Dynamics of Myoblast Transplantation Reveal a Discrete Minority of Precursors with Stem Cell–like Properties as the Myogenic Source

Myoblasts, the precursors of skeletal muscle fibers, can be induced to withdraw from the cell cycle and differentiate in vitro. Recent studies have also identified undifferentiated subpopulations that can self-renew and generate myogenic cells (Baroffio, A., M. Hamann, L. Bernheim, M.-L. Bochaton-Pillat, G. Gabbiani, and C.R. Bader. 1996. Differentiation. 60:47–57; Yoshida, N., S. Yoshida, K. Koishi, K. Masuda, and Y. Nabeshima. 1998. J. Cell Sci. 111:769–779). Cultured myoblasts can also differentiate and contribute to repair and new muscle formation in vivo, a capacity exploited in attempts to develop myoblast transplantation (MT) for genetic modification of adult muscle. Our studies of the dynamics of MT demonstrate that cultures of myoblasts contain distinct subpopulations defined by their behavior in vitro and divergent responses to grafting. By comparing a genomic and a semiconserved marker, we have followed the fate of myoblasts transplanted into muscles of dystrophic mice, finding that the majority of the grafted cells quickly die and only a minority are responsible for new muscle formation. This minority is behaviorally distinct, slowly dividing in tissue culture, but rapidly proliferative after grafting, suggesting a subpopulation with stem cell–like characteristics

Spectral Modelling of Star-Forming Regions in the Ultraviolet: Stellar Metallicity Diagnostics for High Redshift Galaxies

The chemical composition of high redshift galaxies is an important property which gives clues to their past history and future evolution and yet is difficult to measure with current techniques. In this paper we investigate new metallicity indicators, based upon the strengths of stellar photospheric features at rest-frame ultraviolet wavelengths. By combining the evolutionary spectral synthesis code Starburst99 with the output from the non-LTE model atmosphere code WM-basic, we have developed a code that can model the integrated ultraviolet stellar spectra of star-forming regions at metallicities between 1/20 and twice solar. We use our models to explore a number of spectral regions that are sensitive to metallicity and clean of other spectral features. The most promising metallicity indicator is an absorption feature between 1935 A and 2020 A, which arises from the blending of numerous Fe III transitions. We compare our model spectra to observations of two well studied high redshift star-forming galaxies, MS1512-cB58 (a Lyman break galaxy at z = 2.7276), and Q1307-BM1163 (a UV-bright galaxy at z = 1.411). The profiles of the photospheric absorption features observed in these galaxies are well reproduced by the models. In addition, the metallicities inferred from their equivalent widths are in good agreement with previous determinations based on interstellar absorption and nebular emission lines. Our new technique appears to be a promising alternative, or complement, to established methods which have only a limited applicability at high redshifts.Comment: 18 pages, 12 figures, accepted for publication in the Astrophysical Journa

On the Progenitor of the Type II Supernova 2004et in NGC 6946

Supernova (SN) 2004et is the eighth historical SN in the nearby spiral galaxy NGC 6946. Here we report on early photometric and spectroscopic monitoring of this object. SN 2004et is a Type II event, exhibiting a plateau in its light curves, but its spectral and color evolution appear to differ significantly from those of other, more normal Type II-plateau (II-P) SNe. We have analyzed Canada-France-Hawaii Telescope (CFHT) images of the host galaxy taken prior to the SN explosion, identifying a candidate progenitor for the SN. The star's absolute magnitude and intrinsic color imply that it was a yellow, rather than red, supergiant star, with an estimated zero-age main sequence mass of $15^{+5}_{-2} M_\odot$. Although this mass estimate is consistent with estimates and upper limits for the progenitors of other, more normal SNe II-P, the SN 2004et progenitor's unusual color could further imply a pre-explosion evolutionary history analogous to, but less extreme than, that for the progenitors of the peculiar Type II-P SN 1987A or the Type IIb SN 1993J. The identity of the progenitor candidate needs to be verified when the SN has significantly dimmed.Comment: To appear in PASP (Feb 2005). A high resolution PostScript version is available at http://astron.berkeley.edu/~weidong/ms_04et.ps.g

Myogenic cell proliferation and generation of a reversible tumorigenic phenotype are triggered by preirradiation of the recipient site

