hNuf2 inhibition blocks stable kinetochore–microtubule attachment and induces mitotic cell death in HeLa cells

Identification of proteins that couple kinetochores to spindle microtubules is critical for understanding how accurate chromosome segregation is achieved in mitosis. Here we show that the protein hNuf2 specifically functions at kinetochores for stable microtubule attachment in HeLa cells. When hNuf2 is depleted by RNA interference, spindle formation occurs normally as cells enter mitosis, but kinetochores fail to form their attachments to spindle microtubules and cells block in prometaphase with an active spindle checkpoint. Kinetochores depleted of hNuf2 retain the microtubule motors CENP-E and cytoplasmic dynein, proteins previously implicated in recruiting kinetochore microtubules. Kinetochores also retain detectable levels of the spindle checkpoint proteins Mad2 and BubR1, as expected for activation of the spindle checkpoint by unattached kinetochores. In addition, the cell cycle block produced by hNuf2 depletion induces mitotic cells to undergo cell death. These data highlight a specific role for hNuf2 in kinetochore–microtubule attachment and suggest that hNuf2 is part of a molecular linker between the kinetochore attachment site and tubulin subunits within the lattice of attached plus ends

Growers say cannabis legalization excludes small growers, supports illicit markets, undermines local economies

H. Bodwitch is Postdoctoral Fellow, Department of Natural Resource Sciences, McGill University, Quebec, Canada; J. Carah is Senior Freshwater Ecologist, The Nature Conservancy, San Francisco; K.M. Daane is UC Cooperative Extension Specialist, Department of Environmental Science, Policy, and Management, UC Berkeley; C. Getz is Associate Cooperative Extension Specialist, Department of Environmental Science, Policy, and Management, UC Berkeley; T.E. Grantham is Assistant Cooperative Extension Specialist and Adjunct Professor, Department of Environmental Science, Policy, and Management, UC Berkeley; G.M. Hickey is Associate Professor, Department of Natural Resource Sciences, McGill University, Quebec, Canada; H. Wilson is Assistant Cooperative Extension Specialist, Department of Entomology, UC Riverside

Hickey MM, Lam JC, Bezman NA, Rathmell WK, Simon MC.. von Hippel-Lindau mutation in mice recapitulates Chuvash polycythemia via hypoxia-inducible factor-2alpha signaling and splenic erythropoiesis. J Clin Invest 117: 3879-3889

The R200W mutation in the von Hippel-Lindau (VHL) tumor suppressor protein (pVHL) is unique in that it is not associated with tumor development, but rather with Chuvash polycythemia, a heritable disease characterized by elevated hematocrit and increased serum levels of erythropoietin and VEGF. Previous studies have implicated hypoxia-inducible factor-1alpha (HIF-1alpha) signaling in this disorder, although the effects of this mutation on pVHL function are not fully understood. In order to explore the mechanisms underlying the development of this polycythemia, we generated mice homozygous for the R200W mutation (Vhl(R/R)). Vhl(R/R) mice developed polycythemia highly similar to the human disease. The activity of HIF proteins, specifically the HIF-2alpha isoform, was upregulated in ES cells and tissues from Vhl(R/R) mice. Furthermore, we observed a striking phenotype in Vhl(R/R) spleens, with greater numbers of erythroid progenitors and megakaryocytes and increased erythroid differentiation of Vhl(R/R) splenic cells in vitro. These findings suggest that enhanced expression of key HIF-2alpha genes promotes splenic erythropoiesis, resulting in the development of polycythemia in Vhl(R/R) mice. This mouse model is a faithful recapitulation of this VHL-associated syndrome and represents a useful tool for studying polycythemias and investigating potential therapeutics

Understanding interannual, decadal level variability in paralytic shellfish poisoning toxicity in the Gulf of Maine : the HAB Index

