Human Transgene-Free Amniotic-Fluid-Derived Induced Pluripotent Stem Cells for Autologous Cell Therapy

The establishment of a reliable prenatal source of autologous, transgene-free progenitor cells has enormous potential in the development of regenerative-medicine-based therapies for infants born with devastating birth defects. Here, we show that a largely CD117-negative population of human amniotic fluid mesenchymal stromal cells (AF-MSCs) obtained from fetuses with or without prenatally diagnosed anomalies are readily abundant and have limited baseline differentiation potential when compared with bone-marrow-derived MSCs and other somatic cell types. Nonetheless, the AF-MSCs could be easily reprogrammed into induced pluripotent stem cells (iPSCs) using nonintegrating Sendai viral vectors encoding for OCT4, SOX2, KLF4, and cMYC. The iPSCs were virtually indistinguishable from human embryonic stem cells in multiple assays and could be used to generate a relatively homogeneous population of neural progenitors, expressing PAX6, SOX2, SOX3, Musashi-1, and PSA-NCAM, for potential use in neurologic diseases. Further, these neural progenitors showed engraftment potential in vivo and were capable of differentiating into mature neurons and astrocytes in vitro. This study demonstrates the usefulness of AF-MSCs as an excellent source for the generation of human transgene-free iPSCs ideally suited for autologous perinatal regenerative medicine applications.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140204/1/scd.2014.0110.pd

Scanning X-ray nanodiffraction: from the experimental approach towards spatially resolved scattering simulations

An enhancement on the method of X-ray diffraction simulations for applications using nanofocused hard X-ray beams is presented. We combine finite element method, kinematical scattering calculations, and a spot profile of the X-ray beam to simulate the diffraction of definite parts of semiconductor nanostructures. The spot profile could be acquired experimentally by X-ray ptychography. Simulation results are discussed and compared with corresponding X-ray nanodiffraction experiments on single SiGe dots and dot molecules

Independent evolution of the core and accessory gene sets in the genus Neisseria: insights gained from the genome of Neisseria lactamica isolate 020-06

<p>Abstract</p> <p>Background</p> <p>The genus <it>Neisseria </it>contains two important yet very different pathogens, <it>N. meningitidis </it>and <it>N. gonorrhoeae</it>, in addition to non-pathogenic species, of which <it>N. lactamica </it>is the best characterized. Genomic comparisons of these three bacteria will provide insights into the mechanisms and evolution of pathogenesis in this group of organisms, which are applicable to understanding these processes more generally.</p> <p>Results</p> <p>Non-pathogenic <it>N. lactamica </it>exhibits very similar population structure and levels of diversity to the meningococcus, whilst gonococci are essentially recent descendents of a single clone. All three species share a common core gene set estimated to comprise around 1190 CDSs, corresponding to about 60% of the genome. However, some of the nucleotide sequence diversity within this core genome is particular to each group, indicating that cross-species recombination is rare in this shared core gene set. Other than the meningococcal <it>cps </it>region, which encodes the polysaccharide capsule, relatively few members of the large accessory gene pool are exclusive to one species group, and cross-species recombination within this accessory genome is frequent.</p> <p>Conclusion</p> <p>The three <it>Neisseria </it>species groups represent coherent biological and genetic groupings which appear to be maintained by low rates of inter-species horizontal genetic exchange within the core genome. There is extensive evidence for exchange among positively selected genes and the accessory genome and some evidence of hitch-hiking of housekeeping genes with other loci. It is not possible to define a 'pathogenome' for this group of organisms and the disease causing phenotypes are therefore likely to be complex, polygenic, and different among the various disease-associated phenotypes observed.</p

Structural Alterations in a Component of Cytochrome c Oxidase and Molecular Evolution of Pathogenic Neisseria in Humans

