1,573 research outputs found
Control of actin turnover by a salmonella invasion protein.
Salmonella force their way into nonphagocytic host intestinal cells to initiate infection. Uptake is triggered by delivery into the target cell of bacterial effector proteins that stimulate cytoskeletal rearrangements and membrane ruffling. The Salmonella invasion protein A (SipA) effector is an actin binding protein that enhances uptake efficiency by promoting actin polymerization. SipA-bound actin filaments (F-actin) are also resistant to artificial disassembly in vitro. Using biochemical assays of actin dynamics and actin-based motility models, we demonstrate that SipA directly arrests cellular mechanisms of actin turnover. SipA inhibits ADF/cofilin-directed depolymerization both by preventing binding of ADF and cofilin and by displacing them from F-actin. SipA also protects F-actin from gelsolin-directed severing and reanneals gelsolin-severed F-actin fragments. These data suggest that SipA focuses host cytoskeletal reorganization by locally inhibiting both ADF/cofilin- and gelsolin-directed actin disassembly, while simultaneously stimulating pathogen-induced actin polymerization
Deciphering interplay between Salmonella invasion effectors
Bacterial pathogens have evolved a specialized type III secretion system (T3SS) to translocate virulence effector proteins directly into eukaryotic target cells. Salmonellae deploy effectors that trigger localized actin reorganization to force their own entry into non-phagocytic host cells. Six effectors (SipC, SipA, SopE/2, SopB, SptP) can individually manipulate actin dynamics at the plasma membrane, which acts as a ‘signaling hub’ during Salmonella invasion. The extent of crosstalk between these spatially coincident effectors remains unknown. Here we describe trans and cis binary entry effector interplay (BENEFIT) screens that systematically examine functional associations between effectors following their delivery into the host cell. The results reveal extensive ordered synergistic and antagonistic relationships and their relative potency, and illuminate an unexpectedly sophisticated signaling network evolved through longstanding pathogen–host interaction
Polymers for dye transfer inhibition in laundry applications
The deposition of dyes onto lightly colored garments, or onto lighter sections of multicolored garments, during laundry results in fabric discoloration. In particular, there is a requirement to restrict indigo dye transfer between garments. Polymers may be added to detergent formulations as dye transfer inhibitors to prevent dye transfer by blocking the deposition of fugitive dyes in aqueous solution. This article reports the generation of a range of dye transfer inhibitors produced by condensation reactions that are effective in preventing the transfer of unbound indigo dye to a variety of fiber types. Key design rules relating to polymer hydrophilicity and pendant polymer functionality were established for the creation of effective dye transfer inhibitors. Remarkably, polymers at concentrations as low as 0.1 mg/ml were found to be effective in inhibiting indigo deposition on a variety of fiber types, offering great promise for their inclusion within laundry detergent formulations as dye transfer inhibitors
Do Lions Panthera leo Actively Select Prey or Do Prey Preferences Simply Reflect Chance Responses via Evolutionary Adaptations to Optimal Foraging?
Research on coursing predators has revealed that actions throughout the predatory behavioral sequence (using encounter rate, hunting rate, and kill rate as proxy measures of decisions) drive observed prey preferences. We tested whether similar actions drive the observed prey preferences of a stalking predator, the African lion Panthera leo. We conducted two 96 hour, continuous follows of lions in Addo Elephant National Park seasonally from December 2003 until November 2005 (16 follows), and compared prey encounter rate with prey abundance, hunt rate with prey encounter rate, and kill rate with prey hunt rate for the major prey species in Addo using Jacobs' electivity index. We found that lions encountered preferred prey species far more frequently than expected based on their abundance, and they hunted these species more frequently than expected based on this higher encounter rate. Lions responded variably to non-preferred and avoided prey species throughout the predatory sequence, although they hunted avoided prey far less frequently than expected based on the number of encounters of them. We conclude that actions of lions throughout the predatory behavioural sequence, but particularly early on, drive the prey preferences that have been documented for this species. Once a hunt is initiated, evolutionary adaptations to the predator-prey interactions drive hunting success
The N-terminal intrinsically disordered domain of mgm101p is localized to the mitochondrial nucleoid.