Author Posting. © The Author(s), 2013. This is the author's version of the work. It is posted here by permission of Elsevier for personal use, not for redistribution. The definitive version was published in Deep Sea Research Part II: Topical Studies in Oceanography 103 (2014): 264-276, doi:10.1016/j.dsr2.2013.09.018.A major goal in harmful algal bloom (HAB) research has been to identify mechanisms underlying interannual variability in bloom magnitude and impact. Here the focus is on variability in Alexandrium fundyense blooms and paralytic shellfish poisoning (PSP) toxicity in Maine, USA, over 34 years (1978 – 2011). The Maine coastline was divided into two regions - eastern and western Maine, and within those two regions, three measures of PSP toxicity (the percent of stations showing detectable toxicity over the year, the cumulative amount of toxicity per station measured in all shellfish (mussel) samples during that year, and the duration of measurable toxicity) were examined for each year in the time series. These metrics were combined into a simple HAB Index that provides a single measure of annual toxin severity across each region. The three toxin metrics, as well as the HAB Index that integrates them, reveal significant variability in overall toxicity between individual years as well as long-term, decadal patterns or regimes. Based on different conceptual models of the system, we considered three trend formulations to characterize the long-term patterns in the Index – a three-phase (mean-shift) model, a linear two-phase model, and a pulse-decline model. The first represents a “regime shift” or multiple equilibria formulation as might occur with alternating periods of sustained high and low cyst abundance or favorable and unfavorable growth conditions, the second depicts a scenario of more gradual transitions in cyst abundance or growth conditions of vegetative cells, and the third characterizes a ”sawtooth” pattern in which upward shifts in toxicity are associated with major cyst recruitment events, followed by a gradual but continuous decline until the next pulse. The fitted models were compared using both residual sum of squares and Akaike’s Information Criterion. There were some differences between model fits, but none consistently gave a better fit than the others. This statistical underpinning can guide efforts to identify physical and/or biological mechanisms underlying the patterns revealed by the HAB Index. Although A. fundyense cyst survey data (limited to 9 years) do not span the entire interval of the shellfish toxicity records, this analysis leads us to hypothesize that major changes in the abundance of A. fundyense cysts may be a primary factor contributing to the decadal trends in shellfish toxicity in this region. The HAB Index approach taken here is simple but represents a novel and potentially useful tool for resource managers in many areas of the world subject to toxic HABs.Research support provided through the Woods Hole Center for Oceans and Human Health, National Science Foundation (NSF) Grants OCE- 1128041 and OCE-1314642; and National Institute of Environmental Health Sciences (NIEHS) Grant 1-P50-ES021923-01, the ECOHAB Grant program through NOAA Grants NA06NOS4780245 and NA09NOS4780193, the MERHAB Grant program through NOAA Grant NA11NOS4780025, the PCMHAB Grant program through NOAA Grant NA11NOS4780023, and funding through the states of ME, NH, and MA. Funding for J.L. Martin was provided by Fisheries and Oceans Canada

A Close Companion Search Around L Dwarfs Using Aperture Masking Interferometry and Palomar Laser Guide Star Adaptive Optics

We present a close companion search around 16 known early L dwarfs using aperture masking interferometry with Palomar laser guide star adaptive optics (LGS AO). The use of aperture masking allows the detection of close binaries, corresponding to projected physical separations of 0.6-10.0 AU for the targets of our survey. This survey achieved median contrast limits of ΔK ~ 2.3 for separations between 1.2λ/D-4λ/D and ΔK ~ 1.4 at 2/3λ/D. We present four candidate binaries detected with moderate-to-high confidence (90%-98%). Two have projected physical separations less than 1.5 AU. This may indicate that tight-separation binaries contribute more significantly to the binary fraction than currently assumed, consistent with spectroscopic and photometric overluminosity studies. Ten targets of this survey have previously been observed with the Hubble Space Telescope as part of companion searches. We use the increased resolution of aperture masking to search for close or dim companions that would be obscured by full aperture imaging, finding two candidate binaries. This survey is the first application of aperture masking with LGS AO at Palomar. Several new techniques for the analysis of aperture masking data in the low signal-to-noise regime are explored

Half-Dead Colonies of Montastraea Annularis Release Viable Gametes On A Degraded Reef In The Us Virgin Islands

This article contributes to scholarship on Afroeurope by investigating the intersection of blackness, Africanness, and Europeanness in everyday discourses and social practices in the Netherlands and Italy. We examine how young African-descended Europeans are forging new ways of being both African and European through practices of self-making, which should be understood against both the historical background of colonialism and the contemporary politics of othering. Such practices take on an urgency for these youth, often encompassing a reinvention of Africanness and/or blackness as well as a challenge to dominant, exclusionary understandings of Europeanness. Comparing Afro-Dutch and Afro-Italian modes of self-making, centred on African heritage and roots, we discuss: 1) the emergence of a transnational, Afroeuropean imaginary, distinguished from both white Europe and African-American formations; and 2) the diversity of Afroeuropean modes of self-making, all rooted in distinct histories of colonialism, slavery, and immigration, and influenced by global formations of Africanness and blackness. These new Afro and African identities advanced by young Europeans do not turn away from Europeanness (as dominant identity models would assume: the more African, the less European), nor simply add to Europeanness (“multicultural” identities), nor even mix with Europeanness (“hybrid” identities), but are in and of themselves European

PALM-3000 high-order adaptive optics system for Palomar Observatory

Deployed as a multi-user shared facility on the 5.1 meter Hale Telescope at Palomar Observatory, the PALM-3000 highorder upgrade to the successful Palomar Adaptive Optics System will deliver extreme AO correction in the near-infrared, and diffraction-limited images down to visible wavelengths, using both natural and sodium laser guide stars. Wavefront control will be provided by two deformable mirrors, a 3368 active actuator woofer and 349 active actuator tweeter, controlled at up to 3 kHz using an innovative wavefront processor based on a cluster of 17 graphics processing units. A Shack-Hartmann wavefront sensor with selectable pupil sampling will provide high-order wavefront sensing, while an infrared tip/tilt sensor and visible truth wavefront sensor will provide low-order LGS control. Four back-end instruments are planned at first light: the PHARO near-infrared camera/spectrograph, the SWIFT visible light integral field spectrograph, Project 1640, a near-infrared coronagraphic integral field spectrograph, and 888Cam, a high-resolution visible light imager