A study of the generation of diversity in the central nervous system

Developmental biology is concerned with understanding the mechanisms that govern the generation of a whole organism starting from one single cell. In the central nervous system (CNS) the development of different classes of neurons and glial cells involves both extrinsic signals and intrinsic cues that together govern the specification of different cell fates dependent on position within the CNS and the time of generation. Different vertebrate species share many aspects of early development as well as the underlying mechanisms governing the progress of development. Therefore, a plausible assumption is that functional regions in the genome are also conserved between species. In Paper I, we have used a comparative genomics approach to identify Highly Conserved Non‐coding Regions (HCNRs) between the human, mouse and pufferfish genomes. We find HCNRs to be statistically over represented in the proximity of transcription factors associated with spatial patterning in the developing neural tube. We show that HCNRs associated with patterning genes show an overrepresentation of binding sites for three transcription factors (Sox, Pou and Homedomain genes (SPHD)). By combining bioinformatics and large-scale expression analysis, we show that SPHD enriched HCNRs are strong predictors of CNS expression during development (83% vs. 36% of random control genes). This suggested to us that SPHD+ HCNRs may act as CNS enhancers. Further, we isolate a putative HCNR enhancer region and show that it acts as an enhancer both in vivo and in vitro. Based on our findings, we propose a model where Sox and Pou proteins act as common activators of CNS expressed genes, while homeodomain proteins, which have been previously shown to act as repressors, act to restrict expression spatially. While a large number of studies have provided insight into the spatial patterning mechanisms directing the generation of distinct cell types at different positions, little is known about the temporal mechanisms underlying the specification of different cell types from a common pool of progenitors in the CNS. In Paper II, we have addressed the question of how a seemingly homogenous population of progenitor cells in the caudal hindbrain can give rise to distinct subtypes of vagal visceral motoneurons (vMNs). We show that based on molecular marker expression we can distinguish between at least three subtypes of vMNs at early developmental time points and that each subtypes corresponds to a distinct projections pattern in the periphery. We show that these subtypes are generated sequentially and that the decision to become a specific subtype is independent of contacts with peripheral targets and cell‐cell mediated interactions. Further, the homeodomain transcription factor Nkx6.1 and the orphan nuclear receptor Nurr1 are required for the specification of early born subtypes and the maturation of late born subtypes, respectively. In Paper III we were concerned with the origins of oligodendrocytes in the developing spinal cord and hindbrain. Oligodendrocytes have been shown to be generated from a ventrally located domain in the spinal cord and while this ventral origin has been widely accepted, the existence of other origins remained subject to debate. We show, based on in vitro cultures as well as mutant analysis, that dorsal domains in the spinal cord can give rise to oligodendrocyte precursors and that these precursors have the capacity to develop to bona‐fide mature oligodendrocytes based on expression of mature markers. Further we show that, at least at prenatal stages, ventrally and dorsally generated oligodendrocytes exhibit differences in expression profiles, suggesting potential differences between these populations. Additionally, our data suggests that the decrease in BMP signaling, a known inhibitor of oligodendrogenesis, in the dorsal spinal cord over time, due to the increase in the size of the neural tube, may influence the time of induction of the dorsally generated oligodendrocyte precursors in spinal cord. Also, our data from the spinal cord and the hindbrain, show that ventral oligodendrogenesis at different anteroposterior levels is governed by different genetic programs

The World Englishes Paradigm and its Implications for International Students\u27 Acquisition of Standard American English for University-Level Studies in the United States

Because English, as the predominant international language, is now used in many different forms and contexts globally, attitudes are changing towards variety in English, the construct of English proficiency tests, and methods of teaching English. This paper addresses the fact that many students of English are exposed to non-standard indigenized or lingua franca Englishes, thus potentially marginalizing them in their efforts to succeed on international tests of English based on standard American or British conventions. It examines non-standard grammatical features of world Englishes, summarizes the results of studies on bias in English proficiency tests, and details suggestions for best teaching practices enlightened by an understanding of this new English reality. Suggestions for modifications to ESL/EFL teaching methods are informed by empirical studies that demonstrate the success of using the non-standard dialect as a comparative device in English language classrooms whose goal is to teach a standard target dialect

Molecular phylogeny of the portulacaceous cohort

The central focus of this research is the use of chloroplast ndhF sequence data to produce a phylogeny of the Portulacaceae, including an evaluation of the relationships of this family to the Basellaceae, Cactaceae, and Didiereaceae. This cohort was divided into two major clades, both including genera of the Portulacaceae; the Cactaceae were derived from the first, and the Basellaceae and Didiereaceae from the second. Within the latter, a largely Western American assemblage of genera, some formerly identified as basal taxa, was found to be monophyletic. This phylogeny indicated that all recent infrafamilial classifications of the Portulacaceae were flawed by the recognition of non-monophyletic tribes, and that generic limits remain an issue, particularly in Talinum, Calandrinia, and Cistanthe. Rapidly evolving chloroplast sequences were used to evaluate two monophyletic lineages within the cohort: the Didiereaceae and the tribe Anacampseroteae. The sister group of the Didiereaceae was Calyptrotheca (Portulacaceae); present taxonomic understanding of the family was supported. Talinopsis was identified as the basal lineage of the Anacampseroteae, and it was determined that Talinaria was derived from within Anacampseros and that Anacampseros Subg. Tuberosae was polyphyletic

