751 research outputs found
Signaling via interleukin-4, receptor alpha chain is required for successful vaccination against schistosomiasis in BALB/c mice
Radiation-attenuated (RA) schistosome larvae are potent stimulators of innate immune responses at the skin site of exposure (pinna) that are likely to be important factors in the development of Th1-mediated protective immunity. In addition to causing an influx of neutrophils, macrophages, and dendritic cells (DCs) into the dermis, RA larvae induced a cascade of chemokine and cytokine secretion following in vitro culture of pinna biopsy samples. While macrophage inflammatory protein 1 and interleukin-1 (IL-1) were produced transiently within the first few days, the Th1-promoting cytokines IL-12 and IL-18 were secreted at high levels until at least day 14. Assay of C3H/HeJ mice confirmed that IL-12 secretion was not due to lipopolysaccharide contaminants binding Toll-like receptor 4. Significantly, IL-12 p40 secretion was sustained in pinnae from vaccinated mice but not in those from nonprotected infected mice. In contrast, IL-10 was produced from both vaccinated and infected mice. This cytokine regulates IL-12-associated dermal inflammation, since in vaccinated IL-10/ mice, pinna thickness was greatly increased concurrent with elevated levels of IL-12 p40. A significant number of IL-12 p40 cells were detected as emigrants from in vitro-cultured pinnae, and most were within a population of rare large granular cells that were Ia, consistent with their being antigen-presenting cells. Labeling of IL-12 cells for CD11c, CD205, CD8, CD11b, and F4/80 indicated that the majority were myeloid DCs, although a proportion were CD11c F4/80, suggesting that macrophages were an additional source of IL-12 in the skin
A gain-of-function single nucleotide variant creates a new promoter which acts as an orientation-dependent enhancer-blocker
Many single nucleotide variants (SNVs) associated with human traits and genetic diseases are thought to alter the activity of existing regulatory elements. Some SNVs may also create entirely new regulatory elements which change gene expression, but the mechanism by which they do so is largely unknown. Here we show that a single base change in an otherwise unremarkable region of the human α-globin cluster creates an entirely new promoter and an associated unidirectional transcript. This SNV downregulates α-globin expression causing α-thalassaemia. Of note, the new promoter lying between the α-globin genes and their associated super-enhancer disrupts their interaction in an orientation-dependent manner. Together these observations show how both the order and orientation of the fundamental elements of the genome determine patterns of gene expression and support the concept that active genes may act to disrupt enhancer-promoter interactions in mammals as in Drosophila. Finally, these findings should prompt others to fully evaluate SNVs lying outside of known regulatory elements as causing changes in gene expression by creating new regulatory elements
Flexible C : N ratio enhances metabolism of large phytoplankton when resource supply is intermittent
Abstract. Phytoplankton cell size influences particle sinking rate, food web interactions and biogeographical distributions. We present a model in which the uptake, storage and assimilation of nitrogen and carbon are explicitly resolved in different-sized phytoplankton cells. In the model, metabolism and cellular C : N ratio are influenced by the accumulation of carbon polymers such as carbohydrate and lipid, which is greatest when cells are nutrient starved, or exposed to high light. Allometric relations and empirical data sets are used to constrain the range of possible C : N, and indicate that larger cells can accumulate significantly more carbon storage compounds than smaller cells. When forced with extended periods of darkness combined with brief exposure to saturating irradiance, the model predicts organisms large enough to accumulate significant carbon reserves may on average synthesize protein and other functional apparatus up to five times faster than smaller organisms. The advantage of storage in terms of average daily protein synthesis rate is greatest when modeled organisms were previously nutrient starved, and carbon storage reservoirs saturated. Small organisms may therefore be at a disadvantage in terms of average daily growth rate in environments that involve prolonged periods of darkness and intermittent nutrient limitation. We suggest this mechanism is a significant constraint on phytoplankton C : N variability and cell size distribution in different oceanic regimes.
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1SXPS: A deep Swift X-ray Telescope point source catalog with light curves and spectra
We present the 1SXPS (Swift-XRT Point Source) catalog of 151,524 X-ray
point-sources detected by the Swift-XRT in 8 years of operation. The catalog
covers 1905 square degrees distributed approximately uniformly on the sky. We
analyze the data in two ways. First we consider all observations individually,
for which we have a typical sensitivity of ~3e-13 erg/cm2/s (0.3--10 keV). Then
we co-add all data covering the same location on the sky: these images have a
typical sensitivity of ~9e-14 erg/cm2/s (0.3--10 keV). Our sky coverage is
nearly 2.5 times that of 3XMM-DR4, although the catalog is a factor of ~1.5
less sensitive. The median position error is 5.5" (90% confidence), including
systematics. Our source detection method improves on that used in previous XRT
catalogs and we report >68,000 new X-ray sources. The goals and observing
strategy of the Swift satellite allow us to probe source variability on
multiple timescales, and we find ~30,000 variable objects in our catalog. For
every source we give positions, fluxes, time series (in four energy bands and
two hardness ratios), estimates of the spectral properties, spectra and
spectral fits for the brightest sources, and variability probabilities in
multiple energy bands and timescales.Comment: 27 pages, 19 figures; accepted for publication in ApJS. The
accompanying website, http://www.swift.ac.uk/1SXPS is live; the Vizier entry
should be available shortl
Finite-size effects for anisotropic bootstrap percolation: logarithmic corrections
In this note we analyze an anisotropic, two-dimensional bootstrap percolation
model introduced by Gravner and Griffeath. We present upper and lower bounds on
the finite-size effects. We discuss the similarities with the semi-oriented
model introduced by Duarte.Comment: Key words: Bootstrap percolation, anisotropy, finite-size effect
Is \gamma-ray emission from novae affected by interference effects in the 18F(p,\alpha)15O reaction?
