ALBERT

All Library Books, journals and Electronic Records Telegrafenberg

feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • National Academy of Sciences  (158)
  • Frontiers Media  (78)
  • American Physical Society (APS)  (72)
  • Molecular Diversity Preservation International (MDPI)
  • 2015-2019  (310)
Collection
Publisher
Year
  • 1
    Publication Date: 2017-09-01
    Description: The polycomb repressive complex 2 (PRC2) histone methyltransferase plays a central role in epigenetic regulation in development and in cancer, and hence to interrogate its role in a specific developmental transition, methods are needed for disrupting function of the complex with high temporal and spatial precision. The catalytic and substrate recognition functions of PRC2 are coupled by binding of the N-terminal helix of the Ezh2 methylase to an extended groove on the EED trimethyl lysine binding subunit. Disrupting PRC2 function can in principle be achieved by blocking this single interaction, but there are few approaches for blocking specific protein–protein interactions in living cells and organisms. Here, we describe the computational design of proteins that bind to the EZH2 interaction site on EED with subnanomolar affinity in vitro and form tight and specific complexes with EED in living cells. Induction of the EED binding proteins abolishes H3K27 methylation in human embryonic stem cells (hESCs) and at all but the earliest stage blocks self-renewal, pinpointing the first critical repressive H3K27me3 marks in development.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 2
    Publication Date: 2017-09-20
    Description: The polycomb repressive complex 2 (PRC2) histone methyltransferase plays a central role in epigenetic regulation in development and in cancer, and hence to interrogate its role in a specific developmental transition, methods are needed for disrupting function of the complex with high temporal and spatial precision. The catalytic and substrate...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 3
    Publication Date: 2022-10-26
    Description: © The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Weller, R. A., Baker, D. J., Glackin, M. M., Roberts, S. J., Schmitt, R. W., Twigg, E. S., & Vimont, D. J. The challenge of sustaining ocean observations. Frontiers in Marine Science, 6, (2019):105, doi:10.3389/fmars.2019.00105.
    Description: Sustained ocean observations benefit many users and societal goals but could benefit many more. Such information is critical for using ocean resources responsibly and sustainably as the ocean becomes increasingly important to society. The contributions of many nations cooperating to develop the Global Ocean Observing System has resulted in a strong base of global and regional ocean observing networks. However, enhancement of the existing observation system has been constrained by flat funding and limited cooperation among present and potential users. At the same time, a variety of actors are seeking new deployments in remote and newly ice-free regions and new observing capabilities, including biological and biogeochemical sensors. Can these new needs be met? In this paper, a vision for how to sustain ocean observing in the future is presented. A key evolution will be to grow the pool of users, engaging end users across society. Users with shared values need to be brought together with commitment to sustainable use of the ocean in the broadest sense. Present planning for sustained observations builds on the development of the Global Ocean Observing System which has primarily targeted increased scientific understanding of ocean processes and of the ocean's role in climate. We must build on that foundation to develop an Ocean Partnership for Sustained Observing that will incorporate the growing needs of a broad constituency of users beyond climate and make the case for new resources. To be most effective this new Partnership should incorporate the principles of a collective impact organization, enabling closer engagement with the private sector, philanthropies, governments, NGOs, and other groups. Steps toward achieving this new Partnership are outlined in this paper, with the intent of establishing it early in the UN Decade of Ocean Science.
    Description: This activity was supported by the National Oceanic and Atmospheric Administration under Award Number WC133R-11-CQ-0048 and the National Academy of Sciences' Arthur L. Day Fund.
    Keywords: Sustained ; Ocean observation ; Partnership ; Shared value ; Society
    Repository Name: Woods Hole Open Access Server
    Type: Article
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 4
    Publication Date: 2022-10-26
    Description: © The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Hein, C. J., Fallon, A. R., Rosen, P., Hoagland, P., Georgiou, I. Y., FitzGerald, D. M., Morris, M., Baker, S., Marino, G. B., & Fitzsimons, G. Shoreline dynamics along a developed river mouth barrier island: Multi-decadal cycles of erosion and event-driven mitigation. Frontiers in Earth Science, 7(103), (2019), doi:10.3389/feart.2019.00103.
