Cyclin-Dependent Kinase Inhibitor p21 Controls Adult Neural Stem Cell Expansion by Regulating Sox2 Gene Expression

In the adult brain, continual neurogenesis of olfactory neurons is sustained by the existence of neural stem cells (NSCs) in the subependymal niche. Elimination of the cyclin-dependent kinase inhibitor 1A (p21) leads to premature exhaustion of the subependymal NSC pool, suggesting a relationship between cell cycle control and long-term self-renewal, but the molecular mechanisms underlying NSC maintenance by p21 remain unexplored. Here we identify a function of p21 in the direct regulation of the expression of pluripotency factor Sox2, a key regulator of the specification and maintenance of neural progenitors. We observe that p21 directly binds a Sox2 enhancer and negatively regulates Sox2 expression in NSCs. Augmented levels of Sox2 in p21 null cells induce replicative stress and a DNA damage response that leads to cell growth arrest mediated by increased levels of p19(Arf) and p53. Our results show a regulation of NSC expansion driven by a p21/Sox2/p53 axis

No Place Like Home: Examining a Bilingual-Bicultural, Self-Run Substance Abuse Recovery Home for Latinos

Latinos often do not seek substance abuse services, and this might be correlated to the lack of culturally-modified substance abuse treatment approaches. Oxford House is the largest self-help residential recovery program in the U.S., yet few Latinos are among their current residents. In an effort to change this, bilingual-bicultural recovery homes were recently developed for Latinos. This article describes the process in opening these bilingual-bicultural houses and how sociocultural factors such as the family, simpatía, and gender roles impacted the living environment of these houses. In addition, language is highlighted as a key factor to the comfort and success of Latinos living in Oxford Houses. Based on these experiences, the article addresses several obstacles/barriers that impacted this process and possible feasible solutions to these challenges. One challenge is the Latino family system. While this may provide a supportive, cost-effective option for some; it can also perpetuate a cycle of codependence and substance abuse

Treating horse chronic laminitis with allogeneic bone marrow mesenchymal stem cells

La laminitis crónica es una condición incapacitante que afecta el corion laminar de los cascos del caballo. Por lo general, se desarrolla como una lesión colateral de numerosas enfermedades sistémicas primarias. Se cree que el evento fisiopatológico crítico que hace que un casco sea vuelva laminítico es la pérdida de células madre mesenquimales. Esta pérdida perjudica en gran medida la capacidad del corion laminar para regenerarse. Aunque el trabajo previo proporciona credibilidad a esta noción, quedan cuestiones sin resolver que deben abordarse antes de aceptarla como un hecho bien fundado. Aquí, se reexaminó el principio central del modelo fisiopatológico de la laminitis mediante la infusión de células madre mesenquimales alogénicas derivadas de la médula ósea (CMM-AMO), a través de la vena palmar digital, en los cascos de los caballos afectados por laminitis crónica. Los caballos fueron monitoreados clínicamente durante 6 meses, evaluándolos mensualmente utilizando la escala de Obel-Glasgow de cojera modificada y la termografía de cascos. Se tomaron venogramas y biopsias laminares al principio y al final del período de estudio para reunir evidencia sobre la remodelación vascular y la regeneración del corion laminar. Los resultados mostraron que la infusión de CMM-AMO promueve la remodelación vascular y la regeneración del corion laminar, lo que respalda aún más que la pérdida de células madre es el evento crítico que conduce a la laminitis crónica. Este trabajo también demostró que la infusión de CMM-AMO es segura ya que los caballos tratados no desarrollaron manifestaciones clínicas negativas locales o sistémicas en sintonía con reacciones de rechazo, al menos durante el período de 6 meses en que se les dio seguimiento y bajo el esquema terapéutico propuesto.Chronic laminitis is a disabling condition that affects the laminar corium of the horse’s hooves. Commonly, it develops as a collateral injury of numerous primary systemic diseases. It is believed that the critical physiopathological event that renders a hoof laminitic is the loss of mesenchymal stem cells. This loss greatly impairs the ability of the laminar corium to regenerate. Although previous work provides credibility to this notion, there remain unsettled issues that must be addressed before accepting it as a well-founded fact. Here, it was reexamined the central tenet of the physiopathological model of laminitis by infusing allogeneic bone marrow-derived mesenchymal stem cells (ABM-MSCs), through the digital palmar vein, into the hooves of horses afflicted by chronic laminitis. Horses were clinically monitored during 6 mo by evaluating them monthly using the lameness-modified Obel-Glasgow’s scale and hooves thermography. Venograms and lamellar biopsies were taken at the beginning and at the end of the study period to gathered evidence on vascular remodeling and laminar corium regeneration. The results showed that ABM-MSCs infusion promotes vascular remodeling and laminar corium regeneration, further supporting that the loss of stem cells is the critical event leading to chronic laminitis. This work also demonstrated that the infusion of ABM-MSCs is safe since the treated horses did not develop local or systemic, negative clinical manifestations attuned with rejection reactions, at least during the 6-mo period they were follow up and under the therapeutic scheme proposed

Anomalous processes at high temperature and density in a 2-dimensional linear σ\sigma model

We use the 2-dimensional $\sigma$ model as a toy model to study the behavior of anomalous amplitudes in the limit where the constituent quark mass is small. Symmetry arguments tell that the $\pi^o\to\gamma$ amplitude should vanish if $m\to 0$, but we show that this conclusion is spoiled by infrared singularities. When a proper regularization (resummation of a thermal mass, for instance) is taken into account, this amplitude vanishes as expected. We also study the amplitude $\pi^o\sigma\to\gamma$ and show that it does not vanish in the same limit.Comment: 15 pages Latex document, 2 postscript figure

