Inhibition of crossed caudal interneurons by lateral interneurons in lamprey spinal cord during fictive locomotion

Templates of the membrane potential profiles from lateral (LI) interneurons and motoneurons during glutamate- and N-methyl-D-aspartate (NMDA)-induced fictive locomotion showed pronounced plateau phases. In contrast, crossed caudal (CC) interneurons had a less obvious and steeper plateau region that was followed by a clear notch coinciding with the end of the lateral interneuron plateau phase. These results indicate a significant inhibitory input from LI to CC interneurons.     

The conformation of end-groups is one determinant of carotenoid topology suitable for high fidelity molecular recognition: A study of β- and ε-end-groups

Conformation affects a carotenoid’s ability to bind selectively to proteins. We calculated adiabatic energy profiles for rotating the ring end-groups around the C6C7 bond and for flexing of the ring with respect to the polyene chain. The choice of computational methods is important. A low, 4.2 kcal/mol barrier to rotation exists for a β-ring. An 8.3 kcal/mol barrier exists for rotation of an ε-ring. Rotation of the ε-ring is sensitive to substitution at C3. In the absence of external forces neither β- nor ε-rings are rotationally constrained. The nearly parallel alignment of the β-ring to the C6C7 bond axis contrasts to the more perpendicular orientation of the ε-ring. Flexion of a β-ring to the minimized ε-ring conformation requires ∼23 kcal/mol; extension of the ε-ring to the minimized β-ring conformation requires ∼8 kcal/mol. Selectivity associated with β- versus ε-rings is dominated by the inability of the β-ring to flex to minimize protein/ring steric interactions and maximize van der Waal’s attractions with the binding site.     

Delineation of amplification,hybridization and location effects in microarray data yields better-quality normalization

Background  

Oligonucleotide arrays have become one of the most widely used high-throughput tools in biology. Due to their sensitivity to experimental conditions, normalization is a crucial step when comparing measurements from these arrays. Normalization is, however, far from a solved problem. Frequently, we encounter datasets with significant technical effects that currently available methods are not able to correct.     

Erratum

Neurotransmitter receptor trafficking and the regulation of synaptic strength. Traffic 2001:2(7):437–448.     

Characterization of the Rac guanine nucleotide exchange factor P-Rex1 in platelets

Background

Blood platelets undergo a carefully regulated change in shape to serve as the primary mediators of hemostasis and thrombosis. These processes manifest through platelet spreading and aggregation and are dependent on platelet actin cytoskeletal changes orchestrated by the Rho GTPase family member Rac1. To elucidate how Rac1 is regulated in platelets, we captured Rac1-interacting proteins from platelets and identified Rac1-associated proteins by mass spectrometry.

Findings

Here, we demonstrate that Rac1 captures the Rac guanine nucleotide exchange factor P-Rex1 from platelet lysates. Western blotting experiments confirmed that P-Rex1 is expressed in platelets and associated with Rac1. To investigate the functional role of platelet P-Rex1, platelets from P-Rex1 ^-/- -deficient mice were treated with platelet agonists or exposed to platelet activating surfaces of fibrinogen, collagen and thrombin. Platelets from P-Rex1 ^-/- mice responded to platelet agonists and activating surfaces similarly to wild type platelets.

Conclusions

These findings suggest that P-Rex1 is not required for Rac1-mediated platelet activation and that the GEF activities of P-Rex1 may be more specific to GPCR chemokine receptor mediated processes in immune cells and tumor cells.     

Hybrid metabolic flux analysis: combining stoichiometric and statistical constraints to model the formation of complex recombinant products

Background  

Stoichiometric models constitute the basic framework for fluxome quantification in the realm of metabolic engineering. A recurrent bottleneck, however, is the establishment of consistent stoichiometric models for the synthesis of recombinant proteins or viruses. Although optimization algorithms for in silico metabolic redesign have been developed in the context of genome-scale stoichiometric models for small molecule production, still rudimentary knowledge of how different cellular levels are regulated and phenotypically expressed prevents their full applicability for complex product optimization.     

Cumulative viral load and virologic decay patterns after antiretroviral therapy in HIV-infected subjects influence CD4 recovery and AIDS

Background

The impact of viral load (VL) decay and cumulative VL on CD4 recovery and AIDS after highly-active antiretroviral therapy (HAART) is unknown.

Methods and Findings

Three virologic kinetic parameters (first year and overall exponential VL decay constants, and first year VL slope) and cumulative VL during HAART were estimated for 2,278 patients who initiated HAART in the U.S. Military HIV Natural History Study. CD4 and VL trajectories were computed using linear and nonlinear Generalized Estimating Equations models. Multivariate Poisson and linear regression models were used to determine associations of VL parameters with CD4 recovery, adjusted for factors known to correlate with immune recovery. Cumulative VL higher than the sample median was independently associated with an increased risk of AIDS (relative risk 2.38, 95% confidence interval 1.56–3.62, p<0.001). Among patients with VL suppression, first year VL decay and slope were independent predictors of early CD4 recovery (p = 0.001) and overall gain (p<0.05). Despite VL suppression, those with slow decay during the first year of HAART as well as during the entire therapy period (overall), in general, gained less CD4 cells compared to the other subjects (133 vs. 195.4 cells/µL; p = 0.001) even after adjusting for potential confounders.

Conclusions

In a cohort with free access to healthcare, independent of established predictors of AIDS and CD4 recovery during HAART, cumulative VL and virologic decay patterns were associated with AIDS and distinct aspects of CD4 reconstitution.     

Two new species of Campomanesia (Myrtaceae) from Espírito Santo and Bahia, Brazil

Campomanesia macrobracteolata andC. anemonea, apparently closely related species from Espírito Santo and Bahia, Brazil, are described as new and are illustrated. Comparisons are made with two other similar species.