1,786 research outputs found
HIV-1 DIS stem loop forms an obligatory bent kissing intermediate in the dimerization pathway.
The HIV-1 dimerization initiation sequence (DIS) is a conserved palindrome in the apical loop of a conserved hairpin motif in the 5′-untranslated region of its RNA genome. DIS hairpin plays an important role in genome dimerization by forming a ‘kissing complex’ between two complementary hairpins. Understanding the kinetics of this interaction is key to exploiting DIS as a possible human immunodeficiency virus (HIV) drug target. Here, we present a single-molecule Förster resonance energy transfer (smFRET) study of the dimerization reaction kinetics. Our data show the real-time formation and dissociation dynamics of individual kissing complexes, as well as the formation of the mature extended duplex complex that is ultimately required for virion packaging. Interestingly, the single-molecule trajectories reveal the presence of a previously unobserved bent intermediate required for extended duplex formation. The universally conserved A272 is essential for the formation of this intermediate, which is stabilized by Mg(2+), but not by K(+) cations. We propose a 3D model of a possible bent intermediate and a minimal dimerization pathway consisting of three steps with two obligatory intermediates (kissing complex and bent intermediate) and driven by Mg(2+) ions
Geometric-Phase-Effect Tunnel-Splitting Oscillations in Single-Molecule Magnets with Fourth-Order Anisotropy Induced by Orthorhombic Distortion
We analyze the interference between tunneling paths that occurs for a spin
system with both fourth-order and second-order transverse anisotropy. Using an
instanton approach, we find that as the strength of the second-order transverse
anisotropy is increased, the tunnel splitting is modulated, with zeros
occurring periodically. This effect results from the interference of four
tunneling paths connecting easy-axis spin orientations and occurs in the
absence of any magnetic field.Comment: 6 pages, 5 eps figures. Version published in EPL. Expanded from v1:
Appendix added, references added, 1 figure added, others modified
cosmeticall
Multi-Scale Simulation Modeling for Prevention and Public Health Management of Diabetes in Pregnancy and Sequelae
Diabetes in pregnancy (DIP) is an increasing public health priority in the
Australian Capital Territory, particularly due to its impact on risk for
developing Type 2 diabetes. While earlier diagnostic screening results in
greater capacity for early detection and treatment, such benefits must be
balanced with the greater demands this imposes on public health services. To
address such planning challenges, a multi-scale hybrid simulation model of DIP
was built to explore the interaction of risk factors and capture the dynamics
underlying the development of DIP. The impact of interventions on health
outcomes at the physiological, health service and population level is measured.
Of particular central significance in the model is a compartmental model
representing the underlying physiological regulation of glycemic status based
on beta-cell dynamics and insulin resistance. The model also simulated the
dynamics of continuous BMI evolution, glycemic status change during pregnancy
and diabetes classification driven by the individual-level physiological model.
We further modeled public health service pathways providing diagnosis and care
for DIP to explore the optimization of resource use during service delivery.
The model was extensively calibrated against empirical data.Comment: 10 pages, SBP-BRiMS 201
Maternal glycaemic control and risk of neonatal hypoglycaemia in Type 1 diabetes pregnancy: a secondary analysis of the CONCEPTT trial
Aims: To examine the relationship between maternal glycaemic control and risk of neonatal hypoglycaemia using conventional and continuous glucose monitoring (CGM) metrics in the Continuous Glucose Monitoring in Type 1 Diabetes Pregnancy Trial (CONCEPTT) participants. Methods: A secondary analysis of CONCEPTT involving 225 pregnant women and their liveborn infants. Antenatal glycaemia was assessed at 12, 24 and 34 weeks gestation. Intrapartum glycaemia was assessed by CGM measures 24 hours prior to delivery. The primary outcome was neonatal hypoglycaemia defined as glucose concentration 97.7th centile (63.2% vs 33.9%; p<0.0001) and skinfold thickness (p≤0.02). Intrapartum CGM was available for 33 participants, with no differences between mothers of neonates with and without hypoglycaemia. Conclusions: Modest increments in CGM time-in-target (5-7% increase) during the second and third trimesters are associated with reduced risk for neonatal hypoglycaemia. While more intrapartum CGM data are needed, the higher birthweight and skinfold measures associated with neonatal hypoglycaemia, suggest that risk is related to fetal hyperinsulinemia preceding the immediate intrapartum period
Reply: KRAS status analysis and anti-EGFR therapies: is comprehensiveness a biologist's fancy or a clinical necessity?
We thank Dr Lopez-Crapez et al 2010 to have taken cue fro
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