Induced dicentric chromosome formation promotes genomic rearrangements and tumorigenesis

Chromosomal rearrangements can radically alter gene products and their function, driving tumor formation or progression. However, the molecular origins and evolution of such rearrangements are varied and poorly understood, with cancer cells often containing multiple, complex rearrangements. One mechanism that can lead to genomic rearrangements is the formation of a “dicentric” chromosome containing two functional centromeres. Indeed, such dicentric chromosomes have been observed in cancer cells. Here, we tested the ability of a single dicentric chromosome to contribute to genomic instability and neoplastic conversion in vertebrate cells. We developed a system to transiently and reversibly induce dicentric chromosome formation on a single chromosome with high temporal control. We find that induced dicentric chromosomes are frequently damaged and mis-segregated during mitosis, and that this leads to extensive chromosomal rearrangements including translocations with other chromosomes. Populations of pre-neoplastic cells in which a single dicentric chromosome is induced acquire extensive genomic instability and display hallmarks of cellular transformation including anchorage-independent growth in soft agar. Our results suggest that a single dicentric chromosome could contribute to tumor initiation.Leukemia & Lymphoma Society of America (Scholar Award)National Institute of General Medical Sciences (U.S.) (Grant GM088313)American Cancer Society (Research Scholar Grant 121776

A dynamical trichotomy for structured populations experiencing positive density-dependence in stochastic environments

Positive density-dependence occurs when individuals experience increased survivorship, growth, or reproduction with increased population densities. Mechanisms leading to these positive relationships include mate limitation, saturating predation risk, and cooperative breeding and foraging. Individuals within these populations may differ in age, size, or geographic location and thereby structure these populations. Here, I study structured population models accounting for positive density-dependence and environmental stochasticity i.e. random fluctuations in the demographic rates of the population. Under an accessibility assumption (roughly, stochastic fluctuations can lead to populations getting small and large), these models are shown to exhibit a dynamical trichotomy: (i) for all initial conditions, the population goes asymptotically extinct with probability one, (ii) for all positive initial conditions, the population persists and asymptotically exhibits unbounded growth, and (iii) for all positive initial conditions, there is a positive probability of asymptotic extinction and a complementary positive probability of unbounded growth. The main results are illustrated with applications to spatially structured populations with an Allee effect and age-structured populations experiencing mate limitation

Algal Bloom Expansion Increases Cyanotoxin Risk in Food

As advances in global transportation infrastructure make it possible for out of season foods to be available year-round, the need for assessing the risks associated with the food production and expanded distribution are even more important. Risks for foodborne illness are associated with contamination by bacteria, viruses, mold, parasites, natural and synthetic toxins, chemical residues, and conditions that lead to contamination. An increase in the popularity of natural alternatives to pharmaceuticals, herbal remedies and the desire for consuming “super foods” is leading to a change in the dietary patterns of consumers. Similarly, dietary trends are plentiful, with more consumers adopting changes with little medical guidance to dietary plans that are supported by inadequate scientific data. In particular, U.S. consumers are acquiring novel foods that may not be adequately checked for the presence of marine toxins and heat stable toxins in dry or minimally processed foods. Some dry foods cultivated in or processed in regions that may utilize hypoxic agricultural waters high in cyanobacterial or algal contamination. These may perpetuate increased risks for chronic liver, kidney, and neurodegenerative disorders due to intoxication from preventable foodborne agents. Global climate change, which has the effect of potentially expanding the toxic waters into higher latitudes, forecasts an increase in the risk of food contamination with toxins

CDK-dependent phosphorylation and nuclear exclusion coordinately control kinetochore assembly state

Accurate chromosome segregation requires assembly of the multiprotein kinetochore complex. Prior work has identified more than 100 different kinetochore components in human cells. However, little is known about the regulatory processes that specify their assembly upon mitotic entry and disassembly at mitotic exit. In this paper, we used a live-cell imaging–based assay to quantify kinetochore disassembly kinetics and systematically analyze the role of potential regulatory mechanisms in controlling kinetochore assembly state. We find that kinetochore assembly and disassembly was driven primarily by mitotic phosphorylation downstream of cyclin-dependent kinase (CDK). In addition, we demonstrate that nuclear exclusion of the Ndc80 complex helped restrict kinetochore formation to mitosis. Combining constitutive CDK-dependent phosphorylation of CENP-T and forced nuclear localization of the Ndc80 complex partially prevented kinetochore disassembly at mitotic exit and led to chromosome segregation defects in subsequent divisions. In total, we find that the coordinated temporal regulation of outer kinetochore assembly is essential for accurate cell division.Kinship Foundation. Searle Scholars ProgramLeukemia & Lymphoma Society of AmericaNational Institutes of Health (U.S.) (National Institute of General Medical Sciences (U.S.) Grant GM088313)Leukemia & Lymphoma Society of America (Special Fellows Award