Young massive star cluster formation in the Galactic Centre is driven by global gravitational collapse of high-mass molecular clouds

This article has been accepted for publication in Monthly Notices of the Royal Astronomical Society © 2019 The Author(s). Published by Oxford University Press on behalf of the Royal Astronomical Society. All rights reserved.Young massive clusters (YMCs) are the most compact, high-mass stellar systems still forming at the present day. The precursor clouds to such systems are, however, rare due to their large initial gas mass reservoirs and rapid dispersal time-scales due to stellar feedback. None the less, unlike their high-z counterparts, these precursors are resolvable down to the sites of individually forming stars, and hence represent the ideal environments in which to test the current theories of star and cluster formation. Using high angular resolution (1 arcsec / 0.05 pc) and sensitivity ALMA observations of two YMC progenitor clouds in the Galactic Centre, we have identified a suite of molecular line transitions – e.g. c-C3H2 (7 − 6) – that are believed to be optically thin, and reliably trace the gas structure in the highest density gas on star-forming core scales. We conduct a virial analysis of the identified core and proto-cluster regions, and show that half of the cores (5/10) and both proto-clusters are unstable to gravitational collapse. This is the first kinematic evidence of global gravitational collapse in YMC precursor clouds at such an early evolutionary stage. The implications are that if these clouds are to form YMCs, then they likely do so via the ‘conveyor-belt’ mode, whereby stars continually form within dispersed dense gas cores as the cloud undergoes global gravitational collapse. The concurrent contraction of both the cluster-scale gas and embedded (proto-)stars ultimately leads to the high (proto-)stellar density in YMCs

Anomalous mesonic interactions near a chiral phase transition

Using constituent quarks coupled to a linear sigma model at nonzero temperature, I show that many anomalous mesonic amplitudes, such as $\pi^0 \rightarrow \gamma \gamma$, vanish in a chirally symmetric phase. Processes which are allowed, such as $\pi^0 \sigma \rightarrow \gamma \gamma$, are computed to leading order in a loop expansion.Comment: 4 pages, REVTeX, submitted to Phys. Rev. Let

Highlights from the Pierre Auger Observatory

The Pierre Auger Observatory is the world's largest cosmic ray observatory. Our current exposure reaches nearly 40,000 km$^2$ str and provides us with an unprecedented quality data set. The performance and stability of the detectors and their enhancements are described. Data analyses have led to a number of major breakthroughs. Among these we discuss the energy spectrum and the searches for large-scale anisotropies. We present analyses of our X$_{max}$ data and show how it can be interpreted in terms of mass composition. We also describe some new analyses that extract mass sensitive parameters from the 100% duty cycle SD data. A coherent interpretation of all these recent results opens new directions. The consequences regarding the cosmic ray composition and the properties of UHECR sources are briefly discussed.Comment: 9 pages, 12 figures, talk given at the 33rd International Cosmic Ray Conference, Rio de Janeiro 201

Azimuthal asymmetry in the risetime of the surface detector signals of the Pierre Auger Observatory

The azimuthal asymmetry in the risetime of signals in Auger surface detector stations is a source of information on shower development. The azimuthal asymmetry is due to a combination of the longitudinal evolution of the shower and geometrical effects related to the angles of incidence of the particles into the detectors. The magnitude of the effect depends upon the zenith angle and state of development of the shower and thus provides a novel observable, $(\sec \theta)_\mathrm{max}$, sensitive to the mass composition of cosmic rays above $3 \times 10^{18}$ eV. By comparing measurements with predictions from shower simulations, we find for both of our adopted models of hadronic physics (QGSJETII-04 and EPOS-LHC) an indication that the mean cosmic-ray mass increases slowly with energy, as has been inferred from other studies. However, the mass estimates are dependent on the shower model and on the range of distance from the shower core selected. Thus the method has uncovered further deficiencies in our understanding of shower modelling that must be resolved before the mass composition can be inferred from $(\sec \theta)_\mathrm{max}$.Comment: Replaced with published version. Added journal reference and DO

Ultrahigh-energy neutrino follow-up of Gravitational Wave events GW150914 and GW151226 with the Pierre Auger Observatory

On September 14, 2015 the Advanced LIGO detectors observed their first gravitational-wave (GW) transient GW150914. This was followed by a second GW event observed on December 26, 2015. Both events were inferred to have arisen from the merger of black holes in binary systems. Such a system may emit neutrinos if there are magnetic fields and disk debris remaining from the formation of the two black holes. With the surface detector array of the Pierre Auger Observatory we can search for neutrinos with energy above 100 PeV from point-like sources across the sky with equatorial declination from about -65 deg. to +60 deg., and in particular from a fraction of the 90% confidence-level (CL) inferred positions in the sky of GW150914 and GW151226. A targeted search for highly-inclined extensive air showers, produced either by interactions of downward-going neutrinos of all flavors in the atmosphere or by the decays of tau leptons originating from tau-neutrino interactions in the Earth's crust (Earth-skimming neutrinos), yielded no candidates in the Auger data collected within $\pm 500$ s around or 1 day after the coordinated universal time (UTC) of GW150914 and GW151226, as well as in the same search periods relative to the UTC time of the GW candidate event LVT151012. From the non-observation we constrain the amount of energy radiated in ultrahigh-energy neutrinos from such remarkable events.Comment: Published version. Added journal reference and DOI. Added Report Numbe