361 research outputs found
Influence of the photonuclear effect on electron-neutrino-induced electromagnetic cascades under the Landau-Pomeranchuk-Migdal regime in standard rock
The observation of earth skimming neutrinos has been proposed as a rather
sensitive method to detect ultra-high energy (UHE) cosmic neutrinos. Energetic
cosmic neutrinos can interact inside the rock and produce leptons via a charged
current interaction. In the case of an incoming electron neutrino undergoing a
charged current interaction, the produced UHE electron will induce an
underground electromagnetic shower. At high energy (above 7.7 TeV in standard
rock), such showers are subject to LPM (Landau, Pomeranchuk and Migdal)
suppression of the radiative processes cross sections (bremsstrahlung and pair
production). The consequence of this suppression is that showers are elongated.
This effect will increase the detection probability of such events allowing
deeper showers to emerge with detectable energies. On the other hand, the
photonuclear processes which are usually neglected in electromagnetic showers
with respect to radiative processes, turn out to become dominant in the LPM
regime and will reduce the shower length. In this work, we have performed a
complete Monte Carlo study of an underground shower induced by UHE electrons by
taking into account both the LPM suppression and the photonuclear interaction.
We will discuss the effects of both of these processes on the shower length and
on the detectability of such events by ground arrays or fluorescence
telescopes. We show that limits on neutrino fluxes that were obtained using
simulations that were obviously neglecting photonuclear processes are
overoptimistic and should be corrected.Comment: 6 pages, 7 figure
Synergistic role of micronemal proteins in Toxoplasma gondii virulence
Apicomplexan parasites invade cells by a unique mechanism involving discharge of secretory vesicles called micronemes. Microneme proteins (MICs) include transmembrane and soluble proteins expressing different adhesive domains. Although the transmembrane protein TRAP and its homologues are thought to bridge cell surface receptors and the parasite submembranous motor, little is known about the function of other MICs. We have addressed the role of MIC1 and MIC3, two soluble adhesins of Toxoplasma gondii, in invasion and virulence. Single deletion of the MIC1 gene decreased invasion in fibroblasts, whereas MIC3 deletion had no effect either alone or in the mic1KO context. Individual disruption of MIC1 or MIC3 genes slightly reduced virulence in the mouse, whereas doubly depleted parasites were severely impaired in virulence and conferred protection against subsequent challenge. Single substitution of two critical amino acids in the chitin binding–like (CBL) domain of MIC3 abolished MIC3 binding to cells and generated the attenuated virulence phenotype. Our findings identify the CBL domain of MIC3 as a key player in toxoplasmosis and reveal the synergistic role of MICs in virulence, supporting the idea that parasites have evolved multiple ligand–receptor interactions to ensure invasion of different cells types during the course of infection
Heterologous expression of the avirulence gene ACE1 from the fungal rice pathogen Magnaporthe oryzae
The ACE1 and RAP1 genes from the avirulence signalling gene cluster of the rice blast fungus Magnaporthe oryzae were expressed in Aspergillus oryzae and M. oryzae itself. Expression of ACE1 alone produced a polyenyl pyrone (magnaporthepyrone), which is regioselectively epoxidised and hydrolysed to give different diols, 6 and 7, in the two host organisms. Analysis of the three introns present in ACE1 determined that A. oryzae does not process intron 2 correctly, while M. oryzae processes all introns correctly in both appressoria and mycelia. Co-expression of ACE1 and RAP1 in A. oryzae produced an amide 8 which is similar to the PKS-NRPS derived backbone of the cytochalasans. Biological testing on rice leaves showed that neither the diols 6 and 7, nor amide 8 was responsible for the observed ACE1 mediated avirulence, however, gene cluster analysis suggests that the true avirulence signalling compound may be a tyrosine-derived cytochalasan compound.Government of Egypt ScholarshipThe School of Chemistry at the University of Bristol and the Mark Evans ScholarshipKano State Government NigeriaMacArthur FoundationBayero UniversityNigerian Petroleum Technology FundMalaysian Govenment ScholarshipEP/F066104/
Mutations in TUBG1, DYNC1H1, KIF5C and KIF2A cause malformations of cortical development and microcephaly.
International audienceThe genetic causes of malformations of cortical development (MCD) remain largely unknown. Here we report the discovery of multiple pathogenic missense mutations in TUBG1, DYNC1H1 and KIF2A, as well as a single germline mosaic mutation in KIF5C, in subjects with MCD. We found a frequent recurrence of mutations in DYNC1H1, implying that this gene is a major locus for unexplained MCD. We further show that the mutations in KIF5C, KIF2A and DYNC1H1 affect ATP hydrolysis, productive protein folding and microtubule binding, respectively. In addition, we show that suppression of mouse Tubg1 expression in vivo interferes with proper neuronal migration, whereas expression of altered Îł-tubulin proteins in Saccharomyces cerevisiae disrupts normal microtubule behavior. Our data reinforce the importance of centrosomal and microtubule-related proteins in cortical development and strongly suggest that microtubule-dependent mitotic and postmitotic processes are major contributors to the pathogenesis of MCD
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