1,162 research outputs found
Motor neurone and muscle nuclear changes in development and disease
The primary gene defects of hereditary neuromuscular
disorders have not, as yet, been determined. Research has
contributed much to our understanding of many aspects of
these diseases, but since this has been directed towards the
secondary phenomena, the exact role of the nucleus in the
pathogenesis of these genetic disorders remains unclear.
It was felt that a study of the motor neurone and muscle
nucleus in development and disease might reveal the extent
of its participation in some of these disease processes.
1. A quantitative histochemical and histometric study
of the developing anterior horn cell nucleus during fetal life
was undertaken. The result suggested that the 12th to 14th
week period is critical for the differentiation of the spinal
motor neurone.
2. In contrast to this, a similar study of the deve¬
loping muscle cell nuclei revealed no major changes in muscle
nuclear size or composition. During normal post-natal
muscle growth an increase in the number of nuclei per
muscle fibre seems to be responsible for the maintenance
of a constant nucleo-cytoplasmic ratio.
3. The nuclear size of multinucleated myoblasts
arising from both normal and dystrophic muscle in tissue
culture was measured. Myoblasts from dystrophic muscle
exhibited larger nuclei than those from normal muscle.
4. An increase in muscle nuclear size was also
detected in a number of muscle samples from male fetuses
at risk for Duchenne muscular dystrophy. Both of these
findings suggest possible changes in the nucleo-cytoplasmic
relationship.
5. In an attempt to elucidate the extent of the parti¬
cipation of the muscle nucleus in the pathogenic process of
a number of characteristic neuromuscular disorders, the
nuclear size and/or the number of nuclei per cross-sectioned
muscle fibre, were estimated. An increased nuclear size
was observed in Duchenne muscular dystrophy and an increase
in the number of nuclei was detected in chronic neurogenic
atrophies, in diabetic neuropathy and in myotonic dystrophy.
Such a finding would seem to indicate a fundamental difference
in the response of the muscle fibre nucleus to the neurogenic
and myopathic processes.
6. In addition, the growth of the human cervical vertebral
canal and spinal cord during normal fetal development was
studied. The results suggested that these two parts of the
developing body exhibit the same developmental pattern. The
rate of this parallel growth is lower than that of the body
as a whole, but similar to that reported for the brain.
In conclusion, although the techniques used did not
reveal a direct relationship in the developmental pattern of
anterior horn cell nuclei and myonuclei, they did provide
normal values for comparison with data obtained from
diseased neural and muscle tissue. The finding that in
Duchenne muscular dystrophy (from tissue culture, fetuses
at risk and juvenile biopsies) the muscle nuclei are enlarged,
points to an underlying difference from various neuropathies
in which the nuclei are increased in number
Future large-scale water-Cherenkov detector
MEMPHYS (MEgaton Mass PHYSics) is a proposed large-scale water-Cherenkov
experiment to be performed deep underground. It is dedicated to nucleon decay
searches and the detection of neutrinos from supernovae, solar, and atmospheric
neutrinos, as well as neutrinos from a future beam to measure the CP violating
phase in the leptonic sector and the mass hierarchy. This paper provides an
overview of the latest studies on the expected performance of MEMPHYS in view
of detailed estimates of its physics reach, mainly concerning neutrino beams
Study of the performance of a large scale water-Cherenkov detector (MEMPHYS)
MEMPHYS (MEgaton Mass PHYSics) is a proposed large-scale water Cherenkov
experiment to be performed deep underground. It is dedicated to nucleon decay
searches, neutrinos from supernovae, solar and atmospheric neutrinos, as well
as neutrinos from a future Super-Beam or Beta-Beam to measure the CP violating
phase in the leptonic sector and the mass hierarchy. A full simulation of the
detector has been performed to evaluate its performance for beam physics. The
results are given in terms of "Migration Matrices" of reconstructed versus true
neutrino energy, taking into account all the experimental effects.Comment: Updated after JCAP's referee's comment
A Very Intense Neutrino Super Beam Experiment for Leptonic CP Violation Discovery based on the European Spallation Source Linac: A Snowmass 2013 White Paper
Very intense neutrino beams and large neutrino detectors will be needed in
order to enable the discovery of CP violation in the leptonic sector. We
propose to use the proton linac of the European Spallation Source currently
under construction in Lund, Sweden to deliver, in parallel with the spallation
neutron production, a very intense, cost effective and high performance
neutrino beam. The baseline program for the European Spallation Source linac is
that it will be fully operational at 5 MW average power by 2022, producing 2
GeV 2.86 ms long proton pulses at a rate of 14 Hz. Our proposal is to upgrade
the linac to 10 MW average power and 28 Hz, producing 14 pulses/s for neutron
production and 14 pulses/s for neutrino production. Furthermore, because of the
high current required in the pulsed neutrino horn, the length of the pulses
used for neutrino production needs to be compressed to a few s with the
aid of an accumulator ring. A long baseline experiment using this Super Beam
and a megaton underground Water Cherenkov detector located in existing mines
300-600 km from Lund will make it possible to discover leptonic CP violation at
5 significance level in up to 50% of the leptonic Dirac CP-violating
phase range. This experiment could also determine the neutrino mass hierarchy
at a significance level of more than 3 if this issue will not already
have been settled by other experiments by then. The mass hierarchy performance
could be increased by combining the neutrino beam results with those obtained
from atmospheric neutrinos detected by the same large volume detector. This
detector will also be used to measure the proton lifetime, detect cosmological
neutrinos and neutrinos from supernova explosions. Results on the sensitivity
