500 research outputs found
An International Classification of Inherited Metabolic Disorders (ICIMD)
Several initiatives at establishing a classification of inherited metabolic disorders have been published previously, some focusing on pathomechanisms, others on clinical manifestations, while yet another attempted a simplified approach of a comprehensive nosology. Some of these classifications suffered from shortcomings, such as lack of a mechanism for continuous update in light of a rapidly‐evolving field, or lack of widespread input from the metabolic community at large. Our classification – the International Classification of Inherited Metabolic Disorders, or ICIMD – includes 1,450 disorders, and differs from prior approaches in that it benefited from input by a large number of experts in the field, and was endorsed by major metabolic societies around the globe. Several criteria such as pathway involvement and pathomechanisms were considered. The main purpose of the hierarchical, group‐based approach of the ICIMD is an improved understanding of the interconnections between many individual conditions that may share functional, clinical and diagnostic features. The ICIMD aims to include any primary genetic condition in which alteration of a biochemical pathway is intrinsic to specific biochemical, clinical and/or pathophysiological features. As new disorders are discovered, we will seek the opinion of experts in the advisory board prior to inclusion in the appropriate group of the ICIMD, thus guaranteeing the continuing relevance of this classification via regular curation and expert advice
Recommendations and guidelines in the JIMD: suggested procedures and avoidance of conflicts of interest
Effective English Speaking Environment is an Important Factor of the University Integration into the Global Education System
Hsp70 Cochaperones HspBP1 and BAG-1M Differentially Regulate Steroid Hormone Receptor Function
Hsp70 binding protein 1 (HspBP1) and Bcl2-associated athanogene 1 (BAG-1), the functional orthologous nucleotide exchange factors of the heat shock protein 70 kilodalton (Hsc70/Hsp70) chaperones, catalyze the release of ADP from Hsp70 while inducing different conformational changes of the ATPase domain of Hsp70. An appropriate exchange rate of ADP/ATP is crucial for chaperone-dependent protein folding processes. Among Hsp70 client proteins are steroid receptors such as the glucocorticoid receptor (GR), the mineralocorticoid receptor (MR), and the androgen receptor (AR). BAG-1 diversely affects steroid receptor activity, while to date the influence of HspBP1 on steroid receptor function is mostly unknown. Here, we compared the influence of HspBP1 and BAG-1M on Hsp70-mediated steroid receptor folding complexes and steroid receptor activity. Coimmunoprecipitation studies indicated preferential binding of Hsp40 and the steroid receptors to BAG-1M as compared to HspBP1. Furthermore, Hsp70 binding to the ligand-binding domain of GR was reduced in the presence of HspBP1 but not in the presence of BAG-1M as shown by pull-down assays. Reporter gene experiments revealed an inhibitory effect on GR, MR, and AR at a wide range of HspBP1 protein levels and at hormone concentrations at or approaching saturation. BAG-1M exhibited a transition from stimulatory effects at low BAG-1M levels to inhibitory effects at higher BAG-1M levels. Overall, BAG-1M and HspBP1 had differential impacts on the dynamic composition of steroid receptor folding complexes and on receptor function with important implications for steroid receptor physiology
Impact of Nucleon Mass Shift on the Freeze Out Process
The freeze out of a massive nucleon gas through a finite layer with time-like
normal is studied. The impact of in-medium nucleon mass shift on the freeze out
process is investigated. A considerable modification of the thermodynamical
variables temperature, flow-velocity, energy density and particle density has
been found. Due to the nucleon mass shift the freeze out particle distribution
functions are changed noticeably in comparison with evaluations, which use
vacuum nucleon mass.Comment: submitted to Physical Review
Transient trimethylaminuria related to menstruation
BACKGROUND: Trimethylaminuria, or fish odor syndrome, includes a transient or mild malodor caused by an excessive amount of malodorous trimethylamine as a result of body secretions. Herein, we describe data to support the proposal that menses can be an additional factor causing transient trimethylaminuria in self-reported subjects suffering from malodor and even in healthy women harboring functionally active flavin-containing monooxygenase 3 (FMO3). METHODS: FMO3 metabolic capacity (conversion of trimethylamine to trimethylamine N-oxide) was defined as the urinary ratio of trimethylamine N-oxide to total trimethylamine. RESULTS: Self-reported Case (A) that was homozygous for inactive Arg500stop FMO3, showed decreased metabolic capacity of FMO3 (i.e., ~10% the unaffected metabolic capacity) during 120 days of observation. For Case (B) that was homozygous for common [Glu158Lys; Glu308Gly] FMO3 polymorphisms, metabolic capacity of FMO3 was almost ~90%, except for a few days surrounding menstruation showing < 40% metabolic capacity. In comparison, three healthy control subjects that harbored heterozygous polymorphisms for [Glu158Lys; Glu308Gly] FMO3 or homozygous for wild FMO3 showed normal (> 90%) metabolic capacity, however, on days around menstruation the FMO3 metabolic capacity was decreased to ~60–70%. CONCLUSION: Together, these results indicate that abnormal FMO3 capacity is caused by menstruation particularly in the presence, in homozygous form, of mild genetic variants such as [Glu158Lys; Glu308Gly] that cause a reduced FMO3 function
