590 research outputs found
Proteomic analysis of the processes leading to Madurella mycetomatis grain formation in Galleria mellonella larvae
Mycetoma is a neglected chronic and granulomatous infection primarily associated with the fungal pathogen Madurella mycetomatis. Characteristic of this infection is the formation of grains. However, the processes leading to grain formation are not known. In this study, we employed a proteomic approach to characterise M. mycetomatis grain formation in Galleria mellonella larvae and map the processes leading to grain formation over time. For this, at 1 day, 3 days and 7 days post-inoculation, proteins from grains and hemolymph were extracted and analysed by label-free mass spectrometry. A total of 87, 51 and 48 M. mycetomatis proteins and 713, 997, 18 G. mellonella proteins were found in grains on day 1, 3 and 7 post-inoculation respectively. M. mycetomatis proteins were mainly involved in cellular metabolic processes and numerous enzymes were encountered. G. mellonella proteins were primarily involved in the nodulation process. The proteins identified were linked to nodulation and grain formation and four steps of grain formation were identified. The results of this proteomic approach could in the future be used to design novel strategies to interfere with mycetoma grain formation and to combat this difficult to treat infection
Adiabatic following criterion, estimation of the nonadiabatic excitation fraction and quantum jumps
An accurate theory describing adiabatic following of the dark, nonabsorbing
state in the three-level system is developed. An analytical solution for the
wave function of the particle experiencing Raman excitation is found as an
expansion in terms of the time varying nonadiabatic perturbation parameter. The
solution can be presented as a sum of adiabatic and nonadiabatic parts. Both
are estimated quantitatively. It is shown that the limiting value to which the
amplitude of the nonadiabatic part tends is equal to the Fourier component of
the nonadiabatic perturbation parameter taken at the Rabi frequency of the
Raman excitation. The time scale of the variation of both parts is found. While
the adiabatic part of the solution varies slowly and follows the change of the
nonadiabatic perturbation parameter, the nonadiabatic part appears almost
instantly, revealing a jumpwise transition between the dark and bright states.
This jump happens when the nonadiabatic perturbation parameter takes its
maximum value.Comment: 33 pages, 8 figures, submitted to PRA on 28 Oct. 200
Madurella mycetomatis, the main causative agent of eumycetoma, is highly susceptible to olorofim
OBJECTIVES: Eumycetoma is currently treated with a combination of itraconazole therapy and surgery, with limited success. Recently, olorofim, the lead candidate of the orotomides, a novel class of antifungal agents, entered a Phase II trial for the treatment of invasive fungal infections. Here we determined the activity of olorofim against Madurella mycetomatis, the main causative agent of eumycetoma. METHODS: Activity of olorofim against M. mycetomatis was determined by in silico comparison of the target gene, dihydroorotate dehydrogenase (DHODH), and in vitro susceptibility testing. We also investigated the in vitro interaction between olorofim and itraconazole against M. mycetomatis. RESULTS: M. mycetomatis and Aspergillus fumigatus share six out of seven predicted binding residues in their DHODH DNA sequence, predicting susceptibility to olorofim. Olorofim demonstrated excellent potency against M. mycetomatis in vivo with MICs ranging from 0.004 to 0.125 mg/L and an MIC90 of 0.063 mg/L. Olorofim MICs were mostly one dilution step lower than the itraconazole M
The Similarity Hypothesis in General Relativity
Self-similar models are important in general relativity and other fundamental
theories. In this paper we shall discuss the ``similarity hypothesis'', which
asserts that under a variety of physical circumstances solutions of these
theories will naturally evolve to a self-similar form. We will find there is
good evidence for this in the context of both spatially homogenous and
inhomogeneous cosmological models, although in some cases the self-similar
model is only an intermediate attractor. There are also a wide variety of
situations, including critical pheneomena, in which spherically symmetric
models tend towards self-similarity. However, this does not happen in all cases
and it is it is important to understand the prerequisites for the conjecture.Comment: to be submitted to Gen. Rel. Gra
FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium
Background:Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium.
Methods:Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression.
