortney, Mary; Indianapolis, The C.
Background Polycomb Group (PcG) proteins are chromatin modifiers involved in early embryonic development as well as in proliferation of adult stem cells and cancer cells. PcG proteins form large repressive complexes termed Polycomb Repressive Complexes (PRCs) of which PRC1 and PRC2 are well studied. Differentiation of human Embryonic Stem (hES) cells into insulin producing cells has been achieved to limited extent, but several aspects of differentiation remain unexplored. The PcG protein dynamics in human embryonic stem (hES) cells during differentiation into pancreatic lineage has not yet been reported. In the present study, the expression of RING1A, RING1B, BMI1, CBX2, SUZ12, EZH2, EED and JARID2 during differentiation of hES cells towards pancreatic lineage was examined. Results In-house derived hES cell line KIND1 was used to study expression of PcG protein upon spontaneous and directed differentiation towards pancreatic lineage. qRT-PCR analysis showed expression of gene transcripts for various lineages in spontaneously differentiated KIND1 cells, but no differentiation into pancreatic lineage was observed. Directed differentiation induced KIND1 cells grown under feeder-free conditions to transition from definitive endoderm (Day 4), primitive gut tube stage (Day 8) and pancreatic progenitors (Day 12-Day 16) as evident from expression of SOX17, PDX1 and SOX9 by qRT-PCR and Western blotting. In spontaneously differentiating KIND1 cells, RING1A and SUZ12 were upregulated at day 15, while other PcG transcripts were downregulated. qRT-PCR analysis showed transcripts of RING1B, BMI1, SUZ12, EZH2 and EED were upregulated, while RING1A and CBX2 expression remained low and JARID2 was downregulated during directed differentiation of KIND1 cells. Upregulation of BMI1, EZH2 and SUZ12 during differentiation into pancreatic lineage was also confirmed by Western blotting. Histone modifications such as H3K27 trimethylation and monoubiquitinylation of H2AK119 increased during differentiation into pancreatic lineage as seen by Western blotting. Conclusion Our study shows expression of PcG proteins was distinct during spontaneous and directed differentiation. Differentiation into pancreatic lineage was achieved by directed differentiation approach and was associated with increased expression of PcG proteins RING1B, BMI1, EZH2 and SUZ12 accompanied by increase in monoubiquitinylation of H2AK119 and trimethylation of H3K27.
Perhaps you are a paleontologist or have always wondered what it is like to be one. Or you are fascinated by fossils and like to read about the origins and natural history of dinosaurs. Or maybe you are an avid traveler and reader of travelogues. If you are any of these things, then this book is for you. Originally published in 1994 in French, Dinosaur Impressions is the engaging account of thirty years of travel and paleontological exploration by Philippe Taquet, one of the world's most noted paleontologists. Dr. Taquet takes the reader on a surprisingly far-flung tour ranging from the Provence countryside to the Niger desert, from the Brazilian bush to the Mongolian Steppes, and from the Laos jungle to the Moroccan mountains in search of dinosaur bones and what they have to tell us about a vanished world. With wry humor and lively anecdotes, Dr. Taquet retraces the history of paleontological research, along the way discussing the latest theories of dinosaur existence and extinction. Elegantly translated by Kevin Padian, Dinosaur Impressions provides a unique, thoughtful perspective not often encountered in American- and English-language works. This insightful, first-hand account of an exceptional career is also a travelogue par excellence that will enthrall enthusiasts and general readers alike. Philippe Taquet is the Director of the National Museum of Natural History in Paris and is a member of the French Academy of Sciences. Kevin Padian is a professor in the Department of Integrative Biology and Curator of the Museum of Paleontology at the University of California, Berkeley. He is also the editor of The Beginning of the Age of Dinosaurs (Cambridge, 1986) and The Encyclopedia of Dinosaurs (1997).
Mesenchymal stem cells (MSCs) are multipotent cells that have the potential to differentiate into various mesenchymal lineages in vitro and in vivo. Due to their availability from tissues such as bone marrow, synovium, fat, and muscle, and their highly proliferative capacity, MSCs have evoked interest as a potential cell source for repair and regeneration of various types of tissues. Characterization by the expression of a panel of surface markers and the ability of MSCs to undergo multilineage differentiation is the benchmark for identifying this stem cell population. In this chapter, the protocols for the differentiation of MSC to chondrogenic, osteogenic, and adipogenic lineages and histological and immunostaining protocols for confirming trilineage differentiation of the MSC cells are described. PMID:21431531
Yang, Zheng; Schmitt, Jacqueline Frida; Lee, Eng Hin
MicroRNAs (miRs) comprise a class of tiny (?19–24 nucleotide), noncoding RNAs that regulate gene expression posttranscriptionally. Since the discovery of the founding members lin-4 and let-7 as key regulators in the developing nematode, miRs have been found throughout the eukaryotic kingdom. Functions for miRs are wide-ranging and encompass embryogenesis, stem cell biology, tissue differentiation, and human diseases including cancers. In this chapter, we begin by acquainting our readers with miRs and introducing them to their biogenesis. Then, we focus on the roles of miRs in stem cells during tissue development and homeostasis. We use mammalian skin as our main paradigm, but we also consider miR functions in several different types of adult stem cells. We conclude by discussing future challenges that will lead to a comprehensive understanding of miR functions in stem cells and their lineages.
Yi, Rui; Fuchs, Elaine
SUMMARY Cell fate decisions of pluripotent embryonic stem (ES) cells are dictated by activation and repression of lineage-specific genes. Numerous signaling and transcriptional networks progressively narrow and specify the potential of ES cells. Whether specific microRNAs help refine and limit gene expression and, thereby,could be used to manipulate ES cell dif- ferentiation has largely been unexplored. Here, we show that
Kathryn N. Ivey; Alecia Muth; Joshua Arnold; Frank W. King; Ru-Fang Yeh; Jason E. Fish; Edward C. Hsiao; Robert J. Schwartz; Bruce R. Conklin; Harold S. Bernstein; Deepak Srivastava
This Science NetLinks lesson is the first of a two-part series on dinosaurs. This lesson taps into student curiosity about dinosaurs in order to lead them to consider life forms that no longer exist. A variety of activities are suggested, including viewing online video clips, creating dinosaur puppets, and constructing dinosaur eggs.
Advancements in human pluripotent stem cell (hPSC) research have potential to revolutionize therapeutic transplantation. It has been demonstrated that transcription factors may play key roles in regulating maintenance, expansion, and differentiation of hPSCs. In addition to its regulatory functions in hematopoiesis and blood-related disorders, the transcription factor RUNX1 is also required for the formation of definitive blood stem cells. In this study, we demonstrated that expression of endogenous RUNX1a, an isoform of RUNX1, parallels with lineage commitment and hematopoietic emergence from hPSCs, including both human embryonic stem cells and inducible pluripotent stem cells. In a defined hematopoietic differentiation system, ectopic expression of RUNX1a facilitates emergence of hematopoietic progenitor cells (HPCs) and positively regulates expression of mesoderm and hematopoietic differentiation-related factors, including Brachyury, KDR, SCL, GATA2, and PU.1. HPCs derived from RUNX1a hPSCs show enhanced expansion ability, and the ex vivo-expanded cells are capable of differentiating into multiple lineages. Expression of RUNX1a in embryoid bodies (EBs) promotes definitive hematopoiesis that generates erythrocytes with ?-globin production. Moreover, HPCs generated from RUNX1a EBs possess ?9-week repopulation ability and show multilineage hematopoietic reconstitution in vivo. Together, our results suggest that RUNX1a facilitates the process of producing therapeutic HPCs from hPSCs. PMID:23372166
Ran, Dan; Shia, Wei-Jong; Lo, Miao-Chia; Fan, Jun-Bao; Knorr, David A; Ferrell, Patrick I; Ye, Zhaohui; Yan, Ming; Cheng, Linzhao; Kaufman, Dan S; Zhang, Dong-Er
This Encyclopedia Britannica website highlights the history and changes in thought surrounding dinosaurs since they were discovered. Beginning in the 1820s, this site explores the continued findings which have led to present-day theories regarding what dinosaurs were like, as well as what happened to them. Topics covered include dinosaur anatomy, physiology, characteristics of behavior, and the environments in which they lived. Each topic is discussed in a sequential order. This site contains classroom activities with a teacher's guide to help students explore and understand ideas about these creatures, using this website. The teacher's guide contains details about classroom management and assessment, as well as teaching tips. Links are provided for further information.
This lesson plan is part of the DiscoverySchool.com lesson plan library for grades 6-8. It focuses on the science of paleontology, how scientists have made conclusions about the lives of dinosaurs, and the scientific techniques used for gathering information about dinosaurs. It includes objectives, materials, procedures, discussion questions, evaluation ideas, suggested readings, and vocabulary. There are videos available to order which complement this lesson, an audio-enhanced vocabulary list, and links to teaching tools for making custom quizzes, worksheets, puzzles and lesson plans.
This site will appeal to dinosaur lovers of all ages. It comes from the American Museum of Natural History and serves as a companion to a new exhibit highlighting recent discoveries from Mongolia, including one of the most famous finds ever: a Velociraptor that was apparently buried alive by a sand flow while attacking a Protoceratops. The site features animated recreations of the last moments of these dinosaurs and their fossilized remains, as well as a modest image gallery of some of the other specimens from Mongolia, some of them yet to be named. Beginning Monday May 22, a virtual tour of the exhibit (IPIX plug-in required) will be available.
For more than a decade, many scientists have theorized that the disappearance of the dinosaurs may be due to the collision of a huge asteroid with Earth 65 mya. However, many gaps have persisted in the theory. Now NASA scientists offer a detailed explanation of how the impact may have led to the extinction of the dinosaur. In a recent issue of Earth and Planetary Science Letters, a team of scientists from the Jet Propulsion Laboratory's Earth and Space Sciences Division in Pasadena, Calif., write that the location of the impact was key.
Post-Triassic theropod, sauropodomorph, and ornithischian dinosaurs are readily recognized based on the set of traits that typically characterize each of these groups. On the contrary, most of the early members of those lineages lack such specializations, but share a range of generalized traits also seen in more basal dinosauromorphs. Here, we report on a new Late Triassic dinosaur from the Santa Maria Formation of Rio Grande do Sul, southern Brazil. The specimen comprises the disarticulated partial skeleton of a single individual, including most of the skull bones. Based on four phylogenetic analyses, the new dinosaur fits consistently on the sauropodomorph stem, but lacks several typical features of sauropodomorphs, showing dinosaur plesiomorphies together with some neotheropod traits. This is not an exception among basal dinosaurs, the early radiation of which is characterized by a mosaic pattern of character acquisition, resulting in the uncertain phylogenetic placement of various early members of the group.
Cabreira, Sergio F.; Schultz, Cesar L.; Bittencourt, Jonathas S.; Soares, Marina B.; Fortier, Daniel C.; Silva, Lúcio R.; Langer, Max C.
Post-Triassic theropod, sauropodomorph, and ornithischian dinosaurs are readily recognized based on the set of traits that typically characterize each of these groups. On the contrary, most of the early members of those lineages lack such specializations, but share a range of generalized traits also seen in more basal dinosauromorphs. Here, we report on a new Late Triassic dinosaur from the Santa Maria Formation of Rio Grande do Sul, southern Brazil. The specimen comprises the disarticulated partial skeleton of a single individual, including most of the skull bones. Based on four phylogenetic analyses, the new dinosaur fits consistently on the sauropodomorph stem, but lacks several typical features of sauropodomorphs, showing dinosaur plesiomorphies together with some neotheropod traits. This is not an exception among basal dinosaurs, the early radiation of which is characterized by a mosaic pattern of character acquisition, resulting in the uncertain phylogenetic placement of various early members of the group. PMID:22083251
Cabreira, Sergio F; Schultz, Cesar L; Bittencourt, Jonathas S; Soares, Marina B; Fortier, Daniel C; Silva, Lúcio R; Langer, Max C
The observed diversity of dinosaurs reached its highest peak during the mid- and Late Cretaceous, the 50 Myr that preceded their extinction, and yet this explosion of dinosaur diversity may be explained largely by sampling bias. It has long been debated whether dinosaurs were part of the Cretaceous Terrestrial Revolution (KTR), from 125-80 Myr ago, when flowering plants, herbivorous and social insects, squamates, birds and mammals all underwent a rapid expansion. Although an apparent explosion of dinosaur diversity occurred in the mid-Cretaceous, coinciding with the emergence of new groups (e.g. neoceratopsians, ankylosaurid ankylosaurs, hadrosaurids and pachycephalosaurs), results from the first quantitative study of diversification applied to a new supertree of dinosaurs show that this apparent burst in dinosaurian diversity in the last 18 Myr of the Cretaceous is a sampling artefact. Indeed, major diversification shifts occurred largely in the first one-third of the group's history. Despite the appearance of new clades of medium to large herbivores and carnivores later in dinosaur history, these new originations do not correspond to significant diversification shifts. Instead, the overall geometry of the Cretaceous part of the dinosaur tree does not depart from the null hypothesis of an equal rates model of lineage branching. Furthermore, we conclude that dinosaurs did not experience a progressive decline at the end of the Cretaceous, nor was their evolution driven directly by the KTR. PMID:18647715
Lloyd, Graeme T; Davis, Katie E; Pisani, Davide; Tarver, James E; Ruta, Marcello; Sakamoto, Manabu; Hone, David W E; Jennings, Rachel; Benton, Michael J
The observed diversity of dinosaurs reached its highest peak during the mid- and Late Cretaceous, the 50?Myr that preceded their extinction, and yet this explosion of dinosaur diversity may be explained largely by sampling bias. It has long been debated whether dinosaurs were part of the Cretaceous Terrestrial Revolution (KTR), from 125–80?Myr ago, when flowering plants, herbivorous and social insects, squamates, birds and mammals all underwent a rapid expansion. Although an apparent explosion of dinosaur diversity occurred in the mid-Cretaceous, coinciding with the emergence of new groups (e.g. neoceratopsians, ankylosaurid ankylosaurs, hadrosaurids and pachycephalosaurs), results from the first quantitative study of diversification applied to a new supertree of dinosaurs show that this apparent burst in dinosaurian diversity in the last 18 Myr of the Cretaceous is a sampling artefact. Indeed, major diversification shifts occurred largely in the first one-third of the group's history. Despite the appearance of new clades of medium to large herbivores and carnivores later in dinosaur history, these new originations do not correspond to significant diversification shifts. Instead, the overall geometry of the Cretaceous part of the dinosaur tree does not depart from the null hypothesis of an equal rates model of lineage branching. Furthermore, we conclude that dinosaurs did not experience a progressive decline at the end of the Cretaceous, nor was their evolution driven directly by the KTR.
Lloyd, Graeme T; Davis, Katie E; Pisani, Davide; Tarver, James E; Ruta, Marcello; Sakamoto, Manabu; Hone, David W.E; Jennings, Rachel; Benton, Michael J
This Classroom of the Future (COTF) resource explores dinosaurs and the possible causes of their extinction, including orbital changes in the Earth, volcanoes, disease, a supernova, and asteroid impact. The site provides a brief, illustrated essay for each theory, as well as links to related sites.
These twelve dark-line dinosaur drawings can be used as either a research or coloring activity. Overhead transparencies of the drawings can be projected to make large traced images of the animals. The site includes drawings of Ankylosaurus, Barosaurus, Coelophysis, Diplodocus, Iguanodon, Ornithomimus, Pachycephalosaurus, Parasaurolophus, Plateosaurus, Stegosaurus, Triceratops, and Tyrannosaurus rex.
The use of programs on the topic of dinosaurs in interdisciplinary exercises which may include mathematics, science, history, and language arts is described. Reviews of 16 different computer programs are included. Possible misconceptions and how they are dealt with in various programs are discussed. (CW)
Perhaps you are a paleontologist or have always wondered what it is like to be one. Or you are fascinated by fossils and like to read about the origins and natural history of dinosaurs. Or maybe you are an avid traveler and reader of travelogues. If you are any of these things, then this book is for you. Originally published
This is an activity about dinosaurs, fossils, and the work of paleontologists. Learners use hand tools (paint brushes, scoops, and sifters) to unearth fossil specimens in tubs of birdseed. This resource includes definitions of fossils and paleontologists as well as discussion questions to further learning.
Describes an art project for second-grade students where in over five class periods, they create fired clay dinosaur sculptures with dioramas as the background. States that this project, the culminating activity for a sculpture unit, teaches students many art terms and uses of different media. (CMK)
In this classroom activity, young students are introduced to sets and subsets. The activity opens with background information for teachers about cladistics. After brainstorming different ways to group the class itself, students work in small groups to identify subsets of coins. The groups then complete a worksheet that challenges them to group dinosaurs into sets and subsets and share their results with the class.
In somatic cells, a collection of signaling pathways activated by amino acid limitation have been identified and referred to as the amino acid response (AAR). Despite the importance of possible detrimental effects of nutrient limitation during in vitro culture, the AAR has not been investigated in embryonic stem cells (ESC). AAR activation caused the expected increase in transcription factors that mediate specific AAR pathways, as well as the induction of asparagine synthetase, a terminal AAR target gene. Neither AAR activation nor stable knockdown of activating transcription factor (Atf) 4, a transcriptional mediator of the AAR, adversely affected ESC self-renewal or pluripotency. Low-level induction of the AAR over a 12-day period of embryoid body differentiation did alter lineage specification such that the primitive endodermal, visceral endodermal, and endodermal lineages were favored, whereas mesodermal and certain ectodermal lineages were suppressed. Knockdown of Atf4 further enhanced the AAR-induced increase in endodermal formation, suggesting that this phenomenon is mediated by an Atf4-independent mechanism. Collectively, the results indicate that, during differentiation of mouse embryoid bodies in culture, the availability of nutrients, such as amino acids, can influence the formation of specific cell lineages.
Shan, Jixiu; Hamazaki, Takashi; Tang, Tiffany A.; Terada, Naohiro
In this activity, learners explore the size and scale of dinosaurs. Learners listen to "Dinosaurs, Dinosaurs" by Byron Barton to understand some background information about dinosaurs. Then, learners use pipe cleaners or wire to create skeletal dinosaur models to scale based on reference drawings. As a group, learners then make a bar graph of the sizes of the dinosaurs. This activity is featured on page 19 of the "Dinosphere" unit of study for K-2 learners.
Crosslin, Rick; Fortney, Mary; Indianapolis, The C.
In this activity, learners explore dinosaur skeletons. First, learners listen to "Bones, Bones, Dinosaur Bones" by Byron Barton to learn about the difference between pictures of dinosaurs that have skin and muscle (fleshed-out) and those that show skeletons. Then, learners match pictures of dinosaurs to pictures of the dinosaurs' skeletons. Learners can also explore other animal bones and skeletons online and/or reassemble paper dinosaur skeletons. This activity can also be used to help learners explore scale as they realize that large dinosaurs had large skeletons and small dinosaurs had small skeletons. This activity is featured on page 37 of the "Dinosphere" unit of study for K-2 learners.
Crosslin, Rick; Fortney, Mary; Indianapolis, The C.
Continuous renewal of the epidermis and its appendages throughout life depends on the proliferation of a distinct population of cells called stem cells. We have used in situ retrovirus-mediated gene transfer to genetically mark cutaneous epithelial stem cells of adolescent mice, and have followed the fate of the marked progeny after at least 37 epidermal turnovers and five cycles of depilation-induced hair growth. Histological examination of serial sections of labeled pilosebaceous units demonstrated a complex cell lineage. In most instances, labeled cells were confined to one or more follicular compartments or solely to sebaceous glands. Labeled keratinocytes in interfollicular epidermis were confined to distinct columnar units representing epidermal proliferative units. The contribution of hair follicles to the epidermis was limited to a small rim of epidermis at the margin of the follicle, indicating that long term maintenance of interfollicular epidermis was independent of follicle-derived cells. Our results indicate the presence of multiple stem cells in cutaneous epithelium, some with restricted lineages in the absence of major injury.
Ghazizadeh, Soosan; Taichman, Lorne B.
Embryonic stem cells (ESCs) exhibit the dual properties of self-renewal and pluripotency as well as the ability to undergo differentiation that gives rise to all three germ layers. Wnt family members can both promote ESC maintenance and trigger differentiation while also controlling the expression of Snail1, a zinc-finger transcriptional repressor. Snail1 has been linked to events ranging from cell cycle regulation and cell survival to epithelial–mesenchymal transition (EMT) and gastrulation, but its role in self-renewal, pluripotency or lineage commitment in ESCs remains undefined. Here we demonstrate using isogenic pairs of conditional knockout mouse ESCs, that Snail1 exerts Wnt- and EMT independent control over the stem cell transcriptome without affecting self-renewal or pluripotency-associated functions. By contrast, during ESC differentiation, an endogenous Wnt-mediated burst in Snail1 expression regulates neuroectodermal fate while playing a required role in epiblast stem cell exit and the consequent lineage fate decisions that define mesoderm commitment.
Lin, Yongshun; Li, Xiao-Yan; Willis, Amanda L.; Liu, Chengyu; Chen, Guokai; Weiss, Stephen J.
Middle Jurassic to Early Cretaceous deposits from northeastern China have yielded varied theropod dinosaurs bearing feathers. Filamentous integumentary structures have also been described in ornithischian dinosaurs, but whether these filaments can be regarded as part of the evolutionary lineage toward feathers remains controversial. Here we describe a new basal neornithischian dinosaur from the Jurassic of Siberia with small scales around the distal hindlimb, larger imbricated scales around the tail, monofilaments around the head and the thorax, and more complex featherlike structures around the humerus, the femur, and the tibia. The discovery of these branched integumentary structures outside theropods suggests that featherlike structures coexisted with scales and were potentially widespread among the entire dinosaur clade; feathers may thus have been present in the earliest dinosaurs. PMID:25061209
Godefroit, Pascal; Sinitsa, Sofia M; Dhouailly, Danielle; Bolotsky, Yuri L; Sizov, Alexander V; McNamara, Maria E; Benton, Michael J; Spagna, Paul
Summary Understanding how interactions between extracellular signalling pathways and transcription factor networks influence cellular decision making will be crucial for understanding mammalian embryogenesis and for generating specialised cell types in vitro. To this end, pluripotent mouse Embryonic Stem (mES) cells have proven to be a useful model system. However, understanding how transcription factors and signalling pathways affect decisions made by individual cells is confounded by the fact that measurements are generally made on groups of cells, whilst individual mES cells differentiate at different rates and towards different lineages, even in conditions that favour a particular lineage. Here we have used single-cell measurements of transcription factor expression and Wnt/?-catenin signalling activity to investigate their effects on lineage commitment decisions made by individual cells. We find that pluripotent mES cells exhibit differing degrees of heterogeneity in their expression of important regulators from pluripotency, depending on the signalling environment to which they are exposed. As mES cells differentiate, downregulation of Nanog and Oct4 primes cells for neural commitment, whilst loss of Sox2 expression primes cells for primitive streak commitment. Furthermore, we find that Wnt signalling acts through Nanog to direct cells towards a primitive streak fate, but that transcriptionally active ?-catenin is associated with both neural and primitive streak commitment. These observations confirm and extend previous suggestions that pluripotency genes influence lineage commitment and demonstrate how their dynamic expression affects the direction of lineage commitment, whilst illustrating two ways in which the Wnt signalling pathway acts on this network during cell fate assignment.
Trott, Jamie; Martinez Arias, Alfonso
The intestine consists of epithelial cells that secrete digestive enzymes and mucus (gland cells), absorb food particles (enterocytes), and produce hormones (endocrine cells). Intestinal cells are rapidly turned over and need to be replaced. In cnidarians, mitosis of differentiated intestinal cells accounts for much of the replacement; in addition, migratory, multipotent stem cells (interstitial cells) contribute to the production of intestinal cells. In other phyla, intestinal cell replacement is solely the function of stem cells entering the gut from the outside (such as in case of the neoblasts of platyhelmints) or intestinal stem cells located within the midgut epithelium (as in both vertebrates or arthropods). We will attempt in the following to review important aspects of midgut stem cells in different animal groups: where are they located, what types of lineages do they produce, and how do they develop. We will start out with a comparative survey of midgut cell types found across the animal kingdom; then briefly look at the specification of these cells during embryonic development; and finally focus on the stem cells that regenerate midgut cells during adult life. In a number of model systems, including mouse, zebrafish and Drosophila, the molecular pathways controlling ISC proliferation and the specification of intestinal cell types are under intensive investigation. We will highlight findings of the recent literature, focusing on aspects that are shared between the different models and that point at evolutionary ancient mechanisms of intestinal cell formation.
Takashima, Shigeo; Gold, David; Hartenstein, Volker
Since induced pluripotent stem (iPS) cells have differentiation potential into all three germ layer-derived tissues, efficient purification of target cells is required in many fields of iPS research. One useful strategy is isolation of desired cells from differentiated iPS cells by lineage-specific expression of a drug-resistance gene, followed by drug selection. With this strategy, we purified neural stem/progenitor cells (NSCs), a good candidate source for regenerative therapy, from differentiated mouse iPS cells. We constructed a bicistronic expression vector simultaneously expressing blasticidin S resistance gene and DsRed under the control of tandem enhancer of a 257-base pair region of nestin second intron, an NSC-specific enhancer. This construct was efficiently inserted into the iPS genome by piggyBac transposon-mediated gene transfer, and the established subclone was differentiated into NSCs in the presence or absence of blasticidin S. Consequently, incubation with blasticidin S led to purification of NSCs from differentiated iPS cells. Our results suggest that a lineage-specific drug selection strategy is useful for purification of NSCs from differentiated iPS cells and that this strategy can be applied for the purification of other cell types.
Maruyama, Masato; Yamashita, Yuji; Kase, Masahiko; Trifonov, Stefan
Recent fossil discoveries from Early Cretaceous rocks of Liaoning Province, China, have provided a wealth of spectacular specimens. Included in these are the remains of several different kinds of small theropod dinosaurs, many of which are extremely closely related to modern birds. Unique preservation conditions allowed soft tissues of some of these specimens to be preserved. Many dinosaur specimens that preserve feathers and other types of integumentary coverings have been recovered. These fossils show a progression of integumentary types from simple fibers to feathers of modern aspect. The distribution of these features on the bodies of these animals is surprising in that some show large tail plumes, whereas others show the presence of wing-like structures on both fore and hind limbs. The phylogenetic distribution of feather types is highly congruent with models of feather evolution developed from developmental biology.
Norell, Mark A.; Xu, Xing
If the extinction of the dinosaurs was caused by a gigantic meteor that hit the earth 65 million years ago, as many scientists believe, then there should be traces of meteor dust in the geological record. This radio broadcast reports on a group of oceanographers who are drilling into the ocean floor to look for that meteor dust. The clip is 2 minutes in length.
Summary The balance of self-renewal and differentiation in long-term repopulating hematopoietic stem cells (LT-HSC) must be strictly controlled to maintain blood homeostasis and to prevent leukemogenesis. Hematopoietic cytokines can induce differentiation in LT-HSCs; however, the molecular mechanism orchestrating this delicate balance requires further elucidation. We identified the tumor suppressor GADD45G as an instructor of LT-HSC differentiation under the control of differentiation-promoting cytokine receptor signaling. GADD45G immediately induces and accelerates differentiation in LT-HSCs and overrides the self-renewal program by specifically activating MAP3K4-mediated MAPK p38. Conversely, the absence of GADD45G enhances the self-renewal potential of LT-HSCs. Videomicroscopy-based tracking of single LT-HSCs revealed that, once GADD45G is expressed, the development of LT-HSCs into lineage-committed progeny occurred within 36 hr and uncovered a selective lineage choice with a severe reduction in megakaryocytic-erythroid cells. Here, we report an unrecognized role of GADD45G as a central molecular linker of extrinsic cytokine differentiation and lineage choice control in hematopoiesis.
Thalheimer, Frederic B.; Wingert, Susanne; De Giacomo, Pangrazio; Haetscher, Nadine; Rehage, Maike; Brill, Boris; Theis, Fabian J.; Hennighausen, Lothar; Schroeder, Timm; Rieger, Michael A.
This dinosaur reference list has 25 kid-friendly books on a range of related topics. The author, publisher, and publication date are given for each title. The list includes illustrated compilations of the wide variety of dinosaurs that once roamed the Earth, accounts of what it's like to go digging for dinosaurs and theories about what killed off the dinosaurs.
This dinosaur reference list has 18 books that are recommended for learning more about Dinosaurs. The author, publisher, and publishing date are given for each title. The list includes encyclopedias of dinosaurs, real-life tales of fossil hunts, hands-on activities for students, and an examination of the link between birds and dinosaurs.
The intricate molecular mechanisms that regulate embryonic stem (ES) cell pluripotency are incompletely understood. Prior research indicated that activation of JAK-STAT3 pathway or inhibition of ERK/GSK3 signaling maintains mouse ES cell (mESC) pluripotency. Here we demonstrate that inhibition of protein kinase C (PKC) isoforms maintains mESC pluripotency without the activation of STAT3 or inhibition of ERK/GSK3 signaling pathways. Our analyses revealed that the atypical PKC isoform, PKC? plays an important role in inducing lineage commitment in mESCs through a PKC?–NF-?B signaling axis and inhibition of PKC isoforms maintains ES cell-specific epigenetic modifications. Furthermore, inhibition of PKC isoforms permits derivation of germline-competent ES cells from mouse blastocysts and also facilitates reprogramming of mouse embryonic fibroblasts (MEFs) towards induced pluripotent stem cells (iPSCs). Our results indicate that PKC signaling is critical to balancing ES cell self-renewal and lineage commitment.
Dutta, Debasree; Ray, Soma; Home, Pratik; Larson, Melissa; Wolfe, Michael W.; Paul, Soumen
Patients that receive a T-cell depleted (TCD) hematopoietic stem cell transplantation (SCT) show higher risk of graft failure/rejection and of disease relapse than those that receive unmanipulated grafts. The purpose of the present investigation was to analyze the usefulness of chimaerism quantification in bone marrow (BM), peripheral blood (PB), and leukocyte lineages such as T lymphocytes (CD3+,both CD4+ and CD8+), B lymphocytes (CD19+) and myeloid cells (CD15+), for the early detection of graft failure/rejection episodes and disease relapse after TCD-PBSCT. Two of the ten (2/10) patients included in the study showed stable complete chimaerism (CC). The other 8/10 patients showed decreasing mixed chimaerism (MC) and 7 of them had either graft failure (n = 1)/rejection (n = 3) or disease relapse (n = 3). In two patients relapsed from chronic myeloid leukemia, MC was observed in BM and PB, with higher percentages of autologous cells in BM, as well as in leukocyte lineages, with higher percentages of recipient cells in the myeloid lineage than in lymphocytes. Combined analysis of chimaerism and minimal residual disease allowed early diagnosis of relapse and successful rescue therapy with donor leukocyte infusions (DLI), before the onset of hematological relapse. Chimaerism analysis allowed early diagnosis of incipient graft rejection in 3 patients. These patients showed MC both in BM and PB, with greater percentages of recipient cells in PB. Analysis of leukocyte lineages showed higher percentages of autologous cells in T lymphocytes (mainly CD8+) than in B or myeloid cells. Two of these patients were successfully treated with DLI and recovered normal PB counts and BM cellularity, as well as CC. The graft versus recipient hemopoiesis effect harbored by the donor immunocompetent cells infused seems useful forthe treatment of graft rejection, provided that an early diagnosis is made. PMID:12769344
Buño, I; Anta, B; Moreno-López, E; Balsalobre, P; Balas, A; García-Sánchez, F; Serrano, D; Carrión, R; Gómez-Pineda, A; Díez-Martín, J L
In this activity, learners explore dinosaur fossils and skeletons. First, learners listen to "Tyrannosaurus Rex" by Daniel Cohen to learn about T. rex dinosaurs specifically. Then, learners make dinosaur tracings and drawings similar to x-rays. Learners can repeat the activity using pictures of other dinosaurs to compare and contrast various dinosaurs. This activity is featured on page 38 of the "Dinosphere" unit of study for K-2 learners.
Crosslin, Rick; Fortney, Mary; Indianapolis, The C.
In this activity, learners explore dinosaur skeletons, anatomy, and locomotion. Learners compare and contrast dinosaur skeletons and drawings. Learners also work in groups to reassemble "pieces" to form dinosaur skeletons. Finally, learners create and pose paper dinosaur models with moveable parts and list different actions or movements the dinosaurs can do including eating, walking, and sleeping. This activity is featured on page 39 of the "Dinosphere" unit of study for K-2 learners.
Crosslin, Rick; Fortney, Mary; Indianapolis, The C.
Differentiation-associated regulatory programs are central in determining tumor phenotype, and contribute to heterogeneity between tumors and between individual cells within them. The transcriptional programs that control luminal and basal lineage identity in the normal mammary epithelium, as well as progenitor and stem cell function, are active in breast cancers, and show distinct associations with different disease subtypes. Also active in some tumors is the epithelial to mesenchymal transition (EMT) program, which endows carcinoma cells with mesenchymal as well as stem cell traits. The differentiation state of breast cancer cells is thus dictated by the complex combination of regulatory programs, and these can dramatically affect tumor growth and metastatic capacity. Breast cancer differentiation is often viewed along an axis between a basal–mesenchymal–stem cell state and a luminal–epithelial–differentiated state. Here we consider the links, as well as the distinctions, between the three components of this axis: basal versus luminal, mesenchymal versus epithelial, and stem cell versus differentiated identity. Analysis on a multidimensional scale, in which each of these axes is assessed separately, may offer increased resolution of tumor differentiation state. Cancer cells possessing a high degree of stemness would display increased capacity to shift between positions on such a multidimensional scale, and to acquire intermediate phenotypes on its different axes. Further molecular analysis of breast cancer cells with a focus on single-cell profiling, and the development of improved tools for dissection of the circuits controlling gene activity, are essential for the elucidation of the programs dictating breast cancer differentiation state. PMID:24741710
Granit, Roy Z; Slyper, Michal; Ben-Porath, Ittai
Quiescent, multipotent gastric stem cells (GSSCs) in the copper cell region of adult Drosophila midgut can produce all epithelial cell lineages found in the region, including acid-secreting copper cells, interstitial cells and enteroendocrine cells, but mechanisms controlling their quiescence and the ternary lineage differentiation are unknown. By using cell ablation or damage-induced regeneration assays combined with cell lineage tracing and genetic analysis, here we demonstrate that Delta (Dl)-expressing cells in the copper cell region are the authentic GSSCs that can self-renew and continuously regenerate the gastric epithelium after a sustained damage. Lineage tracing analysis reveals that the committed GSSC daughter with activated Notch will invariably differentiate into either a copper cell or an interstitial cell, but not the enteroendocrine cell lineage, and loss-of-function and gain-of-function studies revealed that Notch signaling is both necessary and sufficient for copper cell/interstitial cell differentiation. We also demonstrate that elevated epidermal growth factor receptor (EGFR) signaling, which is achieved by the activation of ligand Vein from the surrounding muscle cells and ligand Spitz from progenitor cells, mediates the regenerative proliferation of GSSCs following damage. Taken together, we demonstrate that Dl is a specific marker for Drosophila GSSCs, whose cell cycle status is dependent on the levels of EGFR signaling activity, and the Notch signaling has a central role in controlling cell lineage differentiation from GSSCs by separating copper/interstitial cell lineage from enteroendocrine cell lineage. PMID:24603358
Wang, Chenhui; Guo, Xingting; Xi, Rongwen
This simple demonstration is about the role of dinosaurs in the carbon cycle and the eventual storage of excess carbon in the form of chalk. Students will come to understand the importance of the carbon cycle, appreciate that it has always been essential for life on earth, and appreciate the role of the oceans as a carbon sink. The instructor guide contains detailed background material, learning goals, alignment to national standards, grade level/time, details on materials and preparation, procedure, assessment ideas, and modifications for alternative learners.
Ectopic bone formation is thought to be responsible for ossification of the posterior longitudinal ligament of the spine (OPLL). Mesenchymal stem cells (MSCs) were isolated from spinal ligaments and shown to play a key role in the process of ectopic ossification. The purpose of this study was to explore the capacity of these MSCs to undergo lineage commitment and to assess the gene expression changes between these committed and uncommitted MSCs between OPLL and non-OPLL patients. Spinal ligament-derived cells were obtained from OPLL patients or patients with cervical spondylotic myelopathy (non-ossified) for comparison (n=8 in each group). MSCs from the two patient cohorts were evaluated for changes in colony forming ability; osteogenic, adipogenic and chondrogenic differentiation potential; and changes in gene expression following induction with lineage-specific conditions. We show that the osteogenic differentiation potential was significantly higher in MSCs from OPLL patients than in those from non-OPLL patients. In addition, alkaline phosphatase activity and several osteogenic-related genes expressions (bone morphogenetic protein 2, runt-related transcription factor 2 and alkaline phosphatase) were significantly higher in the OPLL group than in the non-OPLL group. However, single cell cloning efficiency, adipogenic and chondrogenic differentiation, and the expression of adipogenic and chondrogenic-related genes were equivalent between MSCs harvested from OPLL and non-OPLL patient samples. These findings suggest an increase in the osteogenic differentiation potential of MSCs from OPLL patients and that this propensity toward the osteogenic lineage may be a causal factor in the ossification in these ligaments. PMID:24361881
Harada, Yoshifumi; Furukawa, Ken-Ichi; Asari, Toru; Chin, Shunfu; Ono, Atsushi; Tanaka, Toshihiro; Mizukami, Hiroki; Murakami, Manabu; Yagihashi, Soroku; Motomura, Shigeru; Ishibashi, Yasuyuki
Ribosome biogenesis drives cell growth and proliferation but mechanisms that modulate this process within specific lineages remain poorly understood. Here we identify a Drosophila RNA polymerase I (Pol I) regulatory complex composed of Under-developed (Udd), TAF1B, and a TAF1C-like factor. Disruption of udd or TAF1B results in reduced ovarian germline stem cell (GSC) proliferation. Female GSCs display high levels of rRNA transcription, and Udd becomes enriched in GSCs relative to their differentiating daughters. Increasing Pol I transcription delays differentiation whereas reducing rRNA production induces both morphological changes that accompany multicellular cyst formation and specific decreased expression of the BMP pathway component Mad. These findings demonstrate that modulating rRNA synthesis fosters changes in the cell fate, growth and proliferation of female Drosophila GSCs and their daughters.
Zhang, Qiao; Shalaby, Nevine A.; Buszczak, Michael
Efficient in vitro differentiation into specific cell types is more important than ever after the breakthrough in nuclear reprogramming of somatic cells and its potential for disease modeling and drug screening. Key success factors for neuronal differentiation are the yield of desired neuronal marker expression, reproducibility, length, and cost. Three main neuronal differentiation approaches are stromal-induced neuronal differentiation, embryoid body (EB) differentiation, and direct neuronal differentiation. Here, we describe our neurodifferentiation protocol using small molecules that very efficiently promote neural induction in a 5-stage EB protocol from six induced pluripotent stem cells (iPSC) lines from patients with Parkinson's disease and controls. This protocol generates neural precursors using Dorsomorphin and SB431542 and further maturation into dopaminergic neurons by replacing sonic hedgehog with purmorphamine or smoothened agonist. The advantage of this approach is that all patient-specific iPSC lines tested in this study were successfully and consistently coaxed into the neural lineage.
Mak, Sally K.; Huang, Y. Anne; Iranmanesh, Shifteh; Vangipuram, Malini; Sundararajan, Ramya; Nguyen, Loan; Langston, J. William; Schule, Birgitt
Direct reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) provides an opportunity to develop novel personalized treatment options for numerous diseases and to advance current approaches for cell-based drug discoveries and disease modeling. The ability to differentiate iPSCs into relevant cell types is an important prerequisite for the successful development of iPSC-based treatment and modeling strategies. Here, we describe a protocol for the efficient differentiation of human iPSCs into functional keratinocytes. The protocol employs treating iPSCs with retinoic acid and bone-morphogenetic protein-4 to induce differentiation toward a keratinocyte lineage, which is then followed by the growth of differentiated iPSCs on collagen type I- and collagen type IV-coated dishes to enrich for iPSC-derived keratinocytes.
Kogut, Igor; Roop, Dennis R.; Bilousova, Ganna
Background Silencing of the paternal X chromosome (Xp), a phenomenon known as imprinted X-chromosome inactivation (I-XCI), characterises, amongst mouse extraembryonic lineages, the primitive endoderm and the extraembryonic endoderm (XEN) stem cells derived from it. Results Using a combination of chromatin immunoprecipitation characterisation of histone modifications and single-cell expression studies, we show that whilst the Xp in XEN cells, like the inactive X chromosome in other cell types, globally accumulates the repressive histone mark H3K27me3, a large number of Xp genes locally lack H3K27me3 and escape from I-XCI. In most cases this escape is specific to the XEN cell lineage. Importantly, the degree of escape and the genes concerned remain unchanged upon XEN conversion into visceral endoderm, suggesting stringent control of I-XCI in XEN derivatives. Surprisingly, chemical inhibition of EZH2, a member of the Polycomb repressive complex 2 (PRC2), and subsequent loss of H3K27me3 on the Xp, do not drastically perturb the pattern of silencing of Xp genes in XEN cells. Conclusions The observations that we report here suggest that the maintenance of gene expression profiles of the inactive Xp in XEN cells involves a tissue-specific mechanism that acts partly independently of PRC2 catalytic activity.
