125 research outputs found

    Connecting the Cytoskeleton to the Endoplasmic Reticulum and Golgi

    Get PDF
    A tendency in cell biology is to divide and conquer. For example, decades of painstaking work have led to an understanding of endoplasmic reticulum (ER) and Golgi structure, dynamics, and transport. In parallel, cytoskeletal researchers have revealed a fantastic diversity of structure and cellular function in both actin and microtubules. Increasingly, these areas overlap, necessitating an understanding of both organelle and cytoskeletal biology. This review addresses connections between the actin/microtubule cytoskeletons and organelles in animal cells, focusing on three key areas: ER structure and function; ER-to-Golgi transport; and Golgi structure and function. Making these connections has been challenging for several reasons: the small sizes and dynamic characteristics of some components; the fact that organelle-specific cytoskeletal elements can easily be obscured by more abundant cytoskeletal structures; and the difficulties in imaging membranes and cytoskeleton simultaneously, especially at the ultrastructural level. One major concept is that the cytoskeleton is frequently used to generate force for membrane movement, with two potential consequences: translocation of the organelle, or deformation of the organelle membrane. While initially discussing issues common to metazoan cells in general, we subsequently highlight specific features of neurons, since these highly polarized cells present unique challenges for organellar distribution and dynamics

    Novel Roles for Actin in Mitochondrial Fission

    Get PDF
    Mitochondrial dynamics, including fusion, fission and translocation, are crucial to cellular homeostasis, with roles in cellular polarity, stress response and apoptosis. Mitochondrial fission has received particular attention, owing to links with several neurodegenerative diseases. A central player in fission is the cytoplasmic dynamin-related GTPase Drp1, which oligomerizes at the fission site and hydrolyzes GTP to drive membrane ingression. Drp1 recruitment to the outer mitochondrial membrane (OMM) is a key regulatory event, which appears to require a pre-constriction step in which the endoplasmic reticulum (ER) and mitochondrion interact extensively, a process termed ERMD (ER-associated mitochondrial division). It is unclear how ER-mitochondrial contact generates the force required for pre-constriction or why pre-constriction leads to Drp1 recruitment. Recent results, however, show that ERMD might be an actin-based process in mammals that requires the ER-associated formin INF2 upstream of Drp1, and that myosin II and other actin-binding proteins might be involved. In this Commentary, we present a mechanistic model for mitochondrial fission in which actin and myosin contribute in two ways; firstly, by supplying the force for pre-constriction and secondly, by serving as a coincidence detector for Drp1 binding. In addition, we discuss the possibility that multiple fission mechanisms exist in mammals

    Actin Filaments Target the Oligomeric Maturation of the Dynamin Gtpase Drp1 to Mitochondrial Fission Sites

    Get PDF
    While the dynamin GTPase Drp1 plays a critical role during mitochondrial fission, mechanisms controlling its recruitment to fission sites are unclear. A current assumption is that cytosolic Drp1 is recruited directly to fission sites immediately prior to fission. Using live-cell microscopy, we find evidence for a different model, progressive maturation of Drp1 oligomers on mitochondria through incorporation of smaller mitochondrially-bound Drp1 units. Maturation of a stable Drp1 oligomer does not forcibly lead to fission. Drp1 oligomers also translocate directionally along mitochondria. Ionomycin, a calcium ionophore, causes rapid mitochondrial accumulation of actin filaments followed by Drp1 accumulation at the fission site, and increases fission rate. Inhibiting actin polymerization, myosin IIA, or the formin INF2 reduces both un-stimulated and ionomycin-induced Drp1 accumulation and mitochondrial fission. Actin filaments bind purified Drp1 and increase GTPase activity in a manner that is synergistic with the mitochondrial protein Mff, suggesting a role for direct Drp1/actin interaction. We propose that Drp1 is in dynamic equilibrium on mitochondria in a fission-independent manner, and that fission factors such as actin filaments target productive oligomerization to fission sites

    Controlled and Efficient Hybridization Achieved with DNA Probes Immobilized Solely through Preferential DNA-Substrate Interactions