Evaluating chiral symmetry restoration through the use of sum rules
We pursue the idea of assessing chiral restoration via in-medium
modifications of hadronic spectral functions of chiral partners. The usefulness
of sum rules in this endeavor is illustrated, focusing on the vector and
axial-vector channels. We first present an update on constructing quantitative
results for pertinent vacuum spectral functions. These spectral functions serve
as a basis upon which the in-medium spectral functions can be constructed. A
striking feature of our analysis of the vacuum spectral functions is the need
to include excited resonances, dictated by satisfying the Weinberg-type sum
rules. This includes excited states in both the vector and axial-vector
channels. Preliminary results for the finite temperature vector spectral
function are presented. Based on a rho spectral function tested in dilepton
data which develops a shoulder at low energies, we find that the rho' peak
flattens off. The flattening may be a sign of chiral restoration, though a
study of the finite temperature axial-vector spectral function remains to be
carried out.Comment: 9 pages, conference proceedings from Resonance Workshop at UT Austin,
March 5-7 201
Direction of light propagation to order G^2 in static, spherically symmetric spacetimes: a new derivation
A procedure avoiding any integration of the null geodesic equations is used
to derive the direction of light propagation in a three-parameter family of
static, spherically symmetric spacetimes within the post-post-Minkowskian
approximation. Quasi-Cartesian isotropic coordinates adapted to the symmetries
of spacetime are systematically used. It is found that the expression of the
angle formed by two light rays as measured by a static observer staying at a
given point is remarkably simple in these coordinates. The attention is mainly
focused on the null geodesic paths that we call the "quasi-Minkowskian light
rays". The vector-like functions characterizing the direction of propagation of
such light rays at their points of emission and reception are firstly obtained
in the generic case where these points are both located at a finite distance
from the centre of symmetry. The direction of propagation of the
quasi-Minkowskian light rays emitted at infinity is then straightforwardly
deduced. An intrinsic definition of the gravitational deflection angle relative
to a static observer located at a finite distance is proposed for these rays.
The expression inferred from this definition extends the formula currently used
in VLBI astrometry up to the second order in the gravitational constant G.Comment: 19 pages; revised introduction; added references for introduction;
corrected typos; published in Class. Quantum Gra
In-medium Properties of Hadrons -- Observables
We first briefly review the theoretical basis for calculations of changes of
hadronic properties in dense nuclear matter. These changes have usually been
investigated by means of relativistic heavy-ion reactions. Here we discuss that
observable consequences of such changes can also be seen in more elementary
reactions on nuclei. Particular emphasis is put on a discussion of actual
observables in photonuclear reactions; we discuss in detail - and
vector-meson production. We show that photoproduction of 's can yield
essential information on in-medium properties of the resonance
while the meson properties will probably not be accessible through the
decay channel. However, for mesons the decay
channel, due to its reduced final state interaction, looks more promising in
this respect. Completely free of final state interactions is dilepton
production in the few GeV range. We show that the sensitivity of this decay
channel to changes of hadronic properties in medium in photonuclear reactions
on nuclei is as large as in ultrarelativistic heavy ion collisions. Finally we
discuss that hadron production in nuclei at 10 -- 20 GeV photon energies can
give important information on the hadronization process.Comment: Invited Lecture by U. Mosel at Erice International School on Nuclear
Physics 200
Study of in-medium meson properties in Ap, pA and AA collisions
We propose to investigate the in-medium properties of vector mesons
at the normal nuclear density in Ap(pA) collisions and at higher density in AA
collisions at the ITEP accelerator facility TWAC. Using of the inverse Ap
kinematics will permit us to study the meson production in a wide
momentum interval included the not yet explored range of small meson momenta
relative to the projectile nuclei where the mass modification effect in nuclear
matter is expected to be the strongest. Momentum dependence of the in-medium
meson width will be studied in the traditional pA kinematics. We
intend to use the electromagnetic calorimeter for reconstruction of the
meson invariant mass by detecting photons from the decay. The model calculations and simulations with
RQMD generator show feasibility of the proposed experiment. Available now
intensity of the ion beams provides a possibility to collect large statistics
and make decisive conclusion about the meson properties at density of
normal nuclei. At the second stage of the investigation the meson
properties will be studied in AA collisions at higher density. Interpretation
of these measurements will be based on the results obtained in Ap(pA)
interactions. Further investigation of the in-medium properties of light
unflavored and charmed mesons can be performed at ITEP and at GSI(FAIR) where
higher ion energies will be accessible in near future.Comment: 26 pages, 10 figures, 2 table
- …