Hydrophilic poly(ethylene glycol) diacrylate (PEGDA) hydrogel surfaces resist protein adsorption and are generally thought to be unsuitable for anchorage dependent cells to adhere. Intriguingly, our previous findings revealed that PEGDA superporous hydrogel scaffolds (SPHs) allow anchorage of bone marrow derived human mesenchymal stem cells (hMSCs) and support their long term survival. Therefore, we hypothesized that the physicochemical characteristics of the scaffold impart properties that could foster cellular responses. We examined if hMSCs alter their microenvironment to allow cell attachment by synthesizing their own extracellular matrix (ECM) proteins. Immunofluorescence staining revealed extensive expression of collagen type I, collagen type IV, laminin and fibronectin within hMSC-seeded SPHs by the end of the third week. Whether cultured in serum-free or serum-supplemented medium, hMSC ECM protein gene expression patterns exhibited no substantial changes. The presence of serum proteins is required for initial anchorage of hMSCs within the SPHs but not for the hMSC survival after 24 hours. In contrast to 2D expansion on tissue culture plastic (TCP), hMSCs cultured within SPHs proliferate similarly in the presence or absence of serum. To test whether hMSCs retain their undifferentiated state within the SPHs, cell-seeded constructs were cultured for 3 weeks in stem cell maintenance medium and the expression of hMSC-specific cell surface markers were evaluated by flow cytometry. CD105, CD90, CD73 and CD44 were present to a similar extent in the SPH and in 2D monolayer culture. We further demonstrated multi lineage potential of hMSCs grown in the PEGDA SPHs whereby differentiation into osteoblasts, chondrocytes and adipocytes could be induced. The present study demonstrates the potential of hMSCs to alter the “blank” PEGDA environment to a milieu conducive to cell growth and multi-lineage differentiation by secreting adhesive ECM proteins within the porous network of the SPH scaffolds.
Kollmer, Melanie; Keskar, Vandana; Hauk, Thomas G.; Collins, John M.; Russell, Brenda; Gemeinhart, Richard A.
Taking inspiration from tissue morphogenesis in utero, this study tests the concept of using tissue engineering scaffolds as delivery devices to modulate emergent structure-function relationships at early stages of tissue genesis. We report on the use of a combined computational fluid dynamics (CFD) modeling, advanced manufacturing methods, and experimental fluid mechanics (micro-piv and strain mapping) for the prospective design of tissue engineering scaffold geometries that deliver spatially resolved mechanical cues to stem cells seeded within. When subjected to a constant magnitude global flow regime, the local scaffold geometry dictates the magnitudes of mechanical stresses and strains experienced by a given cell, and in a spatially resolved fashion, similar to patterning during morphogenesis. In addition, early markers of mesenchymal stem cell lineage commitment relate significantly to the local mechanical environment of the cell. Finally, by plotting the range of stress-strain states for all data corresponding to nascent cell lineage commitment (95% CI), we begin to "map the mechanome", defining stress-strain states most conducive to targeted cell fates. In sum, we provide a library of reference mechanical cues that can be delivered to cells seeded on tissue engineering scaffolds to guide target tissue phenotypes in a temporally and spatially resolved manner. Knowledge of these effects allows for prospective scaffold design optimization using virtual models prior to prototyping and clinical implementation. Finally, this approach enables the development of next generation scaffolds cum delivery devices for genesis of complex tissues with heterogenous properties, e.g., organs, joints or interface tissues such as growth plates. PMID:23660249
Song, Min Jae; Dean, David; Knothe Tate, Melissa L
Prostate stem cells are thought to be responsible for generation of all prostate epithelial cells and for tissue maintenance. The lineage relationship between basal and luminal cells in the prostate is not well clarified. We developed a mouse model to trace cell fate and a mouse model with a slowly cycling cell label to provide insight into this question. The results obtained indicate that putative mouse prostate stem cells are likely to reside in the basal layer. PMID:23819124
Zhou, Jianjun; Feigenbaum, Lionel; Yee, Carole; Song, Hongbin; Yates, Clayton
Prostate stem cells are thought to be responsible for generation of all prostate epithelial cells and for tissue maintenance. The lineage relationship between basal and luminal cells in the prostate is not well clarified. We developed a mouse model to trace cell fate and a mouse model with a slowly cycling cell label to provide insight into this question. The results obtained indicate that putative mouse prostate stem cells are likely to reside in the basal layer.
Zhou, Jianjun; Feigenbaum, Lionel; Yee, Carole; Song, Hongbin; Yates, Clayton
In this classroom activity, middle school students learn what distinguishes dinosaurs from other animals. The activity opens with background information for teachers about these prehistoric reptiles. As a class, students compare the stance of lizards and dinosaurs in pictures and try to replicate both reptiles' walks. Students then learn that Museum paleontologists classify birds as dinosaurs, and work in groups to compare a T. rex skeleton with pictures of birds.
Stella is a developmentally regulated gene highly expressed in mouse embryonic stem (ES) cells and in primordial germ cells (PGCs). In human, the gene encoding the STELLA homologue lies on chromosome 12p, which is frequently amplified in long-term cultured human ES cells. However, the role played by STELLA in human ES cells has not been reported. In the present study, we show that during retinoic acid (RA)-induced differentiation of human ES cells, expression of STELLA follows that of VASA, a marker of germline differentiation. By contrast, human embryonal carcinoma cells express STELLA at a higher level compared with both karyotypically normal and abnormal human ES cell lines. We found that over-expression of STELLA does not interfere with maintenance of the stem cell state of human ES cells, but following retinoic acid induction it leads to up-regulation of germline- and endodermal-associated genes, whereas neural markers PAX6 and NEUROD1 are down-regulated. Further, STELLA over-expression facilitates the differentiation of human ES cells into BE12-positive cells, in which the expression of germline- and endodermal-associated genes is enriched, and suppresses differentiation of the neural lineage. Taken together, this finding suggests a role for STELLA in facilitating germline and endodermal differentiation of human ES cells.
Wongtrakoongate, Patompon; Jones, Mark; Gokhale, Paul J.; Andrews, Peter W.
Colon carcinoma is one of the leading causes of death from cancer and is characterized by a heterogenic pool of cells with distinct differentiation patterns. Recently, it was reported that a population of undifferentiated cells from a primary tumor, so-called cancer stem cells (CSC), can reconstitute the original tumor on xenotransplantation. Here, we show that spheroid cultures of these colon CSCs contain expression of CD133, CD166, CD44, CD29, CD24, Lgr5, and nuclear ?-catenin, which have all been suggested to mark the (cancer) stem cell population. More importantly, by using these spheroid cultures or freshly isolated tumor cells from multiple colon carcinomas, we now provide compelling evidence to indicate that the capacity to propagate a tumor with all differentiated progeny resides in a single CSC. Single-cell-cloned CSCs can form an adenocarcinoma on xenotransplantation but do not generate the stroma within these tumors. Moreover, they can self-renew and are capable of multilineage differentiation. Further analysis indicated that the lineage decision is dictated by phosphoinositide 3-kinase (PI3K) signaling in CSCs. These data support the hypothesis that tumor hierarchy can be traced back to a single CSC that contains multilineage differentiation capacity, and provides clues to the regulation of differentiation in colon cancers in vivo.
Vermeulen, L.; Todaro, M.; de Sousa Mello, F.; Sprick, M. R.; Kemper, K.; Perez Alea, M.; Richel, D. J.; Stassi, G.; Medema, J. P.
FAM40B (STRIP2) is a member of the striatin-interacting phosphatase and kinase (STRIPAK) complex that is involved in the regulation of various processes such as cell proliferation and differentiation. Its role for differentiation processes in embryonic stem cells (ESCs) is till now completely unknown. Short hairpin RNA (shRNA)-mediated silencing of Fam40b expression in ESCs and differentiating embryoid bodies (EBs) led to perturbed differentiation to embryonic germ layers and their derivatives including a complete abrogation of cardiomyogenesis. Pluripotency factors such as Nanog, Oct4 and Sox2 as well as epigenetic factors such as histone acetyltransferase type B (HAT1) and DNA (cytosine-5)-methyltransferase 3-? (Dnmt3b) were highly upregulated in Fam40b knockdown EBs as compared with control and scrambled EBs. To examine the relevance of Fam40b for development in vivo, Fam40b was knocked down in developing zebrafish. Morpholino-mediated knockdown of Fam40b led to severe abnormalities of the cardiovascular system, including an impaired expression of ventricular myosin heavy chain (vmhc) and of cardiac myosin light chain 2 (cmlc2) in the heart. We identified the gene product of Fam40b in ESCs as a perinuclear and nucleolar protein with a molecular weight of 96?kDa. We conclude that the expression of Fam40b is essential for the lineage commitment of murine embryonic stem cells (mESCs) into differentiated somatic cells via mechanisms involving pluripotency and epigenetic networks. PMID:25010986
Wagh, V; Doss, M X; Sabour, D; Niemann, R; Meganathan, K; Jagtap, S; Gaspar, J A; Ardestani, M A; Papadopoulos, S; Gajewski, M; Winkler, J; Hescheler, J; Sachinidis, A
Activities and information relating to dinosaurs are presented, including: study of warm- and cold-blooded animals; research about recent dinosaur discoveries; track-making; studying and making fossils; and extinction theories. (CB)
Prime, Carol Spirkoff; Cox, Judy
Human induced pluripotent stem cells (hiPSCs) exhibit pluripotency, proliferation capability, and gene expression similar to those of human embryonic stem cells (hESCs). hESCs readily form cartilaginous tissues in teratomas in vivo; despite extensive effort, however, to date no efficient method for inducing mature chondrocytes in vitro has been established. hiPSCs can also differentiate into cartilage in vivo by teratoma formation, but as with hESCs, no reliable system for in vitro chondrogenic differentiation of hiPSCs has yet been reported. Here, we examined the chondrogenic differentiation capability of hiPSCs using a multistep culture method consisting of embryoid body (EB) formation, cell outgrowth from EBs, monolayer culture of sprouted cells from EBs, and 3-dimensional pellet culture. In this culture process, the cell density of monolayer culture was critical for cell viability and subsequent differentiation capability. Monolayer-cultured cells exhibited fibroblast-like morphology and expressed markers for mesenchymal stem cells. After 2-3 weeks of pellet culture, cells in pellets exhibited a spherical morphology typical of chondrocytes and were surrounded by extracellular matrix that contained acidic proteoglycans. The expression of type II collagen and aggrecan in pellets progressively increased. Histological analysis revealed that over 70% of hiPSC-derived pellets successfully underwent chondrogenic differentiation. Using the same culture method, hESCs showed similar histological changes and gene expression, but differentiated slightly faster and more efficiently than hiPSCs. Our study demonstrates that hiPSCs can be efficiently differentiated into the chondrogenic lineage in vitro via generation of mesenchymal progenitor cells, using a simplified, multistep culture method. PMID:22817676
Koyama, Noriaki; Miura, Masako; Nakao, Kazumasa; Kondo, Eri; Fujii, Toshihito; Taura, Daisuke; Kanamoto, Naotetsu; Sone, Masakatsu; Yasoda, Akihiro; Arai, Hiroshi; Bessho, Kazuhisa; Nakao, Kazuwa
This four-week unit of study for grades 1-3 provides information and activities on 17 different dinosaurs. A 21-item pre- and post-test and a brief history of dinosaurs precede descriptions and full-page drawings of the following dinosaurs: (1) giant plant-eaters (brachiosaurus, brontosaurus, and diplodocus); (2) giant meat-eaters (allosaurus,…
This Science NetLinks lesson is the second of a two-part series on dinosaurs. Activities and discussions in this lesson revolve around comparing and contrasting dinosaurs to animals with which students are familiar. Students consider likenesses and differences through researching various questions and documenting their findings.
Commitment of stem cells to different lineages is regulated by many cues in their local microenvironment. They are particularly sensitive to the mechanical properties of their extracellular matrix. Nuclear lamins are fibrous proteins providing structural function and transcriptional regulation in the cell nucleus. In particular Lamin A/C levels could influence cellular mechanical sensitivity. Here we show that perturbation of the extracellular matrix and nucleus mechanics can direct stem cells lineage specification. We studied the behavior of human mensechymal stem cells (hMSC) cultured on thin highly ordered collagen nanofilms. To tune the mechanical properties of the nanofilms we used the enzyme transglutaminase as a crosslinking agent. AFM imaging and manipulation is used to examine the nano topography and mechanical properties of the films and cells. Film stiffening affects cells morphology, cytoskeleton organization and their elastic response. hMSCs cultured for two weeks on collagen nanofilms initially tune their stiffness with matrix elasticity but later continuously change it with time. We observed upregulation of osteogenic markers on cross-linked films and increased lamin A/C expression. We show that manipulating Lamin-A/C expression in stem cells also directs cell lineage with knockdown favoring adipogenesis and over expression favoring osteogenesis. We found positive correlation between matrix and nucleus mechanics and that they have a synergistic effect on hMSCs differentiation potential.
Ivanovska, Irena; Discher, Dennis
Summary Aging hematopoietic stem cells (HSCs) exhibit defective lineage specification that is thought to be central to increased incidence of myeloid malignancies and compromised immune competence in the elderly. Mechanisms underlying these age-related defects remain largely unknown. We show that the deacetylase Sirtuin (SIRT)1 is required for homeostatic HSC maintenance. Differentiation of young SIRT1-deleted HSCs is skewed toward myeloid lineage associated with a significant decline in the lymphoid compartment, anemia, and altered expression of associated genes. Combined with HSC accumulation of damaged DNA and expression patterns of age-linked molecules, these have striking overlaps with aged HSCs. We further show that SIRT1 controls HSC homeostasis via the longevity transcription factor FOXO3. These findings suggest that SIRT1 is essential for HSC homeostasis and lineage specification. They also indicate that SIRT1 might contribute to delaying HSC aging.
Rimmele, Pauline; Bigarella, Carolina L.; Liang, Raymond; Izac, Brigitte; Dieguez-Gonzalez, Rebeca; Barbet, Gaetan; Donovan, Michael; Brugnara, Carlo; Blander, Julie M.; Sinclair, David A.; Ghaffari, Saghi
The histone H3 Lys 9 (H3K9) methyltransferase Eset is an epigenetic regulator critical for the development of the inner cell mass (ICM). Although ICM-derived embryonic stem (ES) cells are normally unable to contribute to the trophectoderm (TE) in blastocysts, we find that depletion of Eset by shRNAs leads to differentiation with the formation of trophoblast-like cells and induction of trophoblast-associated gene expression. Using chromatin immmunoprecipitation (ChIP) and sequencing (ChIP-seq) analyses, we identified Eset target genes with Eset-dependent H3K9 trimethylation. We confirmed that genes that are preferentially expressed in the TE (Tcfap2a and Cdx2) are bound and repressed by Eset. Single-cell PCR analysis shows that the expression of Cdx2 and Tcfap2a is also induced in Eset-depleted morula cells. Importantly, Eset-depleted cells can incorporate into the TE of a blastocyst and, subsequently, placental tissues. Coimmunoprecipitation and ChIP assays further demonstrate that Eset interacts with Oct4, which in turn recruits Eset to silence these trophoblast-associated genes. Our results suggest that Eset restricts the extraembryonic trophoblast lineage potential of pluripotent cells and links an epigenetic regulator to key cell fate decision through a pluripotency factor.
Yuan, Ping; Han, Jianyong; Guo, Guoji; Orlov, Yuriy L.; Huss, Mikael; Loh, Yuin-Han; Yaw, Lai-Ping; Robson, Paul; Lim, Bing; Ng, Huck-Hui
Cycloneuralians form a rich and diverse element within Cambrian assemblages of exceptionally preserved fossils. Most resemble priapulid worms whereas other Cycloneuralia (Nematoda, Nematomorpha, Kinorhyncha, Loricifera), well known at the present day, have little or no fossil record. First reports of Sirilorica Peel, 2010 from the lower Cambrian Sirius Passet fauna of North Greenland described a tubular lorica covering the abdomen and part of a well developed introvert with a circlet of 6 grasping denticles near the lorica. The introvert is now known to terminate in a narrow mouth tube, while a conical anal field is also developed. Broad muscular bands between the plates in the lorica indicate that it was capable of movement by rhythmic expansion and contraction of the lorica. Sirilorica is regarded as a macrobenthic member of the stem-lineage of the miniaturised, interstitial, present day Loricifera. Like loriciferans, Sirilorica is now known to have grown by moulting. Evidence of the life cycle of Sirilorica is described, including a large post-larval stage and probably an initial larva similar to that of the middle Cambrian fossil Orstenoloricusshergoldii.
Peel, John S.; Stein, Martin; Kristensen, Reinhardt M?bjerg
Summary Pluripotent stem cells display significant heterogeneity in gene expression, but whether this diversity is an inherent feature of the pluripotent state remains unknown. Single-cell gene expression analysis in cell subsets defined by surface antigen expression revealed that human embryonic stem cell cultures exist as a continuum of cell states, even under defined conditions that drive self-renewal. The majority of the population expressed canonical pluripotency transcription factors and could differentiate into derivatives of all three germ layers. A minority subpopulation of cells displayed high self-renewal capacity, consistently high transcripts for all pluripotency-related genes studied, and no lineage priming. This subpopulation was characterized by its expression of a particular set of intercellular signaling molecules whose genes shared common regulatory features. Our data support a model of an inherently metastable self-renewing population that gives rise to a continuum of intermediate pluripotent states, which ultimately become primed for lineage specification.
Hough, Shelley R.; Thornton, Matthew; Mason, Elizabeth; Mar, Jessica C.; Wells, Christine A.; Pera, Martin F.
The metabolic status of dinosaurs has long been debated but remains unresolved as no consistent picture has emerged from a range of anatomical and isotopic evidence. Quantitative analysis of dinosaur energetics, based on general principles applicable to all vertebrates, shows that many features of dinosaur lifestyle are compatible with a physiology similar to that of extant lizards, scaled up to dinosaur body masses and temperatures. The analysis suggests that sufficient metabolic scope would have been available to support observed dinosaur growth rates and allow considerable locomotor activity, perhaps even migration. Since at least one dinosaur lineage evolved true endothermy, this study emphasizes there was no single dinosaur physiology. Many small theropods were insulated with feathers and appear to have been partial or full endotherms. Uninsulated small taxa, and all juveniles, presumably would have been ectothermic, with consequent diurnal and seasonal variations in body temperature. In larger taxa, inertial homeothermy would have resulted in warm and stable body temperatures but with a basal metabolism significantly below that of extant mammals or birds of the same size. It would appear that dinosaurs exhibited a range of metabolic levels to match the broad spectrum of ecological niches they occupied. PMID:23933721
TET family enzymes convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in DNA. Here, we show that Tet1 and Tet2 are Oct4-regulated enzymes that together sustain 5hmC in mouse embryonic stem cells (ESCs) and are induced concomitantly with 5hmC during reprogramming of fibroblasts to induced pluripotent stem cells. ESCs depleted of Tet1 by RNAi show diminished expression of the Nodal antagonist Lefty1 and display hyperactive Nodal signaling and skewed differentiation into the endoderm-mesoderm lineage in embryoid bodies in vitro. In Fgf4- and heparin-supplemented culture conditions, Tet1-depleted ESCs activate the trophoblast stem cell lineage determinant Elf5 and can colonize the placenta in midgestation embryo chimeras. Consistent with these findings, Tet1-depleted ESCs form aggressive hemorrhagic teratomas with increased endoderm, reduced neuroectoderm, and ectopic appearance of trophoblastic giant cells. Thus, 5hmC is an epigenetic modification associated with the pluripotent state, and Tet1 functions to regulate the lineage differentiation potential of ESCs. PMID:21295276
Koh, Kian Peng; Yabuuchi, Akiko; Rao, Sridhar; Huang, Yun; Cunniff, Kerrianne; Nardone, Julie; Laiho, Asta; Tahiliani, Mamta; Sommer, Cesar A; Mostoslavsky, Gustavo; Lahesmaa, Riitta; Orkin, Stuart H; Rodig, Scott J; Daley, George Q; Rao, Anjana
SUMMARY TET-family enzymes convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in DNA. Here we show that Tet1 and Tet2 are Oct4-regulated enzymes that together sustain 5hmC in mouse embryonic stem (ES) cells, and are induced concomitantly with 5hmC during reprogramming of fibroblasts to induced pluripotent stem cells. ES cells depleted of Tet1 by RNAi show diminished expression of the Nodal antagonist Lefty1, and display hyperactive Nodal signalling and skewed differentiation into the endoderm-mesoderm lineage in embryoid bodies in vitro. In Fgf4- and heparin-supplemented culture conditions, Tet1-depleted ES cells activate the trophoblast stem cell lineage determinant Elf5 and can colonize the placenta in mid-gestation embryo chimeras. Consistent with these findings, Tet1-depleted ES cells form aggressive hemorrhagic teratomas with increased endoderm, reduced neuroectoderm and ectopic appearance of trophoblastic giant cells. Thus 5hmC is a novel epigenetic modification associated with the pluripotent state, and Tet1 functions to regulate the lineage differentiation potential of ES cells.
Koh, Kian Peng; Yabuuchi, Akiko; Rao, Sridhar; Huang, Yun; Cunniff, Kerrianne; Nardone, Julie; Laiho, Asta; Tahiliani, Mamta; Sommer, Cesar A.; Mostoslavsky, Gustavo; Lahesmaa, Riitta; Orkin, Stuart H.; Rodig, Scott J.; Daley, George Q.; Rao, Anjana
Bone-marrow adipogenesis is an aging-related phenomenon and is correlated with osteoporosis. The latter is a prevalent bone disease in the elderly leading to increased fracture risk and mortality. It is widely hypothesized that the underlying molecular mechanism includes a shift in the commitment of mesenchymal stem cells (MSCs) from the osteogenic lineage to the adipogenic lineage. Lineage skewing is at least partially a result of transcriptional changes. The nuclear transcription factor peroxisome proliferator-activated receptor gamma (PPAR-gamma) has been proposed as a major decision factor in MSC lineage commitment, promoting adipogenesis at the expense of osteogenesis. Here we found that PPAR-gamma acted unexpectedly to stimulate osteoblast differentiation from human bone marrow-derived MSCs. Both rosiglitazone-mediated activation and overexpression of PPAR-gamma caused acceleration of osteoblast differentiation. Conversely, shRNAi-mediated PPAR-gamma knockdown diminished osteoblast differentiation. MSCs that were treated with rosiglitazone did not preferentially differentiate into adipocytes. However, the rosiglitazone-mediated acceleration of osteoblast differentiation was followed by increased accumulation of reactive oxygen species and apoptosis. In contrast to the osteogenic lineage, cells of the adipogenic lineage were protected from this. Our data support a new concept on bone health that adds to the explanation of the clinically observed suppressive action of activated PPAR-gamma on bone and the associated phenomenon of bone marrow adipogenesis. This concept is based on a higher susceptibility of the osteogenic than the adipogenic lineage to oxidative stress and apoptosis that is preferentially triggered in the osteoblasts by activated PPAR-gamma. PMID:20213769
Bruedigam, Claudia; Eijken, Marco; Koedam, Marijke; van de Peppel, Jeroen; Drabek, Ksenija; Chiba, Hideki; van Leeuwen, Johannes P T M
Scientists have discovered a dinosaur that died right before it laid two eggs. Finding dinosaur eggs inside the female, in almost the same position they were in when she died, might answer some tough questions about dinosaur egg-laying.
American Association for the Advancement of Science (AAAS;)
How hematopoietic stem cells (HSCs) commit to a particular lineage is unclear. A high degree of HSC purification enabled us to address this issue at the clonal level. Single-cell transplantation studies revealed that 40% of the CD34 ? \\/low , c-Kit ? , Sca-1 ? , and lineage marker ? (CD34 ? KSL) cells in adult mouse bone marrow were
Hina Takano; Hideo Ema; Kazuhiro Sudo; Hiromitsu Nakauchi
Umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) have multi-lineage differentiation potential, thus highlighting the feasibility of using UCB-MSCs as a valuable source of stem-cells for cell-based therapy. However, there are no well-defined markers for assessment of the multi-potency of UCB-MSCs. Thus, we focused on the identification of suitable markers by examining cell surface protein expressions of UCB-MSCs as their multi-lineage
Hye Jin Jin; Se Kyong Park; Wonil Oh; Yoon Sun Yang; Seong Who Kim; Soo Jin Choi
Embryonic stem cell (ESC) derivatives offer promise for generating clinically useful tissues for transplantation, yet the specter of producing tumors in patients remains a significant concern. We have developed a simple method that eliminates the tumorigenic potential from differentiated ESC cultures of murine and human origin while purifying lineage-restricted, definitive endoderm-committed cells. A three-stage scheme utilizing magnetic bead sorting and
Brenda Kahan; Joseph Magliocca; Fabiola Merriam; Nathan Treff; Melisa Budde; Jeffrey Nelson; Victoria Browning; Benjamin Ziehr; Jon Odorico
Non-avian dinosaur reproductive and parenting behaviors were mostly similar to those of extant archosaurs. Non-avian dinosaurs were probably sexually dimorphic and some may have engaged in hierarchical rituals. Non-avian coelurosaurs (e.g. Troodontidae, Oviraptorosauria) had two active oviducts, each of which produced single eggs on a daily or greater time scale. The eggs of non-coelurosaurian dinosaurs (e.g. Ornithischia, Sauropoda) were incubated
John R. Horner
Non-avian dinosaur reproductive and parenting behaviors were mostly similar to those of extant archosaurs. Non-avian dinosaurs were probably sexually dimorphic and some may have engaged in hierarchical rituals. Non-avian coelurosaurs (e.g. Troodontidae, Oviraptorosauria) had two active oviducts, each of which pro- duced single eggs on a daily or greater time scale. The eggs of non-coelurosaurian dinosaurs (e.g. Ornithischia, Sauropoda) were
John R. Horner
Despite the long loading times and annoying advertisements, there are a variety of worthwhile Flash and Windows media animations. As might be expected, the animations tend to stress the flashy, violent aspects of dinosaurs, like velociraptor attacks but there are also clips showing dinosaur eggs hatching, dinosaur locomotion, and even an interview with a paleontologist. A fast connection is a must to properly view this site.
This lesson introduces students to the idea that animals prefer certain types of habitats over others and, in fact, cannot live in places that are too different from what they prefer. In this case they will focus on dinosaurs. They will learn about the types of habitats and climates scientists believe dinosaurs tended to prefer and will conclude by drawing background scenes to use in a toy dinosaur home.
In this activity, learners explore the size and scale of dinosaurs. Learners listen to "The Littlest Dinosaurs" by Bernard Most to learn about the different sizes of dinosaurs. Then, learners create a chart of measurements that compare the sizes of the body parts of a T. rex, Triceratops, the learner, and their partner. Learners also convert the measurements into centimeters and meters. This activity is featured on pp. 20-21 of the "Dinosphere" unit of study for K-2 learners.
Crosslin, Rick; Fortney, Mary; Indianapolis, The C.
In this classroom activity, young students learn what distinguishes dinosaurs from other animals. The activity opens with background information for teachers about these prehistoric reptiles. Working in small groups, students look through dinosaur books to gather interesting facts to share. As a class, students use their facts to create a semantic map. Then they explore the differences in dinosaur and lizard legs, and examine how these differences affect their stances. The activity concludes with a student worksheet that challenges them to identify the dinosaurs within a collection of animal illustrations.
Pluripotent stem cell lines have been generated in several domestic animal species; however, these lines traditionally show poor self-renewal and differentiation. Using canine embryonic stem cell (cESC) lines previously shown to have sufficient self-renewal capacity and potency, we generated and compared canine neural stem cell (cNSC) lines derived by lineage selection with epidermal growth factor (EGF) or Noggin along the neural default differentiation pathway, or by directed differentiation with retinoic acid (RA)-induced floating sphere assay. Lineage selection produced large populations of SOX2+ neural stem/progenitor cell populations and neuronal derivatives while directed differentiation produced few and improper neuronal derivatives. Primary canine neural lines were generated from fetal tissue and used as a positive control for differentiation and electrophysiology. Differentiation of EGF- and Noggin-directed cNSC lines in N2B27 with low-dose growth factors (BDNF/NT-3 or PDGF??) produced phenotypes equivalent to primary canine neural cells including 3CB2+ radial progenitors, MOSP+ glia restricted precursors, VIM+/GFAP+ astrocytes, and TUBB3+/MAP2+/NFH+/SYN+ neurons. Conversely, induction with RA and neuronal differentiation produced inadequate putative neurons for further study, even though appropriate neuronal gene expression profiles were observed by RT-PCR (including Nestin, TUBB3, PSD95, STX1A, SYNPR, MAP2). Co-culture of cESC-derived neurons with primary canine fetal cells on canine astrocytes was used to test functional maturity of putative neurons. Canine ESC-derived neurons received functional GABAA- and AMPA-receptor mediated synaptic input, but only when co-cultured with primary neurons. This study presents established neural stem/progenitor cell populations and functional neural derivatives in the dog, providing the proof-of-concept required to translate stem cell transplantation strategies into a clinically relevant animal model.
Wilcox, Jared T.; Lai, Jonathan K. Y.; Semple, Esther; Brisson, Brigitte A.; Gartley, Cathy; Armstrong, John N.; Betts, Dean H.
Abstract The self-renewal and multilineage differentiation of embryonic stem cells (ESC) is largely governed by transcription factors or repressors. Extensive efforts have focused on elucidating critical factors that control the differentiation of specific cell lineages, for instance, myeloid lineages in hematopoietic development. In this study, we found that Twist-2, a basic helix-loop-helix (bHLH) transcription factor, plays a critical role in inhibiting the differentiation of ESC. Murine ES cells, in which Twist-2 expression is silenced by lentivirally delivered shRNA, exhibit an enhanced formation of primary embryoid bodies (EB) and enhanced differentiation into mesodermally derived hematopoietic colonies. Furthermore, Twist-2 silenced (LV-siTwist-2) ESC display significantly increased generation of myeloid lineages (Gr-1+ and F4/80+ cells) during in vitro hematopoietic differentiation. Treatment with the Toll-like receptor (TLR) 4 ligand synergistically stimulates the generation of primary EB formation as well as of hematopoietic progenitors differentiated from LV-siTwist-2 ES cells. Thus, this study reveals the critical role of the transcriptional repressor Twist-2 in regulating the development of myeloid lineage in hematopoietic differentiation from ESC. This study also suggests a potential strategy for directional differentiation of ESC by inhibiting a transcriptional repressor.
Sharabi, Andrew B.; Lee, Sung-Hyung; Goodell, Margaret A.; Huang, Xue F.
Since the discovery of neural stem cells in the mammalian brain, there has been significant interest in understanding their contribution to tissue homeostasis at both the cellular and molecular level. Wnt/?-catenin signaling is crucial for development of the central nervous system and has been implicated in stem cell maintenance in multiple tissues. Based on this, we hypothesized that the Wnt pathway likely controls neural stem cell maintenance and differentiation along the entire developmental continuum. To test this, we performed lineage tracing experiments using the recently developed tamoxifen-inducible Cre at Axin2 mouse strain to follow the developmental fate of Wnt/?-catenin–responsive cells in both the embryonic and postnatal mouse brain. From as early as embryonic day 8.5 onwards, Axin2+ cells can give rise to spatially and functionally restricted populations of adult neural stem cells in the subventricular zone. Similarly, progeny from Axin2+ cells labeled from E12.5 contribute to both the subventricular zone and the dentate gyrus of the hippocampus. Labeling in the postnatal brain, in turn, demonstrates the persistence of long-lived, Wnt/?-catenin–responsive stem cells in both of these sites. These results demonstrate the continued importance of Wnt/?-catenin signaling for neural stem and progenitor cell formation and function throughout developmental time.
Bowman, Angela N.; van Amerongen, Renee; Palmer, Theo D.; Nusse, Roeland
Epithelial homeostasis in the posterior midgut of Drosophila is maintained by multipotent intestinal stem cells (ISCs). ISCs self-renew and produce enteroblasts (EBs) that differentiate into either enterocytes (ECs) or enteroendocrine cells (EEs) in response to differential Notch (N) activation. Various environmental and growth signals dynamically regulate ISC activity, but their integration with differentiation cues in the ISC lineage remains unclear. Here we identify Notch-mediated repression of Tuberous Sclerosis Complex 2 (TSC2) in EBs as a required step in the commitment of EBs into the EC fate. The TSC1/2 complex inhibits TOR signaling, acting as a tumor suppressor in vertebrates and regulating cell growth. We find that TSC2 is expressed highly in ISCs, where it maintains stem cell identity, and that N-mediated repression of TSC2 in EBs is required and sufficient to promote EC differentiation. Regulation of TSC/TOR activity by N signaling thus emerges as critical for maintenance and differentiation in somatic stem cell lineages.
Kapuria, Subir; Karpac, Jason; Biteau, Benoit; Hwangbo, DaeSung; Jasper, Heinrich
Do dinosaurs have bellybuttons? This intriguing question launched a journey into inquiry science that captivated a class of four-year-olds for eight months. As students enjoyed dinosaur books, examined dinosaur artifacts, drew pictures, watched videos, and generally immersed themselves in all things dinosaur, the authors built a culture of…
Murray, Mary; Valentine-Anand, Lesley
In recent years, the idea that Italy was lacking dinosaurs has been denied by a striking series of finds. Several Triassic and Jurassic dinosaur tracksites were discovered in the mid-eastern Alps, in particular within the Dolomia Principale Fm. (Norian) and the Calcari Grigi Fm. (Hettangian to Pliensbachian), while thousands of Cretaceous (Santonian) prints came to light in Puglia (southern Italy).
Cristiano Dal Sasso
In this activity, early learners simulate fossil prints in play dough or clay. Using plastic dinosaur feet to make footprints on their âmudâ (much as dinosaurs walked around their habitat) and harvest items (leaves, corn, twigs, acorns) to make impressions, learners simulate fossil prints. This resource includes open-ended discussion questions to encourage reflection.
Acute leukemias are the most common cancer in childhood and characterized by the uncontrolled production of hematopoietic precursor cells of the lymphoid or myeloid series within the bone marrow. Even when a relatively high efficiency of therapeutic agents has increased the overall survival rates in the last years, factors such as cell lineage switching and the rise of mixed lineages at relapses often change the prognosis of the illness. During lineage switching, conversions from lymphoblastic leukemia to myeloid leukemia, or vice versa, are recorded. The central mechanisms involved in these phenomena remain undefined, but recent studies suggest that lineage commitment of plastic hematopoietic progenitors may be multidirectional and reversible upon specific signals provided by both intrinsic and environmental cues. In this paper, we focus on the current knowledge about cell heterogeneity and the lineage switch resulting from leukemic cells plasticity. A number of hypothetical mechanisms that may inspire changes in cell fate decisions are highlighted. Understanding the plasticity of leukemia initiating cells might be fundamental to unravel the pathogenesis of lineage switch in acute leukemias and will illuminate the importance of a flexible hematopoietic development. PMID:22852088
Dorantes-Acosta, Elisa; Pelayo, Rosana
Acute leukemias are the most common cancer in childhood and characterized by the uncontrolled production of hematopoietic precursor cells of the lymphoid or myeloid series within the bone marrow. Even when a relatively high efficiency of therapeutic agents has increased the overall survival rates in the last years, factors such as cell lineage switching and the rise of mixed lineages at relapses often change the prognosis of the illness. During lineage switching, conversions from lymphoblastic leukemia to myeloid leukemia, or vice versa, are recorded. The central mechanisms involved in these phenomena remain undefined, but recent studies suggest that lineage commitment of plastic hematopoietic progenitors may be multidirectional and reversible upon specific signals provided by both intrinsic and environmental cues. In this paper, we focus on the current knowledge about cell heterogeneity and the lineage switch resulting from leukemic cells plasticity. A number of hypothetical mechanisms that may inspire changes in cell fate decisions are highlighted. Understanding the plasticity of leukemia initiating cells might be fundamental to unravel the pathogenesis of lineage switch in acute leukemias and will illuminate the importance of a flexible hematopoietic development.
Dorantes-Acosta, Elisa; Pelayo, Rosana
Pluripotent stem cells can differentiate into various lineages but undergo genetic and epigenetic changes during long-term cultivation and, therefore, require regular monitoring. The expression patterns of cancer-testis antigens (CTAs) MAGE-A2, -A3, -A4, -A6, -A8, -B2, and GAGE were examined in undifferentiated human embryonic stem (hES) cells, their differentiated derivatives, teratocarcinoma (hEC) cells, and cancer cell lines of neuroectodermal and mesodermal origin. Undifferentiated hES cells and embryoid body cells expressed MAGE-A3, -A6, -A4, -A8, and GAGEs while later differentiated derivatives expressed only MAGE-A8 or MAGE-A4. Likewise, mouse pluripotent stem cells also express CTAs of Magea but not Mageb family. Despite similarity of the hES and hEC cell expression patterns, MAGE-A2 and MAGE-B2 were detected only in hEC cells but not in hES cells. Moreover, our analysis has shown that CTAs are aberrantly expressed in cancer cell lines and display low tissue specificity. The identification of CTA expression patterns in pluripotent stem cells and their derivatives may be useful for isolation of abnormally CTA-expressing cells to improve the safety of stem-cell based therapy.
Lifantseva, Nadya; Koltsova, Anna; Krylova, Tatyana; Yakovleva, Tatyana; Poljanskaya, Galina; Gordeeva, Olga
Herbivorous dinosaurs were abundant, species-rich components of Late Triassic-Cretaceous terrestrial ecosystems. Obligate high-fiber herbivory evolved independently on several occasions within Dinosauria, through the intermediary step of omnivory. Anatomical character complexes associated with this diet exhibit high levels of convergence and morphological disparity, and may have evolved by correlated progression. Dinosaur faunas changed markedly during the Mesozoic, from early faunas dominated by taxa with simple, uniform feeding mechanics to Cretaceous biomes including diverse sophisticated sympatric herbivores; the environmental and biological drivers causing these changes remain unclear. Isotopic, taphonomic, and anatomical evidence implies that niche partitioning reduced competition between sympatric herbivores, via morphological differentiation, dietary preferences, and habitat selection. Large body size in dinosaur herbivores is associated with low plant productivity, and gave these animals prominent roles as ecosystem engineers. Although dinosaur herbivores lived through several major events in floral evolution, there is currently no evidence for plant-dinosaur coevolutionary interactions.
Barrett, Paul M.
Purpose The goals of this study were to optimize radiolabeling of renal lineages differentiated from human embryonic stem (hES) cells\\u000a and use noninvasive imaging (positron emission tomography (PET) and bioluminescence imaging (BLI)) to detect the cells in\\u000a fetal monkeys post-transplant.\\u000a \\u000a \\u000a \\u000a \\u000a Procedures hES cells expressing firefly luciferase (5?×?106) were radiolabeled with the optimized concentration of 10 ?Ci\\/ml 64Cu-PTSM then transplanted under ultrasound guidance into
Alice F. Tarantal; C. Chang I. Lee; Cynthia A. Batchelder; Jared E. Christensen; Daniel Prater; Simon R. Cherry
Were dinosaurs ectotherms or fast-metabolizing endotherms whose activities were unconstrained by temperature? To date, some of the strongest evidence for endothermy comes from the rapid growth rates derived from the analysis of fossil bones. However, these studies are constrained by a lack of comparative data and an appropriate energetic framework. Here we compile data on ontogenetic growth for extant and fossil vertebrates, including all major dinosaur clades. Using a metabolic scaling approach, we find that growth and metabolic rates follow theoretical predictions across clades, although some groups deviate. Moreover, when the effects of size and temperature are considered, dinosaur metabolic rates were intermediate to those of endotherms and ectotherms and closest to those of extant mesotherms. Our results suggest that the modern dichotomy of endothermic versus ectothermic is overly simplistic. PMID:24926017
Grady, John M; Enquist, Brian J; Dettweiler-Robinson, Eva; Wright, Natalie A; Smith, Felisa A
Summary Human pluripotent stem cells (hPSCs) represent a promising source of patient-specific cells for disease modeling, drug screens, and cellular therapies. However, the inability to derive engraftable human hematopoietic stem and progenitor (HSPCs) has limited their characterization to in vitro assays. We report a strategy to re-specify lineage-restricted CD34+CD45+ myeloid precursors derived from hPSCs into multilineage progenitors that can be expanded in vitro and engraft in vivo. HOXA9, ERG, and RORA conferred self-renewal and multilineage potential in vitro and maintained primitive CD34+CD38? cells. Screening cells via transplantation revealed that two additional factors, SOX4 and MYB, were required for engraftment. Progenitors specified with all five factors gave rise to reproducible short-term engraftment with myeloid and erythroid lineages. Erythroid precursors underwent hemoglobin switching in vivo, silencing embryonic and activating adult globin expression. Our combinatorial screening approach establishes a strategy for obtaining transcription factor-mediated engraftment of blood progenitors from human pluripotent cells.
Doulatov, Sergei; Vo, Linda T.; Chou, Stephanie S.; Kim, Peter G.; Arora, Natasha; Li, Hu; Hadland, Brandon K.; Bernstein, Irwin D.; Collins, James J.; Zon, Leonard I.; Daley, George Q.
Mouse embryonic stem cells were previously observed along with mesenchymal stem cells from different sources, after being treated with a mixed ester of hyaluronan with butyric and retinoic acids, to show a significant increase in the yield of cardiogenic and vascular differentiated elements. The aim of the present study was to determine if stem cells derived from primitive fetal cells present in human amniotic fluid (hAFSCs) and cultured in the presence of a mixture of hyaluronic (HA), butyric (BU), and retinoic (RA) acids show a higher yield of differentiation toward the cardiovascular phenotype as compared with untreated cells. During the differentiation process elicited by exposure to HA + BU + RA, genes controlling pluripotency and plasticity of stem cells, such as Sox2, Nanog, and Oct4, were significantly downregulated at the transcriptional level. At this point, a significant increase in expression of genes controlling the appearance of cardiogenic and vascular lineages in HA + BU + RA-treated cells was observed. The protein expression levels typical of cardiac and vascular phenotypes, evaluated by Western blotting, immunofluorescence, and flow cytometry, were higher in hAFSCs cultured in the presence of HA + BU + RA, as compared with untreated control cells. Appearance of the cardiac phenotype was further inferred by ultrastructural analysis using transmission and scanning electron microscopy. These results demonstrate that a mixture of HA + BU + RA significantly increased the yield of elements committed toward cardiac and vascular phenotypes, confirming what we have previously observed in other cellular types.
