572 research outputs found
Histone H1 is essential for mitotic chromosome architecture and segregation in Xenopus laevis egg extracts.
During cell division, condensation and resolution of chromosome arms and the assembly of a functional kinetochore at the centromere of each sister chromatid are essential steps for accurate segregation of the genome by the mitotic spindle, yet the contribution of individual chromatin proteins to these processes is poorly understood. We have investigated the role of embryonic linker histone H1 during mitosis in Xenopus laevis egg extracts. Immunodepletion of histone H1 caused the assembly of aberrant elongated chromosomes that extended off the metaphase plate and outside the perimeter of the spindle. Although functional kinetochores assembled, aligned, and exhibited poleward movement, long and tangled chromosome arms could not be segregated in anaphase. Histone H1 depletion did not significantly affect the recruitment of known structural or functional chromosomal components such as condensins or chromokinesins, suggesting that the loss of H1 affects chromosome architecture directly. Thus, our results indicate that linker histone H1 plays an important role in the structure and function of vertebrate chromosomes in mitosis
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Blood-based bioenergetic profiling is related to differences in brain morphology in African Americans with Type 2 diabetes.
Blood-based bioenergetic profiling has promising applications as a minimally invasive biomarker of systemic bioenergetic capacity. In the present study, we examined peripheral blood mononuclear cell (PBMC) mitochondrial function and brain morphology in a cohort of African Americans with long-standing Type 2 diabetes. Key parameters of PBMC respiration were correlated with white matter, gray matter, and total intracranial volumes. Our analyses indicate that these relationships are primarily driven by the relationship of systemic bioenergetic capacity with total intracranial volume, suggesting that systemic differences in mitochondrial function may play a role in overall brain morphology
Histone H1 is essential for mitotic chromosome architecture and segregation in Xenopus laevis egg extracts
During cell division, condensation and resolution of chromosome arms and the assembly of a functional kinetochore at the centromere of each sister chromatid are essential steps for accurate segregation of the genome by the mitotic spindle, yet the contribution of individual chromatin proteins to these processes is poorly understood. We have investigated the role of embryonic linker histone H1 during mitosis in Xenopus laevis egg extracts. Immunodepletion of histone H1 caused the assembly of aberrant elongated chromosomes that extended off the metaphase plate and outside the perimeter of the spindle. Although functional kinetochores assembled, aligned, and exhibited poleward movement, long and tangled chromosome arms could not be segregated in anaphase. Histone H1 depletion did not significantly affect the recruitment of known structural or functional chromosomal components such as condensins or chromokinesins, suggesting that the loss of H1 affects chromosome architecture directly. Thus, our results indicate that linker histone H1 plays an important role in the structure and function of vertebrate chromosomes in mitosis
Exploring Microbiome Functional Dynamics through Space and Time with Trait-Based Theory
Microbiomes play essential roles in the health and function of animal and plant hosts and drive nutrient cycling across ecosystems. Integrating novel trait-based approaches with ecological theory can facilitate the prediction of microbial functional traits important for ecosystem functioning and health. In particular, the yield-acquisition-stress (Y-A-S) framework considers dominant microbial life history strategies across gradients of resource availability and stress. However, microbiomes are dynamic, and spatial and temporal shifts in taxonomic and trait composition can affect ecosystem functions. We posit that extending the Y-A-S framework to microbiomes during succession and across biogeographic gradients can lead to generalizable rules for how microbiomes and their functions respond to resources and stress across space, time, and diverse ecosystems. We demonstrate the potential of this framework by applying it to the microbiomes hosted by the carnivorous pitcher plant Sarracenia purpurea, which have clear successional trajectories and are distributed across a broad climatic gradient
Precision Primordial He Measurement with CMB Experiments
Big bang nucleosynthesis (BBN) and the cosmic microwave background (CMB) are
two major pillars of cosmology. Standard BBN accurately predicts the primordial
light element abundances (He, D, He and Li), depending on one
parameter, the baryon density. Light element observations are used as a
baryometers. The CMB anisotropies also contain information about the content of
the universe which allows an important consistency check on the Big Bang model.
In addition CMB observations now have sufficient accuracy to not only determine
the total baryon density, but also resolve its principal constituents, H and
He. We present a global analysis of all recent CMB data, with special
emphasis on the concordance with BBN theory and light element observations. We
find and
(fraction of baryon mass as He) using CMB data alone, in agreement with
He abundance observations. With this concordance established we show that
the inclusion of BBN theory priors significantly reduces the volume of
parameter space. In this case, we find
and . We also find that the inclusion of deuterium
abundance observations reduces the and ranges by a factor
of 2. Further light element observations and CMB anisotropy experiments
will refine this concordance and sharpen BBN and the CMB as tools for precision
cosmology.Comment: 7 pages, 3 color figures made minor changes to bring inline with
journal versio
Gender Difference or Parallel Publics? The Dynamics of Defense Spending Opinions in the United States, 1965-2007
Gender is now recognized as an important dividing line in American political life, and
scholars have accumulated evidence that national security issues are an important
reason for gender differences in policy preferences. We therefore expect that the
dynamics of support for defense spending among men and women will differ. In
contrast, several scholars have shown that population subgroups exhibit a ββparallelββ
dynamic in which the evolution of their preferences over time is very similar, despite
differences in the average level of support. Unfortunately, there is little time series
evidence on gendered reactions to policy, including defense spending, that would
allow one to arbitrate between these competing perspectives. In this research note,
we assemble a time series of support for defense spending among men and women
and model the determinants of that support for the period 1967β2007. We find that
women are on average less supportive of defense spending than are men. However,
we also find that the over time variation of support for defense spending among men
and women is very similarβeach is conditioned principally by the past yearβs change
in defense spending and occasionally by war casualties and a trade-off between
defense and civilian spending
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Nephron organoids derived from human pluripotent stem cells model kidney development and injury
Kidney cells and tissues derived from human pluripotent stem cells (hPSCs) would enable organ regeneration, disease modeling, and drug screening in vitro. We established an efficient, chemically defined protocol for differentiating hPSCs into multipotent nephron progenitor cells (NPCs) that can form nephron-like structures. By recapitulating metanephric kidney development in vitro, we generate SIX2+SALL1+WT1+PAX2+ NPCs with 90% efficiency within 9 days of differentiation. The NPCs possess the developmental potential of their in vivo counterparts and form PAX8+LHX1+ renal vesicles that self-pattern into nephron structures. In both 2D and 3D culture, NPCs form kidney organoids containing epithelial nephron-like structures expressing markers of podocytes, proximal tubules, loops of Henle, and distal tubules in an organized, continuous arrangement that resembles the nephron in vivo. We also show that this organoid culture system can be used to study mechanisms of human kidney development and toxicity
Small-Molecule Probes Targeting the Viral PPxY-Host Nedd4 Interface Block Egress of a Broad Range of RNA Viruses.
