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

Arbovirosis y Viruela del Mono - ¿Un diagnóstico diferencial de solapamiento epidemiológico?

Editorial (no abstract)Editorial (Sin resumen

Galilean quantum gravity with cosmological constant and the extended q-Heisenberg algebra

We define a theory of Galilean gravity in 2+1 dimensions with cosmological constant as a Chern-Simons gauge theory of the doubly-extended Newton-Hooke group, extending our previous study of classical and quantum gravity in 2+1 dimensions in the Galilean limit. We exhibit an r-matrix which is compatible with our Chern-Simons action (in a sense to be defined) and show that the associated bi-algebra structure of the Newton-Hooke Lie algebra is that of the classical double of the extended Heisenberg algebra. We deduce that, in the quantisation of the theory according to the combinatorial quantisation programme, much of the quantum theory is determined by the quantum double of the extended q-deformed Heisenberg algebra.Comment: 22 page

Penrose limit, Spontaneous Symmetry Breaking and Holography in PP-Wave Background

We argue that the gauge theory dual to the Type IIB string theory in ten-dimensional pp-wave background can be thought to `live' on an {\it Euclidean} subspace spanning four of the eight transverse coordinates. We then show that light-cone time evolution of the string is identifiable as the RG flow of the gauge theory -- a relation facilitating `holography' of the pp-wave background. The `holography' reorganizes the dual gauge theory into theories defined over Hilbert subspaces of fixed R-charge. The reorganization breaks the SO(4,2)$\times$SO(6) symmetry to a maximal subgroup SO(4)$\times$ SO(4) spontaneously. We argue that the low-energy string modes may be regarded as Goldstone modes resulting from such symmetry breaking pattern.Comment: LateX 24 pages; v2 : new subsection added about relation to usual Yang-Mills, references adde

Light-cone M5 and multiple M2-branes

We present the light-cone gauge fixed Lagrangian for the M5-brane; it has a residual `exotic' gauge invariance with the group of 5-volume preserving diffeomorphisms, SDiff(5), as gauge group. For an M5-brane of topology R2 x M3, for closed 3-manifold M3, we find an infinite tension limit that yields an SO(8)-invariant (1+2)-dimensional field theory with `exotic' SDiff(3) gauge invariance. We show that this field theory is the Carrollian limit of the Nambu bracket realization of the `BLG' model for multiple M2-branes.Comment: 21 pages, revised to clarify some points, to include a discussion of SDiff gauge invariance, and to add two reference

Base-Pair Resolution DNA Methylation Sequencing Reveals Profoundly Divergent Epigenetic Landscapes in Acute Myeloid Leukemia

We have developed an enhanced form of reduced representation bisulfite sequencing with extended genomic coverage, which resulted in greater capture of DNA methylation information of regions lying outside of traditional CpG islands. Applying this method to primary human bone marrow specimens from patients with Acute Myelogeneous Leukemia (AML), we demonstrated that genetically distinct AML subtypes display diametrically opposed DNA methylation patterns. As compared to normal controls, we observed widespread hypermethylation in IDH mutant AMLs, preferentially targeting promoter regions and CpG islands neighboring the transcription start sites of genes. In contrast, AMLs harboring translocations affecting the MLL gene displayed extensive loss of methylation of an almost mutually exclusive set of CpGs, which instead affected introns and distal intergenic CpG islands and shores. When analyzed in conjunction with gene expression profiles, it became apparent that these specific patterns of DNA methylation result in differing roles in gene expression regulation. However, despite this subtype-specific DNA methylation patterning, a much smaller set of CpG sites are consistently affected in both AML subtypes. Most CpG sites in this common core of aberrantly methylated CpGs were hypermethylated in both AML subtypes. Therefore, aberrant DNA methylation patterns in AML do not occur in a stereotypical manner but rather are highly specific and associated with specific driving genetic lesions