Maioli, Margherita; Contini, Giovanni; Santaniello, Sara; Bandiera, Pasquale; Pigliaru, Gianfranco; Sanna, Raimonda; Rinaldi, Salvatore; Delitala, Alessandro P; Montella, Andrea; Bagella, Luigi; Ventura, Carlo
Canonical Wnt signaling plays a rate-limiting role in regulating self-renewal and differentiation in mouse embryonic stem cells (ESCs). We have previously shown that mutation in the Apc (adenomatous polyposis coli) tumor suppressor gene constitutively activates Wnt signaling in ESCs and inhibits their capacity to differentiate towards ecto-, meso-, and endodermal lineages. However, the underlying molecular and cellular mechanisms through which Wnt regulates lineage differentiation in mouse ESCs remain to date largely unknown. To this aim, we have derived and studied the gene expression profiles of several Apc-mutant ESC lines encoding for different levels of Wnt signaling activation. We found that down-regulation of Tcf3, a member of the Tcf/Lef family and a key player in the control of self-renewal and pluripotency, represents a specific and primary response to Wnt activation in ESCs. Accordingly, rescuing Tcf3 expression partially restored the neural defects observed in Apc-mutant ESCs, suggesting that Tcf3 down-regulation is a necessary step towards Wnt-mediated suppression of neural differentiation. We found that Tcf3 down-regulation in the context of constitutively active Wnt signaling does not result from promoter DNA methylation but is likely to be caused by a plethora of mechanisms at both the RNA and protein level as shown by the observed decrease in activating histone marks (H3K4me3 and H3-acetylation) and the upregulation of miR-211, a novel Wnt-regulated microRNA that targets Tcf3 and attenuates early neural differentiation in mouse ESCs. Our data show for the first time that Wnt signaling down-regulates Tcf3 expression, possibly at both the transcriptional and post-transcriptional levels, and thus highlight a novel mechanism through which Wnt signaling inhibits neuro-ectodermal lineage differentiation in mouse embryonic stem cells.
Atlasi, Yaser; Noori, Rubina; Gaspar, Claudia; Franken, Patrick; Sacchetti, Andrea; Rafati, Haleh; Mahmoudi, Tokameh; Decraene, Charles; Calin, George A.; Merrill, Bradley J.; Fodde, Riccardo
Background: Characterisation of stem cells by flow cytometry, their expansion and differentiation are presently of major interest for cell engineering as the basis of a therapeutic concept for transplantation. Haematopoietic stem cells (HSC) express CD34, the adhesion structure which binds 2L-selectin, CD117, a receptor for stem cell factor (SCF; c-kit ligand), and CD133, a transmembrane protein belonging to the family
Katharina Ruzicka; Branka Grskovic; Vladimir Pavlovic; Durdi Qujeq; Alireza Karimi; Mathias M. Mueller
Following haematopoietic stem cell transplantation, monitoring the proportion of donor and recipient haematopoiesis in the patient (chimerism) is an influential tool in directing further treatment choices. Short tandem repeat (STR) analysis is a method of chimerism monitoring using DNA isolated from peripheral blood, bone marrow or specific isolated cell lineages such as CD3+ T cells. For lineage-specific STR analysis on cell populations isolated from peripheral blood, a qualitative estimation of the purity of each isolated population is essential for the correct interpretation of the test data. We describe a rapid, inexpensive method for the determination of purity using a simple flow cytometry method. The method described for assessing the purity of sorted CD3+ cells can be applied to any cell population isolated using the same technology. Data obtained were comparable to results from a commercial polymerase chain reaction (PCR)-based method for the assessment of purity (Non-T Genomic Detection Kit, Accumol, Calgary, AB, Canada) (P?=?0.59). Of the 303 samples tested by flow cytometry, 290 (95.7%) exceeded 90% purity, and 215 (70.95%) were over 99% pure. There were some outlying samples, showing diversity between samples and the unpredictability of purity of isolated cell populations. This flow cytometry method can be easily assimilated into routine testing protocols, allowing purity assessment in multiple-sorted cell populations for lineage-specific chimerism monitoring using a single secondary antibody and giving results comparable to a PCR-based method. As purity of isolated cell lineages is affected by time after venepuncture and storage temperature, assessment of each sample is recommended to give a reliable indication of sample quality and confidence in the interpretation of the results. PMID:24461006
Hanson, V; Adams, B; Lord, J; Barker, A; Poulton, K; Lee, H
Polished pebbles occasionally found within skeletons of giant herbivorous sauropod dinosaurs are very likely to be gastroliths (stomach stones). Here, we show that based on feeding experiments with ostriches and comparative data for relative gastrolith mass in birds, sauropod gastroliths do not represent the remains of an avian-style gastric mill. Feeding experiments with farm ostriches showed that bird gastroliths experience fast abrasion in the gizzard and do not develop a polish. Relative gastrolith mass in sauropods (gastrolith mass much less than 0.1% of body mass) is at least an order of magnitude less than that in ostriches and other herbivorous birds (gastrolith mass approximates 1% of body mass), also arguing against the presence of a gastric mill in sauropods. Sauropod dinosaurs possibly compensated for their limited oral processing and gastric trituration capabilities by greatly increasing food retention time in the digestive system. Gastrolith clusters of some derived theropod dinosaurs (oviraptorosaurs and ornithomimosaurs) compare well with those of birds, suggesting that the gastric mill evolved in the avian stem lineage.
Wings, Oliver; Sander, P. Martin
Despite nearly two centuries of investigation, a comprehensive understanding of dinosaur biology has proven intractable. The recent development of means to study tissue-level growth, age these animals, and make growth curves has revolutionized our knowledge of dinosaur lives. From such data it is now understood that dinosaurs grew both disruptively and determinately; that they rarely if ever exceeded a century in age; that they became giants through accelerated growth and dwarfed through truncated development; that they were likely endothermic, sexually matured like crocodiles, and showed survivorship like populations of large mammals; and that basal birds retained dinosaurian physiology.
Erickson, Gregory M.
Evidence presented on this site is overwhelmingly in favor of birds being the descendants of a maniraptoran dinosaur, probably something similar (but not identical) to a small dromaeosaur. Dr. Jacques Gauthier created the first well-accepted, detailed phylogeny of the diapsids. His work provided strong, compelling support for the theory that birds are theropod dinosaurs. The development of the theory is traced and a list of twenty major skeletal characteristics the first birds shared with many coelurosaurian dinosaurs is included. The site contains many active links for further study.
The oldest unequivocal records of Dinosauria were unearthed from Late Triassic rocks (approximately 230 Ma) accumulated over extensional rift basins in southwestern Pangea. The better known of these are Herrerasaurus ischigualastensis, Pisanosaurus mertii, Eoraptor lunensis, and Panphagia protos from the Ischigualasto Formation, Argentina, and Staurikosaurus pricei and Saturnalia tupiniquim from the Santa Maria Formation, Brazil. No uncontroversial dinosaur body fossils are known from older strata, but the Middle Triassic origin of the lineage may be inferred from both the footprint record and its sister-group relation to Ladinian basal dinosauromorphs. These include the typical Marasuchus lilloensis, more basal forms such as Lagerpeton and Dromomeron, as well as silesaurids: a possibly monophyletic group composed of Mid-Late Triassic forms that may represent immediate sister taxa to dinosaurs. The first phylogenetic definition to fit the current understanding of Dinosauria as a node-based taxon solely composed of mutually exclusive Saurischia and Ornithischia was given as "all descendants of the most recent common ancestor of birds and Triceratops". Recent cladistic analyses of early dinosaurs agree that Pisanosaurus mertii is a basal ornithischian; that Herrerasaurus ischigualastensis and Staurikosaurus pricei belong in a monophyletic Herrerasauridae; that herrerasaurids, Eoraptor lunensis, and Guaibasaurus candelariensis are saurischians; that Saurischia includes two main groups, Sauropodomorpha and Theropoda; and that Saturnalia tupiniquim is a basal member of the sauropodomorph lineage. On the contrary, several aspects of basal dinosaur phylogeny remain controversial, including the position of herrerasaurids, E. lunensis, and G. candelariensis as basal theropods or basal saurischians, and the affinity and/or validity of more fragmentary taxa such as Agnosphitys cromhallensis, Alwalkeria maleriensis, Chindesaurus bryansmalli, Saltopus elginensis, and Spondylosoma absconditum. The identification of dinosaur apomorphies is jeopardized by the incompleteness of skeletal remains attributed to most basal dinosauromorphs, the skulls and forelimbs of which are particularly poorly known. Nonetheless, Dinosauria can be diagnosed by a suite of derived traits, most of which are related to the anatomy of the pelvic girdle and limb. Some of these are connected to the acquisition of a fully erect bipedal gait, which has been traditionally suggested to represent a key adaptation that allowed, or even promoted, dinosaur radiation during Late Triassic times. Yet, contrary to the classical "competitive" models, dinosaurs did not gradually replace other terrestrial tetrapods over the Late Triassic. In fact, the radiation of the group comprises at least three landmark moments, separated by controversial (Carnian-Norian, Triassic-Jurassic) extinction events. These are mainly characterized by early diversification in Carnian times, a Norian increase in diversity and (especially) abundance, and the occupation of new niches from the Early Jurassic onwards. Dinosaurs arose from fully bipedal ancestors, the diet of which may have been carnivorous or omnivorous. Whereas the oldest dinosaurs were geographically restricted to south Pangea, including rare ornithischians and more abundant basal members of the saurischian lineage, the group achieved a nearly global distribution by the latest Triassic, especially with the radiation of saurischian groups such as "prosauropods" and coelophysoids. PMID:19895605
Langer, Max C; Ezcurra, Martin D; Bittencourt, Jonathas S; Novas, Fernando E
In the context of the role of multiple physical factors in dictating stem cell fate, the present paper demonstrates the effectiveness of the intermittently delivered external electric field stimulation towards switching the stem cell fate to specific lineage, when cultured in the absence of biochemical growth factors. In particular, our findings present the ability of human mesenchymal stem cells (hMSCs) to respond to the electric stimuli by adopting extended neural-like morphology on conducting polymeric substrates. Polyaniline (PANI) is selected as the model system to demonstrate this effect, as the electrical conductivity of the polymeric substrates can be systematically tailored over a broad range (10(-9) to 10 S/cm) from highly insulating to conducting by doping with varying concentrations (10(-5) to 1 m) of HCl. On the basis of the culture protocol involving the systematic delivery of intermittent electric field (dc) stimulation, the parametric window of substrate conductivity and electric field strength was established to promote significant morphological extensions, with minimal cellular damage. A time dependent morphological change in hMSCs with significant filopodial elongation was observed after 7 days of electrically stimulated culture. Concomitant with morphological changes, a commensurate increase in the expression of neural lineage commitment markers such as nestin and ?III tubulin was recorded from hMSCs grown on highly conducting substrates, as revealed from the mRNA expression analysis using Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) as well as by immune-fluorescence imaging. Therefore, the present work establishes the key role of intermittent and systematic delivery of electric stimuli as guidance cues in promoting neural-like differentiation of hMSCs, when grown on electroconductive substrates. PMID:24816362
Thrivikraman, Greeshma; Madras, Giridhar; Basu, Bikramjit
We recently described a murine embryonic stem cell (ESC) line engineered to express the activated Notch 4 receptor in a tetracycline (doxcycline; Dox) regulated fashion (tet-notch4 ESCs). Notch 4 induction in Flk1+ hematopoietic and vascular progenitors from this line respecified them to a cardiovascular fate. We reasoned that these cells would be ideal for evaluating the contribution of the cardiomyocyte and vascular lineages to the functional improvement noted following stem cell transplantation in infarcted hearts. Flk-1+ Tet-notch4 cells from d 3 embryoid bodies exposed to doxycycline (Dox+) were compared to uninduced (Dox?) Flk-1+ cells. Mice underwent transplantation of 5 × 105 Dox+ cells, Dox?cells, or an equal volume of serum-free medium after surgically induced myocardial infarction. The mean ejection fraction was 59 ± 15, 46 ± 17, and 39 ± 13% in the Dox+, Dox?, and serum-free medium groups, respectively (P<0.05 for the differences among all 3 groups). Immunohistochemistry of hearts injected with Dox+ grafts expressed myocardial and vascular markers, whereas grafts of Dox? cells expressed primarily vascular markers. We conclude that cardiovascular progenitors are more effective than vascular progenitors in improving function after myocardial infarction. The transplantation of appropriate cell types is critical for maximizing the benefit of cardiovascular cell therapy.—Adler, E. D., Chen, V. C., Bystrup, A., Kaplan, A. D., Giovannone, S., Briley-Saebo, K., Young, W., Kattman, S., Mani, V., Laflamme, M., Zhu, W.-Z., Fayad, Z., Keller, G. The cardiomyocyte lineage is critical for optimization of stem cell therapy in a mouse model of myocardial infarction.
Adler, Eric D.; Chen, Vincent C.; Bystrup, Anne; Kaplan, Aaron D.; Giovannone, Steven; Briley-Saebo, Karen; Young, Wilson; Kattman, Steve; Mani, Venkatesh; Laflamme, Michael; Zhu, Wei-Zhong; Fayad, Zahi; Keller, Gordon
Non-avian dinosaur reproductive and parenting behaviors were mostly similar to those of extant archosaurs. Non-avian dinosaurs were probably sexually dimorphic and some may have engaged in hierarchical rituals. Non-avian coelurosaurs (e.g. Troodontidae, Oviraptorosauria) had two active oviducts, each of which produced single eggs on a daily or greater time scale. The eggs of non-coelurosaurian dinosaurs (e.g. Ornithischia, Sauropoda) were incubated in soils, whereas the eggs of non-avian coelurosaurs (e.g. Troodon, Oviraptor) were incubated with a combination of soil and direct parental contact. Parental attention to the young was variable, ranging from protection from predators to possible parental feeding of nest-bound hatchlings. Semi-altricial hadrosaur hatchlings exited their respective nests near the time of their first linear doubling. Some reproductive behaviors, once thought exclusive to Aves, arose first in non-avian dinosaurs. The success of the Dinosauria may be related to reproductive strategies.
Horner, John R.
Myocardial infarction (MI) is a lead cause of mortality in the Western world. Treatment of acute MI is focused on restoration of antegrade flow which inhibits further tissue loss, but does not restore function to damaged tissue. Chronic therapy for injured myocardial tissue involves medical therapy that attempts to minimize pathologic remodeling of the heart. End stage therapy for chronic heart failure (CHF) involves inotropic therapy to increase surviving cardiac myocyte function or mechanical augmentation of cardiac performance. Not until the point of heart transplantation, a limited resource at best, does therapy focus on the fundamental problem of needing to replace injured tissue with new contractile tissue. In this setting, the potential for stem cell therapy has garnered significant interest for its potential to regenerate or create new contractile cardiac tissue. While to date adult stem cell therapy in clinical trials has suggested potential benefit, there is waning belief that the approaches used to date lead to regeneration of cardiac tissue. As the literature has better defined the pathways involved in cardiac differentiation, preclinical studies have suggested that stem cell pretreatment to direct stem cell differentiation prior to stem cell transplantation may be a more efficacious strategy for inducing cardiac regeneration. Here we review the available literature on pre-transplantation conditioning of stem cells in an attempt to better understand stem cell behavior and their readiness in cell-based therapy for myocardial regeneration.
Mayorga, Maritza; Finan, Amanda; Penn, Marc
Dinosaurs have been fascinating to the widest public since the 1840s, and that interest has grown step-wise ever since. Public interest has been harnessed over the years especially by museums in blockbuster exhibitions, and in the form of best-selling books and films. Here we describe a major educational initiative, the Bristol Dinosaur Project, which has run for ten years and
Michael J. Benton; Remmert Schouten; Edward J. A. Drewitt; Pedro Viegas
Inference of colour patterning in extinct dinosaurs has been based on the relationship between the morphology of melanin-containing organelles (melanosomes) and colour in extant bird feathers. When this relationship evolved relative to the origin of feathers and other novel integumentary structures, such as hair and filamentous body covering in extinct archosaurs, has not been evaluated. Here we sample melanosomes from the integument of 181 extant amniote taxa and 13 lizard, turtle, dinosaur and pterosaur fossils from the Upper-Jurassic and Lower-Cretaceous of China. We find that in the lineage leading to birds, the observed increase in the diversity of melanosome morphologies appears abruptly, near the origin of pinnate feathers in maniraptoran dinosaurs. Similarly, mammals show an increased diversity of melanosome form compared to all ectothermic amniotes. In these two clades, mammals and maniraptoran dinosaurs including birds, melanosome form and colour are linked and colour reconstruction may be possible. By contrast, melanosomes in lizard, turtle and crocodilian skin, as well as the archosaurian filamentous body coverings (dinosaur 'protofeathers' and pterosaur 'pycnofibres'), show a limited diversity of form that is uncorrelated with colour in extant taxa. These patterns may be explained by convergent changes in the key melanocortin system of mammals and birds, which is known to affect pleiotropically both melanin-based colouration and energetic processes such as metabolic rate in vertebrates, and may therefore support a significant physiological shift in maniraptoran dinosaurs. PMID:24522537
Li, Quanguo; Clarke, Julia A; Gao, Ke-Qin; Zhou, Chang-Fu; Meng, Qingjin; Li, Daliang; D'Alba, Liliana; Shawkey, Matthew D
Neoplasms of natural killer (NK)-lineage are rare. Their prognosis is generally poor except for cases of solitary nasal NK-cell lymphoma. The NK-cell Tumor Study Group performed a survey in Japan on patients diagnosed between 1994 and 1998. Of 228 patients selected for analysis, 40 underwent HSCT (15 allografts and 25 autografts). The underlying diseases were myeloid\\/NK cell precursor acute leukemia
R Suzuki; J Suzumiya; S Nakamura; Y Kagami; J-I Kameoka; C Sakai; H Mukai; K Takenaka; T Yoshino; T Tsuzuki; H Sugimori; K Kawa; Y Kodera; K Oshimi
Cretaceous polar dinosaur faunas were taxonomically diverse, which suggests varied strategies for coping with the climatic stress of high latitudes. Some polar dinosaurs, particularly larger taxa such as the duckbill Edmontosaurus Lambe, 1917, were biomechanically and energetically capable of migrating over long distances, up to 2600 km. However, current evidence strongly suggests many polar dinosaurs (including sauropods, large and small theropods,
Phil R. Bell; Eric Snively
brain. (A) The lineage relationship between neural stem cells, progenitor cells, and differentiated cells is illustrated. The hGFAP-cre transgene is expressed in radial glia during embryonic development, and in type B neural stem cells as well as mature astrocytes in the postnatal brain (all three hGFAP-cre-expressing cell types are marked by dashed lines). Of note, mouse GFAP (mGFAP) is not
Yuan Wang; Jiong Yang; Huarui Zheng; Gerald J. Tomasek; Peng Zhang; Paul E. McKeever; Eva Y-H; P. Lee; Yuan Zhu
Primary cilia are sensory organelles that have been shown to play a critical role in lineage commitment. It was our hypothesis that the primary cilium is necessary for chemically induced differentiation of human mesenchymal stem cells (MSC). To investigate this, polaris siRNA was used to inhibit the primary cilia and the mRNA levels of transcription factors Runx2, PPAR? were measured by RT PCR as markers of osteogenic, adipogenic and chondrogenic differentiation, respectively. MSCs with inhibited primary cilia had significantly decreased basal mRNA expression levels of all three lineages specific transcription factors indicating that primary cilia are critical in multiple differentiation pathways. Furthermore, to determine if primary cilia play a role in the differentiation potential of MSCs, progenitor cells transfected with either scrambled or polaris siRNA were cultured in osteo-inductive, chondro-inductive, or adipo-inductive media and lineage commitment was ascertained. Interestingly, within 24 h of culture, cells transfected with polaris siRNA in both osteogenic and adipogenic media lost adhesion and released from the slides; however MSCs in chondrogenic media as well as cells transfected with scrambled siRNA did not. These results suggest that the primary cilium is necessary for the normal progression of chemically induced osteogenic and adipogenic differentiation. As a control, the experiment was repeated with NIH3T3 fibroblasts and none of the effects of inhibited primary cilia were observed indicating that the loss of adhesion may be specific to MSCs. Furthermore after biochemically inducing the cells to differentiate, polaris knockdown resulted in abrogation of both Runx2 and PPAR? mRNA while SOX9 mRNA expression was significantly lower. These results suggest that primary cilia play an essential role not only in the initiation of both osteogenic and adipogenic differentiation, but also in maintaining the phenotype of differentiated cells. Interestingly, chondrogenic differentiation appeared less dependent on a functional primary cilium.
Tummala, Padmaja; Arnsdorf, Emily J.; Jacobs, Christopher R.
Sirt2, a member of the NAD+-dependent protein deacetylase family, is increasingly recognized as a critical regulator of the cell cycle, cellular necrosis and cytoskeleton organization. However, its role in embryonic stem cells (ESCs) remains unclear. Here we demonstrate that Sirt2 is up-regulated during RA (retinoic acid)-induced and embryoid body (EB) differentiation of mouse ESCs. Using lentivirus-mediated shRNA methods, we found that knockdown of Sirt2 compromises the differentiation of mouse ESCs into ectoderm while promoting mesoderm and endoderm differentiation. Knockdown of Sirt2 expression also leads to the activation of GSK3? through decreased phosphorylation of the serine at position 9 (Ser9) but not tyrosine at position 216 (Tyr216). Moreover, the constitutive activation of GSK3? during EB differentiation mimics the effect of Sirt2 knockdown, while down-regulation of GSK3? rescues the effect of Sirt2 knockdown on differentiation. In contrast to the effect on lineage differentiation, Sirt2 knockdown and GSK3? up-regulation do not change the self-renewal state of mouse ESCs. Overall, our report reveals a new function for Sirt2 in regulating the proper lineage commitment of mouse ESCs.
Guo, Xudong; Chen, Long; Wang, Guiying; Xu, Yanxin; Kang, Jiuhong
Activation of the FGF-ERK pathway is necessary for naïve mouse embryonic stem (ES) cells to exit self-renewal and commit to early differentiated lineages. Here we show that genetic ablation of Erk2, the predominant ERK isozyme expressed in ES cells, results in hyper-phosphorylation of ERK1, but an overall decrease in total ERK activity as judged by substrate phosphorylation and immediate-early gene (IEG) induction. Normal induction of this subset of canonical ERK targets, as well as p90RSK phosphorylation, was rescued by transgenic expression of either ERK1 or ERK2 indicating a degree of functional redundancy. In contrast to previously published work, Erk2-null ES cells exhibited no detectable defect in lineage specification to any of the three germ layers when induced to differentiate in either embryoid bodies or in defined neural induction conditions. However, under self-renewing conditions Erk2-null ES cells express increased levels of the pluripotency-associated transcripts, Nanog and Tbx3, a decrease in Nanog-GFP heterogeneity, and exhibit enhanced self-renewal in colony forming assays. Transgenic add-back of ERK2 is capable of restoring normal pluripotent gene expression and self-renewal capacity. We show that ERK2 contributes to the destabilization of ES cell self-renewal by reducing expression of pluripotency genes, such as Nanog, but is not specifically required for the early stages of germ layer specification.
Hamilton, William B.; Kaji, Keisuke; Kunath, Tilo
Do dinosaurs have bellybuttons? This intriguing question launched a journey into inquiry science that captivated a class of four-year-olds for eight months. As students enjoyed dinosaur books, examined dinosaur artifacts, drew pictures, watched videos, and generally immersed themselves in all things dinosaur, the authors built a culture of learning in their classroom that helped these young students develop science-process skills such as observation, measurement, and communication. They share their inspiring learning adventure here.
Valentine-Anand, Lesley; Murray, Mary
Summary The epithelial-to-mesenchymal transition (EMT) is an embryonic process that becomes latent in most normal adult tissues. Recently, we have shown that induction of EMT endows breast epithelial cells with stem cell traits. In this report, we have further characterized the EMT-derived cells and shown that these cells are similar to mesenchymal stem cells (MSCs) with the capacity to differentiate into multiple tissue lineages. For this purpose, we induced EMT by ectopic expression of Twist, Snail or TGF-? in immortalized human mammary epithelial cells (HMECs). We found that the EMT-derived cells and MSCs share many properties including the antigenic profile typical of MSCs, i.e. CD44+, CD24? and CD45?. Conversely, MSCs express EMT-associated genes, such as Twist, Snail and FOXC2. Interestingly, CD140b (PDGFR-?), a marker for naive MSCs, is exclusively expressed in EMT-derived cells and not in their epithelial counterparts. Moreover, functional analyses revealed that EMT-derived cells but not the control cells can differentiate into Alizarin Red S-positive mature osteoblasts, Oil Red O-positive adipocytes and Alcian Blue-positive chondrocytes similar to MSCs. We also observed that EMT-derived cells but not the control cells invade and migrate towards MDA-MB-231 breast cancer cells similar to MSCs. In vivo wound homing assays in nude mice revealed that the EMT-derived cells home to wound sites similar to MSCs. In conclusion, we have demonstrated that the EMT-derived cells are similar to MSCs in gene expression, multi-lineage differentiation, and ability to migrate towards tumor cells and wound sites.
Battula, Venkata L.; Evans, Kurt W.; Hollier, Brett G.; Shi, Yuexi; Marini, Frank C.; Ayyanan, Ayyakkannu; Wang, Rui-Yu; Brisken, Cathrin; Guerra, Rudy; Andreeff, Michael; Mani, Sendurai A.
Human endometrium regenerates on a cyclic basis from candidate stem/progenitors whose genetic programs are yet to be determined. A subpopulation of endometrial stromal cells, displaying key properties of mesenchymal stem cells (MSCs), has been characterized. The endometrial MSC (eMSC) is likely the precursor of the endometrial stromal fibroblast. The goal of this study was to determine the transcriptome and signaling pathways in the eMSC to understand its functional phenotype. Endometrial stromal cells from oocyte donors (n = 20) and patients undergoing benign gynecologic surgery (n = 7) were fluorescence-activated cell sorted into MCAM (CD146)(+)/PDGFRB(+) (eMSC), MCAM (CD146)(-)/PDGFRB(+) (fibroblast), and MCAM (CD146)(+)/PDGFRB(-) (endothelial) populations. The eMSC population contained clonogenic cells with a mesenchymal phenotype differentiating into adipocytes when cultured in adipogenic medium. Gene expression profiling using Affymetrix Human Gene 1.0 ST arrays revealed 762 and 1518 significantly differentially expressed genes in eMSCs vs. stromal fibroblasts and eMSCs vs. endothelial cells, respectively. By principal component and hierarchical clustering analyses, eMSCs clustered with fibroblasts and distinctly from endothelial cells. Endometrial MSCs expressed pericyte markers and were localized by immunofluorescence to the perivascular space of endometrial small vessels. Endometrial MSCs also expressed genes involved in angiogenesis/vasculogenesis, steroid hormone/hypoxia responses, inflammation, immunomodulation, cell communication, and proteolysis/inhibition, and exhibited increased Notch, TGFB, IGF, Hedgehog, and G-protein-coupled receptor signaling pathways, characteristic of adult tissue MSC self-renewal and multipotency. Overall, the data support the eMSC as a clonogenic, multipotent pericyte that displays pathways of self-renewal and lineage specification, the potential to respond to conditions during endometrial desquamation and regeneration, and a genetic program predictive of its differentiated lineage, the stromal fibroblast. PMID:22075475
Spitzer, Trimble L B; Rojas, Angela; Zelenko, Zara; Aghajanova, Lusine; Erikson, David W; Barragan, Fatima; Meyer, Michelle; Tamaresis, John S; Hamilton, Amy E; Irwin, Juan C; Giudice, Linda C
The bone marrow is the principal site where HSCs and more mature blood cells lineage progenitors reside and differentiate in an adult organism. HSCs constitute a minute cell population of pluripotent cells capable of generating all blood cell lineages for a life-time1. The molecular dissection of HSCs homeostasis in the bone marrow has important implications in hematopoiesis, oncology and regenerative medicine. We describe the labeling protocol with fluorescent antibodies and the electronic gating procedure in flow cytometry to score hematopoietic progenitor subsets and HSCs distribution in individual mice (Fig. 1). In addition, we describe a method to extensively enrich hematopoietic progenitors as well as long-term (LT) and short term (ST) reconstituting HSCs from pooled bone marrow cell suspensions by magnetic enrichment of cells expressing c-Kit. The resulting cell preparation can be used to sort selected subsets for in vitro and in vivo functional studies (Fig. 2). Both trabecular osteoblasts2,3 and sinusoidal endothelium4 constitute functional niches supporting HSCs in the bone marrow. Several mechanisms in the osteoblastic niche, including a subset of N-cadherin+ osteoblasts3 and interaction of the receptor tyrosine kinase Tie2 expressed in HSCs with its ligand angiopoietin-15 concur in determining HSCs quiescence. "Hibernation" in the bone marrow is crucial to protect HSCs from replication and eventual exhaustion upon excessive cycling activity6. Exogenous stimuli acting on cells of the innate immune system such as Toll-like receptor ligands7 and interferon-?6 can also induce proliferation and differentiation of HSCs into lineage committed progenitors. Recently, a population of dormant mouse HSCs within the lin- c-Kit+ Sca-1+ CD150+ CD48- CD34- population has been described8. Sorting of cells based on CD34 expression from the hematopoietic progenitors-enriched cell suspension as described here allows the isolation of both quiescent self-renewing LT-HSCs and ST-HSCs9. A similar procedure based on depletion of lineage positive cells and sorting of LT-HSC with CD48 and Flk2 antibodies has been previously described10. In the present report we provide a protocol for the phenotypic characterization and ex vivo cell cycle analysis of hematopoietic progenitors, which can be useful for monitoring hematopoiesis in different physiological and pathological conditions. Moreover, we describe a FACS sorting procedure for HSCs, which can be used to define factors and mechanisms regulating their self-renewal, expansion and differentiation in cell biology and signal transduction assays as well as for transplantation.
Frascoli, Michela; Proietti, Michele; Grassi, Fabio
In this activity (located on page 4 of PDF), learners gain insight into the actual size of dinosaurs and practice making estimations and measurements. Learners measure the lengths of various dinosaurs by measuring lengths of string in field or gym. Learners also estimate and measure these lengths by lying head to foot. Learners also compare and contrast the sizes of different dinosaur species.
Museum, Chicago C.
Amniotic mesenchymal stem cells (AMSCs) express octamer binding transcription factor 4 (Oct-4), which is necessary for maintaining the undifferentiated state of pluripotent stem cells. AMSCs also express CD29, CD44 and vimentin, which are specific markers of mesenchymal cells. We studied the biological characteristics and potential for cell therapy of AMSCs derived from 8-day-old chicken embryos. We induced the AMSCs to differentiate into adipocytes, osteoblasts and myocardial cells and used immunofluorescence, reverse transcription-polymerase chain reaction (RT-PCR) assays to detect the expressions of specific markers of AMSCs and differentiated cells. To assess the differentiation capacity of AMSCs, passage four cells were induced to differentiate into adipocytes, osteoblasts and myocardial cells. These results suggested that AMSCs isolated from chicken embryos exhibited the characteristics of multipotent stem cells. AMSCs, therefore, may be potential candidates for cellular transplantation therapy and tissue engineering. PMID:24047150
Li, X; Gao, Y; Hua, J; Bian, Y; Mu, R; Guan, W; Ma, Y
A major macroevolutionary question concerns how long-term patterns of body-size evolution are underpinned by smaller scale processes along lineages. One outstanding long-term transition is the replacement of basal therapsids (stem-group mammals) by archosauromorphs, including dinosaurs, as the dominant large-bodied terrestrial fauna during the Triassic (approx. 252-201 million years ago). This landmark event preceded more than 150 million years of archosauromorph dominance. We analyse a new body-size dataset of more than 400 therapsid and archosauromorph species spanning the Late Permian-Middle Jurassic. Maximum-likelihood analyses indicate that Cope's rule (an active within-lineage trend of body-size increase) is extremely rare, despite conspicuous patterns of body-size turnover, and contrary to proposals that Cope's rule is central to vertebrate evolution. Instead, passive processes predominate in taxonomically and ecomorphologically more inclusive clades, with stasis common in less inclusive clades. Body-size limits are clade-dependent, suggesting intrinsic, biological factors are more important than the external environment. This clade-dependence is exemplified by maximum size of Middle-early Late Triassic archosauromorph predators exceeding that of contemporary herbivores, breaking a widely-accepted 'rule' that herbivore maximum size greatly exceeds carnivore maximum size. Archosauromorph and dinosaur dominance occurred via opportunistic replacement of therapsids following extinction, but were facilitated by higher archosauromorph growth rates. PMID:22298850
Sookias, Roland B; Butler, Richard J; Benson, Roger B J
A major macroevolutionary question concerns how long-term patterns of body-size evolution are underpinned by smaller scale processes along lineages. One outstanding long-term transition is the replacement of basal therapsids (stem-group mammals) by archosauromorphs, including dinosaurs, as the dominant large-bodied terrestrial fauna during the Triassic (approx. 252–201 million years ago). This landmark event preceded more than 150 million years of archosauromorph dominance. We analyse a new body-size dataset of more than 400 therapsid and archosauromorph species spanning the Late Permian–Middle Jurassic. Maximum-likelihood analyses indicate that Cope's rule (an active within-lineage trend of body-size increase) is extremely rare, despite conspicuous patterns of body-size turnover, and contrary to proposals that Cope's rule is central to vertebrate evolution. Instead, passive processes predominate in taxonomically and ecomorphologically more inclusive clades, with stasis common in less inclusive clades. Body-size limits are clade-dependent, suggesting intrinsic, biological factors are more important than the external environment. This clade-dependence is exemplified by maximum size of Middle–early Late Triassic archosauromorph predators exceeding that of contemporary herbivores, breaking a widely-accepted ‘rule’ that herbivore maximum size greatly exceeds carnivore maximum size. Archosauromorph and dinosaur dominance occurred via opportunistic replacement of therapsids following extinction, but were facilitated by higher archosauromorph growth rates.
Sookias, Roland B.; Butler, Richard J.; Benson, Roger B. J.
Neoplasms of natural killer (NK)-lineage are rare. Their prognosis is generally poor except for cases of solitary nasal NK-cell lymphoma. The NK-cell Tumor Study Group performed a survey in Japan on patients diagnosed between 1994 and 1998. Of 228 patients selected for analysis, 40 underwent HSCT (15 allografts and 25 autografts). The underlying diseases were myeloid/NK cell precursor acute leukemia (n = 4), blastic NK-cell lymphoma (n = 11), aggressive NK-cell leukemia (n = 3), and nasal-type extranodal NK-cell lymphoma (n = 22). At the time of HSCT, 22 patients were in complete remission (CR), 11 were in relapse, and seven were primary refractory. All patients received myeloablative conditioning regimens including total-body irradiation. Sixteen died of disease progression, and six of treatment-related causes. Overall, 4-year survival was 39% with a median follow-up of 50 months; this was significantly better than that of patients who did not undergo HSCT (21%, P = 0.0003). For patients transplanted in CR, the 4-year overall survival was 68%, which was significantly better than that of patients who went into CR but did not undergo HSCT (P = 0.03). These findings suggest that the HSCT is a promising treatment strategy for NK-cell lineage. PMID:16400344
Suzuki, R; Suzumiya, J; Nakamura, S; Kagami, Y; Kameoka, J-I; Sakai, C; Mukai, H; Takenaka, K; Yoshino, T; Tsuzuki, T; Sugimori, H; Kawa, K; Kodera, Y; Oshimi, K
Obtaining sufficient numbers of immunologically matched hematopoietic stem cells (HSCs) poses a major clinical hurdle in bone marrow transplantation therapies. In a recent study in Cell, Riddell et al. (2014) generate induced HSCs from differentiated blood cells, which may serve as a potential solution to this clinical challenge. PMID:24792111
Wahlestedt, Martin; Bryder, David
SUMMARY Medulloblastoma is the most common malignant brain tumor in children, but the cells from which it arises remain unclear. Here we examine the origin of medulloblastoma resulting from mutations in the Sonic hedge- hog (Shh) pathway. We show that activation of Shh signaling in neuronal progenitors causes medulloblas- toma by 3 months of age. Shh pathway activation in stem
Zeng-Jie Yang; Tammy Ellis; Shirley L. Markant; Tracy-Ann Read; Jessica D. Kessler; Melissa Bourboulas; Ulrich Schüller; Robert Machold; Gord Fishell; David H. Rowitch; Brandon J. Wainwright; Robert J. Wechsler-Reya
BackgroundDue to their self-renewal, embryonic stem cells (ESCs) are attractive cells for applications in regenerative medicine and tissue engineering. Although ESC differentiation has been used as a platform for generating bone in vitro and in vivo, the results have been unsatisfactory at best. It is possible that the traditional culture methods, which have been used, are not optimal and that
Akihiro Yamashita; Sandi Nishikawa; Derrick E. Rancourt; Syed A. Aziz
Adult neural stem cells differentiate into neurons, astrocytes, and oligodendrocytes in the mammalian CNS, but the molecular mechanisms that control their differentiation are not yet well understood. Insulin-like growth factor-I (IGF-I) can promote the di...
F. H. Gage J. Hsieh
The chemokine CXCL12 and its receptor CXCR4 play a key role in regulation of hematopoietic stem cells and cell migratory function during morphogenesis. Osteoblasts express both the ligand and the receptor, but little is known about the role of CXCL12-CXCR4 signaling in maintaining skeletal homeostasis. Using Cre-Lox technology to delete CXCR4 in mature osteoblasts in mice, we show here a significant decrease in bone mass and alterations in cancellous bone structure. CXCR4 gene ablation increased the number of colony-forming units (CFU), CFU-positive for alkaline phosphatase (CFU-AP(+)), and mineralizing nodules in bone marrow stromal cell (BMSC) cultures. The adipocyte precursor population decreased in BMSCs harvested from the KO animals. The nonadherent population of BMSCs harvested from the long bone diaphysis of KO animals formed more osteoclasts, a finding that was associated with increased circulatory levels of pyridinoline, a marker of bone resorption. Our data show that osteoblast-specific CXCR4 deletion has profound effects on the mesenchymal stem cell pool and allocation to the osteoblastic and adipocytic cell lineages. They also show that CXCL12/CXCR4 signaling in the mature osteoblast can feedback to regulate the osteoclast precursor pool size and play a multifunctional role in regulating bone formation and resorption. PMID:23704087
Shahnazari, Mohammad; Chu, Vivian; Wronski, Thomas J; Nissenson, Robert A; Halloran, Bernard P
The richness of Mesozoic Dinosauria is examined through the use of a new global database. Mesozoic dinosaurs show a steadily increasing rate of diversification, in part attributable to the development of new innovations driving an increasing variety of behavioral strategies. The data do not suggest that dinosaurs were decreasing in richness leading to extinction during the last ˜10 m.y. of the Cretaceous. Refinement of the dating of dinosaur fossils, rather than the collection of more dinosaurs, is the best way to resolve globally the rate of the Cretaceous-Tertiary dinosaur extinction.
Fastovsky, David E.; Huang, Yifan; Hsu, Jason; Martin-McNaughton, Jamie; Sheehan, Peter M.; Weishampel, David B.
Human pluripotent stem cells (hPSCs) represent a new and exciting field in modern medicine, now the focus of many researchers and media outlets. The hype is well-earned because of the potential of stem cells to contribute to disease modeling, drug screening, and even therapeutic approaches. In this review, we focus first on neural differentiation of these cells. In a second part we compare the various cell types available and their advantages for in vitro modeling. Then we provide a “state-of-the-art” report about two major biomedical applications: (1) the drug and toxicity screening and (2) the neural tissue replacement. Finally, we made an overview about current biomedical research using differentiated hPSCs.
Martinez, Y.; Dubois-Dauphin, M.; Krause, K.-H.
In the last couple of decades the study of dinosaur eggs and babies has proved to be one of the most exciting and profitable areas of dinosaur research. This is the first book solely devoted to this topic and reviews, in scientific detail, our present state of knowledge about this exciting area of palaeontology. Chapters in the book discuss all aspects of the science including the occurrence of eggs, nests and baby skeletons, descriptive osteology of juvenile skeletons, comparative histology of juvenile bone, analyses of eggs and egg shells, palaeoenvironments of nesting sites, nesting behaviour and developmental growth of baby dinosaurs. The volume will be an invaluable addition to the book collections of vertebrate palaeontologists and their graduate students.
Carpenter, Kenneth; Hirsch, Karl F.; Horner, John R.