The mitochondrial genome maintenance gene, MGM101, is essential for yeasts that depend on mitochondrial DNA replication. Previously, in Saccharomyces cerevisiae, it has been found that the carboxy-terminal two-thirds of Mgm101p has a functional core. Furthermore, there is a high level of amino acid sequence conservation in this region from widely diverse species. By contrast, the amino-terminal region, that is also essential for function, does not have recognizable conservation. Using a bioinformatic approach we find that the functional core from yeast and a corresponding region of Mgm101p from the coral Acropora millepora have an ordered structure, while the N-terminal domains of sequences from yeast and coral are predicted to be disordered. To examine whether ordered and disordered domains of Mgm101p have specific or general functions we made chimeric proteins from yeast and coral by swapping the two regions. We find, by an in vivo assay in S.cerevisiae, that the ordered domain of A.millepora can functionally replace the yeast core region but the disordered domain of the coral protein cannot substitute for its yeast counterpart. Mgm101p is found in the mitochondrial nucleoid along with enzymes and proteins involved in mtDNA replication. By attaching green fluorescent protein to the N-terminal disordered domain of yeast Mgm101p we find that GFP is still directed to the mitochondrial nucleoid where full-length Mgm101p-GFP is targeted
Holocene deglaciation and glacier readvances on the Fildes Peninsula and King George Island (Isla 25 de Mayo), South Shetland Islands, NW Antarctic Peninsula
To provide insights into glacier-climate dynamics of the South Shetland Islands (SSI), NW Antarctic Peninsula, we present a new deglaciation and readvance model for the Bellingshausen Ice Cap (BIC) on Fildes Peninsula and for King George Island/Isla 25 de Mayo (KGI) ~62°S. Deglaciation on KGI began after c. 15 ka cal BP and had progressed to within present-day limits on the Fildes Peninsula, its largest ice-free peninsula, by c. 6.6–5.3 ka cal BP. Probability density phase analysis of chronological data constraining Holocene glacier advances on KGI revealed up to eight 95% probability ‘gaps’ during which readvances could have occurred. These are grouped into four stages – Stage 1: a readvance and marine transgression, well-constrained by field data, between c. 7.4–6.6 ka cal BP; Stage 2: four probability ‘gaps’, less well-constrained by field data, between c. 5.3–2.2 ka cal BP; Stage 3: a well-constrained but restricted ‘readvance’ between c. 1.7–1.5 ka; Stage 4: two further minor ‘readvances’, one less well-constrained by field data between c. 1.3–0.7 ka cal BP (68% probability), and a ‘final’ well-constrained ‘readvance’ after 1950 CE) is associated with recent warming/more positive SAM-like conditions
Suppression of Stochastic Domain Wall Pinning Through Control of Gilbert Damping
Finite temperature micromagnetic simulations were used to investigate the magnetisation structure, propagation dynamics and stochastic pinning of domain walls in rare earth-doped Ni80Fe20 nanowires. We first show how the increase of the Gilbert damping, caused by the inclusion rare-earth dopants such as holmium, acts to suppress Walker breakdown phenomena. This allows domain walls to maintain consistent magnetisation structures during propagation. We then employ finite temperature simulations to probe how this affects the stochastic pinning of domain walls at notch-shaped artificial defect sites. Our results indicate that the addition of even a few percent of holmium allows domain walls to pin with consistent and well-defined magnetisation configurations, thus suppressing dynamically-induced stochastic pinning/depinning phenomena. Together, these results demonstrate a powerful, materials science-based solution to the problems of stochastic domain wall pinning in soft ferromagnetic nanowires
Mental health literacy in an educational elite – an online survey among university students
BACKGROUND: Mental health literacy is a prerequisite for early recognition and intervention in mental disorders. The aims of this paper are to determine whether a sample of university students recognise different symptoms of depression and schizophrenia and to reveal factors influencing correct recognition. METHODS: Bivariate and correspondence analyses of the results from an online survey among university students (n = 225). RESULTS: Most participants recognised the specific symptoms of depression. The symptoms of schizophrenia were acknowledged to a lower extent. Delusions of control and hallucinations of taste were not identified as symptoms of schizophrenia. Repeated revival of a trauma for depression and split personality for schizophrenia were frequently mistaken as symptoms of the respective disorders. Bivariate analyses demonstrated that previous interest in and a side job related to mental disorders, as well as previous personal treatment experience had a positive influence on symptom recognition. The correspondence analysis showed that male students of natural science, economics and philosophy are illiterate in recognising the symptoms depression and schizophrenia. CONCLUSION: Among the educational elite, a wide variability in mental health literacy was found. Therefore, it's important for public mental health interventions to focus on the different recognition rates in depression and schizophrenia. Possibilities for contact must be arranged according to interest and activity (e.g., at work). In order to improve mental health literacy, finally, education and/or internship should be integrated in high school or apprenticeship curricula. Special emphasis must be given towards the effects of gender and stereotypes held about mental illnesses
Three little pieces for computer and relativity
Numerical relativity has made big strides over the last decade. A number of
problems that have plagued the field for years have now been mostly solved.
This progress has transformed numerical relativity into a powerful tool to
explore fundamental problems in physics and astrophysics, and I present here
three representative examples. These "three little pieces" reflect a personal
choice and describe work that I am particularly familiar with. However, many
more examples could be made.Comment: 42 pages, 11 figures. Plenary talk at "Relativity and Gravitation:
100 Years after Einstein in Prague", June 25 - 29, 2012, Prague, Czech
Republic. To appear in the Proceedings (Edition Open Access). Collects
results appeared in journal articles [72,73, 122-124
Characteristic Evolution and Matching
I review the development of numerical evolution codes for general relativity
based upon the characteristic initial value problem. Progress in characteristic
evolution is traced from the early stage of 1D feasibility studies to 2D
axisymmetric codes that accurately simulate the oscillations and gravitational
collapse of relativistic stars and to current 3D codes that provide pieces of a
binary black hole spacetime. Cauchy codes have now been successful at
simulating all aspects of the binary black hole problem inside an artificially
constructed outer boundary. A prime application of characteristic evolution is
to extend such simulations to null infinity where the waveform from the binary
inspiral and merger can be unambiguously computed. This has now been
accomplished by Cauchy-characteristic extraction, where data for the
characteristic evolution is supplied by Cauchy data on an extraction worldtube
inside the artificial outer boundary. The ultimate application of
characteristic evolution is to eliminate the role of this outer boundary by
constructing a global solution via Cauchy-characteristic matching. Progress in
this direction is discussed.Comment: New version to appear in Living Reviews 2012. arXiv admin note:
updated version of arXiv:gr-qc/050809
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