Age at menopause in Latin America

OBJECTIVE: To assess the age at menopause (AM) in Latin America urban areas. DESIGN: A total of 17,150 healthy women, aged 40 to 59 years, accompanying patients to healthcare centers in 47 cities of 15 Latin American countries, were surveyed regarding their age, educational level, healthcare coverage, history of gynecological surgery, smoking habit, presence of menses, and the use of contraception or hormone therapy at menopause. The AM was calculated using logit analysis. RESULTS: The mean age of the entire sample was 49.4 ± 5.5 years. Mean educational level was 9.9 ± 4.5 years, and the use of hormone therapy and oral contraception was 22.1% and 7.9%, respectively. The median AM of women in all centers was 48.6 years, ranging from 43.8 years in Asuncion (Paraguay) to 53 years in Cartagena de Indias (Colombia). Logistic regression analysis determined that women aged 49 living in cities at 2,000 meters or more above sea level (OR = 2.0, 95% CI: 1.4-2.9, P less than 0.001) and those with lower educational level (OR = 1.9, 95% CI: 1.3-2.8, P less than 0.001) or living in countries with low gross national product (OR = 2.1, 95% CI: 1.5-2.9, P less than 0.001) were more prone to an earlier onset of menopause. CONCLUSIONS: The AM varies widely in Latin America. Lower income and related poverty conditions influence the onset of menopause. © 2006 by The North American Menopause Society

Supporting Spartina: Interdisciplinary Perspective Shows Spartina As A Distinct Solid Genus

In 2014, a DNA-based phylogenetic study confirming the paraphyly of the grass subtribe Sporobolinae proposed the creation of a large monophyletic genus Sporobolus, including (among others) species previously included in the genera Spartina, Calamovilfa, and Sporobolus. Spartina species have contributed substantially (and continue contributing) to our knowledge in multiple disciplines, including ecology, evolutionary biology, molecular biology, biogeography, experimental ecology, biological invasions, environmental management, restoration ecology, history, economics, and sociology. There is no rationale so compelling to subsume the name Spartina as a subgenus that could rival the striking, global iconic history and use of the name Spartina for over 200 yr. We do not agree with the subjective arguments underlying the proposal to change Spartina to Sporobolus. We understand the importance of both the objective phylogenetic insights and of the subjective formalized nomenclature and hope that by opening this debate we will encourage positive feedback that will strengthen taxonomic decisions with an interdisciplinary perspective. We consider that the strongly distinct, monophyletic clade Spartina should simply and efficiently be treated as the genus Spartina

Tyrannobdella rex N. Gen. N. Sp. and the Evolutionary Origins of Mucosal Leech Infestations

BACKGROUND: Leeches have gained a fearsome reputation by feeding externally on blood, often from human hosts. Orificial hirudiniasis is a condition in which a leech enters a body orifice, most often the nasopharyngeal region, but there are many cases of leeches infesting the eyes, urethra, vagina, or rectum. Several leech species particularly in Africa and Asia are well-known for their propensity to afflict humans. Because there has not previously been any data suggesting a close relationship for such geographically disparate species, this unnerving tendency to be invasive has been regarded only as a loathsome oddity and not a unifying character for a group of related organisms. PRINCIPAL FINDINGS: A new genus and species of leech from Perú was found feeding from the nasopharynx of humans. Unlike any other leech previously described, this new taxon has but a single jaw with very large teeth. Phylogenetic analyses of nuclear and mitochondrial genes using parsimony and Bayesian inference demonstrate that the new species belongs among a larger, global clade of leeches, all of which feed from the mucosal surfaces of mammals. CONCLUSIONS: This new species, found feeding from the upper respiratory tract of humans in Perú, clarifies an expansion of the family Praobdellidae to include the new species Tyrannobdella rex n. gen. n. sp., along with others in the genera Dinobdella, Myxobdella, Praobdella and Pintobdella. Moreover, the results clarify a single evolutionary origin of a group of leeches that specializes on mucous membranes, thus, posing a distinct threat to human health