Bone marrow derived mesenchymal stem cells (BM-MSCs) have been shown to enhance wound healing; however, the mechanisms involved are barely understood. In this study, we examined paracrine factors released by BM-MSCs and their effects on the cells participating in wound healing compared to those released by dermal fibroblasts. Analyses of BM-MSCs with Real-Time PCR and of BM-MSC-conditioned medium by antibody-based
Liwen Chen; Edward E. Tredget; Philip Y. G. Wu; Yaojiong Wu; Patricia Bozza
Mouse embryonic stem (ES) cells are non-transformed cell lines derived directly from the pluripotent founder tissue in the mouse embryo, the epiblast [1–3]. Aggregation of ES cells triggers the generation of a diverse array of cell types, including neuronal cells [4–7]. This capacity for multilineage differentiation is retained during genetic manipulation and clonal expansion . In principle, therefore, ES cells
Meng Li; Larysa Pevny; Robin Lovell-Badge; Austin Smith
Hepatocyte-like cells derived from stem cells hold great potential for clinical and pharmaceutical applications, including high-throughput drug toxicity screening. We report a three-dimensional aggregate culture system for the directed differentiation of adult rat bone marrow-derived stem cells, rat multipotent adult progenitor cells, to hepatocyte-like cells. Compared to adherent monolayer cultures, differentiation in the aggregate culture system resulted in significantly higher expression level of liver-specific transcripts, including an increased albumin mRNA level, and higher levels of albumin and urea secretion. This coincides with the presence of significantly more cells that express intracellular albumin at levels found in primary hepatocytes. The differentiated cell aggregates exhibited cytochrome P450-mediated ethoxyresorufin-O-dealkylation and pentoxyresorufin-O-dealkylation activity. Consistent with these increased mature functions, cells within the aggregates were shown to have many ultrastructural features of mature hepatocytes by transmission electron microscopy. With the scalability of the aggregate culture system and the enhanced differentiation capability, this system may facilitate translation of generating hepatocytes from stem cells to technology. PMID:21548835
Subramanian, Kartik; Owens, Derek Jason; O'Brien, Timothy D; Verfaillie, Catherine M; Hu, Wei-Shou
Understanding the dynamics of cell population allows insight into the control mechanism of the growth and development of mammalian tissues. It is well known that the proliferation and differentiation among stem cells (SCs), intermediate progenitor cells (IPCs), and fully differentiated cells (FDCs) are under different activation and inhibition controls. Secreted factors in negative feedback loops have already been identified as major elements in regulating the numbers of different cell types and in maintaining the equilibrium of cell populations. We have developed a novel spatial dynamic model of cells. We can characterize not only overall cell population dynamics, but also details of temporal-spatial relationship of individual cells within a tissue. In our model, the shape, growth, and division of each cell are modeled using a realistic geometric model. Furthermore, the inhibited growth rate, proliferation and differentiation probabilities of individual cells are modeled through feedback loops controlled by secreted factors of neighboring cells within a proper diffusion radius. With specific proliferation and differentiation probabilities, the actual division type that each cell will take is chosen by a Monte Carlo sampling process. With simulations we found that with proper strengths of inhibitions to growth and stem cell divisions, the whole tissue is capable of achieving a homeostatic size control. We discuss our findings on control mechanisms of the stability of the tissue development. Our model can be applied to study broad issues on tissue development and pattern formation in stem cell and cancer research.
Cao, Youfang; Liang, Claire; Naveed, Hammad; Li, Yingzi; Chen, Meng; Nie, Qing
The piRNA pathway plays an important role in maintaining genome stability in the germ line by silencing transposable elements (TEs) from fly to mammals. As a highly conserved piRNA pathway component, Piwi is widely expressed in both germ cells and somatic cells in the Drosophila ovary and is required for piRNA production in both cell types. In addition to its known role in somatic cap cells to maintain germline stem cells (GSCs), this study has demonstrated that Piwi has novel functions in somatic cells and germ cells of the Drosophila ovary to promote germ cell differentiation. Piwi knockdown in escort cells causes a reduction in escort cell (EC) number and accumulation of undifferentiated germ cells, some of which show active BMP signaling, indicating that Piwi is required to maintain ECs and promote germ cell differentiation. Simultaneous knockdown of dpp, encoding a BMP, in ECs can partially rescue the germ cell differentiation defect, indicating that Piwi is required in ECs to repress dpp. Consistent with its key role in piRNA production, TE transcripts increase significantly and DNA damage is also elevated in the piwi knockdown somatic cells. Germ cell-specific knockdown of piwi surprisingly causes depletion of germ cells before adulthood, suggesting that Piwi might control primordial germ cell maintenance or GSC establishment. Finally, Piwi inactivation in the germ line of the adult ovary leads to gradual GSC loss and germ cell differentiation defects, indicating the intrinsic role of Piwi in adult GSC maintenance and differentiation. This study has revealed new germline requirement of Piwi in controlling GSC maintenance and lineage differentiation as well as its new somatic function in promoting germ cell differentiation. Therefore, Piwi is required in multiple cell types to control GSC lineage development in the Drosophila ovary.
Ma, Xing; Wang, Su; Do, Trieu; Song, Xiaoqing; Inaba, Mayu; Nishimoto, Yoshiya; Liu, Lu-ping; Gao, Yuan; Mao, Ying; Li, Hui; McDowell, William; Park, Jungeun; Malanowski, Kate; Peak, Allison; Perera, Anoja; Li, Hua; Gaudenz, Karin; Haug, Jeff; Yamashita, Yukiko; Lin, Haifan; Ni, Jian-quan; Xie, Ting
Efforts to develop engineered tendons and ligaments have focused on the use of a biomaterial scaffold and a stem cell source. However, the ideal scaffold microenvironment to promote stem cell differentiation and development of organized extracellular matrix is unknown. Through electrospinning, fibre scaffolds can be designed with tailorable architectures to mimic the intended tissue. In this study, the effects of fibre diameter and orientation were examined by electrospinning thin mats, consisting of small (< 1?µm), medium (1-2?µm) or large (> 2?µm) diameter fibres with either random or aligned fibre orientation. C3H10T1/2 model stem cells were cultured on the six different electrospun mats, as well as smooth spin-coated films, and the morphology, growth and expression of tendon/ligament genes were evaluated. The results demonstrated that fibre diameter affects cellular behaviour more significantly than fibre alignment. Initially, cell density was greater on the small fibre diameter mats, but similar cell densities were found on all mats after an additional week in culture. After 2?weeks, gene expression of collagen 1?1 and decorin was increased on all mats compared to films. Expression of the tendon/ligament transcription factor scleraxis was suppressed on all electrospun mats relative to spin-coated films, but expression on the large-diameter fibre mats was consistently greater than on the medium-diameter fibre mats. These results suggest that larger-diameter fibres (e.g. > 2?µm) may be more suitable for in vitro development of a tendon/ligament tissue. Copyright © 2012 John Wiley & Sons, Ltd. PMID:23038413
Cardwell, Robyn D; Dahlgren, Linda A; Goldstein, Aaron S
Describes a curriculum for teaching young children about dinosaurs. Activity topics included Diplodocus eggs, sorting dinosaurs, creating terrariums, and extinction. Describes the incorporation of dinosaur activities into other subject areas and resource materials. (RJC)
Strader, William H.; Rinker, Catherine A.
Presents a lesson plan that uses a constructivist approach for developing and challenging students' different thinking strengths. In the context of musical and bodily-kinesthetic thinking, elementary school students interpret the sounds and movements the dinosaurs made as they negotiated their primitive environments. (CR)
Greenwald, Nina L.
As his geology students' specialized knowledge of the Mesozoic era increased, a high school teacher realized he needed a way to showcase their work. The Mesozoic Resource Center's biggest hit was a walk-through diorama showing how life might have been during each of three Mesozoic periods. Highlights included two gigantic student-built dinosaur…
In this article, the author relates how she uses an art lesson that integrates art, language arts, and science in an enjoyable, creative project about dinosaurs in her kindergarten class. She relates how the children enjoy being illustrators and becoming familiar with well-known children's illustrators. She also relates that she starts her classes…
In this activity, learners interpret three trackways and use measurements and a formula to infer the relative speed of dinosaurs. A portion of the activity details how students can create their own trackways and evaluate the accuracy of the formula. This step-by-step lesson plan includes an illustrated look at stride length and a reproducible worksheet for learners to complete.
History, American M.
Knowledge of pathways governing cellular differentiation to specific phenotype will enable generation of desired cell fates by careful alteration of the governing network by adequate manipulation of the cellular environment. With this aim, we have developed a novel method to reconstruct the underlying regulatory architecture of a differentiating cell population from discrete temporal gene expression data. We utilize an inherent feature of biological networks, that of sparsity, in formulating the network reconstruction problem as a bi-level mixed-integer programming problem. The formulation optimizes the network topology at the upper level and the network connectivity strength at the lower level. The method is first validated by in-silico data, before applying it to the complex system of embryonic stem (ES) cell differentiation. This formulation enables efficient identification of the underlying network topology which could accurately predict steps necessary for directing differentiation to subsequent stages. Concurrent experimental verification demonstrated excellent agreement with model prediction.
Despite evidence for the impact of insulin on intestinal epithelial physiology and pathophysiology, the expression patterns, roles, and regulation of insulin receptor (IR) and IR isoforms in the intestinal epithelium are not well characterized. IR-A is thought to mediate the proliferative effects of insulin or insulin growth factors (IGFs) in fetal or cancer cells. IR-B is considered to be the metabolic receptor for insulin in specialized tissues. This study used a novel Sox9-EGFP reporter mouse that permits isolation of intestinal epithelial stem cells (IESCs), progenitors, enteroendocrine cells and differentiated lineages, the Apc(Min/+) mouse model of precancerous adenoma and normal human intestinal and colorectal cancer (CRC) cell lines. We tested the hypothesis that there is differential expression of IR-A or IR-B in stem and tumor cells versus differentiated intestinal epithelial cells (IECs) and that IR-B impacts cell proliferation. Our findings provide evidence that IR-B expression is significantly lower in highly proliferative IESCs and progenitor cells versus post-mitotic, differentiated IECs and in subconfluent and undifferentiated versus differentiated Caco-2 cells. IR-B is also reduced in Apc(Min/+) tumors and highly tumorigenic CRC cells. These differences in IR-B were accompanied by altered levels of mRNAs encoding muscleblind-like 2 (MBNL2), a known regulator of IR alternative splicing. Forced IR-B expression in subconfluent and undifferentiated Caco-2 cells reduced proliferation and increased biomarkers of differentiation. Our findings indicate that the impact of insulin on different cell types in the intestinal epithelium might differ depending on relative IR-B IR-A expression levels and provide new evidence for the roles of IR-B to limit proliferation of CRC cells. PMID:24127567
Andres, Sarah F; Simmons, James G; Mah, Amanda T; Santoro, M Agostina; Van Landeghem, Laurianne; Lund, P Kay
Mesenchymal stem cells (MSCs) show unexplained differences in differentiation potential. In this study, differentiation of human (h) MSCs derived from embryonic, fetal and adult sources toward cardiomyocytes, endothelial and smooth muscle cells was investigated. Labeled hMSCs derived from embryonic stem cells (hESC-MSCs), fetal umbilical cord, bone marrow, amniotic membrane and adult bone marrow and adipose tissue were co-cultured with neonatal rat cardiomyocytes (nrCMCs) or cardiac fibroblasts (nrCFBs) for 10 days, and also cultured under angiogenic conditions. Cardiomyogenesis was assessed by human-specific immunocytological analysis, whole-cell current-clamp recordings, human-specific qRT-PCR and optical mapping. After co-culture with nrCMCs, significantly more hESC-MSCs than fetal hMSCs stained positive for ?-actinin, whereas adult hMSCs stained negative. Furthermore, functional cardiomyogenic differentiation, based on action potential recordings, was shown to occur, but not in adult hMSCs. Of all sources, hESC-MSCs expressed most cardiac-specific genes. hESC-MSCs and fetal hMSCs contained significantly higher basal levels of connexin43 than adult hMSCs and co-culture with nrCMCs increased expression. After co-culture with nrCFBs, hESC-MSCs and fetal hMSCs did not express ?-actinin and connexin43 expression was decreased. Conduction velocity (CV) in co-cultures of nrCMCs and hESC-MSCs was significantly higher than in co-cultures with fetal or adult hMSCs. In angiogenesis bioassays, only hESC-MSCs and fetal hMSCs were able to form capillary-like structures, which stained for smooth muscle and endothelial cell markers.Human embryonic and fetal MSCs differentiate toward three different cardiac lineages, in contrast to adult MSCs. Cardiomyogenesis is determined by stimuli from the cellular microenvironment, where connexin43 may play an important role.
Ramkisoensing, Arti A.; Pijnappels, Daniel A.; Askar, Said F. A.; Passier, Robert; Swildens, Jim; Goumans, Marie Jose; Schutte, Cindy I.; de Vries, Antoine A. F.; Scherjon, Sicco; Mummery, Christine L.; Schalij, Martin J.; Atsma, Douwe E.
Mesenchymal stem cells (MSCs) show unexplained differences in differentiation potential. In this study, differentiation of human (h) MSCs derived from embryonic, fetal and adult sources toward cardiomyocytes, endothelial and smooth muscle cells was investigated. Labeled hMSCs derived from embryonic stem cells (hESC-MSCs), fetal umbilical cord, bone marrow, amniotic membrane and adult bone marrow and adipose tissue were co-cultured with neonatal rat cardiomyocytes (nrCMCs) or cardiac fibroblasts (nrCFBs) for 10 days, and also cultured under angiogenic conditions. Cardiomyogenesis was assessed by human-specific immunocytological analysis, whole-cell current-clamp recordings, human-specific qRT-PCR and optical mapping. After co-culture with nrCMCs, significantly more hESC-MSCs than fetal hMSCs stained positive for ?-actinin, whereas adult hMSCs stained negative. Furthermore, functional cardiomyogenic differentiation, based on action potential recordings, was shown to occur, but not in adult hMSCs. Of all sources, hESC-MSCs expressed most cardiac-specific genes. hESC-MSCs and fetal hMSCs contained significantly higher basal levels of connexin43 than adult hMSCs and co-culture with nrCMCs increased expression. After co-culture with nrCFBs, hESC-MSCs and fetal hMSCs did not express ?-actinin and connexin43 expression was decreased. Conduction velocity (CV) in co-cultures of nrCMCs and hESC-MSCs was significantly higher than in co-cultures with fetal or adult hMSCs. In angiogenesis bioassays, only hESC-MSCs and fetal hMSCs were able to form capillary-like structures, which stained for smooth muscle and endothelial cell markers.Human embryonic and fetal MSCs differentiate toward three different cardiac lineages, in contrast to adult MSCs. Cardiomyogenesis is determined by stimuli from the cellular microenvironment, where connexin43 may play an important role. PMID:21931658
Ramkisoensing, Arti A; Pijnappels, Daniël A; Askar, Saïd F A; Passier, Robert; Swildens, Jim; Goumans, Marie José; Schutte, Cindy I; de Vries, Antoine A F; Scherjon, Sicco; Mummery, Christine L; Schalij, Martin J; Atsma, Douwe E
Signals of Notch transmembrane receptors function to regulate a wide variety of developmental cell fates. Here we investigate the role of Notch signaling in the development of mesodermal cell types by expressing a tamoxifen-inducible, activated form of Notch1 in embryonic stem cells (ESC). For differentiation of ESC into first mesodermal progenitor cells and then endothelial, mural, cardiac muscle and hematopoietic cells, the OP9 stroma co-culture system was used. Timed activation of Notch signaling by the addition of tamoxifen at various stages during differentiation of ESC into mesodermal cell lineages results in profound alterations in the generation of all of these cells. Differentiation of ESC into Flk1(+) mesodermal cells is inhibited by activated Notch. When Notch signaling is activated in mesodermal cells, generation of cardiac muscle, endothelial and hematopoietic cells is inhibited, favoring the generation of mural cells. Activation of Notch signaling in hematopoietic cells reduces colony formation and maintenance of hematopoiesis. These data suggest that Notch signaling plays a regulatory role in mesodermal development, cardiomyogenesis, the balanced generation of endothelial versus mural cells of blood vessels and hematopoietic development. PMID:16822655
Schroeder, Timm; Meier-Stiegen, Franziska; Schwanbeck, Ralf; Eilken, Hanna; Nishikawa, Satomi; Häsler, Robert; Schreiber, Stefan; Bornkamm, Georg W; Nishikawa, Shin-Ichi; Just, Ursula
Androgens regulate body composition in youth and declining testosterone that occurs with aging is associated with muscle wasting, increased fat mass and osteopenia. Transgenic mice with targeted androgen receptor (AR) overexpression in mesenchymal stem cells (MSC) were generated to explore the role of androgen signaling in the regulation of body composition. Transgenic males, but not females, were shorter and have reduced body weight and visceral fat accumulation. Dual energy x-ray absorptiometry (DXA) revealed significant reductions in fat mass with a reciprocal increase in lean mass, yet no difference in food consumption or locomotor activity was observed. Adipose tissue weight was normal in brown fat but reduced in both gonadal and perirenal depots, and reduced hyperplasia was observed with smaller adipocyte size in visceral and subcutaneous white adipose tissue. Although serum leptin, adiponectin, triglyceride, and insulin levels were no different between the genotypes, intraperitoneal glucose tolerance testing showed improved glucose clearance in transgenic males. High levels of the AR transgene are detected in MSCs but not in mature fat tissue. Reduced fibroblast colony forming units indicate fewer progenitor cells resident in the marrow in vivo. Precocious expression of GLUT4, PPAR? and C/EBP? was observed in proliferating precursor cultures from transgenic mice compared to controls. In more mature cultures, there was little difference between the genotypes. We propose a mechanism where enhanced androgen sensitivity can alter lineage commitment in vivo to reduce progenitor number and fat development, while increasing the expression of key factors to promote smaller adipocytes with improved glucose clearance.
Semirale, Anthony A.; Zhang, Xiaowei; Wiren, Kristine M.
Neural stem cell (NSC) transplantation is a promising therapeutic approach for neurological diseases. However, only a limited number of cells can be transplanted into the brain, resulting in relatively low levels of engraftment. This study investigated the potential of using a cell surface marker to enrich a primary NSC population to increase stable engraftment in the recipient brain. NSCs were enriched from the neonatal mouse forebrain using anti-CD15 (Lewis X antigen, or SSEA-1) in a “gentle” fluorescence-activated cell sorting protocol, which yielded >98% CD15-positive cells. The CD15-positive cells differentiated into neurons, astrocytes, and oligodendrocytes in vitro, after withdrawal of growth factors, demonstrating multipotentiality. CD15-positive cells were expanded in vitro and injected bilaterally into the ventricles of neonatal mice. Cells from enriched and unenriched donor populations were found throughout the neuraxis, in both neurogenic and non-neurogenic regions. Total engraftment was similar at 7 days postinjection, but by 28 days postinjection, after brain organogenesis was complete, the survival of donor cells was significantly increased in CD15-enriched grafts over the unenriched cell grafts. The engrafted cells were heterogeneous in morphology and differentiated into all three neural lineages. Furthermore, in the CD15-enriched grafts, there was a significant shift toward differentiation into oligodendrocytes. This strategy may allow better delivery of therapeutic cells to the developing central nervous system and may be particularly useful for treating diseases involving white matter lesions.
The molecular mechanisms governing early cardiogenesis are still largely unknown. Interestingly, the retinoblastoma protein (Rb), a regulator of cell cycle, has recently emerged as a new candidate regulating cell differentiation. Rb?/? mice die at midgestation and mice lacking E2f1/E2f3, downstream components of the Rb-dependent transcriptional pathway, die of heart failure. To gain insight into the function of Rb pathway in early cardiogenesis, we used Rb?/? embryonic stem (ES) cells differentiating into cardiomyocytes. Rb?/? cells displayed a dramatic delay in expression of cardiac-specific transcription factors and in turn in the whole process of cardiac differentiation. The phenotype of Rb?/? ES cell-derived cardiomyocytes was rescued by reintroducing Rb in cardiac progenitors, by stimulating the BMP-dependent cardiogenic pathway or by overexpression of Nkx2.5. ES cells deficient in the recently identified factor LEK1, a murine homolog of the cardiomyogenic factor 1, or specific disruption of Rb–LEK1 interaction into the nucleus of differentiating ES cells recapitulated the delay in cardiac differentiation of Rb?/? ES cells. Thus, we provide evidence for a novel Rb/LEK1-dependent and BMP-independent transcriptional program, which plays a pivotal role in priming ES cells toward a cardiac fate.
Papadimou, Evangelia; Menard, Claudine; Grey, Corinne; Puceat, Michel
Recent evidence supports and reinforces the concept that environmental cues may reprogramme somatic cells and change their natural fate. In the present review, we concentrate on environmental reprogramming and fate potency of different epithelial cells. These include stratified epithelia, such as the epidermis, hair follicle, cornea and oesophagus, as well as the thymic epithelium, which stands alone among simple and stratified epithelia, and has been shown recently to contain stem cells. In addition, we briefly discuss the pancreas as an example of plasticity of intrinsic progenitors and even differentiated cells. Of relevance, examples of plasticity and fate change characterize pathologies such as oesophageal metaplasia, whose possible cell origin is still debated, but has important implications as a pre-neoplastic event. Although much work remains to be done in order to unravel the full potential and plasticity of epithelial cells, exploitation of this phenomenon has already entered the clinical arena, and might provide new avenues for future cell therapy of these tissues. PMID:24849231
Amici, Alessandro W; Onikoyi, Fatai O; Bonfanti, Paola
Catecholamine release is known to modulate cardiac output by increasing heart rate. Although much is known about catecholamine function and regulation in adults, little is known about the presence and role of catecholamines during heart development. The present study aimed therefore to evaluate the effects of different catecholamines on early heart development in an in vitro setting using embryonic stem (ES) cell-derived cardiomyocytes. Effects of catecholamine depletion induced by reserpine were examined in murine ES cells (line D3, ?PIG44) during differentiation. Cardiac differentiation was assessed by immunocytochemistry, qRT-PCR, quantification of beating clusters, flow cytometry and pharmacological approaches. Proliferation was analyzed by EB cross-section measurements, while functionality of cardiomyocytes was studied by extracellular field potential (FP) measurements using microelectrode arrays (MEAs). To further differentiate between substance-specific effects of reserpine and catecholamine action via ?- and ?-receptors we proved the involvement of adrenergic receptors by application of unspecific ?- and ?-receptor antagonists. Reserpine treatment led to remarkable down-regulation of cardiac-specific genes, proteins and mesodermal marker genes. In more detail, the average ratio of ?40% spontaneously beating control clusters was significantly reduced by 100%, 91.1% and 20.0% on days 10, 12, and 14, respectively. Flow cytometry revealed a significant reduction (by 71.6%, n?=?11) of eGFP positive CMs after reserpine treatment. By contrast, reserpine did not reduce EB growth while number of neuronal cells in reserpine-treated EBs was significantly increased. MEA measurements of reserpine-treated EBs showed lower FP frequencies and weak responsiveness to adrenergic and muscarinic stimulation. Interestingly we found that developmental inhibition after ?- and ?-adrenergic blocker application mimicked developmental changes with reserpine. Using several methodological approaches our data suggest that reserpine inhibits cardiac differentiation. Thus catecholamines play a critical role during development.
Lehmann, Martin; Nguemo, Filomain; Wagh, Vilas; Pfannkuche, Kurt; Hescheler, Jurgen; Reppel, Michael
Human mesenchymal stem cells (hMSCs) present in the bone marrow are the precursors of osteoblasts, chondrocytes and adipocytes, and hold tremendous potential for osteoregenerative therapy. However, achieving directed differentiation into osteoblasts has been a major concern. The use of lithium for enhancing osteogenic differentiation has been documented in animal models but its effect in humans is not clear. We, therefore, performed high throughput transcriptome analysis of lithium-treated hMSCs to identify altered gene expression and its relevance to osteogenic differentiation. Our results show suppression of proliferation and enhancement of alkaline phosphatase (ALP) activity upon lithium treatment of hMSCs under non-osteogenic conditions. Microarray profiling of lithium-stimulated hMSC revealed decreased expression of adipogenic genes (CEBPA, CMKLR1, HSD11B1) and genes involved in lipid biosynthesis. Interestingly, osteoclastogenic factors and immune responsive genes (IL7, IL8, CXCL1, CXCL12, CCL20) were also downregulated. Negative transcriptional regulators of the osteogenic program (TWIST1 and PBX1) were suppressed while genes involved in mineralization like CLEC3B and ATF4 were induced. Gene ontology analysis revealed enrichment of upregulated genes related to mesenchymal cell differentiation and signal transduction. Lithium priming led to enhanced collagen 1 synthesis and osteogenic induction of lithium pretreated MSCs resulted in enhanced expression of Runx2, ALP and bone sialoprotein. However, siRNA-mediated knockdown of RRAD, CLEC3B and ATF4 attenuated lithium-induced osteogenic priming, identifying a role for RRAD, a member of small GTP binding protein family, in osteoblast differentiation. In conclusion, our data highlight the transcriptome reprogramming potential of lithium resulting in higher propensity of lithium “primed” MSCs for osteoblastic differentiation.
Satija, Neeraj Kumar; Sharma, Deepa; Afrin, Farhat; Tripathi, Rajendra P.; Gangenahalli, Gurudutta
Catecholamine release is known to modulate cardiac output by increasing heart rate. Although much is known about catecholamine function and regulation in adults, little is known about the presence and role of catecholamines during heart development. The present study aimed therefore to evaluate the effects of different catecholamines on early heart development in an in vitro setting using embryonic stem (ES) cell-derived cardiomyocytes. Effects of catecholamine depletion induced by reserpine were examined in murine ES cells (line D3, ?PIG44) during differentiation. Cardiac differentiation was assessed by immunocytochemistry, qRT-PCR, quantification of beating clusters, flow cytometry and pharmacological approaches. Proliferation was analyzed by EB cross-section measurements, while functionality of cardiomyocytes was studied by extracellular field potential (FP) measurements using microelectrode arrays (MEAs). To further differentiate between substance-specific effects of reserpine and catecholamine action via ?- and ?-receptors we proved the involvement of adrenergic receptors by application of unspecific ?- and ?-receptor antagonists. Reserpine treatment led to remarkable down-regulation of cardiac-specific genes, proteins and mesodermal marker genes. In more detail, the average ratio of ?40% spontaneously beating control clusters was significantly reduced by 100%, 91.1% and 20.0% on days 10, 12, and 14, respectively. Flow cytometry revealed a significant reduction (by 71.6%, n?=?11) of eGFP positive CMs after reserpine treatment. By contrast, reserpine did not reduce EB growth while number of neuronal cells in reserpine-treated EBs was significantly increased. MEA measurements of reserpine-treated EBs showed lower FP frequencies and weak responsiveness to adrenergic and muscarinic stimulation. Interestingly we found that developmental inhibition after ?- and ?-adrenergic blocker application mimicked developmental changes with reserpine. Using several methodological approaches our data suggest that reserpine inhibits cardiac differentiation. Thus catecholamines play a critical role during development. PMID:23936474
Lehmann, Martin; Nguemo, Filomain; Wagh, Vilas; Pfannkuche, Kurt; Hescheler, Jürgen; Reppel, Michael
Angiosperms first appeared in northern Gondwana during the Early Cretaceous, approximately 135 million years ago. Several authors have hypothesised that the origin of angiosperms, and the tempo and pattern of their subsequent radiation, was mediated by changes in the browsing behaviour of large herbivorous dinosaurs (sauropods and ornithischians). Moreover, the taxonomic and ecological radiation of angiosperms has been associated with the evolution of complex jaw mechanisms among ornithischian dinosaurs. Here, we review critically the evidence for dinosaur-angiosperm interactions during the Cretaceous Period, providing explicit spatiotemporal comparisons between evolutionary and palaeoecological events in both the dinosaur and angiosperm fossil records and an assessment of the direct and indirect evidence for dinosaur diets. We conclude that there are no strong spatiotemporal correlations in support of the hypothesis that dinosaurs were causative agents in the origin of angiosperms; however, dinosaur-angiosperm interactions in the Late Cretaceous may have resulted in some coevolutionary interactions, although direct evidence of such interactions is scanty at present. It is likely that other animal groups (insects, arboreal mammals) had a greater impact on angiosperm diversity during the Cretaceous than herbivorous dinosaurs. Elevated levels of atmospheric CO2 might have played a critical role in the initial stages of the angiosperm radiation. PMID:11569792
Barrett, P M; Willis, K J
This activity features two connected hands-on activities about dinosaur bones. Using chicken or turkey bones and regular household items, learners explore the scientific process of studying fossilized bones. By exposing the bones to vinegar or heat, learners begin to understand how paleontologists use chemical processes to study the bones of animals long dead and gone. Use this bone-themed activity around the Thanksgiving holiday and repurpose some leftovers.
Science, Lawrence H.
This Web site is a firsthand report from an expedition to Patagonia in which the first dinosaur embryos with fossilized skin were found. It tells the story of the find, which was made by scientists who were actually looking for early birds and their ancestors. There are two short English and Spanish audio recordings. A select list of books and articles by the expedition's two lead scientists, including abstracts of and excerpts from their work is included.
This description of the saurischian or "lizard-hipped" dinosaurs discusses the major characteristics that distinguish saurischians from other tetrapods that also have pelves (hips) composed of three elements: the ilium, ischium, and pubis. These are a grasping hand, asymmetrical fingers, a long, mobile neck, and a pubis that points downward and forward at an angle to the ischium. There is also a clarification of the "bird-hipped" designation.
G9a and GLP are conserved protein methyltransferases that play key roles during mammalian development through mono- and dimethylation of histone H3 Lys 9 (H3K9me1/2), modifications associated with transcriptional repression. During embryogenesis, large H3K9me2 chromatin territories arise that have been proposed to reinforce lineage choice by affecting high-order chromatin structure. Here we report that in adult human hematopoietic stem and progenitor cells (HSPCs), H3K9me2 chromatin territories are absent in primitive cells and are formed de novo during lineage commitment. In committed HSPCs, G9a/GLP activity nucleates H3K9me2 marks at CpG islands and other genomic sites within genic regions, which then spread across most genic regions during differentiation. Immunofluorescence assays revealed the emergence of H3K9me2 nuclear speckles in committed HSPCs, consistent with progressive marking. Moreover, gene expression analysis indicated that G9a/GLP activity suppresses promiscuous transcription of lineage-affiliated genes and certain gene clusters, suggestive of regulation of HSPC chromatin structure. Remarkably, HSPCs continuously treated with UNC0638, a G9a/GLP small molecular inhibitor, better retain stem cell-like phenotypes and function during in vitro expansion. These results suggest that G9a/GLP activity promotes progressive H3K9me2 patterning during HSPC lineage specification and that its inhibition delays HSPC lineage commitment. They also inform clinical manipulation of donor-derived HSPCs.
Chen, Xiaoji; Skutt-Kakaria, Kyobi; Davison, Jerry; Ou, Yang-Li; Choi, Edward; Malik, Punam; Loeb, Keith; Wood, Brent; Georges, George; Torok-Storb, Beverly; Paddison, Patrick J.
Background One of the great unresolved controversies in paleobiology is whether extinct dinosaurs were endothermic, ectothermic, or some combination thereof, and when endothermy first evolved in the lineage leading to birds. Although it is well established that high, sustained growth rates and, presumably, high activity levels are ancestral for dinosaurs and pterosaurs (clade Ornithodira), other independent lines of evidence for high metabolic rates, locomotor costs, or endothermy are needed. For example, some studies have suggested that, because large dinosaurs may have been homeothermic due to their size alone and could have had heat loss problems, ectothermy would be a more plausible metabolic strategy for such animals. Methodology/Principal Findings Here we describe two new biomechanical approaches for reconstructing the metabolic rate of 14 extinct bipedal dinosauriforms during walking and running. These methods, well validated for extant animals, indicate that during walking and slow running the metabolic rate of at least the larger extinct dinosaurs exceeded the maximum aerobic capabilities of modern ectotherms, falling instead within the range of modern birds and mammals. Estimated metabolic rates for smaller dinosaurs are more ambiguous, but generally approach or exceed the ectotherm boundary. Conclusions/Significance Our results support the hypothesis that endothermy was widespread in at least larger non-avian dinosaurs. It was plausibly ancestral for all dinosauriforms (perhaps Ornithodira), but this is perhaps more strongly indicated by high growth rates than by locomotor costs. The polarity of the evolution of endothermy indicates that rapid growth, insulation, erect postures, and perhaps aerobic power predated advanced “avian” lung structure and high locomotor costs.
Pontzer, Herman; Allen, Vivian; Hutchinson, John R.
DNA methylation changes dynamically during development and is essential for embryogenesis in mammals. However, how DNA methylation affects developmental gene expression and cell differentiation remains elusive. During embryogenesis, many key transcription factors are used repeatedly, triggering different outcomes depending on the cell type and developmental stage. Here, we report that DNA methylation modulates transcription-factor output in the context of cell differentiation. Using a drug-inducible Gata4 system and a mouse embryonic stem (ES) cell model of mesoderm differentiation, we examined the cellular response to Gata4 in ES and mesoderm cells. The activation of Gata4 in ES cells is known to drive their differentiation to endoderm. We show that the differentiation of wild-type ES cells into mesoderm blocks their Gata4-induced endoderm differentiation, while mesoderm cells derived from ES cells that are deficient in the DNA methyltransferases Dnmt3a and Dnmt3b can retain their response to Gata4, allowing lineage conversion from mesoderm cells to endoderm. Transcriptome analysis of the cells' response to Gata4 over time revealed groups of endoderm and mesoderm developmental genes whose expression was induced by Gata4 only when DNA methylation was lost, suggesting that DNA methylation restricts the ability of these genes to respond to Gata4, rather than controlling their transcription per se. Gata4-binding-site profiles and DNA methylation analyses suggested that DNA methylation modulates the Gata4 response through diverse mechanisms. Our data indicate that epigenetic regulation by DNA methylation functions as a heritable safeguard to prevent transcription factors from activating inappropriate downstream genes, thereby contributing to the restriction of the differentiation potential of somatic cells.
Jakt, Lars Martin; Matsuoka, Chisa; Yamagiwa, Akiko; Niwa, Hitoshi; Okano, Masaki
Nanofibers have recently gained substantial interest for potential applications in tissue engineering. The objective of this study was to determine whether electrospun nanofibers accommodate the viability, growth, and differentiation of human mesenchymal stem cells (hMSCs) as well as their osteogenic (hMSC-Ob) and chondrogenic (hMSC-Ch) derivatives. Poly(D,L-lactide-co-glycolide) (PLGA) beads with a PLA:PGA ratio of 85:15 were electrospun into non-woven fibers with an average diameter of 760±210 nm. The average Young’s modulus of electrospun PLGA nanofibers was 42±26 kPa, per nanoindentation with atomic force microscopy (AFM). Human MSCs were seeded 1–4 weeks at a density of 2×106 cells/mL in PLGA nanofiber sheets. After 2 week culture on PLGA nanofiber scaffold, hMSCs remained as precursors upon immunoblotting with hKL12 antibody. SEM taken up to 7 days after cell seeding revealed that hMSCs, hMSC-Ob and hMSC-Ch apparently attached to PLGA nanofibers. The overwhelming majority of hMSCs was viable and proliferating in PLGA nanofiber scaffolds up to the tested 14 days, as assayed live/dead tests, DNA assay and BrdU. In a separate experiment, hMSCs seeded in PLGA nanofiber scaffolds were differentiated into chodrogenic and osteogenic cells. Histological assays revealed that hMSCs continuously differentiated into chondrogenic cells and osteogenic cells after 2 week incubation in PLGA nanofibers. Taken together, these data represent an original investigation of continuous differentiation of hMSCs into chondrogenic and osteogenic cells in PLGA nanofiber scaffold. Consistent with previous work, these findings also suggest that nanofibers may serve as accommodative milieu for not only hMSCs, but also as a 3D carrier vehicle for lineage specific cells.
Xin, Xuejun; Hussain, Mohammad; Mao, Jeremy J.
Avian genomes are small and streamlined compared with those of other amniotes by virtue of having fewer repetitive elements and less non-coding DNA. This condition has been suggested to represent a key adaptation for flight in birds, by reducing the metabolic costs associated with having large genome and cell sizes. However, the evolution of genome architecture in birds, or any other lineage, is difficult to study because genomic information is often absent for long-extinct relatives. Here we use a novel bayesian comparative method to show that bone-cell size correlates well with genome size in extant vertebrates, and hence use this relationship to estimate the genome sizes of 31 species of extinct dinosaur, including several species of extinct birds. Our results indicate that the small genomes typically associated with avian flight evolved in the saurischian dinosaur lineage between 230 and 250 million years ago, long before this lineage gave rise to the first birds. By comparison, ornithischian dinosaurs are inferred to have had much larger genomes, which were probably typical for ancestral Dinosauria. Using comparative genomic data, we estimate that genome-wide interspersed mobile elements, a class of repetitive DNA, comprised 5-12% of the total genome size in the saurischian dinosaur lineage, but was 7-19% of total genome size in ornithischian dinosaurs, suggesting that repetitive elements became less active in the saurischian lineage. These genomic characteristics should be added to the list of attributes previously considered avian but now thought to have arisen in non-avian dinosaurs, such as feathers, pulmonary innovations, and parental care and nesting. PMID:17344851
Organ, Chris L; Shedlock, Andrew M; Meade, Andrew; Pagel, Mark; Edwards, Scott V
What do paleontologists, dinosaur tracks, and the nature of science have in common? They're combined here in an inquiry activity where students use methods of observation and inference to devise evidence-based explanations for the data they collect about dinosaur tracks, much like the methods used by paleontologists. Students then debate the…
MacKenzie, Ann Haley; McDowell, Brian
The richness of Mesozoic Dinosauria is examined through the use of a new global database. Mesozoic dinosaurs show a steadily increasing rate of diversification, in part attributable to the development of new innovations driving an increasing variety of behavioral strategies. The data do not suggest that dinosaurs were decreasing in richness leading to extinction during the last ˜10 m.y. of
David E. Fastovsky; Yifan Huang; Jason Hsu; Jamie Martin-McNaughton; Peter M. Sheehan; David B. Weishampel
Dinosaur extinction is still a major enigma of Earth history. In this review article, extinctions in the geological record will be briefly mentioned. Many of the imaginative theories for the extinction of the dinosaurs will also be presented. Within the uniformitarian paradigm, the meteorite impact theory, once considered 'outrageous', now is the dominant theory. However, the volcanic theory is still
MICHAEL J. OARD
Early dinosaur evolution has been the subject of several phylogenetic studies and the position of certain basal forms is currently debated. This is the case for the oldest known members of the group, excavated from the Late Triassic Ischigualastian beds of South America, such as Herrerasaurus, Eoraptor, Pisanosaurus, Saturnalia and Staurikosaurus. A new cladistic analysis of the early dinosaur radiation
Max C. Langer; Michael J. Benton
Dinosaurs are one of those science topics that draw children in and teach them about concepts like measuring and using descriptive language. Learning about dinosaurs, although not hands-on like observing and recording caterpillar growth, develops critical thinking and introduces animal diversity and the relations between body form and function.…
The t(8;21) chromosomal translocation activates aberrant expression of the AML1-ETO (AE) fusion protein and is commonly associated with core binding factor acute myeloid leukaemia (CBF AML). Combining a conditional mouse model that closely resembles the slow evolution and the mosaic AE expression pattern of human t(8;21) CBF AML with global transcriptome sequencing, we find that disease progression was characterized by two principal pathogenic mechanisms. Initially, AE expression modified the lineage potential of haematopoietic stem cells (HSCs), resulting in the selective expansion of the myeloid compartment at the expense of normal erythro- and lymphopoiesis. This lineage skewing was followed by a second substantial rewiring of transcriptional networks occurring in the trajectory to manifest leukaemia. We also find that both HSC and lineage-restricted granulocyte macrophage progenitors (GMPs) acquired leukaemic stem cell (LSC) potential being capable of initiating and maintaining the disease. Finally, our data demonstrate that long-term expression of AE induces an indolent myeloproliferative disease (MPD)-like myeloid leukaemia phenotype with complete penetrance and that acute inactivation of AE function is a potential novel therapeutic option. PMID:24124051
Cabezas-Wallscheid, Nina; Eichwald, Victoria; de Graaf, Jos; Löwer, Martin; Lehr, Hans-Anton; Kreft, Andreas; Eshkind, Leonid; Hildebrandt, Andreas; Abassi, Yasmin; Heck, Rosario; Dehof, Anna Katharina; Ohngemach, Svetlana; Sprengel, Rolf; Wörtge, Simone; Schmitt, Steffen; Lotz, Johannes; Meyer, Claudius; Kindler, Thomas; Zhang, Dong-Er; Kaina, Bernd; Castle, John C; Trumpp, Andreas; Sahin, Ugur; Bockamp, Ernesto
Dinosaur researchers have achieved another first: discovering a way to tell the sex of a dinosaur. The secret is in the bone. This radio broadcast reports on the discovery of medullary bone in dinosaurs, which exists in a cavity of the thigh bone in egg-laying female therapod dinosaurs and provides calcium for the shells of eggs. This discovery also further links dinosaurs to birds. The clip is 3 minutes and 41 seconds in length.
BMP4 has been shown to induce C3H10T1/2 pluripotent stem cells to commit to adipocyte lineage. In addition to several proteins identified, microRNAs also play a critical role in the process. In this study, we identified microRNA-140 (miR-140) as a direct downstream component of the BMP4 signaling pathway during the commitment of C3H10T1/2 cells to adipocyte lineage. Overexpression of miR-140 in C3H10T1/2 cells promoted commitment, whereas knockdown of its expression led to impairment. Additional studies indicated that Ostm1 is a bona fide target of miR-140, which is significantly decreased during commitment, and Ostm1 was also demonstrated to function as an anti-adipogenic factor.
Liu, Yuan; Zhang, Zhi-chun; Qian, Shu-wen; Zhang, You-you; Huang, Hai-yan; Tang, Yan; Guo, Liang; Li, Xi; Tang, Qi-Qun
Keratinocyte growth factor and thiazolidinediones and linolenic acid differentiate characterized mammary fat pad adipose stem cells isolated from prepubertal Korean black goat to epithelial and adipogenic lineage.