    Description: Human modifications in response to erosion have altered the natural transport of sediment to and across the coastal zone, thereby potentially exacerbating the impacts of future erosive events. Using a combination of historical shoreline-change mapping, sediment sampling, three-dimensional beach surveys, and hydrodynamic modeling of nearshore and inlet processes, this study explored the feedbacks between periodic coastal erosion patterns and associated mitigation responses, focusing on the open-ocean and inner-inlet beaches of Plum Island and the Merrimack River Inlet, Massachusetts, United States. Installation of river-mouth jetties in the early 20th century stabilized the inlet, allowing residential development in northern Plum Island, but triggering successive, multi-decadal cycles of alternating beach erosion and accretion along the inner-inlet and oceanfront beaches. At a finer spatial scale, the formation and southerly migration of an erosion “hotspot” (a setback of the high-water line by ∼100 m) occurs regularly (every 25–40 years) in response to the refraction of northeast storm waves around the ebb-tidal delta. Growth of the delta progressively shifts the focus of storm wave energy further down-shore, replenishing updrift segments with sand through the detachment, landward migration, and shoreline-welding of swash bars. Monitoring recent hotspot migration (2008–2014) demonstrates erosion (〉30,000 m3 of sand) along a 350-m section of beach in 6 months, followed by recovery, as the hotspot migrated further south. In response to these erosion cycles, local residents and governmental agencies attempted to protect shorefront properties with a variety of soft and hard structures. The latter have provided protection to some homes, but enhanced erosion elsewhere. Although the local community is in broad agreement about the need to plan for long-term coastal changes associated with sea-level rise and increased storminess, real-time responses have involved reactions mainly to short-term (〈5 years) erosion threats. A collective consensus for sustainable management of this area is lacking and the development of a longer-term adaptive perspective needed for proper planning has been elusive. With a deepening understanding of multi-decadal coastal dynamics, including a characterization of the relative contributions of both nature and humans, we can be more optimistic that adaptations beyond mere reactions to shoreline change are achievable.
    Description: This work was supported financially by the National Science Foundation (NSF) Coastal SEES program (awards OCE 1325430 and OCE 1325366). PH also received partial support through the NSF Coupled Natural-Human Systems program (award AGS 1518503) and the Northeast Regional Sea Grant and Woods Hole Sea Grant Programs (NOAA Cooperative Agreement award NA14OAR4170074).
    Keywords: Tidal-inlet dynamics ; Beach erosion ; Coastal adaptation ; Developed beach ; Shoreline change
    Repository Name: Woods Hole Open Access Server
    Type: Article
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 5
    Publication Date: 2016-06-06
    Description: Non-small cell lung cancer (NSCLC) has a 5-y survival rate of ∼16%, with most deaths associated with uncontrolled metastasis. We screened for stem cell identity-related genes preferentially expressed in a panel of cell lines with high versus low metastatic potential, derived from NSCLC tumors of KrasLA1/+;P53R172HΔG/+ (KP) mice. The Musashi-2 (MSI2) protein, a regulator of mRNA translation, was consistently elevated in metastasis-competent cell lines. MSI2 was overexpressed in 123 human NSCLC tumor specimens versus normal lung, whereas higher expression was associated with disease progression in an independent set of matched normal/primary tumor/lymph node specimens. Depletion of MSI2 in multiple independent metastatic murine and human NSCLC cell lines reduced invasion and metastatic potential, independent of an effect on proliferation. MSI2 depletion significantly induced expression of proteins associated with epithelial identity, including tight junction proteins [claudin 3 (CLDN3), claudin 5 (CLDN5), and claudin 7 (CLDN7)] and down-regulated direct translational targets associated with epithelial–mesenchymal transition, including the TGF-β receptor 1 (TGFβR1), the small mothers against decapentaplegic homolog 3 (SMAD3), and the zinc finger proteins SNAI1 (SNAIL) and SNAI2 (SLUG). Overexpression of TGFβRI reversed the loss of invasion associated with MSI2 depletion, whereas overexpression of CLDN7 inhibited MSI2-dependent invasion. Unexpectedly, MSI2 depletion reduced E-cadherin expression, reflecting a mixed epithelial–mesenchymal phenotype. Based on this work, we propose that MSI2 provides essential support for TGFβR1/SMAD3 signaling and contributes to invasive adenocarcinoma of the lung and may serve as a predictive biomarker of NSCLC aggressiveness.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 6