Tests of a Family Gauge Symmetry Model at 10^3 TeV Scale

Based on a specific model with U(3) family gauge symmetry at $10^3$ TeV scale, we show its experimental signatures to search for. Since the gauge symmetry is introduced with a special purpose, its gauge coupling constant and gauge boson mass spectrum are not free. The current structure in this model leads to family number violations via exchange of extra gauge bosons. We investigate present constraints from flavor changing processes and discuss visible signatures at LHC and lepton colliders.Comment: 12 pages, 2 figures, title changed, minor modification, to appear in PL

Footwear\u27s Influence on Positional Parameters in the Static Posture of Children

In early childhood, a child’s motor control is rapidly evolving. Upright posture is being supported through a combination of sensory factors that are influenced by the child’s developing neuromuscular system.1 Footwear has the ability to create a drastic impact on postural stability during this key time in a child’s life. In fact, certain types of footwear may actually be detrimental to the child’s normal development of proprioceptive abilities, compared to being able to feel their natural environment while barefoot. Positional parameters of static posture can be used to evaluate the effects of footwear on postural control.2 PURPOSE: The purpose of this study was to investigate the effect that stiff soled shoes had on the posture of young children between the ages of 4 and 6 years old. METHODS: 13 healthy children between the ages of 4-6 participated in this study. There were 4 males and 9 females. The COP anteroposterior(AP), mediolateral(ML), and radiuses of static upright posture while barefoot and while wearing shoes were evaluated. RESULTS: There was a significant difference between the barefoot and shod conditions for COP AP means (Barefoot 4.57±1.14, Shod 4.44±1.11, p\u3c.05). There were no statistical differences for either COP ML means (Barefoot 15.48±9.14, Shod 11.208±6.836, p\u3e.05), or COP mean radiuses (Barefoot 16.771±8.085, Shod 12.802±5.632, p\u3e.05). CONCLUSION: In conclusion, it appears that the stiff soled shoes limit the position variables of static posture compared to standing barefoot, though our data was only significantly different for the AP direction. The data suggest that the stiff soled shoes are providing a constraint to the organization of the children’s posture, though there is not enough evidence to conclude there are negative effects to a child’s natural proprioception of their environment when shod with these specific shoes. Further investigation into the effects of footwear on posture in children, particularly the dynamics of posture, should be done

Difference of Elbow Extension Velocity During Flat and Mound Throwing

In baseball, players encounter varying forms of throwing that is dependent upon position. Pitchers often throw on a mound, while position players are seen throwing from a flat ground. The throwing motion of a baseball consists of six phases: wind-up, stride, late cocking, acceleration, deceleration, and follow through. Each of these different phases consists of velocities being produced from the lower body through the elbow, which contributes to a potential cause of throwing arm injuries. Given the prominence of elbow injuries to pitchers, investigation into the solution to reducing arm injuries has continued to gain traction. PURPOSE: The purpose of this study was to examine throwing kinematic velocities when throwing from flat ground compared to throwing from a mound. METHODS: Ten healthy individuals (20.2±1.23 years old) with previous pitching experience were recruited for this study. Subjects had 38 retro-reflective markers placed in various anatomical locations to quantify whole body kinematics during the throwing motion using a motion capture system. Subjects completed 10 total throws, five from flat ground, and five from a mound at a throwing distance of 30.5 meters. The five throws from each condition were then averaged. Peak pelvic rotation velocity, peak trunk rotation velocity, peak shoulder horizontal adduction velocity, and peak elbow extension velocity were calculated and analyzed with custom software. Dependent t-tests were ran to compare the flat ground and mound conditions for each dependent variable. RESULTS: There were no statistical differences for any of the dependent variables; peak pelvic rotation velocity (Flat 663.8m/s±80, Mound 586.7m/s±105, p\u3e.05), peak trunk rotation velocity (Flat 905.1m/s±108, Mound 878.2m/s±95, p\u3e.05), peak shoulder horizontal adduction velocity (Flat 1314.2m/s±288, Mound 1339.1m/s±265, p\u3e.05) or peak elbow extension velocity (Flat 2417.8m/s±473, Mound 2401.1m/s±453, p\u3e.05). CONCLUSION: In conclusion, we were unable to elucidate any differences in body kinematics when comparing flat ground to mound throwing. The implications of our study are that it is safe to throw from either the mound or flat ground, as the different throwing condition does not add any additional stress to the arm and the general kinematics of the throw are conserved. Future studies should aim to investigate other potential variables that may contribute to injury, particularly analyzing those variables during specific events during the phases of the throw

Dynamics of the chiral phase transition in the 2+1 dimensional Gross-Neveu model

The phase diagram of the Gross-Neveu (G-N) model in 2+1 dimensions as a function of chemical potential and temperature has a simple curve separating the broken symmetry and unbroken symmetry phases, with chiral symmetry being restored both at high temperature and high density. We study, in leading order in the 1/N expansion, the dynamics of the chiral phase transition for an expanding plasma of quarks in the Gross-Neveu model in 2+1 dimensions assuming boost invariant kinematics. We compare the time evolution of the order parameter (mass of the fermion) for evolutions starting in the unbroken and broken phases. The proper time evolution of the order parameter resembles previous results in the 1+1 dimensional G-N model in the same approximation. The time needed to traverse the transition is insensitive to mu.Comment: 10 pages, 3 figure

The Standard Model of Leptons as a Purely Vectorial Theory

We propose a way to reconcile the Standard Model of leptons with a purely vectorial theory. The observed neutrino is predicted to be massless. The unobservability of its partner and the $V-A$ structure of the weak currents are given the same origin.Comment: 10 pages. Latex, 8 postscript figures included. We have corrected 2 (cancelling) sign misprints, and made explicit that we also recover the usual couplings of the U(1) gauge field B. The conclusions are unchanged. PAR-LPTHE 93/1