The study was conducted to know and investigate the mechanism involved during mesenchymal to epithelial transition to unravel questions related to mammary gland development in prepubertal Korean black goat. We, therefore, biopsied mammary fat pad and isolated adipose cells and characterized with stemness factors (CD34, CD13, CD44, CD106, and vimentin) immunologically and through their genetic expression. Furthermore, characterized cells were differentiated to adipogenic (thiazolidinediones and ?-linolenic acid) and epithelial (keratinocyte growth factor) lineages. Thiazolidinediones/or in combination with ?-linolenic acid demonstrated significant upregulation of adipo-Q, PPAR-?, CEBP-?, LPL, and resistin. Adipose stem cells in induction mixture (5 ?g/ml insulin, 1 ?g/ml hydrocortisone, and 10 ng/ml epidermal growth factor) and subsequent treatment with 10 ng/ml keratinocyte growth factor revealed their trans-differentiating ability to epithelial lineage. From 2 d onwards, the cells under keratinocyte growth factor influenced cells to assume rectangular (2-4 d) to cuboidal (8-10 d) shapes. Ayoub-Shklar stain developed brownish-red pigment in the transformed cells. Though, expressions of K8 and K18 were noted to be highly significant (p?0.01) but expressions of epithelial membrane antigens and epithelial specific antigens were also significant (p?0.05) compared to 0 d. Conclusively, epithelial transformations of mammary adipose stem cells would add up knowledge to develop therapeutic regimen to deal with mammary tissue injury and diseases. PMID:24101555
Reza, A M M T; Shiwani, S; Singh, N K; Lohakare, J D; Lee, S J; Jeong, D K; Han, J Y; Rengaraj, D; Lee, B W
This lesson plan is part of the DiscoverySchool.com lesson plan library for grades 6-8. It focuses on a current controversary among scientists over whether dinosaurs were warm-blooded or cold-blooded. Students research both sides of the argument and then present a debate over this topic. It includes objectives, materials, procedures, discussion questions, evaluation ideas, suggested readings, and vocabulary. There are videos available to order which complement this lesson, and links to teaching tools for making custom quizzes, worksheets, puzzles and lesson plans.
This lesson plan is part of the DiscoverySchool.com lesson plan library for grades 6-8. It focuses on the Mesozoic Era, when dinosaurs roamed the Earth. Through research and activities students learn about the plants and animals that inhabited Earth at that time, and the changes in plant life that occurred due to the development of animal life. It includes objectives, materials, procedures, discussion questions, evaluation ideas, suggested readings, and vocabulary. There are videos available to order which complement this lesson, an audio-enhanced vocabulary list, and links to teaching tools for making custom quizzes, worksheets, puzzles and lesson plans.
In this case study, students write their own “evolution stories” based on information taken from a review article by Paul Sereno on the evolution of dinosaurs published in Science magazine. In the process, they learn to distinguish between the three major groups of dinosaurs based on physical characteristics; trace the ancestry of individual dinosaur species; and interpret a complex evolutionary tree that includes extinctions, speciation events, and changes in the number of taxa over time. The case was designed for use in non-majors introductory science courses, but could also be used in majors’ courses.
Coker, Jeffrey S.; Agnew, Jimmie D.
Stromal cells and mesenchymal stem cells (MSCs), 2 important cell populations within the hematopoietic microenvironment, may play an important role in the development of hematopoietic stem/progenitor cells. We have successfully cultured human umbilical cord blood-derived stromal cells (hUCBDSCs). It has been demonstrated that MSCs also exist in hUCB. However, we have not found any reports on the distinct characteristics of hUCBDSCs and human umbilical cord blood-derived mesenchymal stem cells (hUCBDMSCs). In this study, hUCBDSCs and hUCBDMSCs were isolated from the cord blood of full-term infants using the same density gradient centrifugation and cultured in the appropriate medium. Some biological characteristics and hematopoietic supportive functions were compared in vitro. hUCBDSCs were distinct from hUCBDMSCs in morphology, proliferation, cell cycle, passage, immunophenotype, and the capacity for classical tri-lineage differentiation. Finally, quantitative real-time polymerase chain reaction analysis revealed that granulocyte colony-stimulating factor (G-CSF) gene expression was higher in hUCBDSCs than that in hUCBDMSCs. Enzyme-linked immunosorbent assay revealed that the secretion of G-CSF, thrombopoietin (TPO), and granulocyte macrophage colony-stimulating factor (GM-CSF) by hUCBDSCs was higher than that by hUCBDMSCs. After coculture, the granulocyte/macrophage colony-forming units (CFU-GM) of hematopoietic cells from the hUCBDSC feeder layer was more than that from the hUCBDMSC feeder layer. Flow cytometry was used to detect CD34+ hematopoietic stem/progenitor cell committed differentiation during 14 days of coculture; the results demonstrated that CD14 and CD33 expression in hUCBDSCs was significantly higher than their expression in hUCBDMSCs. This observation was also true for the granulocyte lineage marker, CD15. This marker was expressed beginning at day 7 in hUCBDSCs. It was expressed earlier and at a higher level in hUCBDSCs compared with hUCBDMSCs. In conclusion, hUCBDSCs are different from hUCBDMSCs. hUCBDSCs are superior to hUCBDMSCs in supporting hematopoiesis stem/progenitor cells differentiation into myeloid lineage cells at an early stage in vitro.
Sun, Hao-Ping; Zhang, Xi; Zhang, Cheng; Gao, Lei; Feng, Yi-Mei; Peng, Xian-Gui; Gao, Li
Five factors, mobile terrestrial lifestyle, oviparity, parental care, multi-year maturation and juvenile sociality, contribute to a distinct life history for Mesozoic dinosaurs in comparison to extant archosaurs and mammals. Upright, para-sagittal gait reflects several synapomorphies of Dinosauria, and wide histological sampling suggests that multi-year maturation typified dinosaurs across a range of body sizes. Fossil support for juvenile sociality exceeds that
David J. Varricchio
This Web site, created to complement the Museum's Dinosaurs: Ancient Fossils, New Discoveries exhibit, offers a virtual visit to the Museum, complete with text, photos, video clips, audio interviews, and more and includes much of the information which was in the original exhibit which is now closed. The site includes information on the bio-mechanics of dinosaurs and the reasons behind some of their strange appearances.
ABSTRACT Dinosaur extinction is still a major enigma,of Earth history. In this review article, extinctions in the geological record will be briefly mentioned. Many of the imaginative,theories for the extinction of the dinosaurs,will also be presented. Within the uniformitarian paradigm, the meteorite impact theory, once considered 'outrageous', now is the dominant theory. However, the volcanic theory is still believed by
Michael J. oard
Dinosaurs figure prominently in discussions of mass extinctions and evolutionary metrics, but their usefulness is hampered by archaic taxonomy, imprecise biostratigraphy, and imperfect preservation that bias our understanding of dinosaur diversity. A critical evaluation shows that of 540 genera and 800 species of dinosaurs proposed since 1824, 285 genera and 336 species are probably valid. Nearly half of all genera are based on a single specimen, and complete skulls and skeletons are known for only 20% of all dinosaurs. Dinosaurs are known from every continent. Countries with the greatest known diversity of dinosaurs are (in descending order) the United States, Mongolia, China, Canada, England, and Argentina; the greatest future increases may be expected from Argentina and China. Nearly half of all dinosaur genera are of latest Cretaceous age (Campanian or Maastrichtian). Estimates of the average duration of a dinosaur genus range from 5 million to 10.5 million years, with the most likely value about 7.7 million years. Dinosaurs evolved as rapidly as Cenozoic mammals. Global dinosaur diversity during the Campanian and Maastrichtian is estimated at 100 genera per stage, using a logistic model to estimate future discoveries. A model of increasing diversity and a bottleneck model compensate for the biasis in the preserved fossil record. The number of dinosaurs that have ever lived is estimated at 900-1200 genera. The fossil record of dinosaurs is presently about 25% complete. Dinosaurs disappeared in the Maastrichtian near the peak of their historic diversity.
Recent studies suggested that induced pluripotent stem cells (iPSCs) retain a residual donor cell gene expression which may impact their capacity to differentiate into cell of origin. Here we addressed a contribution of a lineage stage-specific donor cell memory in modulating the functional properties of iPSCs. iPSCs were generated from hepatic lineage cells at an early (hepatoblast-derived, HB-iPSCs) and end stage (adult hepatocyte, AH-iPSCs) of hepatocyte differentiation as well as from mouse fetal fibroblasts (MEF-iPSCs) using a lentiviral vector encoding four pluripotency-inducing factors Oct4, Sox2, Klf4, and c-Myc. All resulting iPS cell lines acquired iPSCs phenotype as judged by the accepted criteria including morphology, expression of pluripotency markers, silencing of transducing factors, capacity of multilineage differentiation in teratoma assay and normal diploid karyotype. However, HB-iPSCs were more efficient in directed differentiation towards hepatocytic lineage as compared to AH-iPSCs, MEF-iPSCs or mESCs. Extensive comparative transcriptome analyses of the early passage iPSCs, donor cells and mESCs revealed that despite global similarities in gene expression patterns between generated iPSCs and mESCs, HB-iPSCs retained a transcriptional memory (7 up- and 17 down-regulated genes) typical of the original cells. Continuous passaging of HB-iPSCs erased most of these differences including a superior capacity for hepatic re-differentiation. These results suggest that retention of lineage stage-specific donor memory in iPSCs may facilitate differentiation into donor cell type. The identified gene set help to improve hepatic differentiation for therapeutic applications and contribute to the better understanding of liver development.
Lee, Seung Bum; Seo, Daekwan; Choi, Dongho; Park, Kye-Yoon; Holczbauer, Agnes; Marquardt, Jens U.; Conner, Elizabeth A.; Factor, Valentina M.; Thorgeirsson, Snorri S.
Fossils of a giant Sauropod, found in Spain, reveal that Europe was home to giant dinosaurs in the Late Jurassic period -- about 150 million years ago. Giant dinosaurs have previously been found mainly in the New World and Africa.
American Association for the Advancement of Science (AAAS;)
Dinosaur National Monument (NM) is internationally known as a repository of significant fossil resources. Located on the Utah-Colorado border, Dinosaur NM is one of eight national park units established primarily for the protection of significant fossil r...
Neural crest stem cells (NCSCs) play an important role in the development and represent a valuable cell source for tissue engineering. However, how mechanical factors in vivo regulate NCSC differentiation is not understood. Here NCSCs were derived from induced pluripotent stem cells and used as a model to determine whether vascular mechanical strain modulates the differentiation of NCSCs into smooth
Xian Li; Julia Chu; Aijun Wang; Yiqian Zhu; Wai Keung Chu; Li Yang; Song Li; Wei-Chun Chin
This site from the National Museum of Natural History's (NMNH) Department of Paleobiology offers an enticing peek into the Smithsonian's large dinosaur collection. Users can browse for their favorite dinosaur alphabetically, by dinosaur groups, or by period, and view photos that are accompanied by brief commentary. A Special Tours section offers an Anatomy Lesson, clickable views of Dinosaur Hall, and a Behind the Scenes look at paleobiologists at work. Additional resources include a Geologic Time Scale and a collection of related links.
Occasional reports in isolated fragments of dinosaur bones have suggested that tumors might represent a population phenomenon. Previous study of humans has demonstrated that vertebral radiology is a powerful diagnostic tool for population screening. The epidemiology of tumors in dinosaurs was here investigated by fluoroscopically screening dinosaur vertebrae for evidence of tumors. Computerized tomography (CT) and cross-sections were obtained where
B. M. Rothschild; D. H. Tanke; M. Helbling; L. D. Martin
Most recent studies of dinosaur phylogeny have concentrated on theropods and ornithischians. As a result, the evolutionary relationships of sauropod dinosaurs are poorly understood. In this paper previous studies of sauropod phylogeny are reviewed and contrasted with the results of a recent cladistic analysis. This analysis forms the basis for a reconstruction of sauropod phylogeny. Sauropods diverged from other dinosaurs
This activity is a printable one-page PDF handout, which focuses on dinosaur movement. Using illustrations that compare a crocodile's hips to a dinosaur's, students answer a series of questions. Fun challenges, Animal Push-Ups and Reptile Races, help students better understand how a hole in the hip socket differentiates dinosaurs from other reptiles.
The objective of this article is to study the network and virtual reality technologies for developing a virtual dinosaur museum, which provides a Web-learning environment for students of all ages and the general public to know more about dinosaurs. We first investigate the method for building the 3D dynamic models of dinosaurs, and then describe…
Tarng, Wernhuar; Liou, Hsin-Hun
Leukemia stem cells (LSC) are resistant to conventional chemotherapy and persistent LSC after chemotherapy are supposed to be a major cause of relapse. However, information on genetic or epigenetic regulation of stem cell properties is still limited and LSC-targeted drugs have scarcely been identified. Epigenetic regulators are associated with many cellular processes including maintenance of stem cells. Of note are polycomb group proteins, because they potentially control stemness, and can be pharmacologically targeted by a selective inhibitor (DZNep). Therefore, we investigated the therapeutic potential of EZH2 inhibition in mixed lineage leukemia (MLL) fusion leukemia. Intriguingly, EZH2 inhibition by DZNep or shRNA not only suppressed MLL fusion leukemia proliferation but also reduced leukemia initiating cells (LIC) frequency. Expression analysis suggested that p16 upregulation was responsible for LICs reduction. Knockdown of p16 canceled the survival advantage of mice treated with DZNep. Chromatin immunoprecipitation assays demonstrated that EZH2 was highly enriched around the transcription-start-site of p16, together with H3K27 methylation marks in MLL/ENL and Hoxa9/Meis1 transduced cells but not in E2A/HLF transduced cells. Although high expression of Hoxa9 in MLL fusion leukemia is supposed to be responsible for the recruitment of EZH2, our data also suggest that there may be some other mechanisms independent of Hoxa9 activation to suppress p16 expression, because expression levels of Hoxa9 and p16 were not inversely related between MLL/ENL and Hoxa9/Meis1 transduced cells. In summary, our findings show that EZH2 is a potential therapeutic target of MLL fusion leukemia stem cells. PMID:24612037
Ueda, Koki; Yoshimi, Akihide; Kagoya, Yuki; Nishikawa, Satoshi; Marquez, Victor E; Nakagawa, Masahiro; Kurokawa, Mineo
By measuring the spacing of fossil footprints it is possible to estimate the speed of the trackmaker, but only after making several assumptions based on footprint size and the behavior of a wide range of living animals. A widely applied method for estimating speed from trackways was developed through the research of R. McNeill Alexander, an expert in biomechanics. This lab is a group exercise designed to lead students step-by-step through the methods and principles involved in estimating speed of movement from trackway data using Alexander's method. First students test the method on humans to see how accurate it is, and then they apply it to measurements taken from a variety of dinosaur trackways. This activity involves having students collect speed and footprint data on subjects while they are running and walking. The footprint data are analyzed and the speed estimates are compared to the actual measured speeds. Students then collect trackway measurements from published illustrations of dinosaur trackways to estimate dinosaur speeds. Students calculate the percent error for their experimental estimates and use this to interpret the results obtained from dinosaur trackways. Spreadsheets may be used to record and carry out the calculations in the analysis. Students are asked to discuss the significance of their results to ongoing debates over the physical capabilities of dinosaurs.
Angiosperm hydraulic performance is crucially affected by the diameters of vessels, the water conducting conduits in the wood. Hydraulic optimality models suggest that vessels should widen predictably from stem tip to base, buffering hydrodynamic resistance accruing as stems, and therefore conductive path, increase in length. Data from 257 species (609 samples) show that vessels widen as predicted with distance from the stem apex across angiosperm orders, habits and habitats. Standardising for stem length, vessels are only slightly wider in warm/moist climates and in lianas, showing that, rather than climate or habit, plant size is by far the main driver of global variation in mean vessel diameter. Terminal twig vessels become wider as plant height increases, while vessel density decreases slightly less than expected tip to base. These patterns lead to testable predictions regarding evolutionary strategies allowing plants to minimise carbon costs per unit leaf area even as height increases. PMID:24847972
Olson, Mark E; Anfodillo, Tommaso; Rosell, Julieta A; Petit, Giai; Crivellaro, Alan; Isnard, Sandrine; León-Gómez, Calixto; Alvarado-Cárdenas, Leonardo O; Castorena, Matiss
Dinosaur remains from the Arabian subcontinent are exceedingly rare, and those that have been documented manifest indeterminate affinities. Consequently the discovery of a small, but diagnostic, accumulation of elements from Campanian-Maastrichtian (?75 Ma) deposits in northwestern Saudi Arabia is significant because it constitutes the first taxonomically identifiable dinosaur material described from the Arabian Peninsula. The fossils include a series of possible lithostrotian titanosaur caudal vertebrae, and some isolated theropod marginal teeth that share unique character states and metric parameters (analyzed using multivariate statistical methods) with derived abelisaurids – this is the first justifiable example of a non-avian carnivorous dinosaur clade from Arabia. The recognition of titanosaurians and abelisaurids from Saudi Arabia extends the palaeogeographical range of these groups along the entire northern Gondwanan margin during the latest Cretaceous. Moreover, given the extreme paucity of coeval occurrences elsewhere, the Saudi Arabian fossils provide a tantalizing glimpse into dinosaurian assemblage diversity within the region.
Kear, Benjamin P.; Rich, Thomas H.; Vickers-Rich, Patricia; Ali, Mohammed A.; Al-Mufarreh, Yahya A.; Matari, Adel H.; Al-Massari, Abdu M.; Nasser, Abdulaziz H.; Halawani, Mohammed A.
One mechanism for disrupting the MLL gene in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) is through partial tandem duplication (MLL-PTD); however, the mechanism by which MLL-PTD contributes to MDS and AML development and maintenance is currently unknown. Herein, we investigated hematopoietic stem/progenitor cell (HSPC) phenotypes of Mll-PTD knock-in mice. Although HSPCs (Lin(-)Sca1(+)Kit(+) (LSK)/SLAM(+) and LSK) in Mll(PTD/WT) mice are reduced in absolute number in steady state because of increased apoptosis, they have a proliferative advantage in colony replating assays, CFU-spleen assays, and competitive transplantation assays over wild-type HSPCs. The Mll(PTD/WT)-derived phenotypic short-term (ST)-HSCs/multipotent progenitors and granulocyte/macrophage progenitors have self-renewal capability, rescuing hematopoiesis by giving rise to long-term repopulating cells in recipient mice with an unexpected myeloid differentiation blockade and lymphoid-lineage bias. However, Mll(PTD/WT) HSPCs never develop leukemia in primary or recipient mice, suggesting that additional genetic and/or epigenetic defects are necessary for full leukemogenic transformation. Thus, the Mll-PTD aberrantly alters HSPCs, enhances self-renewal, causes lineage bias, and blocks myeloid differentiation. These findings provide a framework by which we can ascertain the underlying pathogenic role of MLL-PTD in the clonal evolution of human leukemia, which should facilitate improved therapies and patient outcomes. PMID:22740449
Zhang, Yue; Yan, Xiaomei; Sashida, Goro; Zhao, Xinghui; Rao, Yalan; Goyama, Susumu; Whitman, Susan P; Zorko, Nicholas; Bernot, Kelsie; Conway, Rajeana M; Witte, David; Wang, Qian-Fei; Tenen, Daniel G; Xiao, Zhijian; Marcucci, Guido; Mulloy, James C; Grimes, H Leighton; Caligiuri, Michael A; Huang, Gang
One mechanism for disrupting the MLL gene in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) is through partial tandem duplication (MLL-PTD); however, the mechanism by which MLL-PTD contributes to MDS and AML development and maintenance is currently unknown. Herein, we investigated hematopoietic stem/progenitor cell (HSPC) phenotypes of Mll-PTD knock-in mice. Although HSPCs (Lin?Sca1+Kit+ (LSK)/SLAM+ and LSK) in MllPTD/WT mice are reduced in absolute number in steady state because of increased apoptosis, they have a proliferative advantage in colony replating assays, CFU-spleen assays, and competitive transplantation assays over wild-type HSPCs. The MllPTD/WT-derived phenotypic short-term (ST)–HSCs/multipotent progenitors and granulocyte/macrophage progenitors have self-renewal capability, rescuing hematopoiesis by giving rise to long-term repopulating cells in recipient mice with an unexpected myeloid differentiation blockade and lymphoid-lineage bias. However, MllPTD/WT HSPCs never develop leukemia in primary or recipient mice, suggesting that additional genetic and/or epigenetic defects are necessary for full leukemogenic transformation. Thus, the Mll-PTD aberrantly alters HSPCs, enhances self-renewal, causes lineage bias, and blocks myeloid differentiation. These findings provide a framework by which we can ascertain the underlying pathogenic role of MLL-PTD in the clonal evolution of human leukemia, which should facilitate improved therapies and patient outcomes.
Zhang, Yue; Yan, Xiaomei; Sashida, Goro; Zhao, Xinghui; Rao, Yalan; Goyama, Susumu; Whitman, Susan P.; Zorko, Nicholas; Bernot, Kelsie; Conway, Rajeana M.; Witte, David; Wang, Qian-fei; Tenen, Daniel G.; Xiao, Zhijian; Marcucci, Guido; Mulloy, James C.; Grimes, H. Leighton; Caligiuri, Michael A.
Bone sialoprotein (BSP) is a mineralized, tissue-specific, non-collagenous protein that is normally expressed only in mineralized tissues such as bone, dentin, cementum, and calcified cartilage, and at sites of new mineral formation. The binding of BSP to collagen is thought to be important for initiating bone mineralization and bone cell adhesion to the mineralized matrix. Several recent studies have isolated stem cells from muscle tissue, but their functional properties are still unclear. In this study, we examined the effects of a synthetic collagen-binding peptide (CBP) on the differentiation efficiency of muscle-derived stem cells (MDSCs). The CBP sequence (NGVFKYRPRYYLYKHAYFYPHLKRFPVQ) corresponds to residues 35-62 of bone sialoprotein (BSP), which are located within the collagen-binding domain in BSP. Interestingly, this synthetic CBP inhibited adipogenic differentiation but increased osteogenic differentiation in MDSCs. The CBP also induced expression of osteoblastic marker proteins, including alkaline phosphatase (ALP), type I collagen, Runt-related transcription factor 2 (Runx2), and osteocalcin; prevented adipogenic differentiation in MDSCs; and down-regulated adipose-specific mRNAs, such as adipocyte protein 2 (aP2) and peroxisome proliferator-activated receptor ?. The CBP increased Extracellular signal-regulated kinases (ERK) 1/2 protein phosphorylation, which is important in lineage determination. These observations suggest that this CBP determines the osteogenic or adipogenic lineage in MDSCs by activating ERK1/2. Taken together, a novel CBP could be a useful candidate for regenerating bone and treating osteoporosis, which result from an imbalance in osteogenesis and adipogenesis differentiation. PMID:22342728
Choi, Yoon Jung; Lee, Jue Yeon; Lee, Seung Jin; Chung, Chong-Pyoung; Park, Yoon Jeong
Stem/progenitors have been identified intrahepatically in the canals of Hering and extrahepatically in glands of the biliary tree. Glands of the biliary tree (peribiliary glands) are tubulo-alveolar glands with mucinous and serous acini, located deep within intrahepatic and extrahepatic bile ducts. We have shown that biliary tree stem/progenitors (BTSCs) are multipotent, giving rise in vitro and in vivo to hepatocytes, cholangiocytes or pancreatic islets. Cells with the phenotype of BTSCs are located at the bottom of the peribiliary glands near the fibromuscular layer. They are phenotypically heterogeneous, expressing transcription factors as well as surface and cytoplasmic markers for stem/progenitors of liver (e.g. SOX9/17), pancreas (e.g. PDX1) and endoderm (e.g. SOX17, EpCAM, NCAM, CXCR4, Lgr5, OCT4) but not for mature markers (e.g. albumin, secretin receptor or insulin). Subpopulations co-expressing liver and pancreatic markers (e.g. PDX1+/SOX17+) are EpCAM+/?, and are assumed to be the most primitive of the BTSC subpopulations. Their descendants undergo a maturational lineage process from the interior to the surface of ducts and vary in the mature cells generated: pancreatic cells in hepatopancreatic ducts, liver cells in large intrahepatic bile ducts, and bile duct cells along most of the biliary tree. We hypothesize that there is ongoing organogenesis throughout life, with BTSCs giving rise to hepatic stem cells in the canals of Hering and to committed progenitors within the pancreas. The BTSCs are likely to be central to normal tissue turnover and injury repair and to be key elements in the pathophysiology of liver, pancreas and biliary tree diseases, including oncogenesis.
Carpino, Guido; Cardinale, Vincenzo; Onori, Paolo; Franchitto, Antonio; Berloco, Pasquale Bartolomeo; Rossi, Massimo; Wang, Yunfang; Semeraro, Rossella; Anceschi, Maurizio; Brunelli, Roberto; Alvaro, Domenico; Reid, Lola M; Gaudio, Eugenio
Background Herbivore coexistence on the Late Cretaceous island continent of Laramidia has been a topic of great interest, stemming from the paradoxically high diversity and biomass of these animals in relation to the relatively small landmass available to them. Various hypotheses have been advanced to account for these facts, of which niche partitioning is among the most frequently invoked. However, despite its wide acceptance, this hypothesis has not been rigorously tested. This study uses the fossil assemblage from the Dinosaur Park Formation of Alberta as a model to investigate whether niche partitioning facilitated herbivorous dinosaur coexistence on Laramidia. Specifically, the question of feeding height stratification is examined in light of the role it plays in facilitating modern ungulate coexistence. Results Most herbivorous dinosaur species from the Dinosaur Park Formation were restricted to feeding no higher than approximately 1 m above the ground. There is minimal evidence for feeding height partitioning at this level, with ceratopsids capable of feeding slightly higher than ankylosaurs, but the ecological significance of this is ambiguous. Hadrosaurids were uniquely capable of feeding up to 2 m quadrupedally, or up to 5 m bipedally. There is no evidence for either feeding height stratification within any of these clades, or for change in these ecological relationships through the approximately 1.5 Ma record of the Dinosaur Park Formation. Conclusions Although we cannot reject the possibility, we find no good evidence that feeding height stratification, as revealed by reconstructed maximum feeding heights, played an important role in facilitating niche partitioning among the herbivorous dinosaurs of Laramidia. Most browsing pressure was concentrated in the herb layer, although hadrosaurids were capable of reaching shrubs and low-growing trees that were out of reach from ceratopsids, ankylosaurs, and other small herbivores, effectively dividing the herbivores in terms of relative abundance. Sympatric hadrosaurids may have avoided competing with one another by feeding differentially using bipedal and quadrupedal postures. These ecological relationships evidently proved to be evolutionarily stable because they characterize the herbivore assemblage of the Dinosaur Park Formation through time. If niche partitioning served to facilitate the rich diversity of these animals, it may have been achieved by other means in addition to feeding height stratification. Consideration of other feeding height proxies, including dental microwear and skull morphology, may help to alleviate problems of underdetermination identified here.
The formation of the primitive endoderm covering the inner cell mass of early mouse embryos can be simulated in vitro by the differentiation of mouse embryonic stem (ES) cells in culture following either aggregation of suspended cells or stimulation of cell monolayers with retinoic acid. The developmentally regulated transcription factors GATA-4 and GATA-6 have determining role in mouse extraembryonic endoderm
Callinice D. Capo-chichi; Malgorzata E. Rula; Jennifer L. Smedberg; Lisa Vanderveer; Michael S. Parmacek; Edward E. Morrisey; Andrew K. Godwin; Xiang-Xi Xu
The study of how human embryonic stem cells (hESCs) differentiate into insulin-producing beta cells has twofold significance: first, it provides an in vitro model system for the study of human pancreatic development, and second, it serves as a platform for the ultimate production of beta cells for transplantation into patients with diabetes. The delineation of growth factor interactions regulating pancreas
Xiaofang Xu; Victoria L. Browning; Jon S. Odorico
Embryonic stem (ES) cells represent a suitable model to analyze cell differentiation processes in vitro. Here, we report that pluripotent ES cells of the line BLC 6 differentiate in vitro into neuronal cells possessing the complex electrophysiological and immunocytochemical properties of postmitotic nerve cells. In the course of differentiation BLC 6-derived neurons differentially express voltagedependent (K+, Na+, Ca2+) and receptor-operated
Carsten Strübing; Gudrun Ahnert-Hilger; Jin Shan; Bertram Wiedenmann; Jürgen Hescheler; Anna M. Wobus
Recovery in central nervous system disorders is hindered by the limited ability of the vertebrate central nervous system to regenerate lost cells, replace damaged myelin, and re-establish functional neural connections. Cell transplantation to repair central nervous system disorders is an active area of research, with the goal of reducing functional deficits. Recent animal studies showed that cells of the hematopoietic stem cell (HSC) fraction of bone marrow transdifferentiated into various nonhematopoietic cell lineages. We employed a mouse model of spinal cord injury and directly transplanted HSCs into the spinal cord 1 week after injury. We evaluated functional recovery using the hindlimb motor function score weekly for 5 weeks after transplantation. The data demonstrated a significant improvement in the functional outcome of mice transplanted with hematopoietic stem cells compared with control mice in which only medium was injected. Fluorescent in situ hybridization for the Y chromosome and double immunohistochemistry showed that transplanted cells survived 5 weeks after transplantation and expressed specific markers for astrocytes, oligodendrocytes, and neural precursors, but not for neurons. These results suggest that transplantation of HSCs from bone marrow is an effective strategy for the treatment of spinal cord injury. PMID:14748562
Koshizuka, Shuhei; Okada, Seiji; Okawa, Akihiko; Koda, Masao; Murasawa, Mitsuhiro; Hashimoto, Masayuki; Kamada, Takahito; Yoshinaga, Katsunori; Murakami, Masazumi; Moriya, Hideshige; Yamazaki, Masashi
The exploration industry is changing, exploration technology is changing and the explorationist's job is changing. Resource companies are diversifying internationally and their central organizations are providing advisors rather than services. As a result, the relationship between the resource company and the contractor is changing. Resource companies are promoting standards so that all contract services in all parts of the world will look the same to their advisors. Contractors, for competitive reasons, want to look [open quotes]different[close quotes] from other contractors. The resource companies must encourage competition between contractors to insure the availability of new technology but must also resist the current trend of burdening the contractor with more and more of the risk involved in exploration. It is becoming more and more obvious that geophysical expenditures represent the best [open quotes]value added[close quotes] expenditures in exploration and development budgets. As a result, seismic-related contractors represent the growth component of our industry. The predominant growth is in 3-D seismic technology, and this growth is being further propelled by the computational power of the new generation of massively parallel computers and by recent advances in computer graphic techniques. Interpretation of seismic data involves the analysis of wavelet shapes and amplitudes prior to stacking the data. Thus, modern interpretation involves understanding compressional waves, shear waves, and propagating modes which create noise and interference. Modern interpretation and processing are carried out simultaneously, iteratively, and interactively and involve many physics-related concepts. These concepts are not merely tools for the interpretation, they are the interpretation. Explorationists who do not recognize this fact are going the way of the dinosaurs.
French, W.S. (Grant Tensor Geophysical Corp., Houston, TX (United States))
The discovery of the giant Chicxulub impact crater, buried off the coast of Mexico, unveiled the solution to one of Earth's greatest mysteries--what killed the dinosaurs. Scientists uncovered physical evidence to explain the mass extinction that rocked the Earth 65 million years ago. Step-by-step, The End of the Dinosaurs: Chicxulub Crater and Mass Extinctions tells this great scientific detective story. Charles Frankel recounts the birth of the cosmic hypothesis, which holds that the crash of a meteor on the Earth's surface killed two-thirds of life and all the dinosaurs. He first provides a dramatic account of the impact and its aftermath. Frankel then goes on to detail the controversy that preceded the acceptance of the cosmic hypothesis, the search for the crater, its discovery and ongoing exploration, and the effect of the giant impact on the biosphere. In addition, he reviews other mass extinctions in the fossil record and the threat of asteroids and comets to our planet today. More than 70 photographs and diagrams enhance and help illustrate the material. Filled with drama and interesting science, The End of the Dinosaurs will readily appeal to both the general reader fascinated with the subject and the specialist always searching for more clues to this great mystery. Charles Frankel has written a number of articles on the earth sciences in books and magazines. His many books include Volcanoes of the Solar System (Cambridge University Press 1996).
In 1980 a scientific upheaval was triggered by the advent of the Alvarez-Berkeley group hypothesis. It explained the death of the dinosaurs and most of the life on Earth 65 million years ago by effects of the impact of a meteorite 10 km wide. Although numerous previous impact hypotheses had been largely ignored, that of the Alvarez group arrested the
The genetic and morphological development of colorectal cancer is a paradigm for tumorigenesis. However, the dynamics of clonal evolution underpinning carcinogenesis remain poorly understood. Here we identify multipotential stem cells within human colorectal adenomas and use methylation patterns of nonexpressed genes to characterize clonal evolution. Numerous individual crypts from six colonic adenomas and a hyperplastic polyp were microdissected and characterized for genetic lesions. Clones deficient in cytochrome c oxidase (CCO(-)) were identified by histochemical staining followed by mtDNA sequencing. Topographical maps of clone locations were constructed using a combination of these data. Multilineage differentiation within clones was demonstrated by immunofluorescence. Methylation patterns of adenomatous crypts were determined by clonal bisulphite sequencing; methylation pattern diversity was compared with a mathematical model to infer to clonal dynamics. Individual adenomatous crypts were clonal for mtDNA mutations and contained both mucin-secreting and neuroendocrine cells, demonstrating that the crypt contained a multipotent stem cell. The intracrypt methylation pattern was consistent with the crypts containing multiple competing stem cells. Adenomas were epigenetically diverse populations, suggesting that they were relatively mitotically old populations. Intratumor clones typically showed less diversity in methylation pattern than the tumor as a whole. Mathematical modeling suggested that recent clonal sweeps encompassing the whole adenoma had not occurred. Adenomatous crypts within human tumors contain actively dividing stem cells. Adenomas appeared to be relatively mitotically old populations, pocketed with occasional newly generated subclones that were the result of recent rapid clonal expansion. Relative stasis and occasional rapid subclone growth may characterize colorectal tumorigenesis. PMID:23766371
Humphries, Adam; Cereser, Biancastella; Gay, Laura J; Miller, Daniel S J; Das, Bibek; Gutteridge, Alice; Elia, George; Nye, Emma; Jeffery, Rosemary; Poulsom, Richard; Novelli, Marco R; Rodriguez-Justo, Manuel; McDonald, Stuart A C; Wright, Nicholas A; Graham, Trevor A
SUMMARY The Notch signaling pathway plays important roles in cell-fate determination during embryonic develop- ment and adult life. In this study, we focus on the role of Notch signaling in governing cell-fate choices in human embryonic stem cells (hESCs). Using ge- netic and pharmacological approaches, we achieved both blockade and conditional activation of Notch signaling in several hESC lines. We
Xiaobing Yu; Jizhong Zou; Zhaohui Ye; Holly Hammond; Guibin Chen; Akinori Tokunaga; Prashant Mali; Yue-Ming Li; Curt Civin; Nicholas Gaiano; Linzhao Cheng
BackgroundDuring much of the Late Cretaceous, a shallow, epeiric sea divided North America into eastern and western landmasses. The western landmass, known as Laramidia, although diminutive in size, witnessed a major evolutionary radiation of dinosaurs. Other than hadrosaurs (duck-billed dinosaurs), the most common dinosaurs were ceratopsids (large-bodied horned dinosaurs), currently known only from Laramidia and Asia. Remarkably, previous studies have
Scott D. Sampson; Mark A. Loewen; Andrew A. Farke; Eric M. Roberts; Catherine A. Forster; Joshua A. Smith; Alan L. Titus; Anna Stepanova
Studies of developing and self-renewing tissues have shown that differentiated cell types are typically specified through the actions of multi- stage cell lineages. Such lineages commonly include a stem cell and multiple progenitor (transit amplifying; TA) cell stages, which ultimately give rise to terminally differentiated (TD) cells. In several cases, self-renewal and differen- tiation of stem and progenitor cells within
Wing-Cheong Lo; Ching-Shan Chou; Kimberly K. Gokoffski; Frederic Y.-M. Wan; Arthur D. Lander; Anne L. Calof; Qing Nie
Although the physiology of dinosaurs is still a matter of controversy, there is no doubt that some of them were able to live in environments that were too cold for ectothermic reptiles, as shown by discoveries of Jurassic and Cretaceous polar vertebrate assemblages which contain dinosaurs but lack turtles and crocodiles. This adaptation of dinosaurs to cool climates invalidates hypotheses
Some of the longest standing questions in dinosaur paleontology pertain to their development. Did dinosaurs grow at slow rates similar to extant reptiles or rapidly similar to living birds and mammals? How did some forms attain gigantic proportions? Conversely, how did birds (avian dinosaurs) become miniaturized? New data on dinosaur longevity garnered from bone microstructure (i.e. osteohistology) are making it possible to assess basic life-history parameters of the dinosaurs such as growth rates and timing of developmental events. Analyses of these data in an evolutionary context are enabling the identification of developmental patterns that lead to size changes within the Dinosauria. Furthermore, this rich new database is providing inroads for studying individual and population biology. All in all, paleohistological research is proving to be the most promising avenue towards gaining a comprehensive understanding of dinosaur biology. PMID:16701457
Erickson, Gregory M
A 4-yr-old male's knowledge of 40 dinosaurs was elicited from 2 tasks. The data gathered from these knowledge-production protocols were used to map 2 interrelated semantic networks of dinosaurs, viewed as concept nodes connected by links. The 2 mappings corresponded to 2 sets of dinosaurs (20 each), partitioned on the basis of external criteria: mother's subjective judgment of the S's
Michelene T. Chi; Randi D. Koeske
Written for non-specialists, this detailed survey of dinosaur origins, diversity, and extinction is designed as a series of successive essays covering important and timely topics in dinosaur paleobiology, such as "warm-bloodedness," birds as living dinosaurs, the new, non-flying feathered dinosaurs, dinosaur functional morphology, and cladistic methods in systematics. Its explicitly phylogenetic approach to the group is that taken by dinosaur specialists. The book is not an edited compilation of the works of many individuals, but a unique, cohesive perspective on Dinosauria. Lavishly illustrated with hundreds of new, specially commissioned illustrations by John Sibbick, world-famous illustrator of dinosaurs, the volume includes multi-page drawings as well as sketches and diagrams. First edition Hb (1996): 0-521-44496-9 David E. Fastovsky is Professor of Geosciences at the University of Rhode Island. Fastovsky, the author of numerous scientific publications dealing with Mesozoic vertebrate faunas and their ancient environments, is also scientific co-Editor of Geology. He has undertaken extensive fieldwork studying dinosaurs and their environments in Montana, North Dakota, Arizona, Mexico, and Mongolia. David B. Weishampel is a professor at the Center for Functional Anatomy and Evolution at Johns Hopkins University, School of Medicine. Weishampel is best known for discovering, researching, and naming several rare European dinosaur species. During the 1980s Weishampel gained fame for his work with American paleontologist Jack Horner and later named the famous plant-eating, egg-laying Orodromeus, Horner. Now, a decade after his pioneering studies with Horner, Weishampel is most widely known for his current work on the Romanian dinosaur fauna. He is the author and co-author of many titles, including The Dinosaur Papers, 1676-1906 (Norton, 2003); The Dinosauria, (University of California, 1990); and Dinosaurs of the East Coast, (Johns Hopkins University Press, 1996).
Fastovsky, David E.; Weishampel, David B.
Regenerative medicine consisting of cells and materials provides a new way for the repair and regeneration of tissues and organs. Nano-biomaterials are highlighted due to their advantageous features compared with conventional micro-materials. The aim of this study is to investigate the effects of micro-/nano- sized hydroxyapatite (?/n-HA) on the osteogenic differentiation of rat bone marrow derived mesenchymal stem cells (rBMSCs). ?/n-HA were prepared by a microwave synthesizer and precipitation method, respectively. Different sizes of ?/n-HA were characterized by IR, XRD, SEM, TEM and co-cultured with rBMSCs. It was shown that rBMSCs expressed higher levels of osteoblast-related markers by n-HA than ?-HA stimulation. The size of HA is an important factor for affecting the osteogenic differentiation of rBMSCs. This provides a new avenue for mechanistic studies of stem cell differentiation and a new approach to obtain more committed differentiated cells. PMID:22371072
Huang, Yan; Zhou, Gang; Zheng, Lisha; Liu, Haifeng; Niu, Xufeng; Fan, Yubo
Regenerative medicine consisting of cells and materials provides a new way for the repair and regeneration of tissues and organs. Nano-biomaterials are highlighted due to their advantageous features compared with conventional micro-materials. The aim of this study is to investigate the effects of micro-/nano- sized hydroxyapatite (?/n-HA) on the osteogenic differentiation of rat bone marrow derived mesenchymal stem cells (rBMSCs). ?/n-HA were prepared by a microwave synthesizer and precipitation method, respectively. Different sizes of ?/n-HA were characterized by IR, XRD, SEM, TEM and co-cultured with rBMSCs. It was shown that rBMSCs expressed higher levels of osteoblast-related markers by n-HA than ?-HA stimulation. The size of HA is an important factor for affecting the osteogenic differentiation of rBMSCs. This provides a new avenue for mechanistic studies of stem cell differentiation and a new approach to obtain more committed differentiated cells.
Huang, Yan; Zhou, Gang; Zheng, Lisha; Liu, Haifeng; Niu, Xufeng; Fan, Yubo
Two new specimens of the fossil stem group galliform Paraortygoides messelensis Mayr 2000 (Gallinuloididae) are described from the Middle Eocene of Messel in Germany, including a complete skeleton in which\\u000a the hitherto unknown skull of this species is preserved. The shorter and more protruding crista deltopectoralis of the humerus,\\u000a also for the first time visible in one of the new
Hosted by Tramline Virtual Field Trips, this online field trip was created by educator Theresa Hughes-Feletar to teach young students (grades 1-3) about dinosaurs. Hughes-Feletar's virtual field trip links to a variety of quality websites about dinosaurs to create an integrated learning experience. The field trip links -- or Stops as the website refers to them -- provide information about dinosaur reproduction, fossils, hunting, extinction, and more. A supplemental Teacher's Resources page includes recommended book and music lists, as well as dinosaur curriculum ideas for subjects such as science, math, and art.