    Publication Date: 2018-06-28
    Description: Cerebral malaria (CM) is a serious neurological complication caused by Plasmodium falciparum infection. Currently, the only treatment for CM is the provision of antimalarial drugs; however, such treatment by itself often fails to prevent death or development of neurological sequelae. To identify potential improved treatments for CM, we performed a nonbiased whole-brain transcriptomic time-course analysis of antimalarial drug chemotherapy of murine experimental CM (ECM). Bioinformatics analyses revealed IL33 as a critical regulator of neuroinflammation and cerebral pathology that is down-regulated in the brain during fatal ECM and in the acute period following treatment of ECM. Consistent with this, administration of IL33 alongside antimalarial drugs significantly improved the treatment success of established ECM. Mechanistically, IL33 treatment reduced inflammasome activation and IL1β production in microglia and intracerebral monocytes in the acute recovery period following treatment of ECM. Moreover, treatment with the NLRP3-inflammasome inhibitor MCC950 alongside antimalarial drugs phenocopied the protective effect of IL33 therapy in improving the recovery from established ECM. We further showed that IL1β release from macrophages was stimulated by hemozoin and antimalarial drugs and that this was inhibited by MCC950. Our results therefore demonstrate that manipulation of the IL33–NLRP3 axis may be an effective therapy to suppress neuroinflammation and improve the efficacy of antimalarial drug treatment of CM.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 7
    Publication Date: 2015-02-09
    Description: “Regulatory evolution,” that is, changes in a gene’s expression pattern through changes at its regulatory sequence, rather than changes at the coding sequence of the gene or changes of the upstream transcription factors, has been increasingly recognized as a pervasive evolution mechanism. Many somatic sexually dimorphic features of Drosophila melanogaster are the results of gene expression regulated by the doublesex (dsx) gene, which encodes sex-specific transcription factors (DSXF in females and DSXM in males). Rapid changes in such sexually dimorphic features are likely a result of changes at the regulatory sequence of the target genes. We focused on the Flavin-containing monooxygenase-2 (Fmo-2) gene, a likely direct dsx target, to elucidate how sexually dimorphic expression and its evolution are brought about. We found that dsx is deployed to regulate the Fmo-2 transcription both in the midgut and in fat body cells of the spermatheca (a female-specific tissue), through a canonical DSX-binding site in the Fmo-2 regulatory sequence. In the melanogaster group, Fmo-2 transcription in the midgut has evolved rapidly, in contrast to the conserved spermathecal transcription. We identified two cis-regulatory modules (CRM-p and CRM-d) that direct sexually monomorphic or dimorphic Fmo-2 transcription, respectively, in the midguts of these species. Changes of Fmo-2 transcription in the midgut from sexually dimorphic to sexually monomorphic in some species are caused by the loss of CRM-d function, but not the loss of the canonical DSX-binding site. Thus, conferring transcriptional regulation on a CRM level allows the regulation to evolve rapidly in one tissue while evading evolutionary constraints posed by other tissues.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 8
    Publication Date: 2015-07-06
    Description: Kinetoplastid parasites cause lethal diseases in humans and animals. The kinetoplast itself contains the mitochondrial genome, comprising a huge, complex DNA network that is also an important drug target. Isometamidium, for example, is a key veterinary drug that accumulates in the kinetoplast in African trypanosomes. Kinetoplast independence and isometamidium resistance are observed where certain mutations in the F1-γ-subunit of the two-sector F1Fo-ATP synthase allow for Fo-independent generation of a mitochondrial membrane potential. To further explore kinetoplast biology and drug resistance, we screened a genome-scale RNA interference library in African trypanosomes for isometamidium resistance mechanisms. Our screen identified 14 V-ATPase subunits and all 4 adaptin-3 subunits, implicating acidic compartment defects in resistance; V-ATPase acidifies lysosomes and related organelles, whereas adaptin-3 is responsible for trafficking among these organelles. Independent strains with depleted V-ATPase or adaptin-3 subunits were isometamidium