    Get PDF
    Quantitatively correlating the response of DNA sensors to clinically and biologically significant sample abundances requires optimizing the reproducibility of hybridization between DNA targets and surface-bound DNA probes. 1,2 Although gold surfaces are not used in commercial fluorescence-based DNA arrays, gold offers many useful properties as a model substrate 3 and has been successfully used in systematic studies of the interactions governing DNA hybridization near interfaces. 4-8 The hybridization behavior of surface-immobilized DNA probes strongly depends on the probe conformation and on the lateral spacing between adjacent probes. Hybridization is generally enhanced for DNA probes that extend away from a surface, in part because steric hindrance is lower for such brushlike probes than for DNA directly adsorbed on gold. At surface densities e5 × 10 12 cm -2 , typical probe sequences (15-30 nucleotides) can hybridize with efficiencies >60%, 7-10 but at probe densities >1 × 10 13 cm -2 hybridization efficiency is often reduced because of increased electrostatic repulsion and steric constraints. 11-13 Surfaces with DNA probes in upright conformations can be prepared following a number of strategies, including adsorption via a thiol incorporated at one end (DNA-SH) or coupling DNA probes to bifunctional monolayers. [4][5][6][7][8][14][15][16][17][18] Preparing DNA probes * To whom correspondence should be addressed. E-mail: opdahl

    Breast cancer risk factors in relation to breast density (United States)

    Get PDF
    OBJECTIVES: Evaluate known breast cancer risk factors in relation to breast density. METHODS: We examined factors in relation to breast density in 144,018 New Hampshire (NH) women with at least one mammogram recorded in a statewide mammography registry. Mammographic breast density was measured by radiologists using the BI-RADS classification; risk factors of interest were obtained from patient intake forms and questionnaires. RESULTS: Initial analyses showed a strong inverse influence of age and body mass index (BMI) on breast density. In addition, women with late age at menarche, late age at first birth, premenopausal women, and those currently using hormone therapy (HT) tended to have higher breast density, while those with greater parity tended to have less dense breasts. Analyses stratified on age and BMI suggested interactions, which were formally assessed in a multivariable model. The impact of current HT use, relative to nonuse, differed across age groups, with an inverse association in younger women, and a positive association in older women (p < 0.0001 for the interaction). The positive effects of age at menarche and age at first birth, and the inverse influence of parity were less apparent in women with low BMI than in those with high BMI (p = 0.04, p < 0.0001 and p = 0.01, respectively, for the interactions). We also noted stronger positive effects for age at first birth in postmenopausal women (p = 0.004 for the interaction). The multivariable model indicated a slight positive influence of family history of breast cancer. CONCLUSIONS: The influence of age at menarche and reproductive factors on breast density is less evident in women with high BMI. Density is reduced in young women using HT, but increased in HT users of age 50 or more

    The wide-field, multiplexed, spectroscopic facility WEAVE : survey design, overview, and simulated implementation

    Get PDF
    Funding for the WEAVE facility has been provided by UKRI STFC, the University of Oxford, NOVA, NWO, Instituto de Astrofísica de Canarias (IAC), the Isaac Newton Group partners (STFC, NWO, and Spain, led by the IAC), INAF, CNRS-INSU, the Observatoire de Paris, Région Île-de-France, CONCYT through INAOE, Konkoly Observatory (CSFK), Max-Planck-Institut für Astronomie (MPIA Heidelberg), Lund University, the Leibniz Institute for Astrophysics Potsdam (AIP), the Swedish Research Council, the European Commission, and the University of Pennsylvania.WEAVE, the new wide-field, massively multiplexed spectroscopic survey facility for the William Herschel Telescope, will see first light in late 2022. WEAVE comprises a new 2-degree field-of-view prime-focus corrector system, a nearly 1000-multiplex fibre positioner, 20 individually deployable 'mini' integral field units (IFUs), and a single large IFU. These fibre systems feed a dual-beam spectrograph covering the wavelength range 366-959 nm at R ∼ 5000, or two shorter ranges at R ∼ 20,000. After summarising the design and implementation of WEAVE and its data systems, we present the organisation, science drivers and design of a five- to seven-year programme of eight individual surveys to: (i) study our Galaxy's origins by completing Gaia's phase-space information, providing metallicities to its limiting magnitude for ∼ 3 million stars and detailed abundances for ∼ 1.5 million brighter field and open-cluster stars; (ii) survey ∼ 0.4 million Galactic-plane OBA stars, young stellar objects and nearby gas to understand the evolution of young stars and their environments; (iii) perform an extensive spectral survey of white dwarfs; (iv) survey  ∼ 400 neutral-hydrogen-selected galaxies with the IFUs; (v) study properties and kinematics of stellar populations and ionised gas in z 1 million spectra of LOFAR-selected radio sources; (viii) trace structures using intergalactic/circumgalactic gas at z > 2. Finally, we describe the WEAVE Operational Rehearsals using the WEAVE Simulator.PostprintPeer reviewe

    The wide-field, multiplexed, spectroscopic facility WEAVE: Survey design, overview, and simulated implementation