Dendritic cells (DCs) play a key role in innate and adaptive immunity but the access to sufficient amount of DCs for basic and translational research has been limited.We established a novel ex vivo system to develop and expand DCs from hematopoietic stem/progenitor cells (HPCs). Both human and mouse HPCs were expanded first in feeder culture supplemented with c-Kit ligand (KL, stem cell factor, steel factor or CD117 ligand), Flt3 ligand (fms-like tyrosine kinase 3, Flt3L, FL), thrombopoietin (TPO), IL-3, IL-6, and basic fibroblast growth factor (bFGF), and then in a second feeder culture ectopically expressing all above growth factors plus GM-CSF and IL-15.In the dual culture system, CD34+ HPCs differentiated toward DC progenitors (DCPs), which expanded more than five orders of magnitude. The DCPs showed myeloid DC surface phenotype with up-regulation of transcription factors PU.1 and Id2, and DC-related factors homeostatic chemokine ligand 17 (CCL17) and beta-chemokine receptor 6 (CCR6). Multiplex ELISA array and cDNA microarray analyses revealed that the DCPs shared some features of IL-4 and IL-15 DCs but displayed a pronounced proinflammatory phenotype. DCP-derived DCs showed antigen-uptake and immune activation functions analogous to that of the peripheral blood-derived DCs. Furthermore, bone marrow HPC-derived DCP vaccines of tumor-bearing mice suppressed tumor growth in vivo.This novel approach of generating DCP-DCs, which are different from known IL-4 and IL-15 DCs, overcomes both quantitative and qualitative limitations in obtaining functional autologous DCs from a small number of HPCs with great translational potential. PMID:21106069
Han, Shuhong; Wang, Yichen; Wang, Bei; Patel, Ekta; Okada, Starlyn; Yang, Li-Jun; Moreb, Jan S; Chang, Lung-Ji
The Prince Creek Formation near Ocean Point on the Arctic coastal plain of northern Alaska contains hadrosaur (duck-billed dinosaur) bones, as well as an abundant fauna of mollusks, ostracodes, brachiopods, foraminifers, and palynomorphs. Evaluation of the marine mollusks and ostracodes suggested a Paleocene age for these strata to Marincovich et al. . A fission-track age on zircon of 50.9 +/- 7.7 Ma from an interbedded tephra [Carter et al., 1977] suggested that they could be as young as early Eocene. If the mollusk, ostracod, and fission-track ages are correct, the hadrosaurs would be of early Cenozoic age—one of the few recorded occurrences of dinosaurs younger than Cretaceous. The foraminifers, pollen, and spores, however, strongly suggest a Late Cretaceous age for their beds [Brouwers et al., 1987].
McKee, Edwin H.; Conrad, James E.; Turin, Brent D.
For this actiivty the students will watch a Nova documentary called "The Four-Winged Dinosaur." The documentary follows two teams of scientists as they create replicas of microraptor, a dinosaur with four feathered wings, in an attempt to determine how flight evolved in birds (from the ground up or from the trees down). As the students watch the video, they should think about each hypothesis and pay attention to the lines of evidence presented on both sides of the argument. The students are given specific questions to answer while watching the video that will help them pay attention to key ideas. Outside of class they are responsible for writing a short essay (~1 page, typed) describing which origin of flight hypothesis that they believe is the most plausible and why. Students must support their argument with evidence presented in the video.
The Prince Creek Formation near Ocean Point on the Arctic coastal plain of northern Alaska contains hadrosaur (duck-billed dinosaur) bones, as well as an abundant fauna of mollusks, ostracodes, brachiopods, foraminifers, and palynomorphs. Evaluation of the marine mollusks and ostracodes suggested a Paleocene age for these strata to Marincovich et al. . A fission-track age on zircon of 50.9 +\\/-
Edwin H. McKee; James E. Conrad; Brent D. Turin
Two amateur paleontologists kept their eyes to the ground in Oregon on one of their recent hikes and discovered what are believed to be the first remains of a marine reptile called the plesiosaur to be unearthed in the Pacific Northwest. This radio broadcast reports on the discovery and what it could mean to the understanding of dinosaurs in the area. The clip is 5 minutes and 6 seconds in length.
After looking at vertebrate skeletons and viewing videos dealing with vertebrates, this is a hands-on exercise with data the students can gather from simulated dinosaur trackways. To scale footprints (cut from poster board) are taped to the hallway floor; one of a bipedal theropod and one a quadrapedal sauropod. Students make the appropriate measurements directly from the simulated trackways. These data, plus additional data provided, are the basis for calculations necessary to calculate speed. With this information, various questions are answered.
The developmental pathway that gives rise to mature adipocytes involves two distinct stages: commitment and terminal differentiation. Although the important proteins/factors contributing to terminal adipocyte differentiation have been well defined, the proteins/factors in the commitment of mesenchymal stem cells to the adipocyte lineage cells have not. In this study, we applied proteomics analysis profiling to characterize differences between uncommitted C3H10T1/2 pluripotent stem cells and those that have been committed to the adipocyte lineage by BMP4 or BMP2 with the goal to identify such proteins/factors and to understand the molecular mechanisms that govern the earliest stages of adipocyte lineage commitment. Eight proteins were found to be up-regulated by BMP2, and 27 proteins were up-regulated by BMP4, whereas five unique proteins were up-regulated at least 10-fold by both BMP2/4, including three cytoskeleton-associated proteins (i.e. lysyl oxidase (LOX), translationally controlled tumor protein 1 (TPT1), and ?B-crystallin). Western blotting further confirmed the induction of the expression of these cytoskeleton-associated proteins in the committed C3H10T1/2 induced by BMP2/4. Importantly, knockdown of LOX expression totally prevented the commitment, whereas knockdown of TPT1 and ?B-crystallin expression partially inhibited the commitment. Several published reports suggest that cell shape can influence the differentiation of partially committed precursors of adipocytes, osteoblasts, and chondrocytes. We observed a dramatic change of cell shape during the commitment process, and we showed that knockdown of these cytoskeleton-associated proteins prevented the cell shape change and restored F-actin organization into stress fibers and inhibited the commitment to the adipocyte lineage. Our studies indicate that these differentially expressed cytoskeleton-associate proteins might determine the fate of mesenchymal stem cells to commit to the adipocyte lineage through cell shape regulation.
Huang, Hai-Yan; Hu, Ling-Ling; Song, Tan-Jing; Li, Xi; He, Qun; Sun, Xia; Li, Yi-Ming; Lu, Hao-Jie; Yang, Peng-Yuan; Tang, Qi-Qun
The basal theropod dinosaur clade Ceratosauria, and its subclade Abelisauroidea, is characteristic of late Mesozoic terrestrial vertebrate faunas in western Gondwana (South America, Africa, Madagascar, and India) and Europe. Yet unambiguous records of ceratosaurs have hitherto been absent from Australia, where the theropod assemblage appears to include several typically Laurasian clades. Here, we report the first evidence of ceratosaurs (and potentially abelisauroids) from eastern Gondwana--a diagnostic astragalocalcaneum from the Aptian (121-125 Ma) of Victoria, Australia. Ceratosauria thus occurred in both western and eastern Gondwana during the Early Cretaceous. This fossil adds to the poorly known dinosaur fauna of Australia, a major clade of basal theropods, emphasising that its mid-Cretaceous theropod diversity was surprisingly cosmopolitan despite relative geographic isolation, including clades that have been thought to be typical of both Gondwana and Laurasia--Ceratosauria, Spinosauridae, Carcharodontosauria, Tyrannosauroidea, and Deinonychosauria. Such a contemporaneous association of theropod clades is unknown from other Gondwanan continents and questions the views that the late Mesozoic dinosaur fauna of Australia was dominated by Gondwanan or Laurasian elements, extreme isolation, relictualism, and/or novelty as a `centre of origin'. The cosmopolitan theropod fauna of Australia probably reflects the global distribution of these clades early in their history, prior to significant continental breakup.
Fitzgerald, Erich M. G.; Carrano, Matthew T.; Holland, Timothy; Wagstaff, Barbara E.; Pickering, David; Rich, Thomas H.; Vickers-Rich, Patricia
Monitoring mixed lineage leukemia expression may help identify patients with mixed lineage leukemia-rearranged acute leukemia who are at high risk of relapse after allogeneic hematopoietic stem cell transplantation.
To evaluate the prognostic value of the expression of the mixed lineage leukemia (MLL) gene for predicting the relapse of patients with MLL-rearranged acute leukemia (AL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), the levels of MLL transcripts in bone marrow (BM) specimens were monitored serially by real-time quantitative polymerase chain reaction (RQ-PCR) at predetermined time points in 40 patients with MLL-rearranged AL who were treated with allo-HSCT. These patients were followed for a median of 24.5 months (range, 8 to 60 months). A total of 236 BM samples were collected and analyzed. Of these, 230 were monitored concurrently for minimal residual disease (MRD) by flow cytometry (FCM) for leukemia-associated aberrant immune phenotypes and by RQ-PCR for the expression of the Wilms tumor (WT1) gene. The 3-year cumulative incidence of relapse in patients who experienced MLL-positive patients (MLL > .0000%) (n = 9) after HSCT was 93.5% (95% confidence interval [CI], 87% to 100%) compared with 12.5% (95% CI, 5.6% to 19.4%) for MLL-negative patients (n = 31) (P < .001). For these 2 patient groups, the 3-year overall survival (OS) was 12.5% (95% CI, .8% to 24.2%) and 77.8% (95% CI, 68.4% to 87.2%) (P < .001), respectively, and the 3-year leukemia-free survival (LFS) was 0% and 72.2% (95% CI, 61.1% to 83.3%), respectively (P < .001). MLL positivity was associated with a higher rate of relapse (hazard ratio [HR], 18.643; 95% CI, 3.449 to 57.025; P = .001), lower LFS (HR, 7.267; 95% CI, 2.038 to 25.916; P = .002), and lower OS (HR, 8.259; 95% CI, 2.109 to 32.336; P = .002), as determined by Cox multivariate analysis. The expression of the MLL gene had a higher specificity and sensitivity than WT1 or MRD monitored by FCM for predicting the relapse of the patients with MLL + AL. Our results suggest that monitoring the expression of the MLL gene may help to identify patients with MLL + AL who are at high risk of relapse after allo-HSCT and may provide a guide for suitable intervention. PMID:24631740
Liu, Jing; Wang, Yu; Xu, Lan-Ping; Liu, Dai-Hong; Qin, Ya-Zhen; Chang, Ying-Jun; Liu, Kai-Yan; Huang, Xiao-Jun
The generation of genome-wide data derived from methylated DNA immunoprecipitation followed by sequencing (MeDIP-seq) has become a major tool for epigenetic studies in health and disease. The computational analysis of such data, however, still falls short on accuracy, sensitivity, and speed. We propose a time-efficient statistical method that is able to cope with the inherent complexity of MeDIP-seq data with similar performance compared with existing methods. In order to demonstrate the computational approach, we have analyzed alterations in DNA methylation during the differentiation of human embryonic stem cells (hESCs) to definitive endoderm. We show improved correlation of normalized MeDIP-seq data in comparison to available whole-genome bisulfite sequencing data, and investigated the effect of differential methylation on gene expression. Furthermore, we analyzed the interplay between DNA methylation, histone modifications, and transcription factor binding and show that in contrast to de novo methylation, demethylation is mainly associated with regions of low CpG densities.
Chavez, Lukas; Jozefczuk, Justyna; Grimm, Christina; Dietrich, Jorn; Timmermann, Bernd; Lehrach, Hans; Herwig, Ralf; Adjaye, James
Extracellular nucleotides are potent signaling molecules mediating cell-specific biological functions, mostly within the processes of tissue damage and repair and flogosis. We previously demonstrated that adenosine 5?-triphosphate (ATP) inhibits the proliferation of human bone marrow-derived mesenchymal stem cells (BM-hMSCs), while stimulating, in vitro and in vivo, their migration. Here, we investigated the effects of ATP on BM-hMSC differentiation capacity. Molecular analysis showed that ATP treatment modulated the expression of several genes governing adipogenic and osteoblastic (ie, WNT-pathway-related genes) differentiation of MSCs. Functional studies demonstrated that ATP, under specific culture conditions, stimulated adipogenesis by significantly increasing the lipid accumulation and the expression levels of the adipogenic master gene PPAR? (peroxisome proliferator-activated receptor-gamma). In addition, ATP stimulated osteogenic differentiation by promoting mineralization and expression of the osteoblast-related gene RUNX2 (runt-related transcription factor 2). Furthermore, we demonstrated that ATP stimulated adipogenesis via its triphosphate form, while osteogenic differentiation was induced by the nucleoside adenosine, resulting from ATP degradation induced by CD39 and CD73 ectonucleotidases expressed on the MSC membrane. The pharmacological profile of P2 purinergic receptors (P2Rs) suggests that adipogenic differentiation is mainly mediated by the engagement of P2Y1 and P2Y4 receptors, while stimulation of the P1R adenosine-specific subtype A2B is involved in adenosine-induced osteogenic differentiation. Thus, we provide new insights into molecular regulation of MSC differentiation.
Zini, Roberta; Rossi, Lara; Salvestrini, Valentina; Ferrari, Davide; Manfredini, Rossella; Lemoli, Roberto M.
Prolonged ex vivo culture of human bone marrow mesenchymal stem cells influences their supportive activity toward NOD/SCID-repopulating cells and committed progenitor cells of B lymphoid and myeloid lineages
Background Bone marrow mesenchymal stem cells support proliferation and differentiation of hematopoietic progenitor cells in vitro. Since these cells constitute a rare subset of bone marrow cells, mesenchymal stem cell preparations for clinical purposes require a preparative step of ex vivo multiplication. The aim of our study was to analyze the influence of culture duration on mesenchymal stem cell supportive activity. Design and Methods Mesenchymal stem cells were expanded for up to ten passages. These cells and CD34+ cells were seeded in cytokine-free co-cultures after which the phenotype, clonogenic capacity and in vivo repopulating activity of harvested hematopoietic cells were assessed. Results Early passage mesenchymal stem cells supported hematopoietic progenitor cell expansion and differentiation toward both B lymphoid and myeloid lineages. Late passage mesenchymal stem cells did not support hematopoietic progenitor cell and myeloid cell outgrowth but maintained B-cell supportive ability. In vitro maintenance of NOD/SCID mouse repopulating cells cultured for 1 week in contact with mesenchymal stem cells was effective until the fourth passage of the mesenchymal cells and declined thereafter. The levels of engraftment of CD34+ cells in NOD/SCID mice was higher when these cells were co-injected with early passage mesenchymal stem cells; however mesenchymal cells expanded beyond nine passages were ineffective in promoting CD34+ cell engraftment. Non-contact cultures indicated that mesenchymal stem cell supportive activity involved diffusible factors. Among these, interleukins 6 and 8 contributed to the supportive activity of early passage mesenchymal stem cells but not to those of late passage cells. The phenotype, as well as fat, bone and cartilage differentiation capacity, of mesenchymal stem cells did not change during their culture. Conclusions Extended culture of mesenchymal stem cells alters the ability of these cells to support hematopoietic progenitor cells without causing concomitant changes in their phenotype or differentiation capacity.
Briquet, Alexandra; Dubois, Sophie; Bekaert, Sandrine; Dolhet, Marie; Beguin, Yves; Gothot, Andre
Jaw muscles are key components of the head and critical to testing hypotheses of soft-tissue homology, skull function, and evolution. Dinosaurs evolved an extraordinary diversity of cranial forms adapted to a variety of feeding behaviors. However, disparate evolutionary transformations in head shape and function among dinosaurs and their living relatives, birds and croc- odylians, impair straightforward reconstructions of muscles, and
Casey M. Holliday
This activity explores vertebrate paleontology/paleobiology of the Mesozoic. It focuses on dinosaur osteology using skeletons and models at The Field Museum in Chicago. Students will compare the morphology of several types of bones between a variety of ornithischian and saurischian dinosaurs.
Neural stem cells (NSCs) can be isolated from different regions of the central nervous system. There has been controversy whether regional differences amongst stem and progenitor cells are cell intrinsic and whether these differences are maintained during expansion in culture. The identification of inherent regional differences has important implications for the use of these cells in neural repair. Here, we compared NSCs derived from the spinal cord and embryonic cortex. We found that while cultured cortical and spinal cord derived NSCs respond similarly to mitogens and are equally neuronogenic, they retain and maintain through multiple passages gene expression patterns indicative of the region from which they were isolated (e.g Emx2 and HoxD10). Further microarray analysis identified 229 genes that were differentially expressed between cortical and spinal cord derived neurospheres, including many Hox genes, Nuclear receptors, Irx3, Pace4, Lhx2, Emx2 and Ntrk2. NSCs in the cortex express LeX. However, in the embryonic spinal cord there are two lineally related populations of NSCs: one that expresses LeX and one that does not. The LeX negative population contains few markers of regional identity but is able to generate LeX expressing NSCs that express markers of regional identity. LeX positive cells do not give rise to LeX-negative NSCs. These results demonstrate that while both embryonic cortical and spinal cord NSCs have similar self-renewal properties and multipotency, they retain aspects of regional identity, even when passaged long-term in vitro. Furthermore, there is a population of a LeX negative NSC that is present in neurospheres derived from the embryonic spinal cord but not the cortex.
Kelly, Theresa K.; Karsten, Stanislav L.; Geschwind, Daniel H.; Kornblum, Harley I.
Several lines of evidence are presented in this text that can help us estimate how dinosaurs could move. A good sequence of preserved footprints (called a trackway) can be extrapolated to give a rough estimate of how fast a particular animal was traveling at that moment. The morphology (shape and structure, or anatomy) of dinosaurs may be a more useful tool, but it is much more difficult to use properly. We can compare dinosaurs with extant (living) animals whose motion we understand better, and make assumptions based on the similarities and differences between the two. This is called the morphological paradigm. We can use the laws of physics and apply them to our dinosaurs. This is called biomechanics. Specific dinosaurs are used as examples and active links lead to more information on each.
The Cretaceous-Paleogene mass extinction approximately 66 million years ago is conventionally thought to have been a turning point in mammalian evolution. Prior to that event and for the first two-thirds of their evolutionary history, mammals were mostly confined to roles as generalized, small-bodied, nocturnal insectivores, presumably under selection pressures from dinosaurs. Release from these pressures, by extinction of non-avian dinosaurs at the Cretaceous-Paleogene boundary, triggered ecological diversification of mammals. Although recent individual fossil discoveries have shown that some mammalian lineages diversified ecologically during the Mesozoic era, comprehensive ecological analyses of mammalian groups crossing the Cretaceous-Paleogene boundary are lacking. Such analyses are needed because diversification analyses of living taxa allow only indirect inferences of past ecosystems. Here we show that in arguably the most evolutionarily successful clade of Mesozoic mammals, the Multituberculata, an adaptive radiation began at least 20 million years before the extinction of non-avian dinosaurs and continued across the Cretaceous-Paleogene boundary. Disparity in dental complexity, which relates to the range of diets, rose sharply in step with generic richness and disparity in body size. Moreover, maximum dental complexity and body size demonstrate an adaptive shift towards increased herbivory. This dietary expansion tracked the ecological rise of angiosperms and suggests that the resources that were available to multituberculates were relatively unaffected by the Cretaceous-Paleogene mass extinction. Taken together, our results indicate that mammals were able to take advantage of new ecological opportunities in the Mesozoic and that at least some of these opportunities persisted through the Cretaceous-Paleogene mass extinction. Similar broad-scale ecomorphological inventories of other radiations may help to constrain the possible causes of mass extinctions. PMID:22419156
Wilson, Gregory P; Evans, Alistair R; Corfe, Ian J; Smits, Peter D; Fortelius, Mikael; Jernvall, Jukka
Background A new investigation of the sedimentology and ichnology of the Early Jurassic Moyeni tracksite in Lesotho, southern Africa has yielded new insights into the behavior and locomotor dynamics of early dinosaurs. Methodology/Principal Findings The tracksite is an ancient point bar preserving a heterogeneous substrate of varied consistency and inclination that includes a ripple-marked riverbed, a bar slope, and a stable algal-matted bar top surface. Several basal ornithischian dinosaurs and a single theropod dinosaur crossed its surface within days or perhaps weeks of one another, but responded to substrate heterogeneity differently. Whereas the theropod trackmaker accommodated sloping and slippery surfaces by gripping the substrate with its pedal claws, the basal ornithischian trackmakers adjusted to the terrain by changing between quadrupedal and bipedal stance, wide and narrow gauge limb support (abduction range?=?31°), and plantigrade and digitigrade foot posture. Conclusions/Significance The locomotor adjustments coincide with changes in substrate consistency along the trackway and appear to reflect ‘real time’ responses to a complex terrain. It is proposed that these responses foreshadow important locomotor transformations characterizing the later evolution of the two main dinosaur lineages. Ornithischians, which shifted from bipedal to quadrupedal posture at least three times in their evolutionary history, are shown to have been capable of adopting both postures early in their evolutionary history. The substrate-gripping behavior demonstrated by the early theropod, in turn, is consistent with the hypothesized function of pedal claws in bird ancestors.
Wilson, Jeffrey A.; Marsicano, Claudia A.; Smith, Roger M. H.
Approximately 6 million people worldwide are suffering from severe visual impairments or blindness due to corneal diseases. Corneal allogeneic transplantation is often required to restore vision; however, shortage in corneal grafts and immunorejections remain major challenges. The molecular basis of corneal diseases is poorly understood largely due to lack of appropriate cellular models. Here, we described a robust differentiation of human-induced pluripotent stem cells (hiPSCs) derived from hair follicles or skin fibroblasts into corneal epithelial-like cells. We found that BMP4, coupled with corneal fibroblast-derived conditioned medium and collagen IV allowed efficient corneal epithelial commitment of hiPSCs in a manner that recapitulated corneal epithelial lineage development with high purity. Organotypic reconstitution assays suggested the ability of these cells to stratify into a corneal-like epithelium. This model allowed us identifying miR-450b-5p as a molecular switch of Pax6, a major regulator of eye development. miR-450b-5p and Pax6 were reciprocally distributed at the presumptive epidermis and ocular surface, respectively. miR-450b-5p inhibited Pax6 expression and corneal epithelial fate in vitro, altogether, suggesting that by repressing Pax6, miR-450b-5p triggers epidermal specification of the ectoderm, while its absence allows ocular epithelial development. Additionally, miR-184 was detectable in early eye development and corneal epithelial differentiation of hiPSCs. The knockdown of miR-184 resulted in a decrease in Pax6 and K3, in line with recent findings showing that a point mutation in miR-184 leads to corneal dystrophy. Altogether, these data indicate that hiPSCs are valuable for modeling corneal development and may pave the way for future cell-based therapy. PMID:22367714
Shalom-Feuerstein, Ruby; Serror, Laura; De La Forest Divonne, Stephanie; Petit, Isabelle; Aberdam, Edith; Camargo, Livia; Damour, Odile; Vigouroux, Clotilde; Solomon, Abraham; Gaggioli, Cédric; Itskovitz-Eldor, Joseph; Ahmad, Sajjad; Aberdam, Daniel
A latest Cretaceous (68 to 65 million years ago) vertebrate microfossil assemblage discovered at Kakanaut in northeastern Russia reveals that dinosaurs were still highly diversified in Arctic regions just before the Cretaceous-Tertiary mass extinction event. Dinosaur eggshell fragments, belonging to hadrosaurids and non-avian theropods, indicate that at least several latest Cretaceous dinosaur taxa could reproduce in polar region and were probably year-round residents of high latitudes. Palaeobotanical data suggest that these polar dinosaurs lived in a temperate climate (mean annual temperature about 10°C), but the climate was apparently too cold for amphibians and ectothermic reptiles. The high diversity of Late Maastrichtian dinosaurs in high latitudes, where ectotherms are absent, strongly questions hypotheses according to which dinosaur extinction was a result of temperature decline, caused or not by the Chicxulub impact.
Godefroit, Pascal; Golovneva, Lina; Shchepetov, Sergei; Garcia, Géraldine; Alekseev, Pavel
A latest Cretaceous (68 to 65 million years ago) vertebrate microfossil assemblage discovered at Kakanaut in northeastern Russia reveals that dinosaurs were still highly diversified in Arctic regions just before the Cretaceous-Tertiary mass extinction event. Dinosaur eggshell fragments, belonging to hadrosaurids and non-avian theropods, indicate that at least several latest Cretaceous dinosaur taxa could reproduce in polar region and were probably year-round residents of high latitudes. Palaeobotanical data suggest that these polar dinosaurs lived in a temperate climate (mean annual temperature about 10 degrees C), but the climate was apparently too cold for amphibians and ectothermic reptiles. The high diversity of Late Maastrichtian dinosaurs in high latitudes, where ectotherms are absent, strongly questions hypotheses according to which dinosaur extinction was a result of temperature decline, caused or not by the Chicxulub impact. PMID:19089398
Godefroit, Pascal; Golovneva, Lina; Shchepetov, Sergei; Garcia, Géraldine; Alekseev, Pavel
This is a task from the Illustrative Mathematics website that is one part of a complete illustration of the standard to which it is aligned. Each task has at least one solution and some commentary that addresses important asects of the task and its potential use. Here are the first few lines of the commentary for this task: Quincy is a tour guide at a museum of science and history. During a tour of the museum, he tells some visitors about a fossilized dinosaur bone that is...
A latest Cretaceous (68 to 65 million years ago) vertebrate microfossil assemblage discovered at Kakanaut in northeastern\\u000a Russia reveals that dinosaurs were still highly diversified in Arctic regions just before the Cretaceous–Tertiary mass extinction\\u000a event. Dinosaur eggshell fragments, belonging to hadrosaurids and non-avian theropods, indicate that at least several latest\\u000a Cretaceous dinosaur taxa could reproduce in polar region and were
Pascal Godefroit; Lina Golovneva; Sergei Shchepetov; Géraldine Garcia; Pavel Alekseev
Previously, we reported that the conformational transition of collagen I matrix plays, along with differentiation stimuli, a regulatory role in determination of differentiation lineage of bone marrow stromal sells via distinct signaling pathways specific for the structural state of the matrix. The present study addresses mechanisms underlying differential structural conformation-specific effects of collagen matrices on differentiation into diverse lineages. The
Josh Mauney; Vladimir Volloch
This site presents theories about why the dinosaurs became extinct. The first page provides background information covering not only the "great dying" at the K-T boundary but also the mass extinction at the end of the Paleozoic Era. The author covers six factors that complicate the study of mass extinction including time resolution, the Signor-Lipps Effect, and falsifiability. A link then takes the reader to a second page where invalid extinction hypotheses are explained. These range from "hay fever killed the dinosaurs" to "the dinosaurs just faded away," (no causation implied). The final link leads us to current thinking about extinction including volcanism, plate tectonics, and the Alvarez Hypothesis.
The herbivorous sauropod dinosaurs of the Jurassic and Cretaceous periods were the largest terrestrial animals ever, surpassing the largest herbivorous mammals by an order of magnitude in body mass. Several evolutionary lineages among Sauropoda produced giants with body masses in excess of 50 metric tonnes by conservative estimates. With body mass increase driven by the selective advantages of large body size, animal lineages will increase in body size until they reach the limit determined by the interplay of bauplan, biology, and resource availability. There is no evidence, however, that resource availability and global physicochemical parameters were different enough in the Mesozoic to have led to sauropod gigantism. We review the biology of sauropod dinosaurs in detail and posit that sauropod gigantism was made possible by a specific combination of plesiomorphic characters (phylogenetic heritage) and evolutionary innovations at different levels which triggered a remarkable evolutionary cascade. Of these key innovations, the most important probably was the very long neck, the most conspicuous feature of the sauropod bauplan. Compared to other herbivores, the long neck allowed more efficient food uptake than in other large herbivores by covering a much larger feeding envelope and making food accessible that was out of the reach of other herbivores. Sauropods thus must have been able to take up more energy from their environment than other herbivores. The long neck, in turn, could only evolve because of the small head and the extensive pneumatization of the sauropod axial skeleton, lightening the neck. The small head was possible because food was ingested without mastication. Both mastication and a gastric mill would have limited food uptake rate. Scaling relationships between gastrointestinal tract size and basal metabolic rate (BMR) suggest that sauropods compensated for the lack of particle reduction with long retention times, even at high uptake rates. The extensive pneumatization of the axial skeleton resulted from the evolution of an avian-style respiratory system, presumably at the base of Saurischia. An avian-style respiratory system would also have lowered the cost of breathing, reduced specific gravity, and may have been important in removing excess body heat. Another crucial innovation inherited from basal dinosaurs was a high BMR. This is required for fueling the high growth rate necessary for a multi-tonne animal to survive to reproductive maturity. The retention of the plesiomorphic oviparous mode of reproduction appears to have been critical as well, allowing much faster population recovery than in megaherbivore mammals. Sauropods produced numerous but small offspring each season while land mammals show a negative correlation of reproductive output to body size. This permitted lower population densities in sauropods than in megaherbivore mammals but larger individuals. Our work on sauropod dinosaurs thus informs us about evolutionary limits to body size in other groups of herbivorous terrestrial tetrapods. Ectothermic reptiles are strongly limited by their low BMR, remaining small. Mammals are limited by their extensive mastication and their vivipary, while ornithsichian dinosaurs were only limited by their extensive mastication, having greater average body sizes than mammals.
Sander, P Martin; Christian, Andreas; Clauss, Marcus; Fechner, Regina; Gee, Carole T; Griebeler, Eva-Maria; Gunga, Hanns-Christian; Hummel, Jurgen; Mallison, Heinrich; Perry, Steven F; Preuschoft, Holger; Rauhut, Oliver W M; Remes, Kristian; Tutken, Thomas; Wings, Oliver; Witzel, Ulrich
Sauropod dinosaurs are a group of herbivorous dinosaurs which exceeded all other terrestrial vertebrates in mean and maximal body size. Sauropod dinosaurs were also the most successful and long-lived herbivorous tetrapod clade, but no abiological factors such as global environmental parameters conducive to their gigantism can be identified. These facts justify major efforts by evolutionary biologists and paleontologists to understand sauropods as living animals and to explain their evolutionary success and uniquely gigantic body size. Contributions to this research program have come from many fields and can be synthesized into a biological evolutionary cascade model of sauropod dinosaur gigantism (sauropod gigantism ECM). This review focuses on the sauropod gigantism ECM, providing an updated version based on the contributions to the PLoS ONE sauropod gigantism collection and on other very recent published evidence. The model consist of five separate evolutionary cascades (“Reproduction”, “Feeding”, “Head and neck”, “Avian-style lung”, and “Metabolism”). Each cascade starts with observed or inferred basal traits that either may be plesiomorphic or derived at the level of Sauropoda. Each trait confers hypothetical selective advantages which permit the evolution of the next trait. Feedback loops in the ECM consist of selective advantages originating from traits higher in the cascades but affecting lower traits. All cascades end in the trait “Very high body mass”. Each cascade is linked to at least one other cascade. Important plesiomorphic traits of sauropod dinosaurs that entered the model were ovipary as well as no mastication of food. Important evolutionary innovations (derived traits) were an avian-style respiratory system and an elevated basal metabolic rate. Comparison with other tetrapod lineages identifies factors limiting body size.
Sander, P. Martin
This interactive resource adapted from the Museum of Paleontology at the University of California, Berkeley shows how a dinosaur can be buried under sediment after it dies, become a fossil, and then become exposed and discovered by paleontologists.
Foundation, Wgbh E.
Dromaeosaurid theropod dinosaurs possess a strongly recurved, hypertrophied and hyperextensible ungual claw on pedal digit II. This feature is usually suggested to have functioned as a device for disembowelling herbivorous dinosaurs during predation. However, modelling of dromaeosaurid hindlimb function using a robotic model and comparison of pedal ungual morphology with extant analogue taxa both indicate that this distinctive claw did not function as a slashing weapon, but may have acted as an aid to prey capture.
Manning, Phillip L; Payne, David; Pennicott, John; Barrett, Paul M; Ennos, Roland A
Students investigate the intelligence of dinosaurs by comparing the relative size of brain and body mass to living animals. Students plot the living animals to determine a general relationship of brain and body mass and then use that relation to interpret a range of dinosaurs. The activity gives students practice in graphical data comparison and other methods of data analysis. Students also investigate how well this method works and what weaknesses it might have.
This Columbia University course webpage includes a syllabus of the course with lecture notes and readings, as well as the lab syllabus with complete lab instructions. The topics covered by this course and labs include what a dinosaur is, their discovery, geologic time, cladistics and relationships of organisms, Earth cycles, major formations and locations containing dinosaur fossils, and their extinction. There is also textbook, midterm, final, and term paper information along with links to additional information to enhance class lectures.
By means of laser desorption post-ionization time-of flight mass specrometry (TOF) and high-pressure liquid chromatography (HPLC), fullerene C60 have been found in a fossil of dinosaur egg shell from Xixia (N33.3 E111.4), China. These techniques verified also mat fullerene C70 is virtually absent from identical egg fossil of dinosaur at XiXia. Preliminary results suggest that C60 occurrence and C70 absence
Wang Zhenxia; Li Xuepeng; Wang Wenmin; Xu Xunjiang; Zi Chao Tang; Rong-Bin Huang; Lan-Sun Zheng
Dinosaurs were the rulers of the land 65 million years ago. In this videotape, children learn more about the different kinds of dinosaurs by viewing vivid illustrations and fossil discoveries. Students compare the dinosaurs to their modern kin--snakes, lizards, and crocodiles. Students also listen to different theories to try to answer the big…
Small Late Jurassic theropod dinosaurs are rare worldwide. In Europe these carnivorous dinosaurs are represented primarily by only two skeletons of Compsognathus, neither of which is well preserved. Here we describe a small new theropod dinosaur from the Late Jurassic period of Schamhaupten in southern Germany. Being exquisitely preserved and complete from the snout to the distal third of the
Ursula B. Göhlich; Luis M. Chiappe
Quadrupedality evolved four independent times in dinosaurs; however, the constraints associated with these transitions in limb anatomy and function remain poorly understood, in particular the evolution of forearm posture and rotational ability (i.e., active pronation and supination). Results of previous qualitative studies are inconsistent, likely due to an inability to quantitatively assess the likelihood of their conclusions. We attempt to quantify antebrachial posture and mobility using the radius bone because its morphology is distinct between extant sprawled taxa with a limited active pronation ability and parasagittal taxa that have an enhanced ability to actively pronate the manus. We used a sliding semi-landmark, outline-based geometric morphometric approach of the proximal radial head and a measurement of the angle of curvature of the radius in a sample of 189 mammals, 49 dinosaurs, 35 squamates, 16 birds, and 5 crocodilians. Our results of radial head morphology showed that quadrupedal ceratopsians, bipedal non-hadrosaurid ornithopods, and theropods had limited pronation/supination ability, and sauropodomorphs have unique radial head morphology that likely allowed limited rotational ability. However, the curvature of the radius showed that no dinosaurian clade had the ability to cross the radius about the ulna, suggesting parallel antebrachial elements for all quadrupedal dinosaurs. We conclude that the bipedal origins of all quadrupedal dinosaur clades could have allowed for greater disparity in forelimb posture than previously appreciated, and future studies on dinosaur posture should not limit their classifications to the overly simplistic extant dichotomy. PMID:24058633
VanBuren, Collin S; Bonnan, Matthew
The unearthing of a complete skull and skeleton of the early dinosaur Herrerasaurus ischigualastensis sheds light on the early evolution of dinosaurs. Discovered in the Upper Triassic Ischigualasto Formation of Argentina, the fossils show that Herrerasaurus, a primitive theropod, was an agile, bipedal predator with a short forelimb specialized for grasping and raking. The fossils clarify anatomical features of the common ancestor of all dinosaurs. Herrerasaurus and younger dinosaurs from Upper Triassic beds in Argentina suggest that the dinosaurian radiation was well under way before dinosaurs dominated terrestrial vertebrate communities in taxonomic diversity and abundance. PMID:17789086
Sereno, P C; Novas, F E
Gideon Mantell and the Discovery of Dinosaurs is a scholarly yet accessible biography--the first in a generation--of a pioneering dinosaur hunter and scholar. Gideon Mantell discovered the Iguanodon (a famous tale set right in this book) and several other dinosaur species, spent over twenty-five years restoring Iguanodon fossils, and helped establish the idea of an Age of Reptiles that ended with their extinction at the conclusion of the Mesozoic Era. He had significant interaction with such well-known figures as James Parkinson, Georges Cuvier, Charles Lyell, Roderick Murchison, Charles Darwin, and Richard Owen. Dennis Dean, a well-known scholar of geology and the Victorian era, here places Mantell's career in its cultural context, employing original research in archives throughout the world, including the previously unexamined Mantell family papers in New Zealand.
Dean, Dennis R.
The largest specimen of the four-winged dromaeosaurid dinosaur Microraptor gui includes preserved gut contents. Previous reports of gut contents and considerations of functional morphology have indicated that Microraptor hunted in an arboreal environment. The new specimen demonstrates that this was not strictly the case, and offers unique insights into the ecology of nonavian dinosaurs early in the evolution of flight. The preserved gut contents are composed of teleost fish remains. Several morphological adaptations of Microraptor are identified as consistent with a partially piscivorous diet, including dentition with reduced serrations and forward projecting teeth on the anterior of the dentary. The feeding habits of Microraptor can now be understood better than that of any other carnivorous nonavian dinosaur, and Microraptor appears to have been an opportunistic and generalist feeder, able to exploit the most common prey in both the arboreal and aquatic microhabitats of the Early Cretaceous Jehol ecosystem. PMID:23888864
Xing, Lida; Persons, W Scott; Bell, Phil R; Xu, Xing; Zhang, Jianping; Miyashita, Tetsuto; Wang, Fengping; Currie, Philip J
Postnatal stem cells regulate the ho- meostasis of the majority of our tissues. They con- tinuously generate new progenitors and mature, functional cells to replace old cells, which cannot assume the tissue function anymore and are elimi- nated. Blood, skin, gut mucosa, muscle, cartilage, nerves, cornea, retina, liver, and many other structures are regulated by stem cells. As a result
...Department of the Interior, National Park Service, Dinosaur National Monument, Dinosaur, CO AGENCY: National Park Service, Interior...Department of the Interior, National Park Service, Dinosaur National Monument, Dinosaur, CO, has...
Finding topics that inspire students is an important aspect of any physics course. Virtually everyone is fascinated by Tyrannosaurus rex, and the excitement of the class is palpable when we explore scaling effects in T. rex and other bipedal theropod dinosaurs as part of our discussion of mechanics and elasticity. In this paper, we explore the role of longitudinal stress in the femur bones due to the weight of the dinosaur in determining how the geometry of the femur changes with size of the theropod. This is one area of allometry the study of how different biological characteristics scale with size.1
Lee, Scott A.
Several dinosaur bone and eggshell fossil samples unearthed at different sites in China were analyzed by means of nuclear microscopy. Concentrations and distributions of elements such as Na, Mg, Al, P, S, Ca, Cr, Mn, Fe, Cu, Zn, As, Br, Sr, Y, Ce, Pb and U, etc. were obtained for each sample. The results of quantitative PIXE and RBS analyses show unusually high concentrations of U and Ce in several samples obtained from a period near the K-T boundary (between Cretaceous and Tertiary periods, 65 million years ago), suggesting that some form of environmental pollution could be the cause of dinosaur extinction.
Wu, Xiankang; Orli?, I.; Tang, S. M.; Wang, Yiming; Wang, Xiaohong; Zhu, Jieqing
Recently, a team of researchers in a remote area of eastern Utah led by Utah state paleontologist James I. Kirkland made an important discovery that has been described as a type of dinosaur Ã¢ÂÂmissing linkÃ¢ÂÂ. Essentially, this Ã¢ÂÂlinkÃ¢ÂÂ represents a rather primitive plant-eater that evolved from the meat-eating raptors that also gave rise to modern birds. The dinosaur has been named Falcarius utahensis, which means Ã¢ÂÂsickle-maker from UtahÃ¢ÂÂ, largely due to its claws. The results of this important find were documented in this ThursdayÃ¢ÂÂs edition of the journal Nature, and this material supports earlier contentions that link the plant-eating dinosaurs known as therizinosaurs to raptors. Matthew Lamanna from the Carnegie Museum of Natural History remarked that Ã¢ÂÂItÃ¢ÂÂs an extremely significant find. Before this discovery, the oldest known animal recognized as a therizinosaur came from China, and this one is just as old and seems to be more primitive anatomically. It appears to be the final piece of the puzzle.Ã¢ÂÂThe first link leads to an article from this WednesdayÃ¢ÂÂs Washington Post that offers some perspective on the find from the paleontologist James I. Kirkland. The second link will take visitors to a fine news story from the National GeographicÃ¢ÂÂs website that provides a good perspective on this important discovery. The third link offers some informed insights from NatureÃ¢ÂÂs own Michael Hopkins on this discovery. The fourth link leads to a very informative site from BBC on dinosaurs, which includes fact files on a number of dinosaurs, a timeline, and some interactive games and screensavers. The fifth link will take visitors to a very useful FAQ site, offered by the United States Geological Survey, which answers a number of common queries about dinosaurs, such as Ã¢ÂÂWhere did dinosaurs live?Ã¢ÂÂ and Ã¢ÂÂDid dinosaurs communicate?Ã¢ÂÂ. The final link leads to the homepage of that noted University of Chicago paleontologist, Paul Sereno. Here visitors can learn about his work and expeditions, among other things.
This site refers to the discovery of a fossilized dinosaur heart that was reported in the April 21, 2000 issue of the Journal Science. This heart of a small herbivore called a Thescelosaurus reveals a structure "more like that of a bird or a mammal than those of reptiles, adding substantially to evidence suggesting that at least some dinosaurs had high metabolic rates." The site, from the Center for the Exploration of the Dinosaurian World, a collaboration between North Carolina State University and the North Carolina Museum of Natural Sciences, offers up-to-date information about and images of the important discovery.
