26 research outputs found
Angelman syndrome in an inbred family
Angelman syndrome (AS) is characterized by severe mental retardation, absent speech, puppet-like movements, inappropriate laughter, epilepsy, and abnormal electroencephalogram. The majority of AS patients (≃ 65%) have a maternal deficiency within chromosomal region 15q11-q13, caused by maternal deletion or paternal uniparental disomy (UPD). Approximately 35% of AS patients exhibit neither detectable deletion nor UPD, but a subset of these patients have abnormal methylation at several loci in the 15q11-q13 interval. We describe here three patients with Angelman syndrome belonging to an extended inbred family. High resolution chromosome analysis combined with DNA analysis using 14 marker loci from the 15q11-q13 region failed to detect a deletion in any of the three patients. Paternal UPD of chromosome 15 was detected in one case, while the other two patients have abnormal methylation at D15S9, D15S63, and SNRPN. Although the three patients are distantly related, the chromosome 15q11-q13 haplotypes are different, suggesting that independent mutations gave rise to AS in this family
Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures
Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo
Neonatal Marfan syndrome with congenital arachnodactyly, flexion contractures, and severe cardiac valve insufficiency
Interactions between asteroid fragments during atmospheric entry
The current work explores the interactions between asteroid fragments and the associated flow topology to motivate a physically consistent representation of the fragmentation process following a fragmentation event during atmospheric entry. Multibody aerodynamic simulations run with computational fluid dynamics (CFD) solvers were used to generate a lookup table of forces detailing the interactions of two spheres. Trajectory simulations parsing the resulting database to determine the relative motions of any two spherical fragments were then validated with hypersonic wind tunnel experiments. A following series of fragment interaction simulations yielded categorization of the fragments' final relative states and an estimate of the total time of interaction. The fragment interaction model was nondimensionalized to permit study over a wide range of possible asteroid impacts. The interaction parameters are presented with explicit semi-analytic equations, defining the asteroid fragment-flow interaction model and thereby eliminating the need to perform a separate fragment interaction simulation for each fragmentation event in an atmospheric entry model. Finally, a set of illustrative examples demonstrates the efficacy of the model in a variety of fragmentation situations
Belang van de DNA diagnostiek van medium-chain Acyl-CoA dehydrogenase defici\uebntie bij wiegedood
FMRP is associated to the ribosomes via RNA
The FMR1 transcript is alternatively spliced and generates different
splice variants coding for FMR1 proteins (FMRP) with a predicted molecular
mass of 70-80 kDa. FMRP is widely expressed and localized in the
cytoplasm. To study a possible interaction with other cellular components,
FMRP was isolated and characterized under non-denaturing conditions. Under
physiological salt conditions FMRP appears to have a molecular mass of >
600 kDa, indicating a binding to other cellular components. This
interaction is disrupted in the presence of high salt concentrations. The
dissociation conditions to free FMRP from the complex are similar to the
dissociation of FMRP from RNA as shown before. The binding of FMRP from
the complex is also disrupted by RNAse treatment. That the association of
FMRP to a high molecular weight complex possibly occurs via RNA, is
further supported by the observation that the binding of FMRP, containing
an lle304Asn substitution, to the high molecular weight complex is
reduced. An equal reduced binding of mutated FMRP to RNA in vitro was
observed before under the same conditions. The reduced binding of FMRP
with the lle304Asn substitution further indicates that the interaction to
the complex indeed occurs via FMRP and not via other RNA binding proteins.
In a reconstitution experiment where the low molecular mass FMRP (70-80
kDa) is mixed with a reticulocyte lysate (enriched in ribosomes) it was
shown that FMRP can associate to ribosomes and that this binding most
likely occurs via RNA
Abnormal dendritic spine characteristics in the temporal and visual cortices of patients with fragile-X syndrome: a quantitative examination
Characterization of EcoRI mutation in fucosidosis patients: A stop codon in the open reading frame
Protein kinase C alpha controls erythropoietin receptor signaling.
Protein kinase C (PKC) is implied in the activation of multiple targets of
erythropoietin (Epo) signaling, but its exact role in Epo receptor (EpoR)
signal transduction and in the regulation of erythroid proliferation and
differentiation remained elusive. We analyzed the effect of PKC inhibitors
with distinct modes of action on EpoR signaling in primary human
erythroblasts and in a recently established murine erythroid cell line.
Active PKC appeared essential for Epo-induced phosphorylation of the Epo
receptor itself, STAT5, Gab1, Erk1/2, AKT, and other downstream targets.
Under the same conditions, stem cell factor-induced signal transduction
was not impaired. LY294002, a specific inhibitor of phosphoinositol
3-kinase, also suppressed Epo-induced signal transduction, which could be
partially relieved by activators of PKC. PKC inhibitors or LY294002 did
not affect membrane expression of the EpoR, the association of JAK2 with
the EpoR, or the in vitro kinase activity of JAK2. The data suggest that
PKC controls EpoR signaling instead of being a downstream effector. PKC
and phosphoinositol 3-kinase may act in concert to regulate association of
the EpoR complex such that it is responsive to ligand stimulation. Reduced
PKC-activity inhibited Epo-dependent differentiation, although it did not
effect Epo-dependent "renewal divisions" induced in the presence of Epo,
stem cell factor, and dexamethasone