595 research outputs found
Metabolic Profiling of IDH Mutation and Malignant Progression in Infiltrating Glioma.
Infiltrating low grade gliomas (LGGs) are heterogeneous in their behavior and the strategies used for clinical management are highly variable. A key factor in clinical decision-making is that patients with mutations in the isocitrate dehydrogenase 1 and 2 (IDH1/2) oncogenes are more likely to have a favorable outcome and be sensitive to treatment. Because of their relatively long overall median survival, more aggressive treatments are typically reserved for patients that have undergone malignant progression (MP) to an anaplastic glioma or secondary glioblastoma (GBM). In the current study, ex vivo metabolic profiles of image-guided tissue samples obtained from patients with newly diagnosed and recurrent LGG were investigated using proton high-resolution magic angle spinning spectroscopy (1H HR-MAS). Distinct spectral profiles were observed for lesions with IDH-mutated genotypes, between astrocytoma and oligodendroglioma histologies, as well as for tumors that had undergone MP. Levels of 2-hydroxyglutarate (2HG) were correlated with increased mitotic activity, axonal disruption, vascular neoplasia, and with several brain metabolites including the choline species, glutamate, glutathione, and GABA. The information obtained in this study may be used to develop strategies for in vivo characterization of infiltrative glioma, in order to improve disease stratification and to assist in monitoring response to therapy
Progression of lumbar disc degeneration over a decade: a heritability study
Lumbar disc degeneration (LDD) is prevalent, age-related and contributes to low back pain. Cross-sectional LDD as determined by MRI scan is known to be highly heritable. The authors postulated that the rate of progression might also be controlled by genetic factors
Cooling dynamics of a dilute gas of inelastic rods: a many particle simulation
We present results of simulations for a dilute gas of inelastically colliding
particles. Collisions are modelled as a stochastic process, which on average
decreases the translational energy (cooling), but allows for fluctuations in
the transfer of energy to internal vibrations. We show that these fluctuations
are strong enough to suppress inelastic collapse. This allows us to study large
systems for long times in the truely inelastic regime. During the cooling stage
we observe complex cluster dynamics, as large clusters of particles form,
collide and merge or dissolve. Typical clusters are found to survive long
enough to establish local equilibrium within a cluster, but not among different
clusters. We extend the model to include net dissipation of energy by damping
of the internal vibrations. Inelatic collapse is avoided also in this case but
in contrast to the conservative system the translational energy decays
according to the mean field scaling law, E(t)\propto t^{-2}, for asymptotically
long times.Comment: 10 pages, 12 figures, Latex; extended discussion, accepted for
publication in Phys. Rev.
The Star Formation History and Dust Content in the Far Outer Disc of M31
We present a detailed analysis of two fields located 26 kpc (~5 scalelengths)
from the centre of M31. One field samples the major axis populations--the Outer
Disc field--while the other is offset by ~18' and samples the Warp in the
stellar disc. The CMDs based on HST/ACS imaging reach old main-sequence
turn-offs (~12.5 Gyr). We apply the CMD-fitting technique to the Warp field to
reconstruct the star formation history (SFH). We find that after undergoing
roughly constant SF until about 4.5 Gyr ago, there was a rapid decline in
activity and then a ~1.5 Gyr lull, followed by a strong burst lasting 1.5 Gyr
and responsible for 25% of the total stellar mass in this field. This burst
appears to be accompanied by a decline in metallicity which could be a
signature of the inflow of metal-poor gas. The onset of the burst (~3 Gyr ago)
corresponds to the last close passage of M31 and M33 as predicted by detailed
N-body modelling, and may have been triggered by this event. We reprocess the
deep M33 outer disc field data of Barker et al. (2011) in order to compare
consistently-derived SFHs. This reveals a similar duration burst that is
exactly coeval with that seen in the M31 Warp field, lending further support to
the interaction hypothesis. The complex SFHs and the smoothly-varying
age-metallicity relations suggest that the stellar populations observed in the
far outer discs of both galaxies have largely formed in situ rather than
migrated from smaller galactocentric radii. The strong differential reddening
affecting the CMD of the Outer Disc field prevents derivation of the SFH.