Environmental influences have profound yet reversible effects on the behavior of resident cells. Earlier data have indicated that the amount of muscle formed from implanted myogenic cells is greatly augmented by prior irradiation (18 Gy) of the host mouse muscle. Here we confirm this phenomenon, showing that it varies between host mouse strains. However, it is unclear whether it is due to secretion of proliferative factors or reduction of antiproliferative agents. To investigate this further, we have exploited the observation that the immortal myogenic C2 C12 cell line forms tumors far more rapidly in irradiated than in nonirradiated host muscle. We show that the effect of preirradiation on tumor formation is persistent and dose dependent. However, C2 C12 cells are not irreversibly compelled to form undifferentiated tumor cells by the irradiated muscle environment and are still capable of forming large amounts of muscle when reimplanted into a nonirradiated muscle. In a clonal analysis of this effect, we discovered that C2 C12 cells have a bimodal propensity to form tumors; some clones form no tumors even after extensive periods in irradiated graft sites, whereas others rapidly form extensive tumors. This illustrates the subtle interplay between the phenotype of implanted cells and the factors in the muscle environment

The Rest Frame Optical Spectra of Lyman Break Galaxies: Star Formation, Extinction, Abundances, and Kinematics

We present the first results of a spectroscopic survey of Lyman break galaxies in the near-infrared aimed at detecting the emission lines of [O II], [O III], and Hbeta from the H II regions of star forming galaxies at z = 3. From observations of 19 objects with the Keck and VLT telescopes, we reach the following main conclusions. Contrary to expectations, the star formation rates deduced from the Hbeta luminosity are on average no larger than those implied by the stellar continuum at 1500 A; presumably any differential extinction between rest-frame optical and UV is small compared with the relative uncertainties in the calibrations of these two star formation tracers. For the galaxies in our sample, the abundance of O can only be determined to within one order of magnitude. Even so, it seems well established that LBGs are the most metal-enriched structures at z = 3, apart from QSOs, with abundances greater than about 1/10 solar. They are also significantly overluminous for their metallicities; this is probably an indication that their mass-to-light ratios are small compared with present-day galaxies. At face value their velocity dispersions, sigma = 50 - 115 km/s imply virial masses of about 10^{10} solar masses within half-light radii of 2.5 kpc. However, we are unable to establish if the widths of the emission lines do reflect the motions of the H II regions within the gravitational potential of the galaxies, even though in two cases we see hints of rotation curves. All 19 LBGs observed show evidence for galactic-scale superwinds; such outflows are important for regulating star formation, distributing metals over large volumes, and allowing Lyman continuum photons to escape and ionize the IGM.Comment: 44 pages, LaTeX, 13 Postscript Figures. Accepted for publication in the Astrophysical Journal, Vol. 554, No. 2 (Jun 20, 2001

Effects of the Distribution of Female Primates on the Number of Males

The spatiotemporal distribution of females is thought to drive variation in mating systems, and hence plays a central role in understanding animal behavior, ecology and evolution. Previous research has focused on investigating the links between female spatiotemporal distribution and the number of males in haplorhine primates. However, important questions remain concerning the importance of spatial cohesion, the generality of the pattern across haplorhine and strepsirrhine primates, and the consistency of previous findings given phylogenetic uncertainty. To address these issues, we examined how the spatiotemporal distribution of females influences the number of males in primate groups using an expanded comparative dataset and recent advances in Bayesian phylogenetic and statistical methods. Specifically, we investigated the effect of female distributional factors (female number, spatial cohesion, estrous synchrony, breeding season duration and breeding seasonality) on the number of males in primate groups. Using Bayesian approaches to control for uncertainty in phylogeny and the model of trait evolution, we found that the number of females exerted a strong influence on the number of males in primate groups. In a multiple regression model that controlled for female number, we found support for temporal effects, particularly involving female estrous synchrony: the number of males increases when females are more synchronously receptive. Similarly, the number of males increases in species with shorter birth seasons, suggesting that greater breeding seasonality makes defense of females more difficult for male primates. When comparing primate suborders, we found only weak evidence for differences in traits between haplorhines and strepsirrhines, and including suborder in the statistical models did not affect our conclusions or give compelling evidence for different effects in haplorhines and strepsirrhines. Collectively, these results demonstrate that male monopolization is driven primarily by the number of females in groups, and secondarily by synchrony of female reproduction within groups

Evolutionary Trends of the Pharyngeal Dentition in Cypriniformes (Actinopterygii: Ostariophysi)