Three closely related bacterial species within the genus Neisseria are of importance to human disease and health. Neisseria meningitidis is a major cause of meningitis, while Neisseria gonorrhoeae is the agent of the sexually transmitted disease gonorrhea and Neisseria lactamica is a common, harmless commensal of children. Comparative genomics have yet to yield clear insights into which factors dictate the unique host-parasite relationships exhibited by each since, as a group, they display remarkable conservation at the levels of nucleotide sequence, gene content and synteny. Here, we discovered two rare alterations in the gene encoding the CcoP protein component of cytochrome cbb3 oxidase that are phylogenetically informative. One is a single nucleotide polymorphism resulting in CcoP truncation that acts as a molecular signature for the species N. meningitidis. We go on to show that the ancestral ccoP gene arose by a unique gene duplication and fusion event and is specifically and completely distributed within species of the genus Neisseria. Surprisingly, we found that strains engineered to express either of the two CcoP forms conditionally differed in their capacity to support nitrite-dependent, microaerobic growth mediated by NirK, a nitrite reductase. Thus, we propose that changes in CcoP domain architecture and ensuing alterations in function are key traits in successive, adaptive radiations within these metapopulations. These findings provide a dramatic example of how rare changes in core metabolic proteins can be connected to significant macroevolutionary shifts. They also show how evolutionary change at the molecular level can be linked to metabolic innovation and its reversal as well as demonstrating how genotype can be used to infer alterations of the fitness landscape within a single host

On looking into words (and beyond): Structures, Relations, Analyses

On Looking into Words is a wide-ranging volume spanning current research into word structure and morphology, with a focus on historical linguistics and linguistic theory. The papers are offered as a tribute to Stephen R. Anderson, the Dorothy R. Diebold Professor of Linguistics at Yale, who is retiring at the end of the 2016-2017 academic year. The contributors are friends, colleagues, and former students of Professor Anderson, all important contributors to linguistics in their own right. As is typical for such volumes, the contributions span a variety of topics relating to the interests of the honorand. In this case, the central contributions that Anderson has made to so many areas of linguistics and cognitive science, drawing on synchronic and diachronic phenomena in diverse linguistic systems, are represented through the papers in the volume. The 26 papers that constitute this volume are unified by their discussion of the interplay between synchrony and diachrony, theory and empirical results, and the role of diachronic evidence in understanding the nature of language. Central concerns of the volume include morphological gaps, learnability, increases and declines in productivity, and the interaction of different components of the grammar. The papers deal with a range of linked synchronic and diachronic topics in phonology, morphology, and syntax (in particular, cliticization), and their implications for linguistic theory

On looking into words (and beyond): Structures, Relations, Analyses

On Looking into Words is a wide-ranging volume spanning current research into word structure and morphology, with a focus on historical linguistics and linguistic theory. The papers are offered as a tribute to Stephen R. Anderson, the Dorothy R. Diebold Professor of Linguistics at Yale, who is retiring at the end of the 2016-2017 academic year. The contributors are friends, colleagues, and former students of Professor Anderson, all important contributors to linguistics in their own right. As is typical for such volumes, the contributions span a variety of topics relating to the interests of the honorand. In this case, the central contributions that Anderson has made to so many areas of linguistics and cognitive science, drawing on synchronic and diachronic phenomena in diverse linguistic systems, are represented through the papers in the volume. The 26 papers that constitute this volume are unified by their discussion of the interplay between synchrony and diachrony, theory and empirical results, and the role of diachronic evidence in understanding the nature of language. Central concerns of the volume include morphological gaps, learnability, increases and declines in productivity, and the interaction of different components of the grammar. The papers deal with a range of linked synchronic and diachronic topics in phonology, morphology, and syntax (in particular, cliticization), and their implications for linguistic theory