resistant, and chemical inhibition of the V-ATPase phenocopied this effect. While drug accumulation in the kinetoplast continued after V-ATPase subunit depletion, acriflavine-induced kinetoplast loss was specifically tolerated in these cells and in cells depleted for adaptin-3 or endoplasmic reticulum membrane complex subunits, also identified in our screen. Consistent with kinetoplast dispensability, V-ATPase defective cells were oligomycin resistant, suggesting ATP synthase uncoupling and bypass of the normal Fo-A6-subunit requirement; this subunit is the only kinetoplast-encoded product ultimately required for viability in bloodstream-form trypanosomes. Thus, we describe 30 genes and 3 protein complexes associated with kinetoplast-dependent growth. Mutations affecting these genes could explain natural cases of dyskinetoplasty and multidrug resistance. Our results also reveal potentially conserved communication between the compartmentalized two-sector rotary ATPases.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 9
    Publication Date: 2017-06-20
    Description: Galactosaminogalactan and Pel are cationic heteropolysaccharides produced by the opportunistic pathogens Aspergillus fumigatus and Pseudomonas aeruginosa, respectively. These exopolysaccharides both contain 1,4-linked N-acetyl-d-galactosamine and play an important role in biofilm formation by these organisms. Proteins containing glycoside hydrolase domains have recently been identified within the biosynthetic pathway of each exopolysaccharide. Recombinant hydrolase domains from these proteins (Sph3h from A. fumigatus and PelAh from P. aeruginosa) were found to degrade their respective polysaccharides in vitro. We therefore hypothesized that these glycoside hydrolases could exhibit antibiofilm activity and, further, given the chemical similarity between galactosaminogalactan and Pel, that they might display cross-species activity. Treatment of A. fumigatus with Sph3h disrupted A. fumigatus biofilms with an EC50 of 0.4 nM. PelAh treatment also disrupted preformed A. fumigatus biofilms with EC50 values similar to those obtained for Sph3h. In contrast, Sph3h was unable to disrupt P. aeruginosa Pel-based biofilms, despite being able to bind to the exopolysaccharide. Treatment of A. fumigatus hyphae with either Sph3h or PelAh significantly enhanced the activity of the antifungals posaconazole, amphotericin B, and caspofungin, likely through increasing antifungal penetration of hyphae. Both enzymes were noncytotoxic and protected A549 pulmonary epithelial cells from A. fumigatus-induced cell damage for up to 24 h. Intratracheal administration of Sph3h was well tolerated and reduced pulmonary fungal burden in a neutropenic mouse model of invasive aspergillosis. These findings suggest that glycoside hydrolases can exhibit activity against diverse microorganisms and may be useful as therapeutic agents by degrading biofilms and attenuating virulence.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 10
    Publication Date: 2015-10-27
    Description: The fundamental features of growth may be universal, because growth trajectories of most animals are very similar, but a unified mechanistic theory of growth remains elusive. Still needed is a synthetic explanation for how and why growth rates vary as body size changes, both within individuals over their ontogeny and between populations and species over their evolution. Here, we use Bertalanffy growth equations to characterize growth of ray-finned fishes in terms of two parameters, the growth rate coefficient, K, and final body mass, m∞. We derive two alternative empirically testable hypotheses and test them by analyzing data from FishBase. Across 576 species, which vary in size at maturity by almost nine orders of magnitude, K scaled as m∞−0.23. This supports our first hypothesis that growth rate scales as m∞−0.25 as predicted by metabolic scaling theory; it implies that species that grow to larger mature sizes grow faster as juveniles. Within fish species, however, K scaled as m∞−0.35. This supports our second hypothesis, which predicts that growth rate scales as m∞−0.33 when all juveniles grow at the same rate. The unexpected disparity between across- and within-species scaling challenges existing theoretical interpretations. We suggest that the similar ontogenetic programs of closely related populations constrain growth to m∞−0.33 scaling, but as species diverge over evolutionary time they evolve the near-optimal m∞−0.25 scaling predicted by metabolic scaling theory. Our findings have important practical implications because fish supply essential protein in human diets, and sustainable yields from wild harvests and aquaculture depend on growth rates.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...