International audienceBACKGROUND: The fish order Cypriniformes is one of the most diverse ray-finned fish groups in the world with more than 3000 recognized species. Cypriniformes are characterized by a striking distribution of their dentition: namely the absence of oral teeth and presence of pharyngeal teeth on the last gill arch (fifth ceratobranchial). Despite this limited localisation, the diversity of tooth patterns in Cypriniformes is astonishing. Here we provide a further description of this diversity using X-ray microtomography and we map the resulting dental characters on a phylogenetic tree to explore evolutionary trends. RESULTS: We performed a pilot survey of dental formulae and individual tooth shapes in 34 adult species of Cypriniformes by X-ray microtomography (using either conventional X-ray machine, or synchrotron microtomography when necessary) or by dissecting. By mapping morphological results in a phylogenetic tree, it emerges that the two super-families Cobitoidea and Cyprinoidea have followed two distinct evolutionary pathways. Furthermore, our analysis supports the hypothesis of a three-row dentition as ancestral for Cyprinoidea and a general trend in tooth row reduction in most derived lineages. Yet, this general scheme must be considered with caution as several events of tooth row gain and loss have occurred during evolutionary history of Cyprinoidea. SIGNIFICANCE: Dentition diversity in Cypriniformes constitutes an excellent model to study the evolution of complex morphological structures. This morphological survey clearly advocates for extending the use of X-ray microtomography to study tooth morphology in Cypriniformes. Yet, our survey also underlines that improved knowledge of Cypriniformes life traits, such as feeding habits, is required as current knowledge is not sufficient to conclude on the link between diet and dental morphology

Dating the Origin of Language Using Phonemic Diversity

Language is a key adaptation of our species, yet we do not know when it evolved. Here, we use data on language phonemic diversity to estimate a minimum date for the origin of language. We take advantage of the fact that phonemic diversity evolves slowly and use it as a clock to calculate how long the oldest African languages would have to have been around in order to accumulate the number of phonemes they possess today. We use a natural experiment, the colonization of Southeast Asia and Andaman Islands, to estimate the rate at which phonemic diversity increases through time. Using this rate, we estimate that present-day languages date back to the Middle Stone Age in Africa. Our analysis is consistent with the archaeological evidence suggesting that complex human behavior evolved during the Middle Stone Age in Africa, and does not support the view that language is a recent adaptation that has sparked the dispersal of humans out of Africa. While some of our assumptions require testing and our results rely at present on a single case-study, our analysis constitutes the first estimate of when language evolved that is directly based on linguistic data

COVID-19 trajectories among 57 million adults in England: a cohort study using electronic health records

BACKGROUND: Updatable estimates of COVID-19 onset, progression, and trajectories underpin pandemic mitigation efforts. To identify and characterise disease trajectories, we aimed to define and validate ten COVID-19 phenotypes from nationwide linked electronic health records (EHR) using an extensible framework. METHODS: In this cohort study, we used eight linked National Health Service (NHS) datasets for people in England alive on Jan 23, 2020. Data on COVID-19 testing, vaccination, primary and secondary care records, and death registrations were collected until Nov 30, 2021. We defined ten COVID-19 phenotypes reflecting clinically relevant stages of disease severity and encompassing five categories: positive SARS-CoV-2 test, primary care diagnosis, hospital admission, ventilation modality (four phenotypes), and death (three phenotypes). We constructed patient trajectories illustrating transition frequency and duration between phenotypes. Analyses were stratified by pandemic waves and vaccination status. FINDINGS: Among 57 032 174 individuals included in the cohort, 13 990 423 COVID-19 events were identified in 7 244 925 individuals, equating to an infection rate of 12·7% during the study period. Of 7 244 925 individuals, 460 737 (6·4%) were admitted to hospital and 158 020 (2·2%) died. Of 460 737 individuals who were admitted to hospital, 48 847 (10·6%) were admitted to the intensive care unit (ICU), 69 090 (15·0%) received non-invasive ventilation, and 25 928 (5·6%) received invasive ventilation. Among 384 135 patients who were admitted to hospital but did not require ventilation, mortality was higher in wave 1 (23 485 [30·4%] of 77 202 patients) than wave 2 (44 220 [23·1%] of 191 528 patients), but remained unchanged for patients admitted to the ICU. Mortality was highest among patients who received ventilatory support outside of the ICU in wave 1 (2569 [50·7%] of 5063 patients). 15 486 (9·8%) of 158 020 COVID-19-related deaths occurred within 28 days of the first COVID-19 event without a COVID-19 diagnoses on the death certificate. 10 884 (6·9%) of 158 020 deaths were identified exclusively from mortality data with no previous COVID-19 phenotype recorded. We observed longer patient trajectories in wave 2 than wave 1. INTERPRETATION: Our analyses illustrate the wide spectrum of disease trajectories as shown by differences in incidence, survival, and clinical pathways. We have provided a modular analytical framework that can be used to monitor the impact of the pandemic and generate evidence of clinical and policy relevance using multiple EHR sources. FUNDING: British Heart Foundation Data Science Centre, led by Health Data Research UK