Results:Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95 confidence interval=1.02-1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2.
Conclusion:Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2. © 2014 Cancer Research UK
D* Production in Deep Inelastic Scattering at HERA
This paper presents measurements of D^{*\pm} production in deep inelastic
scattering from collisions between 27.5 GeV positrons and 820 GeV protons. The
data have been taken with the ZEUS detector at HERA. The decay channel
(+ c.c.) has been used in the study. The
cross section for inclusive D^{*\pm} production with
and is 5.3 \pms 1.0 \pms 0.8 nb in the kinematic region
{ GeV and }. Differential cross
sections as functions of p_T(D^{*\pm}), and are
compared with next-to-leading order QCD calculations based on the photon-gluon
fusion production mechanism. After an extrapolation of the cross section to the
full kinematic region in p_T(D^{*\pm}) and (D^{*\pm}), the charm
contribution to the proton structure function is
determined for Bjorken between 2 10 and 5 10.Comment: 17 pages including 4 figure
The development of a novel diagnostic PCR for Madurella mycetomatis using a comparative genome approach
BACKGROUND: Eumycetoma is a neglected tropical disease most commonly caused by the fungus Madurella mycetomatis. Identification of eumycetoma causative agents can only be reliably performed by molecular identification, most commonly by species-specific PCR. The current M. mycetomatis specific PCR primers were recently discovered to cross-react with Madurella pseudomycetomatis. Here, we used a comparative genome approach to develop a new M. mycetomatis specific PCR for species identification. METHODOLOGY: Predicted-protein coding sequences unique to M. mycetomatis were first identified in BLASTCLUST based on E-value, size and presence of orthologues. Primers were then developed for 16 unique sequences and evaluated against 60 M. mycetomatis isolates and other eumycetoma causing agents including the Madurella sibling species. Out of the 16, only one was found to be specific to M. mycetomatis. CONCLUSION: We have discovered a predicted-protein coding sequence unique to M. mycetomatis and have developed a new species-specific PCR to be used as a novel diagnostic marker for M. mycetomatis
Observation of Scaling Violations in Scaled Momentum Distributions at HERA
Charged particle production has been measured in deep inelastic scattering
(DIS) events over a large range of and using the ZEUS detector. The
evolution of the scaled momentum, , with in the range 10 to 1280
, has been investigated in the current fragmentation region of the Breit
frame. The results show clear evidence, in a single experiment, for scaling
violations in scaled momenta as a function of .Comment: 21 pages including 4 figures, to be published in Physics Letters B.
Two references adde
Observation of hard scattering in photoproduction events with a large rapidity gap at HERA
Events with a large rapidity gap and total transverse energy greater than 5
GeV have been observed in quasi-real photoproduction at HERA with the ZEUS
detector. The distribution of these events as a function of the
centre of mass energy is consistent with diffractive scattering. For total
transverse energies above 12 GeV, the hadronic final states show predominantly
a two-jet structure with each jet having a transverse energy greater than 4
GeV. For the two-jet events, little energy flow is found outside the jets. This
observation is consistent with the hard scattering of a quasi-real photon with
a colourless object in the proton.Comment: 19 pages, latex, 4 figures appended as uuencoded fil
Constraining Cut-off Physics in the Cosmic Microwave Background
We investigate the ability to constrain oscillatory features in the
primordial power spectrum using current and future cosmic microwave background
observations. In particular, we study the observability of an oscillation
arising from imprints of physics at the cut-off energy scale. We perform a
likelihood analysis on the WMAP data set, and find that the current data set
constrains the amplitude of the oscillations to be less than 0.77 at 2-sigma,
consistent with a power spectrum without oscillations. In addition, we
investigate the fundamental limitations in the measurement of oscillation
parameters by studying the constraints from a cosmic variance limited
experiment. We find that such an experiment is capable of constraining the
amplitude of such oscillations to be below 0.005, implying that reasonable
models with cut-off energy scales Lambda>200 H_infl are unobservable through
the microwave background.Comment: 16 pages, 7 figures; PRD accepted versio
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