to leptonic CP violation and the neutrino mass hierarchy are presented.Comment: 28 page
CHC22 and CHC17 clathrins have distinct biochemical properties and display differential regulation and function
Clathrins are cytoplasmic proteins that play essential roles in endocytosis and other membrane traffic pathways. Upon recruitment to intracellular membranes, the canonical clathrin triskelion assembles into a polyhedral protein coat that facilitates vesicle formation and captures cargo molecules for transport. The triskelion is formed by trimerization of three clathrin heavy-chain subunits. Most vertebrates have two isoforms of clathrin heavy chains, CHC17 and CHC22, generating two clathrins with distinct cellular functions. CHC17 forms vesicles at the plasma membrane for receptor-mediated endocytosis and at the trans-Golgi network for organelle biogenesis. CHC22 plays a key role in intracellular targeting of the insulin-regulated glucose transporter 4 (GLUT4), accumulates at the site of GLUT4 sequestration during insulin resistance, and has also been implicated in neuronal development. Here, we demonstrate that CHC22 and CHC17 share morphological features, in that CHC22 forms a triskelion and latticed vesicle coats. However, cellular CHC22-coated vesicles were distinct from those formed by CHC17. The CHC22 coat was more stable to pH change and was not removed by the enzyme complex that disassembles the CHC17 coat. Moreover, the two clathrins were differentially recruited to membranes by adaptors, and CHC22 did not support vesicle formation or transferrin endocytosis at the plasma membrane in the presence or absence of CHC17. Our findings provide biochemical evidence for separate regulation and distinct functional niches for CHC17 and CHC22 in human cells. Furthermore, the greater stability of the CHC22 coat relative to the CHC17 coat may be relevant to its excessive accumulation with GLUT4 during insulin resistance. [Abstract copyright: Copyright © 2017, The American Society for Biochemistry and Molecular Biology.
SIRT2 Maintains Genome Integrity and Suppresses Tumorigenesis Through Regulating APC/C Activity
Members of sirtuin family regulate multiple critical biological processes, yet their role in carcinogenesis remains controversial. To investigate the physiological functions of SIRT2 in development and tumorigenesis, we disrupted Sirt2 in mice. We demonstrated that SIRT2 regulates the anaphase-promoting complex/cyclosome activity through deacetylation of its coactivators, APC(CDH1) and CDC20. SIRT2 deficiency caused increased levels of mitotic regulators, including Aurora-A and -B that direct centrosome amplification, aneuploidy, and mitotic cell death. Sirt2-deficient mice develop gender-specific tumorigenesis, with females primarily developing mammary tumors, and males developing more hepatocellular carcinoma (HCC). Human breast cancers and HCC samples exhibited reduced SIRT2 levels compared with normal tissues. These data demonstrate that SIRT2 is a tumor suppressor through its role in regulating mitosis and genome integrity
High intensity neutrino oscillation facilities in Europe
The EUROnu project has studied three possible options for future, high intensity neutrino oscillation facilities in Europe. The first is a Super Beam, in which the neutrinos come from the decay of pions created by bombarding targets with a 4 MW proton beam from the CERN High Power Superconducting Proton Linac. The far detector for this facility is the 500 kt MEMPHYS water Cherenkov, located in the Fréjus tunnel. The second facility is the Neutrino Factory, in which the neutrinos come from the decay of μ+ and μ− beams in a storage ring. The far detector in this case is a 100 kt magnetized iron neutrino detector at a baseline of 2000 km. The third option is a Beta Beam, in which the neutrinos come from the decay of beta emitting isotopes, in particular He6 and Ne18, also stored in a ring. The far detector is also the MEMPHYS detector in the Fréjus tunnel. EUROnu has undertaken conceptual designs of these facilities and studied the performance of the detectors. Based on this, it has determined the physics reach of each facility, in particular for the measurement of CP violation in the lepton sector, and estimated the cost of construction. These have demonstrated that the best facility to build is the Neutrino Factory. However, if a powerful proton driver is constructed for another purpose or if the MEMPHYS detector is built for astroparticle physics, the Super Beam also becomes very attractive
Search for composite and exotic fermions at LEP 2
A search for unstable heavy fermions with the DELPHI detector at LEP is
reported. Sequential and non-canonical leptons, as well as excited leptons and
quarks, are considered. The data analysed correspond to an integrated
luminosity of about 48 pb^{-1} at an e^+e^- centre-of-mass energy of 183 GeV
and about 20 pb^{-1} equally shared between the centre-of-mass energies of 172
GeV and 161 GeV. The search for pair-produced new leptons establishes 95%
confidence level mass limits in the region between 70 GeV/c^2 and 90 GeV/c^2,
depending on the channel. The search for singly produced excited leptons and
quarks establishes upper limits on the ratio of the coupling of the excited
fermio
Search for lightest neutralino and stau pair production in light gravitino scenarios with stau NLSP
Promptly decaying lightest neutralinos and long-lived staus are searched for
in the context of light gravitino scenarios. It is assumed that the stau is the
next to lightest supersymmetric particle (NLSP) and that the lightest
neutralino is the next to NLSP (NNLSP). Data collected with the Delphi detector
at centre-of-mass energies from 161 to 183 \GeV are analysed. No evidence of
the production of these particles is found. Hence, lower mass limits for both
kinds of particles are set at 95% C.L.. The mass of gaugino-like neutralinos is
found to be greater than 71.5 GeV/c^2. In the search for long-lived stau,
masses less than 70.0 to 77.5 \GeVcc are excluded for gravitino masses from 10
to 150 \eVcc . Combining this search with the searches for stable heavy leptons
and Minimal Supersymmetric Standard Model staus a lower limit of 68.5 \GeVcc
may be set for the stau mas
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