691 research outputs found
Gravitational waves from defect-driven phase transitions: domain walls
We discuss the gravitational wave spectrum produced by first-order phase
transitions seeded by domain wall networks. This setup is important for many
two-step phase transitions as seen for example in the singlet extension of the
standard model. Whenever the correlation length of the domain wall network is
larger than the typical bubble size, this setup leads to a gravitational wave
signal that is shifted to lower frequencies and with an enhanced amplitude
compared to homogeneous phase transitions without domain walls. We discuss our
results in light of the recent PTA hints for gravitational waves.Comment: 20 pages, 6 figure
Proteolysis of SNAP-25 by types E and A botulinal neurotoxins
Clostridial neurotoxins, tetanus toxin (TeTx) and the seven related but serologically distinct botulinal neurotoxins (BoNT/A to BoNT/G), are potent inhibitors of synaptic vesicle exocytosis in nerve endings. Recently it was reported that the light chains of clostridial neurotoxins act as zinc-dependent metalloproteases which specifically cleave synaptic target proteins such as synaptobrevin/VAMPs, HPC-1/syntaxin (BoNT/C1), and SNAP-25 (BoNT/A). We show here that BoNT/E, like BoNT/A, cleaves SNAP-25, as generated by in vitro translation or by expression in Escherichia coli. BoNT/E cleaves the Arg180-Ile181 bond. This site is different from that of BoNT/A, which cleaves SNAP-25 between the amino acid residues Gln197 and Arg198. These findings further support the view that clostridial neurotoxins have evolved from an ancestral protease recognizing the exocytotic fusion machinery of synaptic vesicles whereby individual toxins target different members of the membrane fusion complex
Galactic Point Sources of TeV Antineutrinos
High energy cosmic ray experiments have identified an excess from the region
of the Galactic Plane in a limited energy range around eV (EeV). This
is very suggestive of neutrons as candidate primaries, because the directional
signal requires relatively-stable neutral primaries, and time-dilated neutrons
can reach Earth from typical Galactic distances when the neutron energy exceeds
an EeV. We here point out that if the Galactic messengers are neutrons, then
those with energies below an EeV will decay in flight, providing a flux of
cosmic antineutrinos above a TeV which is {\it observable} at a kilometer-scale
neutrino observatory. The expected event rate per year above 1 TeV in a
detector such as IceCube, for example, is 20 antineutrino showers (all flavors)
and a directional signal of 4 events. A measurement of
this flux can serve to identify the first extraterrestrial point source of TeV
antineutrinos.Comment: matches published versio
A review of wildland fire spread modelling, 1990-present, 1: Physical and quasi-physical models
In recent years, advances in computational power and spatial data analysis
(GIS, remote sensing, etc) have led to an increase in attempts to model the
spread and behaviour of wildland fires across the landscape. This series of
review papers endeavours to critically and comprehensively review all types of
surface fire spread models developed since 1990. This paper reviews models of a
physical or quasi-physical nature. These models are based on the fundamental
chemistry and/or physics of combustion and fire spread. Other papers in the
series review models of an empirical or quasi-empirical nature, and
mathematical analogues and simulation models. Many models are extensions or
refinements of models developed before 1990. Where this is the case, these
models are also discussed but much less comprehensively.Comment: 31 pages + 8 pages references + 2 figures + 5 tables. Submitted to
International Journal of Wildland Fir
Altered thiol chemistry in human amyotrophic lateral sclerosis-linked mutants of superoxide dismutase 1
Neurodegenerative diseases share a common characteristic, the presence of intracellular or extracellular deposits of protein aggregates in nervous tissues. Amyotrophic Lateral Sclerosis (ALS) is a severe and fatal neurodegenerative disorder, which affects preferentially motoneurons. Changes in the redox state of superoxide dismutase 1 (SOD1) are associated with the onset and development of familial forms of ALS. In human SOD1 (hSOD1), a conserved disulfide bond and two free cysteine residues can engage in anomalous thiol/disulfide exchange resulting in non-native disulfides, a hallmark of ALS that is related to protein misfolding and aggregation. Because of the many competing reaction pathways, traditional bulk techniques fall short at quantifying individual thiol/disulfide exchange reactions. Here, we adapt recently developed single-bond chemistry techniques to study individual disulfide isomerization reactions in hSOD1. Mechanical unfolding of hSOD1 leads to the formation of a polypeptide loop held by the disulfide. This loop behaves as a molecular jump rope that brings reactive Cys-111 close to the disulfide. Using force-clamp spectroscopy, we monitor nucleophilic attack of Cys-111 at either sulfur of the disulfide and determine the selectivity of the reaction. Disease-causing mutations G93A and A4V show greatly altered reactivity patterns, which may contribute to the progression of familial ALS
Myb-binding protein 1A (MYBBP1A) is essential for early embryonic development, controls cell cycle and mitosis, and acts as a tumor suppressor
MYBBP1A is a predominantly nucleolar transcriptional regulator involved in rDNA synthesis and p53 activation via
acetylation. However little further information is available as to its function. Here we report that MYBBP1A is
developmentally essential in the mouse prior to blastocyst formation. In cell culture, down-regulation of MYBBP1A
decreases the growth rate of wild type mouse embryonic stem cells, mouse embryo fibroblasts (MEFs) and of human HeLa
cells, where it also promotes apoptosis. HeLa cells either arrest at G2/M or undergo delayed and anomalous mitosis. At
mitosis, MYBBP1A is localized to a parachromosomal region and gene-expression profiling shows that its down-regulation
affects genes controlling chromosomal segregation and cell cycle. However, MYBBP1A down-regulation increases the
growth rate of the immortalized NIH3T3 cells. Such Mybbp1a down-regulated NIH3T3 cells are more susceptible to Ras-induced
transformation and cause more potent Ras-driven tumors. We conclude that MYBBP1A is an essential gene with
novel roles at the pre-mitotic level and potential tumor suppressor activity.NHMRC: This work was supported by Associazione Italiana Ricerche sul Cancro (AIRC) grant 8929 and European Community FP7 201681 ââPrepobediaââ to FB, the
Australian National Health and Medical Research Council to RK and TJG (project ID000115). The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript
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