The 18F(p,\alpha)15O reaction rate is crucial for constraining model
predictions of the \gamma-ray observable radioisotope 18F produced in novae.
The determination of this rate is challenging due to particular features of the
level scheme of the compound nucleus, 19Ne, which result in interference
effects potentially playing a significant role. The dominant uncertainty in
this rate arises from interference between J\pi=3/2+ states near the proton
threshold (Sp = 6.411 MeV) and a broad J\pi=3/2+ state at 665 keV above
threshold. This unknown interference term results in up to a factor of 40
uncertainty in the astrophysical S-factor at nova temperatures. Here we report
a new measurement of states in this energy region using the 19F(3He,t)19Ne
reaction. In stark contrast with previous assumptions we find at least 3
resonances between the proton threshold and Ecm=50 keV, all with different
angular distributions. None of these are consistent with J\pi= 3/2+ angular
distributions. We find that the main uncertainty now arises from the unknown
proton-width of the 48 keV resonance, not from possible interference effects.
Hydrodynamic nova model calculations performed indicate that this unknown width
affects 18F production by at least a factor of two in the model considered.Comment: 5 pages, 4 figures. Accepted for publication in Phys. Rev. Let
The Mannose Receptor (CD206) is an important pattern recognition receptor (PRR) in the detection of the infective stage of the helminth Schistosoma mansoni and modulates IFNγ production.
In this study, infective larvae of the parasitic helminth Schistosoma mansoni were shown to contain a large number of glycosylated components specific for the Mannose Receptor (MR; CD206), which is an important pattern recognition receptor (PRR) of the innate immune system. MR ligands were particularly rich in excretory/secretory (E/S) material released during transformation of cercariae into schistosomula, a process critical for infection of the host. E/S material from carboxyfluorescein diacetate succinimidyl ester (CFDA-SE)-labelled cercariae showed enhanced binding by cells lines that over-express the MR. Conversely, uptake was significantly lower by bone marrow-derived macrophages (MΦ) from MR(-/-) mice, although they were more active as judged by enhanced pro-inflammatory cytokine production and CD40 expression. After natural percutaneous infection of MR(-/-) mice with CFDA-SE-labelled parasites, there were fewer cells in the skin and draining lymph nodes that were CFDA-SE(+) compared with wild-type mice, implying reduced uptake and presentation of larval parasite antigen. However, antigen-specific proliferation of skin draining lymph node cells was significantly enhanced and they secreted markedly elevated levels of IFNγ but decreased levels of IL-4. In conclusion, we show that the MR on mononuclear phagocytic cells, which are plentiful in the skin, plays a significant role in internalising E/S material released by the invasive stages of the parasite which in turn modulates their production of pro-inflammatory cytokines. In the absence of the MR, antigen-specific CD4(+) cells are Th1 biased, suggesting that ligation of the MR by glycosylated E/S material released by schistosome larvae modulates the production of CD4(+) cell specific IFNγ
Observations of red-giant variable stars by Aboriginal Australians
Aboriginal Australians carefully observe the properties and positions of
stars, including both overt and subtle changes in their brightness, for
subsistence and social application. These observations are encoded in oral
tradition. I examine two Aboriginal oral traditions from South Australia that
describe the periodic changing brightness in three pulsating, red-giant
variable stars: Betelgeuse (Alpha Orionis), Aldebaran (Alpha Tauri), and
Antares (Alpha Scorpii). The Australian Aboriginal accounts stand as the only
known descriptions of pulsating variable stars in any Indigenous oral tradition
in the world. Researchers examining these oral traditions over the last
century, including anthropologists and astronomers, missed the description of
these stars as being variable in nature as the ethnographic record contained
several misidentifications of stars and celestial objects. Arguably,
ethnographers working on Indigenous Knowledge Systems should have academic
training in both the natural and social sciences.Comment: The Australian Journal of Anthropology (2018
The abundance of 44Ti in core collapse supernovae : Measuring the 44Ti(α, p)47V reaction
Publisher PD
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