Instead, we quantify this reddening and find that the fine-scale distribution
of dust precisely follows that of the HI gas. This indicates that the outer HI
disc of M31 contains a substantial amount of dust and therefore suggests
significant metal enrichment in these parts, consistent with inferences from
our CMD analysis.Comment: Abstract shortened. 17 pages, 12 figures (+ 6 pages & 5 figures in
Appendix). MNRAS, in pres
Monomeric C-Reactive Protein in Serum With Markedly Elevated CRP Levels Shares Common Calcium-Dependent Ligand Binding Properties With an in vitro Dissociated Form of C-Reactive Protein
A monomeric form of C-reactive protein (CRP) which precipitates with cell wall pneumococcal C polysaccharide (CWPS) and retains the ability to reversibly bind to its ligand phosphocholine has been produced through urea-induced dissociation at an optimized concentration of 3 M urea over a 10 weeks period. Dissociated samples were purified via size exclusion chromatography and characterized by western blot, phosphocholine affinity chromatography and CWPS precipitation. Human serum samples from patients with raised CRP levels (>100 mg/L as determined by the clinical laboratory assay) were purified by affinity and size exclusion chromatography and analyzed (n = 40) to determine whether circulating monomeric CRP could be detected ex vivo. All 40 samples tested positive for pentameric CRP via western blot and enzyme linked immunosorbent assay (ELISA) analysis. Monomeric C-reactive protein was also identified in all 40 patient samples tested, with an average level recorded of 1.03 mg/L (SE = ±0.11). Both the in vitro monomeric C-reactive protein and the human serum monomeric protein displayed a molecular weight of approximately 23 kDa, both were recognized by the same anti-CRP monoclonal antibody and both reversibly bound to phosphocholine in a calcium-dependent manner. In common with native pentameric CRP, the in vitro mCRP precipitated with CWPS. These overlapping characteristics suggest that a physiologically relevant, near-native monomeric CRP, which retains the structure and binding properties of native CRP subunits, has been produced through in vitro dissociation of pentameric CRP and also isolated from serum with markedly elevated CRP levels. This provides a clear route toward the in-depth study of the structure and function of physiological monomeric CRP
Evaluating the landscape of fear between apex predatory sharks and mobile sea turtles across a large dynamic seascape
The ‘‘landscape of fear’’ model has been proposed as a unifying concept in ecology, describing, in part, how animals behave and move about in their environment. The basic model predicts that as an animal’s landscape changes from low to high risk of predation,
prey species will alter their behavior to risk avoidance. However, studies investigating and evaluating the landscape of fear model across large spatial scales (tens to hundreds of thousands of square kilometers) in dynamic, open, aquatic systems involving apex predators and highly mobile prey are lacking. To address this knowledge gap, we investigated predator–prey relationships between tiger sharks (Galeocerdo cuvier) and loggerhead turtles (Caretta caretta) in the North Atlantic Ocean. This included the use of satellite tracking to examine shark and turtle distributions as well as their surfacing behaviors under varying levels of home range overlap. Our findings revealed patterns that deviated from our a priori predictions based on the landscape of fear model. Specifically, turtles did not alter their surfacing behaviors to risk avoidance when overlap in shark–turtle core home range was high. However, in areas of high overlap with turtles, sharks exhibited modified surfacing behaviors that may enhance predation opportunity. We suggest that turtles may be an important factor in determining shark distribution, whereas for turtles, other life history trade-offs may play a larger role in
defining their habitat use. We propose that these findings are a result of both biotic and physically driven factors that independently or synergistically affect predator–prey interactions in this system. These results have implications for evolutionary biology, community ecology, and wildlife conservation. Further, given the difficulty in studying highly migratory marine species, our approach and conclusions may be applied to the study of other predator–prey systems.Bald Head Island ConservancyBritish Chelonia GroupNatural Environmental Research CouncilWAVE Foundation/Newport Aquarium CincinnatiPADI project AWARESEATURTLE.ORGWhitener Foundation (NC); an Endangered Species Act Section 6 Cooperative Agreement with
NOAA Fisheries and the Grays Reef National Marine Sanctuary (South Carolina and Georgia)Batchelor FoundationDinsey Conservation Fun
The spatially-resolved star formation history of the M31 outer disc
We present deep Hubble Space Telescope Advanced Camera for Surveys
observations of the stellar populations in two fields lying at 20 and 23 kpc
from the centre of M31 along the south-west semi-major axis. These data enable
the construction of colour-magnitude diagrams reaching the oldest main-sequence
turn-offs (~13 Gyr) which, when combined with another field at 25 kpc from our
previous work, we use to derive the first precision constraints on the
spatially-resolved star formation history of the M31 disc. The star formation
rates exhibit temporal as well as field-to-field variations, but are generally
always within a factor of two of their time average. There is no evidence of
inside-out growth over the radial range probed. We find a median age of ~7.5
Gyr, indicating that roughly half of the stellar mass in the M31 outer disc was
formed before z ~ 1. We also find that the age-metallicity relations (AMRs) are
smoothly increasing from [Fe/H]~-0.4 to solar metallicity between 10 and 3 Gyr
ago, contrary to the flat AMR of the Milky Way disc at a similar number of
scale lengths. Our findings provide insight on the roles of stellar feedback
and radial migration in the formation and evolution of large disc galaxies.Comment: 5 pages, 4 figures. Re-submitted to MNRAS after addressing the
referee's comment
Genome sequence of an Australian kangaroo, Macropus eugenii, provides insight into the evolution of mammalian reproduction and development.