On looking into words (and beyond): Structures, Relations, Analyses

On Looking into Words is a wide-ranging volume spanning current research into word structure and morphology, with a focus on historical linguistics and linguistic theory. The papers are offered as a tribute to Stephen R. Anderson, the Dorothy R. Diebold Professor of Linguistics at Yale, who is retiring at the end of the 2016-2017 academic year. The contributors are friends, colleagues, and former students of Professor Anderson, all important contributors to linguistics in their own right. As is typical for such volumes, the contributions span a variety of topics relating to the interests of the honorand. In this case, the central contributions that Anderson has made to so many areas of linguistics and cognitive science, drawing on synchronic and diachronic phenomena in diverse linguistic systems, are represented through the papers in the volume. The 26 papers that constitute this volume are unified by their discussion of the interplay between synchrony and diachrony, theory and empirical results, and the role of diachronic evidence in understanding the nature of language. Central concerns of the volume include morphological gaps, learnability, increases and declines in productivity, and the interaction of different components of the grammar. The papers deal with a range of linked synchronic and diachronic topics in phonology, morphology, and syntax (in particular, cliticization), and their implications for linguistic theory

On looking into words (and beyond): Structures, Relations, Analyses

On Looking into Words is a wide-ranging volume spanning current research into word structure and morphology, with a focus on historical linguistics and linguistic theory. The papers are offered as a tribute to Stephen R. Anderson, the Dorothy R. Diebold Professor of Linguistics at Yale, who is retiring at the end of the 2016-2017 academic year. The contributors are friends, colleagues, and former students of Professor Anderson, all important contributors to linguistics in their own right. As is typical for such volumes, the contributions span a variety of topics relating to the interests of the honorand. In this case, the central contributions that Anderson has made to so many areas of linguistics and cognitive science, drawing on synchronic and diachronic phenomena in diverse linguistic systems, are represented through the papers in the volume. The 26 papers that constitute this volume are unified by their discussion of the interplay between synchrony and diachrony, theory and empirical results, and the role of diachronic evidence in understanding the nature of language. Central concerns of the volume include morphological gaps, learnability, increases and declines in productivity, and the interaction of different components of the grammar. The papers deal with a range of linked synchronic and diachronic topics in phonology, morphology, and syntax (in particular, cliticization), and their implications for linguistic theory

On looking into words (and beyond): Structures, Relations, Analyses

On Looking into Words is a wide-ranging volume spanning current research into word structure and morphology, with a focus on historical linguistics and linguistic theory. The papers are offered as a tribute to Stephen R. Anderson, the Dorothy R. Diebold Professor of Linguistics at Yale, who is retiring at the end of the 2016-2017 academic year. The contributors are friends, colleagues, and former students of Professor Anderson, all important contributors to linguistics in their own right. As is typical for such volumes, the contributions span a variety of topics relating to the interests of the honorand. In this case, the central contributions that Anderson has made to so many areas of linguistics and cognitive science, drawing on synchronic and diachronic phenomena in diverse linguistic systems, are represented through the papers in the volume. The 26 papers that constitute this volume are unified by their discussion of the interplay between synchrony and diachrony, theory and empirical results, and the role of diachronic evidence in understanding the nature of language. Central concerns of the volume include morphological gaps, learnability, increases and declines in productivity, and the interaction of different components of the grammar. The papers deal with a range of linked synchronic and diachronic topics in phonology, morphology, and syntax (in particular, cliticization), and their implications for linguistic theory

On looking into words (and beyond): Structures, Relations, Analyses

On Looking into Words is a wide-ranging volume spanning current research into word structure and morphology, with a focus on historical linguistics and linguistic theory. The papers are offered as a tribute to Stephen R. Anderson, the Dorothy R. Diebold Professor of Linguistics at Yale, who is retiring at the end of the 2016-2017 academic year. The contributors are friends, colleagues, and former students of Professor Anderson, all important contributors to linguistics in their own right. As is typical for such volumes, the contributions span a variety of topics relating to the interests of the honorand. In this case, the central contributions that Anderson has made to so many areas of linguistics and cognitive science, drawing on synchronic and diachronic phenomena in diverse linguistic systems, are represented through the papers in the volume. The 26 papers that constitute this volume are unified by their discussion of the interplay between synchrony and diachrony, theory and empirical results, and the role of diachronic evidence in understanding the nature of language. Central concerns of the volume include morphological gaps, learnability, increases and declines in productivity, and the interaction of different components of the grammar. The papers deal with a range of linked synchronic and diachronic topics in phonology, morphology, and syntax (in particular, cliticization), and their implications for linguistic theory