Mucopolysaccharidosis II (MPS II, Hunter syndrome in humans) is an X-linked inherited lysosomal storage disease caused by a deficiency in the lysosomal enzyme iduronate-2-sulfatase (I2S). I2S ...catalyses a step in the catabolism of glycosaminoglycans (GAGs) dermatan sulfate and heparan sulfate, and when it is deficient or absent GAGs accumulate in tissues and organs. Male knockout mice (IdS-KO), which lack the gene coding for I2S, exhibit many of the characteristics seen in the human disease. Compared to wild-type control mice, urine GAG excretion was elevated at 4 weeks of age and remained high throughout the lifespan, and tissue GAG levels were elevated as early as 7 weeks of age. Liver, spleen and other organs were significantly larger in the IdS-KO mice than in the wild-type. Radiographic examination revealed sclerosis and enlargement of the skull at 4 weeks of age and appendicular bone enlargement at 10-13 weeks of age. Micro CT scans showed severe periosteal bone formation at the lateral aspect of the distal tibia and calcification of the calcaneus tendon. This model was used in the development of idursulfase for treatment of MPS II and may continue to be useful in the evaluation of treatment strategies of this chronic and progressive disorder.
Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is an X‐linked disease caused by a deficiency of the enzyme iduronate‐2‐sulphatase (IDS), which results in the lysosomal accumulation of ...glycosaminoglycans (GAG). This paper describes a knockout mouse model of MPS II which has been used to assess the effect of enzyme replacement therapy. Therapy with IDS results in a marked decrease in urinary GAGs, as well as reduced GAG accumulation in several tissues. These studies have been used to support the first clinical trial of recombinant IDS in patients with Hunter syndrome.
Worcester Foundation for Biomedical Research, Shrewsbury,
Massachusetts
McCracken, John A.,
Edward E. Custer, and
Justin C. Lamsa.
In many nonprimate mammalian species,
cyclical regression of the ...corpus luteum (luteolysis) is caused by the
episodic pulsatile secretion of uterine PGF 2 , which acts
either locally on the corpus luteum by a countercurrent mechanism or,
in some species, via the systemic circulation. Hysterectomy in these
nonprimate species causes maintenance of the corpora lutea, whereas in
primates, removal of the uterus does not influence the cyclical
regression of the corpus luteum. In several nonprimate species, the
episodic pattern of uterine PGF 2 secretion appears to be
controlled indirectly by the ovarian steroid hormones estradiol-17
and progesterone. It is proposed that, toward the end of the luteal
phase, loss of progesterone action occurs both centrally in the
hypothalamus and in the uterus due to the catalytic reduction
(downregulation) of progesterone receptors by progesterone. Loss of
progesterone action may permit the return of estrogen action, both
centrally in the hypothalamus and peripherally in the uterus. Return of central estrogen action appears to cause the hypothalamic oxytocin pulse generator to alter its frequency and produce a series of intermittent episodes of oxytocin secretion. In the uterus, returning estrogen action concomitantly upregulates endometrial oxytocin receptors. The interaction of neurohypophysial oxytocin with oxytocin receptors in the endometrium evokes the secretion of luteolytic pulses
of uterine PGF 2 . Thus the uterus can be regarded as a
transducer that converts intermittent neural signals from the hypothalamus, in the form of episodic oxytocin secretion, into luteolytic pulses of uterine PGF 2 . In ruminants,
portions of a finite store of luteal oxytocin are released
synchronously by uterine PGF 2 pulses. Luteal oxytocin in
ruminants may thus serve to amplify neural oxytocin signals that are
transduced by the uterus into pulses of PGF 2 . Whether
such amplification of episodic PGF 2 pulses by luteal
oxytocin is a necessary requirement for luteolysis in ruminants remains
to be determined. Recently, oxytocin has been reported to be produced
by the endometrium and myometrium of the sow, mare, and rat. It is
possible that uterine production of oxytocin may act as a supplemental
source of oxytocin during luteolysis in these species. In primates,
oxytocin and its receptor and PGF 2 and its receptor have
been identified in the corpus luteum and/or ovary. Therefore, it is
possible that oxytocin signals of ovarian and/or neural origin may be
transduced locally at the ovarian level, thus explaining why luteolysis
and ovarian cyclicity can proceed in the absence of the uterus in primates. However, it remains to be established whether the
intraovarian process of luteolysis is mediated by arachidonic acid
and/or its metabolite PGF 2 and whether the central
oxytocin pulse generator identified in nonprimate species plays a
mediatory role during luteolysis in primates. Regardless of the
mechanism, intraovarian luteolysis in primates (progesterone
withdrawal) appears to be the primary stimulus for the subsequent
production of endometrial prostaglandins associated with menstruation.