Crocodilians and birds show extensive parental care of their young, but whether this behaviour evolved independently in these two groups of living archosaurs is unknown - in part because features of parenting among related fossil groups such as dinosaurs are unclear. A dramatic specimen of the small ornithischian dinosaur Psittacosaurus sp. (Dalian Natural History Museum D2156) from Liaoning in China reveals a single adult clustered with 34 juveniles within an area of 0.5 square metres, providing strong evidence for post-hatching parental care in Dinosauria. PMID:15356619
Meng, Qingjin; Liu, Jinyuan; Varricchio, David J; Huang, Timothy; Gao, Chunling
The dinosaur bones first discovered in 1877 in the Upper Jurassic Morrison Formation at Morrison, Colorado were the first major find of dinosaur skeletons in the western U.S. and led to the recognition of four new dinosaur genera (Apatosaurus, Allosaurus, Diplodocus, and Stegosaurus). Eight articles dealing with these bones which appeared as research reports in the annual reports of the Friends of Dinosaur Ridge from 1990-1999 are condensed and summarized with some additional comments. Two of the articles are about the mineralogy and preservation of the bones; two are about the physical description of the bone occurrence; two are about the history of the site, and two are about use of novel instrumental methods (ground-penetrating radar and a directional scintillometer) to search for new bones.
Modreski, P. J.
Mesozoic mammals are commonly portrayed as shrew- or rat-sized animals that were mainly insectivorous, probably nocturnal and lived in the shadow of dinosaurs. The largest known Mesozoic mammal represented by substantially complete remains is Repenomamus robustus, a triconodont mammal from the Lower Cretaceous of Liaoning, China. An adult individual of R. robustus was the size of a Virginia opossum. Here
Yaoming Hu; Jin Meng; Yuanqing Wang; Chuankui Li
In this lesson, students read and discuss articles presenting two alternative theories about the extinction of dinosaurs. They are encouraged to use the criteria that scientists use to get the best solution. Students will learn that: some evolutionary change is rapid and discontinuous; extinction plays in role in macroevolution; and scientists use specific criteria in deciding which theory is better.
Palaeobiodiversity analysis underpins macroevolutionary investigations, allowing identification of mass extinctions and adaptive radiations. However, recent large-scale studies on marine invertebrates indicate that geological factors play a central role in moulding the shape of diversity curves and imply that many features of such curves represent sampling artefacts, rather than genuine evolutionary events. In order to test whether similar biases affect diversity estimates for terrestrial taxa, we compiled genus-richness estimates for three Mesozoic dinosaur clades (Ornithischia, Sauropodomorpha and Theropoda). Linear models of expected genus richness were constructed for each clade, using the number of dinosaur-bearing formations available through time as a proxy for the amount of fossiliferous rock outcrop. Modelled diversity estimates were then compared with observed patterns. Strong statistically robust correlations demonstrate that almost all aspects of ornithischian and theropod diversity curves can be explained by geological megabiases, whereas the sauropodomorph record diverges from modelled predictions and may be a stronger contender for identifying evolutionary signals. In contrast to other recent studies, we identify a marked decline in dinosaur genus richness during the closing stages of the Cretaceous Period, indicating that the clade decreased in diversity for several million years prior to the final extinction of non-avian dinosaurs at the Cretaceous-Palaeocene boundary. PMID:19403535
Barrett, Paul M; McGowan, Alistair J; Page, Victoria
Although Kansas is best known for an abundance of marine fossils from the Late Cretaceous, there may be up to 16 dinosaur records from the state. These are (in order of discovery): 1) the Mudge tracks from the Dakota Formation of Clay County; 2) the hadrosaur, Claosaurus agilis, from the Niobrara Chalk of Logan County; 3) the Snow track from
Gregory A. Liggett
Modern crocodilians and birds are the only living representatives of the Archosauria, a group that also includes non-avian dinosaurs and pterosaurs. Modern crocodilians originated during the early Cretaceous period and dispersed globally. Examples of physiological similarities between living crocodilians and birds include similar amino acids in ?-keratins among crocodiles, turtles and birds; oviduct homologies between crocodilians and birds; similar forelimb
Peter Brazaitis; Myrna E. Watanabe
In 2008, a new basal neoceratopsian was discovered in the Tando beds (Albian) of Tando Basin in South Korea. It represents\\u000a the first ceratopsian dinosaur in the Korean peninsula and is assigned to Koreaceratops hwaseongensis gen. et sp. nov. Autapomorphies of Koreaceratops include very tall neural spines over five times higher than the associated centra in the distal caudals, and
Yuong-Nam Lee; Michael J. Ryan; Yoshitsugu Kobayashi
Triassic tracks and trackways assigned to dinosaur trackmakers or closest relatives have been mentioned from several Middle to the latest Triassic successions from both northern and southern Pangea. At present, the earliest gondwanan records are those from the Middle Triassic Los Rastros Formation in west-central Argentina. A reanalysis of Los Rastros ichnites at the Ischichuca area, including new material, has
Claudia A. Marsicano; Nadia S. Domnanovich; Adriana C. Mancuso
Hadrosaurids were the most diverse and abundant dinosaurs at the end of the Cretaceous. However, their phylogeny is incompletely known and the relationships of many taxa, particularly European and South American, remains unresolved. Questions remain regarding the timing of their origin and which attributes might have allowed these animals to diversify and colonize nearly all continents by the late Campanian.
Several dinosaur bone and eggshell fossil samples unearthed at different sites in China were analyzed by means of nuclear microscopy. Concentrations and distributions of elements such as Na, Mg, Al, P, S, Ca, Cr, Mn, Fe, Cu, Zn, As, Br, Sr, Y, Ce, Pb and U, etc. were obtained for each sample. The results of quantitative PIXE and RBS analyses
Xiankang Wu; I. Orli?; S. M. Tang; Yiming Wang; Xiaohong Wang; Jieqing Zhu
This Web site, created to complement an American Museum of Natural History exhibition, reports on one of the most famous fossil finds in the world (the fighting dinosaurs of Mongolia) and other ancient animal fossils discovered in the Gobi Desert. Although the exhibit is closed, there is useful information on the fossil finds and three short video clips.
Palaeobiodiversity analysis underpins macroevolutionary investigations, allowing identification of mass extinctions and adaptive radiations. However, recent large-scale studies on marine invertebrates indicate that geological factors play a central role in moulding the shape of diversity curves and imply that many features of such curves represent sampling artefacts, rather than genuine evolutionary events. In order to test whether similar biases affect diversity estimates for terrestrial taxa, we compiled genus-richness estimates for three Mesozoic dinosaur clades (Ornithischia, Sauropodomorpha and Theropoda). Linear models of expected genus richness were constructed for each clade, using the number of dinosaur-bearing formations available through time as a proxy for the amount of fossiliferous rock outcrop. Modelled diversity estimates were then compared with observed patterns. Strong statistically robust correlations demonstrate that almost all aspects of ornithischian and theropod diversity curves can be explained by geological megabiases, whereas the sauropodomorph record diverges from modelled predictions and may be a stronger contender for identifying evolutionary signals. In contrast to other recent studies, we identify a marked decline in dinosaur genus richness during the closing stages of the Cretaceous Period, indicating that the clade decreased in diversity for several million years prior to the final extinction of non-avian dinosaurs at the Cretaceous–Palaeocene boundary.
Barrett, Paul M.; McGowan, Alistair J.; Page, Victoria
Examination of the history of Dinosaur National Monument reveals ten themes that form a convenient framework for this and future studies of the Monument. These themes are as follows: Exploration to 1900; Early settlement of the area, 1850-1880; Ranching t...
S. F. Mehls
Oviraptorosaurians are an unusual group of theropod dinosaurs, with highly specialized skulls. Here we report a new oviraptorosaurian, Incisivosaurus gauthieri, gen. et sp. nov., from the lowest part of the Lower Cretaceous Yixian Formation of China. This oviraptorosaurian displays a number of characters closer to more typical theropods, such as a low skull and toothed jaws, thus greatly reducing the
Xing Xu; Yen-Nien Cheng; Xiao-Lin Wang; Chun-Hsiang Chang
Although the dinosaurian hypothesis of bird origins is widely accepted, debate remains about how the ancestor of birds first learned to fly. Here we provide new evidence suggesting that basal dromaeosaurid dinosaurs were four-winged animals and probably could glide, representing an intermediate stage towards the active, flapping-flight stage. The new discovery conforms to the predictions of early hypotheses that proavians
Xing Xu; Zhonghe Zhou; Xiaolin Wang; Xuewen Kuang; Fucheng Zhang; Xiangke Du
The central dogma in stem cell biology has been that cells isolated from a particular tissue can renew and differentiate into lineages of the tissue it resides in. Several studies have challenged this idea by demonstrating that tissue specific cell have considerable plasticity and can cross-lineage restriction boundary and give rise to cell types of other lineages. However, the lack
Uma Lakshmipathy; Catherine Verfaillie
The extinction of non-avian dinosaurs 65 million years ago is a perpetual topic of fascination, and lasting debate has focused on whether dinosaur biodiversity was in decline before end-Cretaceous volcanism and bolide impact. Here we calculate the morphological disparity (anatomical variability) exhibited by seven major dinosaur subgroups during the latest Cretaceous, at both global and regional scales. Our results demonstrate both geographic and clade-specific heterogeneity. Large-bodied bulk-feeding herbivores (ceratopsids and hadrosauroids) and some North American taxa declined in disparity during the final two stages of the Cretaceous, whereas carnivorous dinosaurs, mid-sized herbivores, and some Asian taxa did not. Late Cretaceous dinosaur evolution, therefore, was complex: there was no universal biodiversity trend and the intensively studied North American record may reveal primarily local patterns. At least some dinosaur groups, however, did endure long-term declines in morphological variability before their extinction. PMID:22549833
Brusatte, Stephen L; Butler, Richard J; Prieto-Márquez, Albert; Norell, Mark A
This activity sheet for young children is designed to be completed during a visit to the Museum's fourth floor Fossil Halls. The printable two-page handout includes notes about how paleontologists use tools to find and dig out fossils, a scavenger hunt in the Hall of Saurischian Dinosaurs for two vegetarian dinosaurs, a scavenger hunt for protective body parts in the Hall of Ornithischian Dinosaurs and a collection of fun facts.
Non-avian dinosaurs are mostly medium to large-sized animals, and to date all known mature specimens are larger than the most primitive bird, Archaeopteryx. Here we report on a new dromaeosaurid dinosaur, Microraptor zhaoianus gen. et sp. nov., from the Early Cretaceous Jiufotang Formation of Liaoning, China. This is the first mature non-avian dinosaur to be found that is smaller than
Xing Xu; Zhonghe Zhou; Xiaolin Wang
The rise and diversification of the dinosaurs in the Late Triassic, from 230 to 200 million years ago, is a classic example of an evolutionary radiation with supposed competitive replacement. A comparison of evolutionary rates and morphological disparity of basal dinosaurs and their chief "competitors," the crurotarsan archosaurs, shows that dinosaurs exhibited lower disparity and an indistinguishable rate of character evolution. The radiation of Triassic archosaurs as a whole is characterized by declining evolutionary rates and increasing disparity, suggesting a decoupling of character evolution from body plan variety. The results strongly suggest that historical contingency, rather than prolonged competition or general "superiority," was the primary factor in the rise of dinosaurs. PMID:18787166
Brusatte, Stephen L; Benton, Michael J; Ruta, Marcello; Lloyd, Graeme T
In the 19th century, the race to uncover dinosaur fossils and name new dinosaur species inspired two rival scientists, Edward Drinker Cope and Othniel Charles Marsh, to behave in ways that were the antithesis of scientific methods. Subterfuge, theft, and espionage were the ingredients of the Great Dinosaur Feud. Because students often enjoy controversy, as evidenced by popular television programs today, the authors use the controversy of the dinosaur feud to illustrate the human side of science, and the triumph of science in spite of inappropriate competition.
Carpinelli, Amy; Wandersee, James; Clary, Renee
Working as part of a joint expedition, scientists from India and the United States (including the well-known paleontologist Paul Sereno from the University of Chicago) announced this Wednesday that they discovered a new carnivorous dinosaur species in the Narmada River region in western India. Based on the bones located by the team, this newly discovered species of dinosaur was between 25-30 feet long, had a horn above its skull, and was relatively heavy. As part of a collaborative effort with Jeff Wilson of the University of Michigan, Sereno reconstructed the dinosaur skull and presented a model to their Indian colleagues at Punjab University. It is believed that the new species (named Rajasaurus narmadensis) roamed the Southern Hemisphere land masses that constitute modern-day Madagascar, Africa, and South America. Utilizing these new findings, scientists hope to shed additional light on the potential cause of the dinosaurs' extinction, a subject that is often debated within the community of paleontologists.The first link leads to a news article about this recent find from Newind.com. The second link will take visitors to another news article from the Chicago Sun-Times that talks about Sereno's latest find. The third link leads to Paul Sereno's personal Web site from the University of Chicago, and contains interesting information about his numerous expeditions and his various experiences as an educator and scientist. The fourth link leads to the Project Exploration Web site, an organization founded by Sereno and his wife, Gabrielle Lyon, that is dedicated to making science "accessible to the public-with a special focus on city kids and girls." Here visitors can learn about the groups' many outreach programs, along with reading about events sponsored by the organization. The fifth link leads to a fabulous Web site provided by the BBC geared towards young people that features fact files on dinosaurs, a detailed chronology of their time on Earth, and several interactive games. The sixth and final link leads to a brief piece from Scientific American.com that talks a bit about the controversy surrounding the cause of the mass extinction of dinosaurs approximately 65 million years ago.
Megaherbivorous dinosaur coexistence on the Late Cretaceous island continent of Laramidia has long puzzled researchers, owing to the mystery of how so many large herbivores (6–8 sympatric species, in many instances) could coexist on such a small (4–7 million km2) landmass. Various explanations have been put forth, one of which–dietary niche partitioning–forms the focus of this study. Here, we apply traditional morphometric methods to the skulls of megaherbivorous dinosaurs from the Dinosaur Park Formation (upper Campanian) of Alberta to infer the ecomorphology of these animals and to test the niche partitioning hypothesis. We find evidence for niche partitioning not only among contemporaneous ankylosaurs, ceratopsids, and hadrosaurids, but also within these clades at the family and subfamily levels. Consubfamilial ceratopsids and hadrosaurids differ insignificantly in their inferred ecomorphologies, which may explain why they rarely overlap stratigraphically: interspecific competition prevented their coexistence.
Mallon, Jordan C.; Anderson, Jason S.
Megaherbivorous dinosaur coexistence on the Late Cretaceous island continent of Laramidia has long puzzled researchers, owing to the mystery of how so many large herbivores (6-8 sympatric species, in many instances) could coexist on such a small (4-7 million km(2)) landmass. Various explanations have been put forth, one of which-dietary niche partitioning-forms the focus of this study. Here, we apply traditional morphometric methods to the skulls of megaherbivorous dinosaurs from the Dinosaur Park Formation (upper Campanian) of Alberta to infer the ecomorphology of these animals and to test the niche partitioning hypothesis. We find evidence for niche partitioning not only among contemporaneous ankylosaurs, ceratopsids, and hadrosaurids, but also within these clades at the family and subfamily levels. Consubfamilial ceratopsids and hadrosaurids differ insignificantly in their inferred ecomorphologies, which may explain why they rarely overlap stratigraphically: interspecific competition prevented their coexistence. PMID:23874409
Mallon, Jordan C; Anderson, Jason S
Dinosaurs arose in the early Triassic in the aftermath of the greatest mass extinction ever and became hugely successful in the Mesozoic. Their initial diversification is a classic example of a large-scale macroevolutionary change. Diversifications at such deep-time scales can now be dissected, modelled and tested. New fossils suggest that dinosaurs originated early in the Middle Triassic, during the recovery of life from the devastating Permo-Triassic mass extinction. Improvements in stratigraphic dating and a new suite of morphometric and comparative evolutionary numerical methods now allow a forensic dissection of one of the greatest turnovers in the history of life. Such studies mark a move from the narrative to the analytical in macroevolutionary research, and they allow us to begin to answer the proposal of George Gaylord Simpson, to explore adaptive radiations using numerical methods. PMID:24456985
Benton, Michael J; Forth, Jonathan; Langer, Max C
Variability of dinosaur eggshell assigned to Megaloolithidae, from the Upper Cretaceous of Suterranya (Upper Campanian-Early Maastrichtian, Catalonia, South-Central Pyrenees), is described and compared with other Catalan, Argentinean, French, and Indian contemporaneous eggshells. Two-variable statistics using eggshell thickness and external diameter of eggshell units show discontinuous heterogeneity in the studied sample. Highly significant, stronger heterogeneity is also observed when comparing eggshell
X. Panadés; I Blas
Eleven collagen peptide sequences recovered from chemical extracts of dinosaur bones were mapped onto molecular models of the vertebrate collagen fibril derived from extant taxa. The dinosaur peptides localized to fibril regions protected by the close packing of collagen molecules, and contained few acidic amino acids. Four peptides mapped to collagen regions crucial for cell-collagen interactions and tissue development. Dinosaur peptides were not represented in more exposed parts of the collagen fibril or regions mediating intermolecular cross-linking. Thus functionally significant regions of collagen fibrils that are physically shielded within the fibril may be preferentially preserved in fossils. These results show empirically that structure-function relationships at the molecular level could contribute to selective preservation in fossilized vertebrate remains across geological time, suggest a ‘preservation motif’, and bolster current concepts linking collagen structure to biological function. This non-random distribution supports the hypothesis that the peptides are produced by the extinct organisms and suggests a chemical mechanism for survival.
San Antonio, James D.; Schweitzer, Mary H.; Jensen, Shane T.; Kalluri, Raghu; Buckley, Michael; Orgel, Joseph P. R. O.
Eleven collagen peptide sequences recovered from chemical extracts of dinosaur bones were mapped onto molecular models of the vertebrate collagen fibril derived from extant taxa. The dinosaur peptides localized to fibril regions protected by the close packing of collagen molecules, and contained few acidic amino acids. Four peptides mapped to collagen regions crucial for cell-collagen interactions and tissue development. Dinosaur peptides were not represented in more exposed parts of the collagen fibril or regions mediating intermolecular cross-linking. Thus functionally significant regions of collagen fibrils that are physically shielded within the fibril may be preferentially preserved in fossils. These results show empirically that structure-function relationships at the molecular level could contribute to selective preservation in fossilized vertebrate remains across geological time, suggest a 'preservation motif', and bolster current concepts linking collagen structure to biological function. This non-random distribution supports the hypothesis that the peptides are produced by the extinct organisms and suggests a chemical mechanism for survival.
San Antonio, James D.; Schweitzer, Mary H.; Jensen, Shane T.; Kalluri, Raghu; Buckley, Michael; Orgel, Joseph P.R.O. (Harvard-Med); (IIT); (NCSU); (UPENN); (Manchester); (Orthovita)
Upper Triassic rocks in northwestern Argentina preserve the most complete record of dinosaurs before their rise to dominance in the Early Jurassic. Here, we describe a previously unidentified basal theropod, reassess its contemporary Eoraptor as a basal sauropodomorph, divide the faunal record of the Ischigualasto Formation with biozones, and bracket the formation with (40)Ar/(39)Ar ages. Some 230 million years ago in the Late Triassic (mid Carnian), the earliest dinosaurs were the dominant terrestrial carnivores and small herbivores in southwestern Pangaea. The extinction of nondinosaurian herbivores is sequential and is not linked to an increase in dinosaurian diversity, which weakens the predominant scenario for dinosaurian ascendancy as opportunistic replacement. PMID:21233386
Martinez, Ricardo N; Sereno, Paul C; Alcober, Oscar A; Colombi, Carina E; Renne, Paul R; Montañez, Isabel P; Currie, Brian S
The author's son has been an engineer since birth. He never asked "why" as a toddler, it was always "how's it work?" So that he wanted a STEM-based home education was no big surprise. In this article, the author considers what kind of curricula would work best for her complex kid.
This booklet describes how to make large two-dimensional models of dinosaur skeletons which can be effective teaching tools. Small laminated wood dinosaur models are enlarged, traced, and transferred to tri-wall cardboard (one-half inch thick) and cut out with a saber saw. Parts are then slotted and numbered for easy assembly. The result is a kit…
Jacob, Beth; Dempsey, Bill
Non-avian theropod dinosaurs with preserved integumentary coverings are becoming more common; but apart from the multiple specimens of Caudipteryx, which have true feathers, animals that are reasonably complete and entirely articulated that show these structures in relation to the body have not been reported. Here we report on an enigmatic small theropod dinosaur that is covered with filamentous feather-like structures
Qiang Ji; Mark A. Norell; Ke-Qin Gao; Shu-An Ji; Dong Ren
This informational text introduces students to the dinosaurs found near the polar regions and discusses the adaptations that allowed these dinosaurs to survive in a dark and cold environment. The text is written at a kindergarten through grade one reading level. This is a PDF containing the informational text and a glossary.
...Public Property 1 2009-07-01 2009-07-01 false Dinosaur National Monument. 7.63 Section 7.63 Parks, Forests...REGULATIONS, AREAS OF THE NATIONAL PARK SYSTEM Â§ 7.63 Dinosaur National Monument. (a) Commercial hauling....
...Public Property 1 2013-07-01 2013-07-01 false Dinosaur National Monument. 7.63 Section 7.63 Parks, Forests...REGULATIONS, AREAS OF THE NATIONAL PARK SYSTEM Â§ 7.63 Dinosaur National Monument. (a) Commercial hauling....
Designed to present interesting facts about science and to heighten the curiosity of primary age students, this book contains activities about the natural world and numerous black and white illustrations. Activities that focus on the dinosaur are organized into five sections. These include: (1) "Dinosaur Facts/Then and Now" (exploring bird and…
...Public Property 1 2010-07-01 2010-07-01 false Dinosaur National Monument. 7.63 Section 7.63 Parks, Forests...REGULATIONS, AREAS OF THE NATIONAL PARK SYSTEM Â§ 7.63 Dinosaur National Monument. (a) Commercial hauling....
The unearthing of a complete skull and skeleton of the early dinosaur Herrerasaurus ischigualastensis sheds light on the early evolution of dinosaurs. Discovered in the Upper Triassic Ischigualasto Formation of Argentina, the fossils show that Herrerasaurus, a primitive theropod, was an agile, bipedal predator with a short forelimb specialized for grasping and raking. The fossils clarify anatomical features of the
Paul C. Sereno; Fernando E. Novas
Understanding the genetic basis of the physical and behavioral traits that separate humans from other primates is a challenging but intriguing topic. The adaptive functions of the expansion and/or reduction in human brain size have long been explored. From a brain transcriptome project we have identified a KRAB-Zn finger protein-encoding gene (M003-A06) that has rapidly evolved since the human-chimpanzee separation. Quantitative RT-PCR analysis of different human tissues indicates that M003-A06 expression is enriched in the human fetal brain in addition to the fetal heart. Furthermore, analysis with use of immunofluorescence staining, neurosphere culturing and Western blotting indicates that the mouse ortholog of M003-A06, Zfp568, is expressed mainly in the embryonic stem (ES) cells and fetal as well as adult neural stem cells (NSCs). Conditional gene knockout experiments in mice demonstrates that Zfp568 is both an NSC maintaining- and a brain size-regulating gene. Significantly, molecular genetic analyses show that human M003-A06 consists of 2 equilibrated allelic types, H and C, one of which (H) is human-specific. Combined contemporary genotyping and database mining have revealed interesting genetic associations between the different genotypes of M003-A06 and the human head sizes. We propose that M003-A06 is likely one of the genes contributing to the uniqueness of the human brain in comparison to other higher primates.
Lai, Kuan-Yu; Lu, Li-Chen; Chen, Pau-Chung; Tsai, Shih-Feng; Wu, Chung-I; Hsieh, Wu-Shiun; Shen, Che-Kun James
Epigenetic silencing of retroviral transgene expression in pluripotent stem cells (PSC) and their differentiated progeny constitutes a major roadblock for PSC-based gene therapy. As ubiquitous chromatin opening elements (UCOEs) have been successfully employed to stabilize transgene expression in murine hematopoietic and pluripotent stem cells as well as their differentiated progeny, we here investigated UCOE activity in their human counterparts to establish a basis for future clinical application of the element. To this end, we demonstrate profound anti-silencing activity of the A2UCOE in several human iPS and ES cell lines including their progeny obtained upon directed cardiac or hematopoietic differentiation. We also provide evidence for A2UCOE activity in murine iPSC-derived hepatocyte-like cells, thus establishing efficacy of the element in cells of different germ layers. Finally, we investigated combinations of the A2UCOE with viral promoter/enhancer elements again demonstrating profound stabilization of transgene expression. In all these settings the effect of the A2UCOE was associated with strongly reduced promoter DNA-methylation. Thus, our data clearly support the concept of the A2UCOE as a generalized strategy to prevent epigenetic silencing in PSC and their differentiated progeny and strongly favors its application to stabilize transgene expression in PSC-based cell and gene therapy approaches. PMID:24290698
Ackermann, Mania; Lachmann, Nico; Hartung, Susann; Eggenschwiler, Reto; Pfaff, Nils; Happle, Christine; Mucci, Adele; Göhring, Gudrun; Niemann, Heiner; Hansen, Gesine; Schambach, Axel; Cantz, Tobias; Zweigerdt, Robert; Moritz, Thomas
The rise of dinosaurs was a major event in vertebrate history, but the timing of the origin and early diversification of the group remain poorly constrained. Here, we describe Nyasasaurus parringtoni gen. et sp. nov., which is identified as either the earliest known member of, or the sister–taxon to, Dinosauria. Nyasasaurus possesses a unique combination of dinosaur character states and an elevated growth rate similar to that of definitive early dinosaurs. It demonstrates that the initial dinosaur radiation occurred over a longer timescale than previously thought (possibly 15 Myr earlier), and that dinosaurs and their immediate relatives are better understood as part of a larger Middle Triassic archosauriform radiation. The African provenance of Nyasasaurus supports a southern Pangaean origin for Dinosauria.
Nesbitt, Sterling J.; Barrett, Paul M.; Werning, Sarah; Sidor, Christian A.; Charig, Alan J.
The rise of dinosaurs was a major event in vertebrate history, but the timing of the origin and early diversification of the group remain poorly constrained. Here, we describe Nyasasaurus parringtoni gen. et sp. nov., which is identified as either the earliest known member of, or the sister-taxon to, Dinosauria. Nyasasaurus possesses a unique combination of dinosaur character states and an elevated growth rate similar to that of definitive early dinosaurs. It demonstrates that the initial dinosaur radiation occurred over a longer timescale than previously thought (possibly 15 Myr earlier), and that dinosaurs and their immediate relatives are better understood as part of a larger Middle Triassic archosauriform radiation. The African provenance of Nyasasaurus supports a southern Pangaean origin for Dinosauria. PMID:23221875
Nesbitt, Sterling J; Barrett, Paul M; Werning, Sarah; Sidor, Christian A; Charig, Alan J
It was traditionally thought that the oldest known dinosaur assemblages were not diverse, and that their early diversification and numerical dominance over other tetrapods occurred during the latest Triassic. However, new evidence gathered from the lower levels of the Ischigualasto Fm. of Argentina challenges this view. New dinosaur remains are described from this stratigraphical unit, including the new species Chromogisaurus
Martin D. Ezcurra
The objective of the present study is to determine whether di(2-ethylhexyl) phthalate (DEHP) exposure at adulthood increases rat Leydig cell number and to investigate the possible mechanism. 90-day-old Long-Evans rats were randomly divided into 3 groups, and were gavaged with the corn oil (control) or 10 or 750 mg/kg DEHP daily for 7 days, and then received an intraperitoneal injection of 75 mg/kg ethane dimethanesulfonate (EDS) to eliminate Leydig cells. Serum testosterone concentrations were assessed by RIA, and the mRNA levels of Leydig cell genes were measured by qPCR. EDS eliminated all Leydig cells in the control testis on day 4 post-EDS, as judged by undetectable serum testosterone level and no 3?-hydroxysteroid dehydrogenase positive (3?-HSD(pos)) cells in the interstitium. However, in DEHP-treated groups, there were detectable serum testosterone concentrations and some oval-shaped 3?-HSD(pos) cells in the interstitium. These 3?-HSD(pos) cells were not stained by the antibody against 11?-hydroxysteroid dehydrogenase 1 (11?-HSD1), a marker for Leydig cells at a more advanced stage. The disappearance of mRNAs of Leydig cell biomarkers including Lhcgr, Cyp11a1, Cyp17a1, Insl3 and Hsd11b1 in the control testis was observed on day 4 post-EDS. However, there were detectable concentrations of Lhcgr, Cyp11a1 and Cyp17a1 mRNAs but undetectable concentrations of Insl3, Hsd17b3 and Hsd11b1 in the DEHP-treated testes, indicating that these 3?-HSD(pos) cells were newly formed progenitor Leydig cells. The mRNA level for nestin (Nes, biomarker for stem Leydig cells) was significantly increased in the control testis on day 4 post-EDS, but not in the DEHP treated testes, suggesting that these nestin positive stem cells were differentiated into progenitor Leydig cells in the DEHP-treated testes. The present study suggests that DEHP increases the differentiation of stem cells into progenitor Leydig cells. PMID:23391632
Guo, Jingjing; Li, Xing-Wang; Liang, Yong; Ge, Yufei; Chen, Xiaomin; Lian, Qing-Quan; Ge, Ren-Shan
An embryonic skeleton of a nonavian theropod dinosaur was found preserved in an egg from Upper Cretaceous rocks in the Gobi Desert of Mongolia. Cranial features identify the embryo as a member of Oviraptoridae. Two embryo-sized skulls of dromaeosaurids, similar to that of Velociraptor, were also recovered in the nest. The eggshell microstructure is similar to that of ratite birds
Mark A. Norell; James M. Clark; Dashzeveg Demberelyin; Barsbold Rhinchen; Luis M. Chiappe; Amy R. Davidson; Malcolm C. McKenna; Perle Altangerel; Michael J. Novacek
Lamin A (LMNA)-linked lipodystrophies may be either genetic (associated with LMNA mutations) or acquired (associated with the use of human immunodeficiency virus protease inhibitors [PIs]), and in both cases they share clinical features such as anomalous distribution of body fat or generalized loss of adipose tissue, metabolic alterations, and early cardiovascular complications. Both LMNA-linked lipodystrophies are characterized by the accumulation of the lamin A precursor prelamin A. The pathological mechanism by which prelamin A accumulation induces the lipodystrophy associated phenotypes remains unclear. Since the affected tissues in these disorders are of mesenchymal origin, we have generated an LMNA-linked experimental model using human mesenchymal stem cells treated with a PI, which recapitulates the phenotypes observed in patient biopsies. This model has been demonstrated to be a useful tool to unravel the pathological mechanism of the LMNA-linked lipodystrophies, providing an ideal system to identify potential targets to generate new therapies for drug discovery screening. We report for the first time that impaired adipogenesis is a consequence of the interaction between accumulated prelamin A and Sp1 transcription factor, sequestration of which results in altered extracellular matrix gene expression. In fact, our study shows a novel, essential, and finely tuned role for Sp1 in adipose lineage differentiation in human mesenchymal stem cells. These findings define a new physiological experimental model to elucidate the pathological mechanisms LMNA-linked lipodystrophies, creating new opportunities for research and treatment not only of LMNA-linked lipodystrophies but also of other adipogenesis-associated metabolic diseases.
Ruiz de Eguino, Garbine; Infante, Arantza; Schlangen, Karin; Aransay, Ana M.; Fullaondo, Ane; Soriano, Mario; Garcia-Verdugo, Jose Manuel; Martin, Angel G.
Ornithischia (the 'bird-hipped' dinosaurs) encompasses bipedal, facultative quadrupedal and quadrupedal taxa. Primitive ornithischians were small bipeds, but large body size and obligate quadrupedality evolved independently in all major ornithischian lineages. Numerous pelvic and hind limb features distinguish ornithischians from the majority of other non-avian dinosaurs. However, some of these features, notably a retroverted pubis and elongate iliac preacetabular process, appeared convergently in maniraptoran theropods, and were inherited by their avian descendants. During maniraptoran/avian evolution these pelvic modifications led to significant changes in the functions of associated muscles, involving alterations to the moment arms and the activation patterns of pelvic musculature. However, the functions of these features in ornithischians and their influence on locomotion have not been tested and remain poorly understood. Here, we provide quantitative tests of bipedal ornithischian muscle function using computational modelling to estimate 3D hind limb moment arms for the most complete basal ornithischian, Lesothosaurus diagnosticus. This approach enables sensitivity analyses to be carried out to explore the effects of uncertainties in muscle reconstructions of extinct taxa, and allows direct comparisons to be made with similarly constructed models of other bipedal dinosaurs. This analysis supports some previously proposed qualitative inferences of muscle function in basal ornithischians. However, more importantly, this work highlights ambiguities in the roles of certain muscles, notably those inserting close to the hip joint. Comparative analysis reveals that moment arm polarities and magnitudes in Lesothosaurus, basal tetanuran theropods and the extant ostrich are generally similar. However, several key differences are identified, most significantly in comparisons between the moment arms of muscles associated with convergent osteological features in ornithischians and birds. Craniad migration of the iliofemoralis group muscles in birds correlates with increased leverage and use of medial femoral rotation to counter stance phase adduction moments at the hip. In Lesothosaurus the iliofemoralis group maintains significantly higher moment arms for abduction, consistent with the hip abduction mode of lateral limb support hypothesized for basal dinosaurs. Sensitivity analysis highlights ambiguity in the role of musculature associated with the retroverted pubis (puboischiofemoralis externus group) in ornithischians. However, it seems likely that this musculature may have predominantly functioned similarly to homologous muscles in extant birds, activating during the swing phase to adduct the lower limb through lateral rotation of the femur. Overall the results suggest that locomotor muscle leverage in Lesothosaurus (and by inference basal ornithischians in general) was more similar to that of other non-avian dinosaurs than the ostrich, representing what was probably the basal dinosaur condition. This work thereby contradicts previous hypotheses of ornithischian-bird functional convergence. PMID:22211275
Bates, Karl T; Maidment, Susannah C R; Allen, Vivian; Barrett, Paul M
The oldest theropod dinosaurs are known from the Carnian of Argentina and Brazil. However, the evolutionary diversification of this group after its initial radiation but prior to the Triassic–Jurassic boundary is still poorly understood because of a sparse fossil record near that boundary. Here, we report on a new basal theropod, Daemonosaurus chauliodus gen. et sp. nov., from the latest Triassic ‘siltstone member’ of the Chinle Formation of the Coelophysis Quarry at Ghost Ranch, New Mexico. Based on a comprehensive phylogenetic analysis, Daemonosaurus is more closely related to coeval neotheropods (e.g. Coelophysis bauri) than to Herrerasauridae and Eoraptor. The skeletal structure of Daemonosaurus and the recently discovered Tawa bridge a morphological gap between Eoraptor and Herrerasauridae on one hand and neotheropods on the other, providing additional support for the theropod affinities of both Eoraptor and Herrerasauridae and demonstrating that lineages from the initial radiation of Dinosauria persisted until the end of the Triassic. Various features of the skull of Daemonosaurus, including the procumbent dentary and premaxillary teeth and greatly enlarged premaxillary and anterior maxillary teeth, clearly set this taxon apart from coeval neotheropods and demonstrate unexpected disparity in cranial shape among theropod dinosaurs just prior to the end of the Triassic.
Sues, Hans-Dieter; Nesbitt, Sterling J.; Berman, David S; Henrici, Amy C.
Convergent morphologies are thought to indicate functional similarity, arising because of a limited number of evolutionary or developmental pathways. Extant taxa displaying convergent morphologies are used as analogues to assess function in extinct taxa with similar characteristics. However, functional studies of extant taxa have shown that functional similarity can arise from differing morphologies, calling into question the paradigm that form and function are closely related. We test the hypothesis that convergent skeletal morphology indicates functional similarity in the fossil record using ornithischian dinosaurs. The rare transition from bipedality to quadrupedality occurred at least three times independently in this clade, resulting in a suite of convergent osteological characteristics. We use homology rather than analogy to provide an independent line of evidence about function, reconstructing soft tissues using the extant phylogenetic bracket and applying biomechanical concepts to produce qualitative assessments of muscle leverage. We also optimize character changes to investigate the sequence of character acquisition. Different lineages of quadrupedal ornithischian dinosaur stood and walked differently from each other, falsifying the hypothesis that osteological convergence indicates functional similarity. The acquisition of features correlated with quadrupedalism generally occurs in the same order in each clade, suggesting underlying developmental mechanisms that act as evolutionary constraints.
Maidment, Susannah C. R.; Barrett, Paul M.
What explains why some groups of organisms, like birds, are so species rich? And what explains their extraordinary ecological diversity, ranging from large, flightless birds to small migratory species that fly thousand of kilometers every year? These and similar questions have spurred great interest in adaptive radiation, the diversification of ecological traits in a rapidly speciating group of organisms. Although the initial formulation of modern concepts of adaptive radiation arose from consideration of the fossil record, rigorous attempts to identify adaptive radiation in the fossil record are still uncommon. Moreover, most studies of adaptive radiation concern groups that are less than 50 million years old. Thus, it is unclear how important adaptive radiation is over temporal scales that span much larger portions of the history of life. In this issue, Benson et al. test the idea of a “deep-time” adaptive radiation in dinosaurs, compiling and using one of the most comprehensive phylogenetic and body-size datasets for fossils. Using recent phylogenetic statistical methods, they find that in most clades of dinosaurs there is a strong signal of an “early burst” in body-size evolution, a predicted pattern of adaptive radiation in which rapid trait evolution happens early in a group's history and then slows down. They also find that body-size evolution did not slow down in the lineage leading to birds, hinting at why birds survived to the present day and diversified. This paper represents one of the most convincing attempts at understanding deep-time adaptive radiations.
Moen, Daniel; Morlon, Helene
What explains why some groups of organisms, like birds, are so species rich? And what explains their extraordinary ecological diversity, ranging from large, flightless birds to small migratory species that fly thousand of kilometers every year? These and similar questions have spurred great interest in adaptive radiation, the diversification of ecological traits in a rapidly speciating group of organisms. Although the initial formulation of modern concepts of adaptive radiation arose from consideration of the fossil record, rigorous attempts to identify adaptive radiation in the fossil record are still uncommon. Moreover, most studies of adaptive radiation concern groups that are less than 50 million years old. Thus, it is unclear how important adaptive radiation is over temporal scales that span much larger portions of the history of life. In this issue, Benson et al. test the idea of a "deep-time" adaptive radiation in dinosaurs, compiling and using one of the most comprehensive phylogenetic and body-size datasets for fossils. Using recent phylogenetic statistical methods, they find that in most clades of dinosaurs there is a strong signal of an "early burst" in body-size evolution, a predicted pattern of adaptive radiation in which rapid trait evolution happens early in a group's history and then slows down. They also find that body-size evolution did not slow down in the lineage leading to birds, hinting at why birds survived to the present day and diversified. This paper represents one of the most convincing attempts at understanding deep-time adaptive radiations. PMID:24802950
Moen, Daniel; Morlon, Hélène
Abelisaurids are a clade of large, bizarre predatory dinosaurs, most notable for their high, short skulls and extremely reduced forelimbs. They were common in Gondwana during the Cretaceous, but exceedingly rare in the Northern Hemisphere. The oldest definitive abelisaurids so far come from the late Early Cretaceous of South America and Africa, and the early evolutionary history of the clade is still poorly known. Here, we report a new abelisaurid from the Middle Jurassic of Patagonia, Eoabelisaurus mefi gen. et sp. nov., which predates the so far oldest known secure member of this lineage by more than 40 Myr. The almost complete skeleton reveals the earliest evolutionary stages of the distinctive features of abelisaurids, such as the modification of the forelimb, which started with a reduction of the distal elements. The find underlines the explosive radiation of theropod dinosaurs in the Middle Jurassic and indicates an unexpected diversity of ceratosaurs at that time. The apparent endemism of abelisauroids to southern Gondwana during Pangean times might be due to the presence of a large, central Gondwanan desert. This indicates that, apart from continent-scale geography, aspects such as regional geography and climate are important to reconstruct the biogeographical history of Mesozoic vertebrates.
Pol, Diego; Rauhut, Oliver W. M.