Budding of filoviruses, arenaviruses, and rhabdoviruses is facilitated by subversion of host proteins, such as Nedd4 E3 ubiquitin ligase, by viral PPxY late (L) budding domains expressed within the matrix proteins of these RNA viruses. As L domains are important for budding and are highly conserved in a wide array of RNA viruses, they represent potential broad-spectrum targets for the development of antiviral drugs. To identify potential competitive blockers, we used the known Nedd4 WW domain-PPxY interaction interface as the basis of an in silico screen. Using PPxY-dependent budding of Marburg (MARV) VP40 virus-like particles (VLPs) as our model system, we identified small-molecule hit 1 that inhibited Nedd4-PPxY interaction and PPxY-dependent budding. This lead candidate was subsequently improved with additional structure-activity relationship (SAR) analog testing which enhanced antibudding activity into the nanomolar range. Current lead compounds 4 and 5 exhibit on-target effects by specifically blocking the MARV VP40 PPxY-host Nedd4 interaction and subsequent PPxY-dependent egress of MARV VP40 VLPs. In addition, lead compounds 4 and 5 exhibited antibudding activity against Ebola and Lassa fever VLPs, as well as vesicular stomatitis and rabies viruses (VSV and RABV, respectively). These data provide target validation and suggest that inhibition of the PPxY-Nedd4 interaction can serve as the basis for the development of a novel class of broad-spectrum, host-oriented antivirals targeting viruses that depend on a functional PPxY L domain for efficient egress.
IMPORTANCE: There is an urgent and unmet need for the development of safe and effective therapeutics against biodefense and high-priority pathogens, including filoviruses (Ebola and Marburg) and arenaviruses (e.g., Lassa and Junin) which cause severe hemorrhagic fever syndromes with high mortality rates. We along with others have established that efficient budding of filoviruses, arenaviruses, and other viruses is critically dependent on the subversion of host proteins. As disruption of virus budding would prevent virus dissemination, identification of small-molecule compounds that block these critical viral-host interactions should effectively block disease progression and transmission. Our findings provide validation for targeting these virus-host interactions as we have identified lead inhibitors with broad-spectrum antiviral activity. In addition, such inhibitors might prove useful for newly emerging RNA viruses for which no therapeutics would be available
A soliton menagerie in AdS
We explore the behaviour of charged scalar solitons in asymptotically global
AdS4 spacetimes. This is motivated in part by attempting to identify under what
circumstances such objects can become large relative to the AdS length scale.
We demonstrate that such solitons generically do get large and in fact in the
planar limit smoothly connect up with the zero temperature limit of planar
scalar hair black holes. In particular, for given Lagrangian parameters we
encounter multiple branches of solitons: some which are perturbatively
connected to the AdS vacuum and surprisingly, some which are not. We explore
the phase space of solutions by tuning the charge of the scalar field and
changing scalar boundary conditions at AdS asymptopia, finding intriguing
critical behaviour as a function of these parameters. We demonstrate these
features not only for phenomenologically motivated gravitational Abelian-Higgs
models, but also for models that can be consistently embedded into eleven
dimensional supergravity.Comment: 62 pages, 21 figures. v2: added refs and comments and updated
appendice
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Enhanced Short-Term Wind Power Forecasting and Value to Grid Operations: Preprint
The current state of the art of wind power forecasting in the 0- to 6-hour time frame has levels of uncertainty that are adding increased costs and risk on the U.S. electrical grid. It is widely recognized within the electrical grid community that improvements to these forecasts could greatly reduce the costs and risks associated with integrating higher penetrations of wind energy. The U.S. Department of Energy has sponsored a research campaign in partnership with the National Oceanic and Atmospheric Administration (NOAA) and private industry to foster improvements in wind power forecasting. The research campaign involves a three-pronged approach: 1) a 1-year field measurement campaign within two regions; 2) enhancement of NOAA's experimental 3-km High-Resolution Rapid Refresh (HRRR) model by assimilating the data from the field campaign; and 3) evaluation of the economic and reliability benefits of improved forecasts to grid operators. This paper and presentation provides an overview of the regions selected, instrumentation deployed, data quality and control, assimilation of data into HRRR, and preliminary results of HRRR performance analysis
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