    Full text link
    WEAVE, the new wide-field, massively multiplexed spectroscopic survey facility for the William Herschel Telescope, will see first light in late 2022. WEAVE comprises a new 2-degree field-of-view prime-focus corrector system, a nearly 1000-multiplex fibre positioner, 20 individually deployable 'mini' integral field units (IFUs), and a single large IFU. These fibre systems feed a dual-beam spectrograph covering the wavelength range 366-959\,nm at R5000R\sim5000, or two shorter ranges at R20000R\sim20\,000. After summarising the design and implementation of WEAVE and its data systems, we present the organisation, science drivers and design of a five- to seven-year programme of eight individual surveys to: (i) study our Galaxy's origins by completing Gaia's phase-space information, providing metallicities to its limiting magnitude for \sim3 million stars and detailed abundances for 1.5\sim1.5 million brighter field and open-cluster stars; (ii) survey 0.4\sim0.4 million Galactic-plane OBA stars, young stellar objects and nearby gas to understand the evolution of young stars and their environments; (iii) perform an extensive spectral survey of white dwarfs; (iv) survey 400\sim400 neutral-hydrogen-selected galaxies with the IFUs; (v) study properties and kinematics of stellar populations and ionised gas in z<0.5z<0.5 cluster galaxies; (vi) survey stellar populations and kinematics in 25000\sim25\,000 field galaxies at 0.3z0.70.3\lesssim z \lesssim 0.7; (vii) study the cosmic evolution of accretion and star formation using >1>1 million spectra of LOFAR-selected radio sources; (viii) trace structures using intergalactic/circumgalactic gas at z>2z>2. Finally, we describe the WEAVE Operational Rehearsals using the WEAVE Simulator.Comment: 41 pages, 27 figures, accepted for publication by MNRA

    MS_HistoneDB, a manually curated resource for proteomic analysis of human and mouse histones

    Get PDF

    The wide-field, multiplexed, spectroscopic facility WEAVE: Survey design, overview, and simulated implementation

    Get PDF
    WEAVE, the new wide-field, massively multiplexed spectroscopic survey facility for the William Herschel Telescope, will see first light in late 2022. WEAVE comprises a new 2-degree field-of-view prime-focus corrector system, a nearly 1000-multiplex fibre positioner, 20 individually deployable 'mini' integral field units (IFUs), and a single large IFU. These fibre systems feed a dual-beam spectrograph covering the wavelength range 366−959\,nm at R∼5000, or two shorter ranges at R∼20000. After summarising the design and implementation of WEAVE and its data systems, we present the organisation, science drivers and design of a five- to seven-year programme of eight individual surveys to: (i) study our Galaxy's origins by completing Gaia's phase-space information, providing metallicities to its limiting magnitude for ∼3 million stars and detailed abundances for ∼1.5 million brighter field and open-cluster stars; (ii) survey ∼0.4 million Galactic-plane OBA stars, young stellar objects and nearby gas to understand the evolution of young stars and their environments; (iii) perform an extensive spectral survey of white dwarfs; (iv) survey ∼400 neutral-hydrogen-selected galaxies with the IFUs; (v) study properties and kinematics of stellar populations and ionised gas in z1 million spectra of LOFAR-selected radio sources; (viii) trace structures using intergalactic/circumgalactic gas at z>2. Finally, we describe the WEAVE Operational Rehearsals using the WEAVE Simulator

    A Qualitative Evaluation of the Motivations, Experiences, and Impact of a Mental Wellbeing Peer Support Group for Black University Students in England and Wales: The Case of Black Students Talk

    No full text
    Online peer support programs could address mental wellbeing concerns reported by Black students. The current evaluation explored Black university students’ motivations, experiences, and perceived impacts of an online mental wellbeing peer support group (Black Students Talk [BST]) in England and Wales. We conducted two focus groups with Black Students Talk attendees and one with facilitators. Data were analyzed using inductive thematic analysis. Three main themes and eight sub-themes where identified related to (i) Motivation: Impact of racism on mental wellbeing; (ii) Experience: The Black Students Talk experience; and (iii) Impact: Mental wellbeing outcomes. Benefits of Black Students Talk for Black students included advice, rest, validation, and support in the context of their race and experiences of racism. Facilitators had a unique sub-theme concerning their training and support. While racism exists at universities, online peer support can offer valuable benefits for Black students’ mental wellbeing, social connectedness, and Black-only networks. Programs need to be co-created and delivered by trained Black students who receive reflective practice with a Black practitioner. Further independent evaluations using insights from survey and interview data are needed
    corecore