The oldest theropod dinosaurs are known from the Carnian of Argentina and Brazil. However, the evolutionary diversification of this group after its initial radiation but prior to the Triassic-Jurassic boundary is still poorly understood because of a sparse fossil record near that boundary. Here, we report on a new basal theropod, Daemonosaurus chauliodus gen. et sp. nov., from the latest Triassic 'siltstone member' of the Chinle Formation of the Coelophysis Quarry at Ghost Ranch, New Mexico. Based on a comprehensive phylogenetic analysis, Daemonosaurus is more closely related to coeval neotheropods (e.g. Coelophysis bauri) than to Herrerasauridae and Eoraptor. The skeletal structure of Daemonosaurus and the recently discovered Tawa bridge a morphological gap between Eoraptor and Herrerasauridae on one hand and neotheropods on the other, providing additional support for the theropod affinities of both Eoraptor and Herrerasauridae and demonstrating that lineages from the initial radiation of Dinosauria persisted until the end of the Triassic. Various features of the skull of Daemonosaurus, including the procumbent dentary and premaxillary teeth and greatly enlarged premaxillary and anterior maxillary teeth, clearly set this taxon apart from coeval neotheropods and demonstrate unexpected disparity in cranial shape among theropod dinosaurs just prior to the end of the Triassic. PMID:21490016
Sues, Hans-Dieter; Nesbitt, Sterling J; Berman, David S; Henrici, Amy C
Background Four main dinosaur sites have been investigated in latest Cretaceous deposits from the Amur/Heilongjiang Region: Jiayin and Wulaga in China (Yuliangze Formation), Blagoveschensk and Kundur in Russia (Udurchukan Formation). More than 90% of the bones discovered in these localities belong to hollow-crested lambeosaurine saurolophids, but flat-headed saurolophines are also represented: Kerberosaurus manakini at Blagoveschensk and Wulagasaurus dongi at Wulaga. Methodology/Principal Findings Herein we describe a new saurolophine dinosaur, Kundurosaurus nagornyi gen. et sp. nov., from the Udurchukan Formation (Maastrichtian) of Kundur, represented by disarticulated cranial and postcranial material. This new taxon is diagnosed by four autapomorphies. Conclusions/Significance A phylogenetic analysis of saurolophines indicates that Kundurosaurus nagornyi is nested within a rather robust clade including Edmontosaurus spp., Saurolophus spp., and Prosaurolophus maximus, possibly as a sister-taxon for Kerberosaurus manakini also from the Udurchukan Formation of Far Eastern Russia. The high diversity and mosaic distribution of Maastrichtian hadrosaurid faunas in the Amur-Heilongjiang region are the result of a complex palaeogeographical history and imply that many independent hadrosaurid lineages dispersed without any problem between western America and eastern Asia at the end of the Cretaceous.
Godefroit, Pascal; Bolotsky, Yuri L.; Lauters, Pascaline
Transcription factors are key regulators of hematopoietic stem cells (HSCs) and act through their ability to bind DNA and impact on gene transcription. Their functions are interpreted in the complex landscape of chromatin, but current knowledge on how this is achieved is very limited. C/EBP? is an important transcriptional regulator of hematopoiesis, but its potential functions in HSCs have remained elusive. Here we report that C/EBP? serves to protect adult HSCs from apoptosis and to maintain their quiescent state. Consequently, deletion of Cebpa is associated with loss of self-renewal and HSC exhaustion. By combining gene expression analysis with genome-wide assessment of C/EBP? binding and epigenetic configurations, we show that C/EBP? acts to modulate the epigenetic states of genes belonging to molecular pathways important for HSC function. Moreover, our data suggest that C/EBP? acts as a priming factor at the HSC level where it actively promotes myeloid differentiation and counteracts lymphoid lineage choice. Taken together, our results show that C/EBP? is a key regulator of HSC biology, which influences the epigenetic landscape of HSCs in order to balance different cell fate options.
Hasemann, Marie S.; Lauridsen, Felicia K. B.; Waage, Johannes; Jakobsen, Janus S.; Frank, Anne-Katrine; Schuster, Mikkel B.; Rapin, Nicolas; Bagger, Frederik O.; Hoppe, Philipp S.; Schroeder, Timm; Porse, Bo T.
Current protocols for in vitro differentiation of human induced pluripotent stem cells (hiPSCs) to generate dopamine (DA) neurons are laborious and time-expensive. In order to accelerate the overall process, we have established a fast protocol by expressing the developmental transcription factors ASCL1, NURR1, and LMX1A. With this method, we were able to generate mature and functional dopaminergic neurons in as few as 21 days, skipping all the intermediate steps for inducting and selecting embryoid bodies and rosette-neural precursors. Strikingly, the resulting neuronal conversion process was very proficient, with an overall efficiency that was more than 93% of all the coinfected cells. hiPSC-derived DA neurons expressed all the critical molecular markers of the DA molecular machinery and exhibited sophisticated functional features including spontaneous electrical activity and dopamine release. This one-step protocol holds important implications for in vitro disease modeling and is particularly amenable for exploitation in high-throughput screening protocols.
Theka, Ilda; Caiazzo, Massimiliano; Dvoretskova, Elena; Leo, Damiana; Ungaro, Federica; Curreli, Sebastiano; Manago, Francesca; Dell'Anno, Maria Teresa; Pezzoli, Gianni; Gainetdinov, Raul R.; Dityatev, Alexander
This activity illustrates the carbon cycle using an age-appropriate hook, and it includes thorough discussion and hands-on experimentation. Students learn about the geological (ancient) carbon cycle, they investigate the role of dinosaurs in the carbon cycle, and the eventual storage of carbon in the form of chalk. Students discover how the carbon cycle has been occurring for millions of years and is necessary for life on Earth. Finally, they may extend their knowledge to the concept of global warming and how engineers are working to understand the carbon cycle and reduce harmful carbon dioxide emissions.
In 1868 Thomas Huxley first proposed that dinosaurs were the direct ancestors of birds and subsequent analyses have identified a suite of ‘avian’ characteristics in theropod dinosaurs. Ossified uncinate processes are found in most species of extant birds and also occur in extinct non-avian maniraptoran dinosaurs. Their presence in these dinosaurs represents another morphological character linking them to Aves, and further supports the presence of an avian-like air-sac respiratory system in theropod dinosaurs, prior to the evolution of flight. Here we report a phylogenetic analysis of the presence of uncinate processes in Aves and non-avian maniraptoran dinosaurs indicating that these were homologous structures. Furthermore, recent work on Canada geese has demonstrated that uncinate processes are integral to the mechanics of avian ventilation, facilitating both inspiration and expiration. In extant birds, uncinate processes function to increase the mechanical advantage for movements of the ribs and sternum during respiration. Our study presents a mechanism whereby uncinate processes, in conjunction with lateral and ventral movements of the sternum and gastral basket, affected avian-like breathing mechanics in extinct non-avian maniraptoran dinosaurs.
Codd, Jonathan R; Manning, Phillip L; Norell, Mark A; Perry, Steven F
Background Wheat leaf rust (Puccinia triticina Eriks; Pt) and stem rust fungi (P. graminis f.sp. tritici; Pgt) are significant economic pathogens having similar host ranges and life cycles, but different alternate hosts. The Pt genome, currently estimated at 135 Mb, is significantly larger than Pgt, at 88 Mb, but the reason for the expansion is unknown. Three genomic loci of Pt conserved proteins were characterized to gain insight into gene content, genome complexity and expansion. Results A bacterial artificial chromosome (BAC) library was made from P. triticina race 1, BBBD and probed with Pt homologs of genes encoding two predicted Pgt secreted effectors and a DNA marker mapping to a region of avirulence. Three BACs, 103 Kb, 112 Kb, and 166 Kb, were sequenced, assembled, and open reading frames were identified. Orthologous genes were identified in Pgt and local conservation of gene order (microsynteny) was observed. Pairwise protein identities ranged from 26 to 99%. One Pt BAC, containing a RAD18 ortholog, shares syntenic regions with two Pgt scaffolds, which could represent both haplotypes of Pgt. Gene sequence is diverged between the species as well as within the two haplotypes. In all three BAC clones, gene order is locally conserved, however, gene shuffling has occurred relative to Pgt. These regions are further diverged by differing insertion loci of LTR-retrotransposon, Gypsy, Copia, Mutator, and Harbinger mobile elements. Uncharacterized Pt open reading frames were also found; these proteins are high in lysine and similar to multiple proteins in Pgt. Conclusions The three Pt loci are conserved in gene order, with a range of gene sequence divergence. Conservation of predicted haustoria expressed secreted protein genes between Pt and Pgt is extended to the more distant poplar rust, Melampsora larici-populina. The loci also reveal that genome expansion in Pt is in part due to higher occurrence of repeat-elements in this species.
Describes an activity in which students construct relationships between their leg lengths, stride lengths, and movements in order to estimate the speeds of the dinosaurs that made various fossilized tracks. (WRM)
Caton, Randall; Otts, Charlotte
This informational text introduces students to the dinosaurs found near the polar regions and discusses the adaptations that allowed these dinosaurs to survive in a dark and cold environment. The text is written at a kindergarten through grade one reading level. This is an onscreen version that contains recorded narration allowing students to listen to the text as they read along. Highlighted vocabulary words have individually recorded definitions heard by clicking on the links.
This informational text introduces students to the dinosaurs found near the polar regions and discusses the adaptations that allowed these dinosaurs to survive in a dark and cold environment. The text is written at a grade two through grade three reading level. This version is a full-color PDF that can be printed, cut and folded to form a book. Each book contains color photographs and illustrations.
This informational text introduces students to the dinosaurs found near the polar regions and discusses the adaptations that allowed these dinosaurs to survive in a dark and cold environment. The text is written at a kindergarten through grade one reading level. This version is a full-color PDF that can be printed, cut and folded to form a book. Each book contains color photographs and illustrations.
This informational text introduces students to the dinosaurs found near the polar regions and discusses the adaptations that allowed these dinosaurs to survive in a dark and cold environment. The text is written at a grade two through grade three reading level. This is an onscreen version that contains recorded narration allowing students to listen to the text as they read along. Highlighted vocabulary words have individually recorded definitions heard by clicking on the links.
LARGE carnivorous animals, the top members of the trophic chain, are rare, and flesh-eating dinosaurs were rarer still. For years the only known giant theropods were Tyrannosaums rex1 and the poorly known Deinocheirus mirificus2, both from the Northern Hemisphere, but many important new dinosaurs have been dis-covered in the Southern Hemisphere during the past decade, con-siderably increasing our knowledge of
Rodolfo A. Coria; Leonardo Salgado
We have identified a very early stage of B lineage cells in the CD45R (B220)+CD24 (HSA)? pre-pro-B fraction of mouse bone marrow delineated by expression of AA4.1, a molecule found on stem cells and early B lineage cells. These cells are B lineage precursors based on their capacity to generate B lineage cells rapidly in stromal-dependent culture and their expression
Yue-Sheng Li; Robert Wasserman; Kyoko Hayakawa; Richard R. Hardy
The record of dinosaur body-fossils in the Brazilian Mesozoic is restricted to the Triassic of Rio Grande do Sul and Cretaceous of various parts of the country. This includes 21 named species, two of which were regarded as nomina dubia, and 19 consensually assigned to Dinosauria. Additional eight supraspecific taxa have been identified based on fragmentary specimens and numerous dinosaur footprints known in Brazil. In fact, most Brazilian specimens related to dinosaurs are composed of isolated teeth and vertebrae. Despite the increase of fieldwork during the last decade, there are still no dinosaur body-fossils of Jurassic age and the evidence of ornithischians in Brazil is very limited. Dinosaur faunas from this country are generally correlated with those from other parts of Gondwana throughout the Mesozoic. During the Late Triassic, there is a close correspondence to Argentina and other south-Pangaea areas. Mid-Cretaceous faunas of northeastern Brazil resemble those of coeval deposits of North Africa and Argentina. Southern hemisphere spinosaurids are restricted to Africa and Brazil, whereas abelisaurids are still unknown in the Early Cretaceous of the latter. Late Cretaceous dinosaur assemblages of south-central Brazil are endemic only to genus or, more conspicuously, to species level, sharing closely related taxa with Argentina, Madagascar, Indo-Pakistan and, to a lesser degree, continental Africa. PMID:21437375
Bittencourt, Jonathas S; Langer, Max C
Six independent lines of evidence point to the existence of heme-containing compounds and/or hemoglobin breakdown products in extracts of trabecular tissues of the large theropod dinosaur Tyrannosaurus rex. These include signatures from nuclear magnetic resonance and electron spin resonance that indicate the presence of a paramagnetic compound consistent with heme. In addition, UV/visible spectroscopy and high performance liquid chromatography data are consistent with the Soret absorbance characteristic of this molecule. Resonance Raman profiles are also consistent with a modified heme structure. Finally, when dinosaurian tissues were extracted for protein fragments and were used to immunize rats, the resulting antisera reacted positively with purified avian and mammalian hemoglobins. The most parsimonious explanation of this evidence is the presence of blood-derived hemoglobin compounds preserved in the dinosaurian tissues.
Schweitzer, Mary H.; Marshall, Mark; Carron, Keith; Bohle, D. Scott; Busse, Scott C.; Arnold, Ernst V.; Barnard, Darlene; Horner, J. R.; Starkey, Jean R.
Background Tyrannosaurus rex and other tyrannosaurid fossils often display multiple, smooth-edged full-thickness erosive lesions on the mandible, either unilaterally or bilaterally. The cause of these lesions in the Tyrannosaurus rex specimen FMNH PR2081 (known informally by the name ‘Sue’) has previously been attributed to actinomycosis, a bacterial bone infection, or bite wounds from other tyrannosaurids. Methodology/Principal Findings We conducted an extensive survey of tyrannosaurid specimens and identified ten individuals with full-thickness erosive lesions. These lesions were described, measured and photographed for comparison with one another. We also conducted an extensive survey of related archosaurs for similar lesions. We show here that these lesions are consistent with those caused by an avian parasitic infection called trichomonosis, which causes similar abnormalities on the mandible of modern birds, in particular raptors. Conclusions/Significance This finding represents the first evidence for the ancient evolutionary origin of an avian transmissible disease in non-avian theropod dinosaurs. It also provides a valuable insight into the palaeobiology of these now extinct animals. Based on the frequency with which these lesions occur, we hypothesize that tyrannosaurids were commonly infected by a Trichomonas gallinae-like protozoan. For tyrannosaurid populations, the only non-avian dinosaur group that show trichomonosis-type lesions, it is likely that the disease became endemic and spread as a result of antagonistic intraspecific behavior, consumption of prey infected by a Trichomonas gallinae-like protozoan and possibly even cannibalism. The severity of trichomonosis-related lesions in specimens such as Tyrannosaurus rex FMNH PR2081 and Tyrannosaurus rex MOR 980, strongly suggests that these animals died as a direct result of this disease, mostly likely through starvation.
Wolff, Ewan D. S.; Salisbury, Steven W.; Horner, John R.; Varricchio, David J.
The succession of Maastrichtian deposits in the Tremp basin (South Pyrenean area, Spain) has provided long sections, with numerous dinosaur sites found in the Arén and Tremp Formations. The dinosaur record consists on titanosaur sauropods, dromaeosaurid theropods, hadrosaur ornithopods (including lambeosaurines) and nodosaurid ankylosaurians. Correlation of the sections enabled a clear succession of dinosaur localities to be established and thereby
Violeta Riera; Oriol Oms; Rodrigo Gaete; Àngel Galobart
The investigation of cell lineages and clonal organization in tissues is facilitated by techniques that allow labelling of clonal cell lineages. Here, we describe a novel transgenic mouse that allows clonal cell lineages to be traced in virtually any tissue. A green fluorescent cell lineage is generated by a random mutation at an enhanced green fluorescent protein gene that carries a premature stop codon, ensuring clonality. The transgenic system allows efficient detection of mutations and stem-cell fate mapping in the epidermis using live mice, as well as in the kidney and liver post-mortem. Cell lineages that descended from single epidermal stem cells were found to be capable of generating three adjacent corneocytes using the system, providing evidence for horizontal migration of epidermal cells between epidermal proliferative units (EPUs), in contrast to the classical EPU model. The transgenic mouse system is expected to provide a novel tool for stem-cell lineage studies.
Ro, Simon; Rannala, Bruce
Improved outcome with hematopoietic stem cell transplantation in a poor prognostic subgroup of patients with mixed-lineage-leukemia-rearranged acute leukemia: Results from a prospective, multi-center study.
The purpose of this study is to define the role for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in mixed-lineage-leukemia (MLL)-rearranged acute leukemia, which is now poorly understood. A prospective, multi-center cohort study to determine whether allo-HSCT could decrease relapse rates and improve long-term survival of MLL+ leukemia patients was performed. Fifty-six consecutive patients diagnosed with MLL-rearranged acute leukemia undergoing allo-HSCT from two transplant centers in China were enrolled between October 2007 and October 2012. The trial was registered at www.chictr.org as # ChiCTR-ONC-12002739. The incidences of grades II to IV acute graft versus host disease (aGVHD) and of grades III and IV aGVHD were 28.8% (CI, 16.87-40.8%), and 14.2% (CI, 5.4-23.0%), respectively. The cumulative incidences for chronic GVHD (cGVHD) at 2 years after HSCT were 35.2% (CI, 21.2-49.2%). Up to April 30, 2013, 12 patients had relapsed and 11 died from relapse, and 37 patients were still alive without disease recurrence. The relapse and NRM rates at 3 years were 25.3% (CI, 12.7-37.9%) and 18.0% (CI, 2.6-33.4%), respectively. The probalities of overall survival and leukemia free survival were 61.8% (CI, 46.0-77.6%) and 56.3% (CI, 38.1-74.5%) at 3 years, respectively. Patients transplanted during their hematological first complete remission (CR1) had a lower relapse rate (17.9% vs. 48.1%, P = 0.03) compared with patients transplanted beyond CR1. The median overall survival for the 29 patients not receiving allo-HSCT during the study period was 145 days from diagnosis. This study showed that allo-HSCT could be a valuable treatment choice for MLL+ acute leukemia. PMID:24122923
Wang, Yu; Yu, Wang; Liu, Qi-Fa; Qi-Fa, Liu; Qin, Ya-Zhen; Ya-Zhen, Qin; Liu, Dai-Hong; Dai-Hong, Liu; Xu, Lan-Ping; Lan-Ping, Xu; Jiang, Bin; Bin, Jiang; Jiang, Qian; Qian, Jiang; Dai, Min; Min, Dai; Yu, Si-Jian; Si-Jian, Yu; Jiang, Xin-Miao; Xin-Miao, Jiang; Liu, Yan-Rong; Yan-Rong, Liu; Huang, Xiao-Jun; Xiao-Jun, Huang
Physical cues from the extracellular environment influence the lineage commitment of stem cells. Now, experiments on human mesenchymal stem cells cultured on photodegradable hydrogels show that the cells' fate can also be determined by past physical environments.
Eyckmans, Jeroen; Chen, Christopher S.
Spectacular fossils from the Early Cretaceous Jehol Group of northeastern China have greatly expanded our knowledge of the diversity and palaeobiology of dinosaurs and early birds, and contributed to our understanding of the origin of birds, of flight, and of feathers. Pennaceous (vaned) feathers and integumentary filaments are preserved in birds and non-avian theropod dinosaurs, but little is known of their microstructure. Here we report that melanosomes (colour-bearing organelles) are not only preserved in the pennaceous feathers of early birds, but also in an identical manner in integumentary filaments of non-avian dinosaurs, thus refuting recent claims that the filaments are partially decayed dermal collagen fibres. Examples of both eumelanosomes and phaeomelanosomes have been identified, and they are often preserved in life position within the structure of partially degraded feathers and filaments. Furthermore, the data here provide empirical evidence for reconstructing the colours and colour patterning of these extinct birds and theropod dinosaurs: for example, the dark-coloured stripes on the tail of the theropod dinosaur Sinosauropteryx can reasonably be inferred to have exhibited chestnut to reddish-brown tones. PMID:20107440
Zhang, Fucheng; Kearns, Stuart L; Orr, Patrick J; Benton, Michael J; Zhou, Zhonghe; Johnson, Diane; Xu, Xing; Wang, Xiaolin
The dinosaur eggs of southern France occur in continental, fine-grained red-beds, rich in carbonate. The last eggs in the region occur in the magnetic polarity interval 30 normal. Estimates of the accumulation rate of these sediments on the basis of the magneto-stratigraphy leads to placement of the time of disappearance of the dinosaurs in this region of 200,000 to 400,000 years earlier than the Cretaceous-Tertiary boundary. In the Red Deer Valley, Canada, estimates of average accumulation rate lead to a time of disappearance of the dinosaurs of 135,000 to 157,000 years earlier than the Cretaceous-Tertiary boundary. In the central part of Poland, in the Nasilow Quarry, the paleomagnetic pattern shows 7 m of chalk of reversed polarity containing in its upper part the marine Cretaceous-Tertiary biostratigraphic boundary. A greensand deposit contains numerous re-deposited Maastrichtian fossils. The fossils show no signs of wear and are of very different sizes including 1 mm thick juvenile belemnites. The deposit was described as a lag-sediment. Among the various fossils are teeth of mosasaurs. Thus there is coincidence in time between the extinction of mosasaurs and other Cretaceous organisms. This leads to the conclusion, that extinction of terrestrial dinosaurs took place earlier than extinction of marine dinosaurs at the Cretaceous-Tertiary boundary.
Hansen, H. J.
Prior studies of Mesozoic biodiversity document a diversity peak for dinosaur species in the Campanian stage of the Late Cretaceous, yet have failed to provide explicit causal mechanisms. We provide evidence that a marked increase in North American dinosaur biodiversity can be attributed to dynamic orogenic episodes within the Western Interior Basin (WIB). Detailed fossil occurrences document an association between the shift from Sevier-style, latitudinally arrayed basins to smaller Laramide-style, longitudinally arrayed basins and a well substantiated decreased geographic range/increased taxonomic diversity of megaherbivorous dinosaur species. Dispersal-vicariance analysis demonstrates that the nearly identical biogeographic histories of the megaherbivorous dinosaur clades Ceratopsidae and Hadrosauridae are attributable to rapid diversification events within restricted basins and that isolation events are contemporaneous with known tectonic activity in the region. SymmeTREE analysis indicates that megaherbivorous dinosaur clades exhibited significant variation in diversification rates throughout the Late Cretaceous. Phylogenetic divergence estimates of fossil clades offer a new lower boundary on Laramide surficial deformation that precedes estimates based on sedimentological data alone.
Gates, Terry A.; Prieto-Marquez, Albert; Zanno, Lindsay E.
Sauropod dinosaur bones are common in Mesozoic terrestrial sediments, but sauropod skulls are exceedingly rare—cranial materials are known for less than one third of sauropod genera and even fewer are known from complete skulls. Here we describe the first complete sauropod skull from the Cretaceous of the Americas, Abydosaurus mcintoshi, n. gen., n. sp., known from 104.46 ± 0.95 Ma (megannum) sediments from Dinosaur National Monument, USA. Abydosaurus shares close ancestry with Brachiosaurus, which appeared in the fossil record ca. 45 million years earlier and had substantially broader teeth. A survey of tooth shape in sauropodomorphs demonstrates that sauropods evolved broad crowns during the Early Jurassic but did not evolve narrow crowns until the Late Jurassic, when they occupied their greatest range of crown breadths. During the Cretaceous, brachiosaurids and other lineages independently underwent a marked diminution in tooth breadth, and before the latest Cretaceous broad-crowned sauropods were extinct on all continental landmasses. Differential survival and diversification of narrow-crowned sauropods in the Late Cretaceous appears to be a directed trend that was not correlated with changes in plant diversity or abundance, but may signal a shift towards elevated tooth replacement rates and high-wear dentition. Sauropods lacked many of the complex herbivorous adaptations present within contemporaneous ornithischian herbivores, such as beaks, cheeks, kinesis, and heterodonty. The spartan design of sauropod skulls may be related to their remarkably small size—sauropod skulls account for only 1/200th of total body volume compared to 1/30th body volume in ornithopod dinosaurs.
Chure, Daniel; Britt, Brooks B.; Whitlock, John A.; Wilson, Jeffrey A.
Sauropod dinosaur bones are common in Mesozoic terrestrial sediments, but sauropod skulls are exceedingly rare--cranial materials are known for less than one third of sauropod genera and even fewer are known from complete skulls. Here we describe the first complete sauropod skull from the Cretaceous of the Americas, Abydosaurus mcintoshi, n. gen., n. sp., known from 104.46 +/- 0.95 Ma (megannum) sediments from Dinosaur National Monument, USA. Abydosaurus shares close ancestry with Brachiosaurus, which appeared in the fossil record ca. 45 million years earlier and had substantially broader teeth. A survey of tooth shape in sauropodomorphs demonstrates that sauropods evolved broad crowns during the Early Jurassic but did not evolve narrow crowns until the Late Jurassic, when they occupied their greatest range of crown breadths. During the Cretaceous, brachiosaurids and other lineages independently underwent a marked diminution in tooth breadth, and before the latest Cretaceous broad-crowned sauropods were extinct on all continental landmasses. Differential survival and diversification of narrow-crowned sauropods in the Late Cretaceous appears to be a directed trend that was not correlated with changes in plant diversity or abundance, but may signal a shift towards elevated tooth replacement rates and high-wear dentition. Sauropods lacked many of the complex herbivorous adaptations present within contemporaneous ornithischian herbivores, such as beaks, cheeks, kinesis, and heterodonty. The spartan design of sauropod skulls may be related to their remarkably small size--sauropod skulls account for only 1/200th of total body volume compared to 1/30th body volume in ornithopod dinosaurs. PMID:20179896
Chure, Daniel; Britt, Brooks B; Whitlock, John A; Wilson, Jeffrey A
The Museum's two Dinosaur Halls follow the evolutionary development of two distinct groups of dinosaurs, the Sauriscans and Ornithischians. This comprehensive guide to the halls' resources is designed to help you maximize your trip to the Museum. It includes detailed background information about the Museum's collection, a map of the Dinosaur Halls that shows the location of the exhibits and specimens that are highlighted on the elementary school tour and several pre-, during-, and post-visit activities to do with your students. There is a listing of related Museum exhibits and suggestions for how to tie them into your field trip and notes about how the topics featured in the halls address performance standards and curriculum requirements.
Ankylosaurian dinosaurs are most notable for their abundant and morphologically diverse osteoderms, which would have given them a spiky appearance in life. Isolated osteoderms are relatively common and provide important information about the structure of the ankylosaur dermis, but fossilized impressions of the soft-tissue epidermis of ankylosaurs are rare. Nevertheless, well-preserved integument exists on several ankylosaur fossils that shows osteoderms were covered by a single epidermal scale, but one or many millimeter-sized ossicles may be present under polygonal, basement epidermal scales. Evidence for the taxonomic utility of ankylosaurid epidermal scale architecture is presented for the first time. This study builds on previous osteological work that argues for a greater diversity of ankylosaurids in the Dinosaur Park Formation of Alberta than has been traditionally recognized and adds to the hypothesis that epidermal skin impressions are taxonomically relevant across diverse dinosaur clades. PMID:24105904
Arbour, Victoria M; Burns, Michael E; Bell, Phil R; Currie, Philip J
Late Jurassic dinosaurian assemblages show close taxonomic correspondence over wide geographical ranges. Presently available if meager evidence suggests that this is also the case for Early Cretaceous communities. Cretaceous dinosaurian assemblages of Campanian and Maastrichtian age show considerable geographical differentiation but also some wide-ranging genera. Northern Hemisphere terrestrial ecosystems were dominated by hadrosaurs and ceratopsians, both herbivores with advanced capabilities for oral food-processing, whereas Southern Hemisphere biota were characterized by the abundance of titanosaurid sauropods, which relied on gut processing. Very close taxonomic similarities exist between the Campanian and early Maastrichtian dinosaurian assemblages of Mongolia and western North America, which, in part, is matched by similarities among other tetrapods such as mammals. Endemic dinosaurs in the Southern Hemisphere appear to reflect major changes in continental configuration. Some evidence exists for interchange of fuanal elements between North and South America. In absence of late Maastrichtian dinosaurian assemblages from most regions, scenarios concerning the terminal Cretaceous extinction of the Dinosauria should be regarded with caution because they are exclusively based on the conditions in western North America.
Sauropodomorph dinosaurs include the largest land animals to have ever lived, some reaching up to 10 times the mass of an African elephant. Despite their status defining the upper range for body size in land animals, it remains unknown whether sauropodomorphs evolved larger-sized genomes than non-avian theropods, their sister taxon, or whether a relationship exists between genome size and body size in dinosaurs, two questions critical for understanding broad patterns of genome evolution in dinosaurs. Here we report inferences of genome size for 10 sauropodomorph taxa. The estimates are derived from a Bayesian phylogenetic generalized least squares approach that generates posterior distributions of regression models relating genome size to osteocyte lacunae volume in extant tetrapods. We estimate that the average genome size of sauropodomorphs was 2.02 pg (range of species means: 1.77–2.21 pg), a value in the upper range of extant birds (mean = 1.42 pg, range: 0.97–2.16 pg) and near the average for extant non-avian reptiles (mean = 2.24 pg, range: 1.05–5.44 pg). The results suggest that the variation in size and architecture of genomes in extinct dinosaurs was lower than the variation found in mammals. A substantial difference in genome size separates the two major clades within dinosaurs, Ornithischia (large genomes) and Saurischia (moderate to small genomes). We find no relationship between body size and estimated genome size in extinct dinosaurs, which suggests that neutral forces did not dominate the evolution of genome size in this group.
Organ, Chris L.; Brusatte, Stephen L.; Stein, Koen
Exceptionally preserved sauropod eggshells discovered in Upper Cretaceous (Campanian) deposits in Patagonia, Argentina, contain skeletal remains and soft tissues of embryonic Titanosaurid dinosaurs. To preserve these labile embryonic remains, the rate of mineral precipitation must have superseded post-mortem degradative processes, resulting in virtually instantaneous mineralization of soft tissues. If so, mineralization may also have been rapid enough to retain fragments of original biomolecules in these specimens. To investigate preservation of biomolecular compounds in these well-preserved sauropod dinosaur eggshells, we applied multiple analytical techniques. Results demonstrate organic compounds and antigenic structures similar to those found in extant eggshells.
Schweitzer, M.H; Chiappe, L; Garrido, A.C; Lowenstein, J.M; Pincus, S.H
Sauropoda is one of the most diverse and geographically widespread clades of herbivorous dinosaurs, and until now, their remains have now been recovered from all continental landmasses except Antarctica. We report the first record of a sauropod dinosaur from Antarctica, represented by an incomplete caudal vertebra from the Late Cretaceous of James Ross Island. The size and morphology of the specimen allows its identification as a lithostrotian titanosaur. Our finding indicates that advanced titanosaurs achieved a global distribution at least by the Late Cretaceous.
Cerda, Ignacio A.; Paulina Carabajal, Ariana; Salgado, Leonardo; Coria, Rodolfo A.; Reguero, Marcelo A.; Tambussi, Claudia P.; Moly, Juan J.
An oviraptosaurian specimen (Dinosauria, Theropoda) from an Upper Cretaceous formation in China retains a pair of shelled eggs in the pelvis, providing direct evidence that oviraptorosaurian dinosaurs laid paired elongatoolithid eggs. The presence of the paired eggs suggests that theropod dinosaurs had two functional oviducts (like crocodiles) but that each oviduct produced only one egg at a time and that an entire egg clutch was laid through multiple ovipositions (like birds). The orientations of the eggs inside the skeleton and in clutches indicate that the mother came to the center of the nest to lay eggs. PMID:15831749
Sato, Tamaki; Cheng, Yen-nien; Wu, Xiao-chun; Zelenitsky, Darla K; Hsiao, Yu-fu
Previous attempts to determine palaeoenvironmental preferences in dinosaurs have generally been qualitative assessments based upon data from restricted geographical areas. Here, we use a global database of Cretaceous herbivorous dinosaurs to identify significant associations between clades and broad palaeoenvironmental categories (‘terrestrial’, ‘coastal’, ‘marine’). Nodosaurid ankylosaurs and hadrosaurids show significant positive associations with marine sediments, while marginocephalians (Ceratopsia, Pachycephalosauria), saurischians (herbivorous theropods, Sauropoda) and ankylosaurid ankylosaurs are significantly positively associated with terrestrial sediments. These results provide quantitative support for the hypothesis that some clades (Nodosauridae, Hadrosauridae) were more abundant in coastal and/or fluvial environments, while others (e.g. Marginocephalia, Ankylosauridae) preferentially inhabited more distal environments.
Butler, Richard J.; Barrett, Paul M.
The central brain of Drosophila consists of the supraesophageal ganglion (SPG) and the subesophageal ganglion (SEG), both of which are generated by neural stem cell-like neuroblasts during embryonic and postembryonic development. Considerable information has been obtained on postembryonic development of the neuroblasts and their lineages in the SPG. In contrast, very little is known about neuroblasts, neural lineages, or any other aspect of the postembryonic development in the SEG. Here we characterize the neuroanatomy of the larval SEG in terms of tracts, commissures, and other landmark features as compared to a thoracic ganglion. We then use clonal MARCM labeling to identify all adult-specific neuroblast lineages in the late larval SEG and find a surprisingly small number of neuroblast lineages, 13 paired and one unpaired. The Hox genes Dfd, Scr, and Antp are expressed in a lineage-specific manner in these lineages during postembryonic development. Hox gene loss-of-function causes lineage-specific defects in axonal targeting and reduction in neural cell numbers. Moreover, it results in the formation of novel ectopic neuroblast lineages. Apoptosis block also results in ectopic lineages suggesting that Hox genes are required for lineage-specific termination of proliferation through programmed cell death. Taken together, our findings show that postembryonic development in the SEG is mediated by a surprisingly small set of identified lineages and requires lineage-specific Hox gene action to ensure the correct formation of adult-specific neurons in the Drosophila brain. PMID:24713419
Kuert, Philipp A; Hartenstein, Volker; Bello, Bruno C; Lovick, Jennifer K; Reichert, Heinrich
Entomophthoromycota is one of six major phylogenetic lineages among the former phylum Zygomycota. These early terrestrial fungi share evolutionarily ancestral characters such as coenocytic mycelium and gametangiogamy as a sexual process resulting in zygospore formation. Previous molecular studies have shown the monophyly of Entomophthoromycota, thus justifying raising the taxonomic status of these fungi to a phylum. Multi-gene phylogenies have identified five major lineages of Entomophthoromycota. In this review we provide a detailed discussion about the biology and taxonomy of these lineages: I) Basidiobolus (Basidiobolomycetes: Basidiobolaceae; primarily saprobic); II) Conidiobolus (Entomophthoromycetes, Ancylistaceae; several clades of saprobes and invertebrate pathogens), as well as three rapidly evolving entomopathogenic lineages in the family Entomophthoraceae centering around; III) Batkoa; IV) Entomophthora and allied genera; and V) the subfamily Erynioideae which includes Zoophthora and allied genera. Molecular phylogenic analysis has recently determined the relationships of several taxa that were previously unresolved based on morphology alone: Eryniopsis, Macrobiotophthora, Massospora, Strongwellsea and two as yet undescribed genera of Basidiobolaceae. PMID:24027349
Gryganskyi, A P; Humber, R A; Smith, M E; Hodge, K; Huang, B; Voigt, K; Vilgalys, R
Fossils of the Early Cretaceous dinosaur, Nigersaurus taqueti, document for the first time the cranial anatomy of a rebbachisaurid sauropod. Its extreme adaptations for herbivory at ground-level challenge current hypotheses regarding feeding function and feeding strategy among diplodocoids, the larger clade of sauropods that includes Nigersaurus. We used high resolution computed tomography, stereolithography, and standard molding and casting techniques to reassemble the extremely fragile skull. Computed tomography also allowed us to render the first endocast for a sauropod preserving portions of the olfactory bulbs, cerebrum and inner ear, the latter permitting us to establish habitual head posture. To elucidate evidence of tooth wear and tooth replacement rate, we used photographic-casting techniques and crown thin sections, respectively. To reconstruct its 9-meter postcranial skeleton, we combined and size-adjusted multiple partial skeletons. Finally, we used maximum parsimony algorithms on character data to obtain the best estimate of phylogenetic relationships among diplodocoid sauropods. Nigersaurus taqueti shows extreme adaptations for a dinosaurian herbivore including a skull of extremely light construction, tooth batteries located at the distal end of the jaws, tooth replacement as fast as one per month, an expanded muzzle that faces directly toward the ground, and hollow presacral vertebral centra with more air sac space than bone by volume. A cranial endocast provides the first reasonably complete view of a sauropod brain including its small olfactory bulbs and cerebrum. Skeletal and dental evidence suggests that Nigersaurus was a ground-level herbivore that gathered and sliced relatively soft vegetation, the culmination of a low-browsing feeding strategy first established among diplodocoids during the Jurassic.
Sereno, Paul C.; Wilson, Jeffrey A.; Witmer, Lawrence M.; Whitlock, John A.; Maga, Abdoulaye; Ide, Oumarou; Rowe, Timothy A.
The evolutionary radiation of dinosaurs in the Late Triassic and Early Jurassic was a pivotal event in the Earth's history but is poorly understood, as previous studies have focused on vague driving mechanisms and have not untangled different macroevolutionary components (origination, diversity, abundance and disparity). We calculate the morphological disparity (morphospace occupation) of dinosaurs throughout the Late Triassic and Early Jurassic and present new measures of taxonomic diversity. Crurotarsan archosaurs, the primary dinosaur 'competitors', were significantly more disparate than dinosaurs throughout the Triassic, but underwent a devastating extinction at the Triassic-Jurassic boundary. However, dinosaur disparity showed only a slight non-significant increase after this event, arguing against the hypothesis of ecological release-driven morphospace expansion in the Early Jurassic. Instead, the main jump in dinosaur disparity occurred between the Carnian and Norian stages of the Triassic. Conversely, dinosaur diversity shows a steady increase over this time, and measures of diversification and faunal abundance indicate that the Early Jurassic was a key episode in dinosaur evolution. Thus, different aspects of the dinosaur radiation (diversity, disparity and abundance) were decoupled, and the overall macroevolutionary pattern of the first 50Myr of dinosaur evolution is more complex than often considered. PMID:18812311
Brusatte, Stephen L; Benton, Michael J; Ruta, Marcello; Lloyd, Graeme T
Rich Muller, a Berkeley Lab physicist, discusses Nobel laureate Luis Alvarez and colleagues' 1979 discovery that an asteroid impact killed the dinosaurs. He also discusses what scientists have learned in the subsequent 27 years. Alvarez's team detected unusual amounts of iridium in sedimentary layers. They attributed the excess iridium to an impact from a large asteroid. His talk was presented June 30, 2006.
Recent discoveries in the late Cretaceous (Campanian) Two Medicine Formation of western Montana indicate that some dinosaur species, like some modern species of birds and crocodiles, nested in colonies. I report here evidence that members of one species returned to the same nesting area for many years. There are also indications that, after hatching, some species remained in their respective
John R. Horner
Rich Muller, a Berkeley Lab physicist, discusses Nobel laureate Luis Alvarez and colleagues' 1979 discovery that an asteroid impact killed the dinosaurs. He also discusses what scientists have learned in the subsequent 27 years. Alvarez's team detected unusual amounts of iridium in sedimentary layers. They attributed the excess iridium to an impact from a large asteroid. His talk was presented June 30, 2006.
Rich Muller, a Berkeley Lab physicist, discusses Nobel laureate Luis Alvarez and colleagues' 1979 discovery that an asteroid impact killed the dinosaurs. He also discusses what scientists have learned in the subsequent 27 years. Alvarez's team detected unusual amounts of iridium in sedimentary layers. They attributed the excess iridium to an impact from a large asteroid. His talk was presented June 30, 2006.
This is somewhat extended version of the talk given at the Gran Sasso Summer Institute: Massive Neutrinos in Physics and Astrophysics. It describes general ideas about mirror world, extra spatial dimensions and dinosaur extinction. Some suggestions are made how these seemingly different things can be related to each other.
Z. K. Silagadze
For middle school students who have seen only pictures of dinosaurs in books, in the movies, or on the internet, trying to comprehend the size of these gargantuan animals can be difficult. This lesson provides a way for students to visualize changing scal
Gloyna, Lisa; Martin, Patti; Browning, Sandra; West, Sandra
A soft tissue structure has been discovered on the head of the duck-billed dinosaur Edmontosaurus. Its similarity to a cock's comb and other sexually dimorphic structures of birds suggests that potential sexual signals existed in these extinct animals. PMID:24456984
Horner, John R
Therizinosauroidea (`segnosaurs') are little-known group of Asian dinosaurs with an unusual combination of features that, until recently, obscured their evolutionary relationships. Suggested affinities include Ornithischia, Sauropodomorpha,, Theropoda and Saurischia sedis mutabilis. Here we describe a new therizinosauroid from the Yixian Formation (Early Cretaceous, Liaoning, China). This new taxon provides fresh evidence that therizinosauroids are nested within the coelurosaurian theropods. Our
Xing Xu; Zhi-Lu Tang; Xiao-Lin Wang
Ornithischia is one of the two major groups of dinosaurs, with heterodontosauridae as one of its major clades. Heterodontosauridae is characterized by small, gracile bodies and a problematic phylogenetic position. Recent phylogenetic work indicates that it represents the most basal group of all well-known ornithischians. Previous heterodontosaurid records are mainly from the Early Jurassic period (205-190 million years ago) of
Xiao-Ting Zheng; Hai-Lu You; Xing Xu; Zhi-Ming Dong
Dates of divergence derived from molecular data have been used to place the beginning of the radiation of modern mammalian orders in the Cretaceous, long before the final extinction of the dinosaurs. These molecular dates have been used to challenge the idea that the ordinal diversification of mammals was triggered by the availability of ‘empty niches’ left vacant by the
Lindell Bromham; Matthew J. Phillips; David Penny
The dinosaur eggs of southern France occur in continental, fine-grained red-beds, rich in carbonate. The last eggs in the region occur in the magnetic polarity interval 30 normal. Estimates of the accumulation rate of these sediments on the basis of the m...
H. J. Hansen
Abelisauroid predators have been recorded almost exclusively from South America, India and Madagascar, a distribution thought to document persistent land connections exclusive of Africa. Here, we report fossils from three stratigraphic levels in the Cretaceous of Niger that provide definitive evidence that abelisauroid dinosaurs and their immediate antecedents were also present on Africa. The fossils include an immediate abelisauroid antecedent
Paul C. Sereno; Jeffrey A. Wilson; Jack L. Conrad
Surprising new anatomical information has come to light for the early dinosaurs Eoraptor lunensis and Herrerasaurus ischigualastensis. Eoraptor has a mid mandibular jaw joint, and Herrerasaurus has a promaxillary fenestra at the anterior end of the antorbital fossa. Initial cladistic interpretation placed Herrerasaurus outside Dinosauria. Since then, Eoraptor and Herrerasaurus have been placed at the base of Saurischia or within
Paul C. Sereno