BACKGROUND: We present the genome sequence of the tammar wallaby, Macropus eugenii, which is a member of the kangaroo family and the first representative of the iconic hopping mammals that symbolize Australia to be sequenced. The tammar has many unusual biological characteristics, including the longest period of embryonic diapause of any mammal, extremely synchronized seasonal breeding and prolonged and sophisticated lactation within a well-defined pouch. Like other marsupials, it gives birth to highly altricial young, and has a small number of very large chromosomes, making it a valuable model for genomics, reproduction and development. RESULTS: The genome has been sequenced to 2 × coverage using Sanger sequencing, enhanced with additional next generation sequencing and the integration of extensive physical and linkage maps to build the genome assembly. We also sequenced the tammar transcriptome across many tissues and developmental time points. Our analyses of these data shed light on mammalian reproduction, development and genome evolution: there is innovation in reproductive and lactational genes, rapid evolution of germ cell genes, and incomplete, locus-specific X inactivation. We also observe novel retrotransposons and a highly rearranged major histocompatibility complex, with many class I genes located outside the complex. Novel microRNAs in the tammar HOX clusters uncover new potential mammalian HOX regulatory elements. CONCLUSIONS: Analyses of these resources enhance our understanding of marsupial gene evolution, identify marsupial-specific conserved non-coding elements and critical genes across a range of biological systems, including reproduction, development and immunity, and provide new insight into marsupial and mammalian biology and genome evolution
Ecological Determinants of Highly Pathogenic Avian Influenza (H5N1) Outbreaks in Bangladesh
BACKGROUND: The agro-ecology and poultry husbandry of the south Asian and south-east Asian countries share common features, however, with noticeable differences. Hence, the ecological determinants associated with risk of highly pathogenic avian influenza (HPAI-H5N1) outbreaks are expected to differ between Bangladesh and e.g., Thailand and Vietnam. The primary aim of the current study was to establish ecological determinants associated with the risk of HPAI-H5N1 outbreaks at subdistrict level in Bangladesh. The secondary aim was to explore the performance of two different statistical modeling approaches for unmeasured spatially correlated variation. METHODOLOGY/PRINCIPAL FINDINGS: An ecological study at subdistrict level in Bangladesh was performed with 138 subdistricts with HPAI-H5N1 outbreaks during 2007-2008, and 326 subdistricts with no outbreaks. The association between ecological determinants and HPAI-H5N1 outbreaks was examined using a generalized linear mixed model. Spatial clustering of the ecological data was modeled using 1) an intrinsic conditional autoregressive (ICAR) model at subdistrict level considering their first order neighbors, and 2) a multilevel (ML) model with subdistricts nested within districts. Ecological determinants significantly associated with risk of HPAI-H5N1 outbreaks at subdistrict level were migratory birds' staging areas, river network, household density, literacy rate, poultry density, live bird markets, and highway network. Predictive risk maps were derived based on the resulting models. The resulting models indicate that the ML model absorbed some of the covariate effect of the ICAR model because of the neighbor structure implied in the two different models. CONCLUSIONS/SIGNIFICANCE: The study identified a new set of ecological determinants related to river networks, migratory birds' staging areas and literacy rate in addition to already known risk factors, and clarified that the generalized concept of free grazing duck and duck-rice cultivation interacted ecology are not significant determinants for Bangladesh. These findings will refine current understanding of the HPAI-H5N1 epidemiology in Bangladesh
- …