Butterfly surveys in Albania during 2014 including the discovery of two new species for the country

During field surveys conducted in Albania in 2014, we encountered 90 species of butterflies. Anthocharis damone Boisduval, 1836 is a new species for the fauna of Albania while Apatura metis Freyer, 1829 is confirmed for the country. With these discoveries the number of butterfly species known to occur in Albania has risen to 200 and our surveys added many new sites for species considered rare and local in Albania. In addition, the life cycles of Lycaena ottomana (Lefèbvre, 1830) and Apatura metis from Albania are documented and discussed

Discovery of > 200 RR Lyrae Variables in M62: An Oosterhoff I Globular Cluster with a Predominantly Blue HB

We report on the discovery of a large number of RR Lyrae variable stars in the moderately metal-rich Galactic globular cluster M62 (NGC 6266), which places it among the top three most RR Lyrae-rich globular clusters known. Likely members of the cluster in our studied field, from our preliminary number counts, include about 130 fundamental-mode (RRab) pulsators, with = 0.548 d, and about 75 first-overtone (RRc) pulsators, with = 0.300 d. The average periods and the position of the RRab variables with well-defined light curves in the Bailey diagram both suggest that the cluster is of Oosterhoff type I. However, the morphology of the cluster's horizontal branch (HB) is strikingly similar to that of the Oosterhoff type II globular cluster M15 (NGC 7078), with a dominant blue HB component and a very extended blue tail. Since M15 and M62 differ in metallicity by about one dex, we conclude that metallicity, at a fixed HB type, is a key parameter determining the Oosterhoff status of a globular cluster and the position of its variables in the Bailey diagram.Comment: 5 pages, 4 figures. ApJ Letters, in pres

Classical Cepheid Pulsation Models. III. The Predictable Scenario

Within the current uncertainties in the treatment of the coupling between pulsation and convection, limiting amplitude, nonlinear, convective models appear the only viable approach for providing theoretical predictions about the intrinsic properties of radial pulsators. In this paper we present the results of a comprehensive set of Cepheid models computed within such theoretical framework for selected assumptions on their original chemical composition.Comment: 24 pages, 1 latex file containing 6 tables, 10 postscript figures, accepted for publication on Ap

A new LMC K-band distance from precision measurements of nearby red clump stars

High-precision (sigma < 0.01) new JHK observations of 226 of the brightest and nearest red clump stars in the solar neighbourhood are used to determine distance moduli for the LMC. The resulting K- and H-band values of 18.47\pm0.02 and 18.49\pm0.06 imply that any correction to the K-band Cepheid PL relation due to metallicity differences between Cepheids in the LMC and in the solar neighborhood must be quite small.Comment: 7 pages, 4 figure

Structure of the Large Magellanic Cloud from 2MASS

We derive structural parameters and evidence for extended tidal debris from star count and preliminary standard candle analyses of the Large Magellanic Cloud based on Two Micron All Sky Survey (2MASS) data. The full-sky coverage and low extinction in K_s presents an ideal sample for structural analysis of the LMC. The star count surface densities and deprojected inclination for both young and older populations are consistent with previous work. We use the full areal coverage and large LMC diameter to Galactrocentric distance ratio to infer the same value for the disk inclination based on perspective. A standard candle analysis based on a sample of carbon long-period variables (LPV) in a narrow color range, 1.6<J-K_s<1.7 allows us to probe the three-dimensional structure of the LMC along the line of sight. The intrinsic brightness distribution of carbon LPVs in selected fields implies that \sigma_M\simlt 0.2^m for this color cut. The sample provides a {\it direct} determination of the LMC disk inclination: $42.3^\circ\pm 7.2^\circ$. Distinct features in the photometric distribution suggest several distinct populations. We interpret this as the presence of an extended stellar component of the LMC, which may be as thick as 14 kpc, and intervening tidal debris at roughly 15 kpc from the LMC.Comment: 24 pages, 9 figures. Submitted to Ap