Red-green color vision impairment in Duchenne muscular dystrophy

The present study evaluated the color vision of 44 patients with Duchenne muscular dystrophy (DMD) (mean age 14.8 years; SD 4.9) who were submitted to a battery of four different color tests: Cambridge Colour Test (CCT), Neitz Anomaloscope, Ishihara, and American Optical Hardy-Rand-Rittler (AO H-R-R). Patients were divided into two groups according to the region of deletion in the dystrophin gene: upstream of exon 30 (n=12) and downstream of exon 30 (n=32). The control group was composed of 70 age-matched healthy male subjects with no ophthalmological complaints. Of the patients with DMD, 47% (21/44) had a red-green color vision defect in the CCT, confirmed by the Neitz Anomaloscope with statistical agreement (P<.001). The Ishihara and the AO H-R-R had a lower capacity to detect color defects--5% and 7%, respectively, with no statistical similarity between the results of these two tests nor between CCT and Anomaloscope results (P>.05). Of the patients with deletion downstream of exon 30, 66% had a red-green color defect. No color defect was found in the patients with deletion upstream of exon 30. A negative correlation between the color thresholds and age was found for the controls and patients with DMD, suggesting a nonprogressive color defect. The percentage (66%) of patients with a red-green defect was significantly higher than the expected <10% for the normal male population (P<.001). In contrast, patients with DMD with deletion upstream of exon 30 had normal color vision. This color defect might be partially explained by a retina impairment related to dystrophin isoform Dp260.     

C-reactive protein collaborates with plasma lectins to boost immune response against bacteria

Although human C-reactive protein (CRP) becomes upregulated during septicemia, its role remains unclear, since purified CRP showed no binding to many common pathogens. Contrary to previous findings, we show that purified human CRP (hCRP) binds to Salmonella enterica, and that binding is enhanced in the presence of plasma factors. In the horseshoe crab, Carcinoscorpius rotundicauda, CRP is a major hemolymph protein. Incubation of hemolymph with a range of bacteria resulted in CRP binding to all the bacteria tested. Lipopolysaccharide-affinity chromatography of the hemolymph co-purified CRP, galactose-binding protein (GBP) and carcinolectin-5 (CL5). Yeast two-hybrid and pull-down assays suggested that these pattern recognition receptors (PRRs) form pathogen recognition complexes. We show the conservation of PRR crosstalk in humans, whereby hCRP interacts with ficolin (CL5 homologue). This interaction stabilizes CRP binding to bacteria and activates the lectin-mediated complement pathway. We propose that CRP does not act alone but collaborates with other plasma PRRs to form stable pathogen recognition complexes when targeting a wide range of bacteria for destruction.     

SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis

A progressive loss of neurons with age underlies a variety of debilitating neurological disorders, including Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS), yet few effective treatments are currently available. The SIR2 gene promotes longevity in a variety of organisms and may underlie the health benefits of caloric restriction, a diet that delays aging and neurodegeneration in mammals. Here, we report that a human homologue of SIR2, SIRT1, is upregulated in mouse models for AD, ALS and in primary neurons challenged with neurotoxic insults. In cell-based models for AD/tauopathies and ALS, SIRT1 and resveratrol, a SIRT1-activating molecule, both promote neuronal survival. In the inducible p25 transgenic mouse, a model of AD and tauopathies, resveratrol reduced neurodegeneration in the hippocampus, prevented learning impairment, and decreased the acetylation of the known SIRT1 substrates PGC-1alpha and p53. Furthermore, injection of SIRT1 lentivirus in the hippocampus of p25 transgenic mice conferred significant protection against neurodegeneration. Thus, SIRT1 constitutes a unique molecular link between aging and human neurodegenerative disorders and provides a promising avenue for therapeutic intervention.     

Results of satellite tagging of Atlantic bluefin tuna, <Emphasis Type="Italic">Thunnus thynnus</Emphasis>, off the coast of Ireland

Pop-up satellite archival tags were attached to six Atlantic bluefin tuna (Thunnus thynnus) off the west coast of Ireland in autumn 2003 and 2004. The satellite tags measured pressure, ambient temperature and light for the term of deployment. Radio pop-up satellite endpoint positions, light and sea surface temperature estimations of geolocation indicate that two fish tagged minutes apart off the coast of County Donegal, migrated to the eastern and western Atlantic Ocean over the following 8 months. The two fish were 5218 km apart at the termination of the experiment. After tagging in September and popping up the following March and April, one fish had traveled to the western Atlantic while the other was located in the waters off the southwest coast of Portugal. A third fish tagged off the coast of County Donegal in October 2004 moved into the Mediterranean Sea and was caught by a fishing vessel southeast of Malta on 11 June 2005. The results link bluefin tuna feeding on European foraging grounds with known eastern breeding regions and western Atlantic waters.     

Mechanical hemolysis in blood flow: user-independent predictions with the solution of a partial differential equation

This paper presents for the first time numerical predictions of mechanical blood hemolysis obtained by solving a hyperbolic partial differential equation (PDE) modelling the hemolysis in a Eulerian frame of reference. This provides hemolysis predictions over the entire computational domain as an alternative to the Lagrangian approach consisting in evaluating cell hemolysis along their trajectories. The solution of a PDE over a computational domain, such as in the approach presented herein, yields a unique solution. This is a clear advantage over the Lagrangian approach, which requires the human-made choice of a limited number of trajectories for integration and inevitably results in the incomplete coverage of the computational domain. The hyperbolic hemolysis model is solved with a Discontinuous Galerkin finite element method. The solution algorithm also includes adaptive remeshing to provide high accuracy simulations. Predictions of the modified index of hemolysis (MIH) are presented for flows in dialysis cannulae and sudden contractions. MIH predictions for cannulae differ significantly from those obtained by other authors using the Lagrangian approach. The predictions for flows in sudden contractions are used, along with our own experimental measurements, to assess the value of the threshold shear stress required for hemolysis that is included in the hemolysis model.     

QM/MM studies of enzymes

Combined quantum-mechanics/molecular-mechanics (QM/MM) methods are making rapid progress both methodologically and with respect to their range of application. Mechanistic studies on enzymes, including contributions towards the understanding of enzyme catalysis, continue to be a major target. They are joined by calculations of pK(a) values, redox properties, ground- and excited-state spectroscopic parameters, and excited-state dynamics. Methodological advances include improved QM/MM schemes, in particular new approaches for an effective treatment of the QM-MM electrostatic interactions, and the incorporation of new efficient and accurate QM methods in QM/MM schemes.