In contrast, luteolysis in nonprimate species appears to depend on the
prior production of endometrial prostaglandins. In primates, uterine
prostaglandin production may reflect a vestigial mechanism that has
been retained during evolution from an earlier dependence on uterine
prostaglandin production for luteolysis.
Snow is an important driver of ecosystem processes in cold biomes. Snow accumulation determines ground temperature, light conditions, and moisture availability during winter. It also affects the ...growing season’s start and end, and plant access to moisture and nutrients. Here, we review the current knowledge of the snow cover’s role for vegetation, plant-animal interactions, permafrost conditions, microbial processes, and biogeochemical cycling. We also compare studies of natural snow gradients with snow experimental manipulation studies to assess time scale difference of these approaches. The number of tundra snow studies has increased considerably in recent years, yet we still lack a comprehensive overview of how altered snow conditions will affect these ecosystems. Specifically, we found a mismatch in the timing of snowmelt when comparing studies of natural snow gradients with snow manipulations. We found that snowmelt timing achieved by snow addition and snow removal manipulations (average 7.9 days advance and 5.5 days delay, respectively) were substantially lower than the temporal variation over natural spatial gradients within a given year (mean range 56 days) or among years (mean range 32 days). Differences between snow study approaches need to be accounted for when projecting snow dynamics and their impact on ecosystems in future climates.
Central diffraction at ALICE Lämsä, J W; Orava, R
Journal of instrumentation,
02/2011, Letnik:
6, Številka:
2
Journal Article
Recenzirano
The ALICE experiment is shown to be well suited for studies of exclusive final statesfrom central diffractive reactions. The gluon-rich environment of the central system allows detailedQCD studies ...and searches for exotic meson states, such as glueballs, hybrids and new charmoniumlikestates. It would also provide a good testing ground for detailed studies of heavy quarkonia. Due to its central barrel performance, ALICE can accurately measure the low-mass central systemswith good purity. The efficiency of the Forward Multiplicity Detector (FMD) and the ForwardShower Counter (FSC) system for detecting rapidity gaps is shown to be adequate for the proposedstudies. With this detector arrangement, valuable new data can be obtained by tagging centraldiffractive processes.
The nature of b-quark jet hadronisation has been investigated using data taken at the Z peak by the DELPHI detector at LEP. Two complementary methods are used to reconstruct the energy of weakly ...decaying b-hadrons,
. The average value of
is measured to be 0.699±0.011. The resulting
distribution is then analysed in the framework of two choices for the perturbative contribution (parton shower and Next to Leading Log QCD calculation) in order to extract measurements of the non-perturbative contribution to be used in studies of b-hadron production in other experimental environments than LEP. In the parton shower framework, data favour the Lund model ansatz and corresponding values of its parameters have been determined within PYTHIA 6.156 from DELPHI data:
with a correlation factor
ρ
=92.2%.
Combining the data on the b-quark fragmentation distributions with those obtained at the Z peak by ALEPH, OPAL and SLD, the average value of
is found to be 0.7092±0.0025 and the non-perturbative fragmentation component is extracted. Using the combined distribution, a better determination of the Lund parameters is also obtained:
with a correlation factor
ρ
=92.6%.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We present an updated measurement of time-dependent CP-violating asymmetries in neutral B decays with the BABAR detector at the PEP-II asymmetric B Factory at SLAC. This result uses an additional ...sample of Upsilon(4S) decays collected in 2001, bringing the data available to 32 x 10(6) BB macro pairs. We select events in which one neutral B meson is fully reconstructed in a final state containing charmonium and the flavor of the other neutral B meson is determined from its decay products. The amplitude of the CP-violating asymmetry, which in the standard model is proportional to sin2 beta, is derived from the decay time distributions in such events. The result sin2 beta = 0.59+/-0.14(stat)+/-0.05(syst) establishes CP violation in the B(0) meson system. We also determine absolute value of lambda = 0.93+/-0.09(stat)+/-0.03(syst), consistent with no direct CP violation.
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