Interactions among oscillatory pathways in NF-kappa B signaling

Background  

Sustained stimulation with tumour necrosis factor alpha (TNF-alpha) induces substantial oscillations—observed at both the single cell and population levels—in the nuclear factor kappa B (NF-kappa B) system. Although the mechanism has not yet been elucidated fully, a core system has been identified consisting of a negative feedback loop involving NF-kappa B (RelA:p50 hetero-dimer) and its inhibitor I-kappa B-alpha. Many authors have suggested that this core oscillator should couple to other oscillatory pathways.     

Enhanced Amphiphilic Profile of a Short β-Stranded Peptide Improves Its Antimicrobial Activity

SB056 is a novel semi-synthetic antimicrobial peptide with a dimeric dendrimer scaffold. Active against both Gram-negative and -positive bacteria, its mechanism has been attributed to a disruption of bacterial membranes. The branched peptide was shown to assume a β-stranded conformation in a lipidic environment. Here, we report on a rational modification of the original, empirically derived linear peptide sequence [WKKIRVRLSA-NH₂, SB056-lin]. We interchanged the first two residues [KWKIRVRLSA-NH₂, β-SB056-lin] to enhance the amphipathic profile, in the hope that a more regular β-strand would lead to a better antimicrobial performance. MIC values confirmed that an enhanced amphiphilic profile indeed significantly increases activity against both Gram-positive and -negative strains. The membrane binding affinity of both peptides, measured by tryptophan fluorescence, increased with an increasing ratio of negatively charged/zwitterionic lipids. Remarkably, β-SB056-lin showed considerable binding even to purely zwitterionic membranes, unlike the original sequence, indicating that besides electrostatic attraction also the amphipathicity of the peptide structure plays a fundamental role in binding, by stabilizing the bound state. Synchrotron radiation circular dichroism and solid-state ¹⁹F-NMR were used to characterize and compare the conformation and mobility of the membrane bound peptides. Both SB056-lin and β-SB056-lin adopt a β-stranded conformation upon binding POPC vesicles, but the former maintains an intrinsic structural disorder that also affects its aggregation tendency. Upon introducing some anionic POPG into the POPC matrix, the sequence-optimized β-SB056-lin forms well-ordered β-strands once electro-neutrality is approached, and it aggregates into more extended β-sheets as the concentration of anionic lipids in the bilayer is raised. The enhanced antimicrobial activity of the analogue correlates with the formation of these extended β-sheets, which also leads to a dramatic alteration of membrane integrity as shown by ³¹P-NMR. These findings are generally relevant for the design and optimization of other membrane-active antimicrobial peptides that can fold into amphipathic β-strands.     

Effect of Mass Supplementation with Ready-to-Use Supplementary Food during an Anticipated Nutritional Emergency

Background

Previous studies have shown the benefits of ready-to-use supplementary food (RUSF) distribution in reducing the incidence and prevalence of severe acute malnutrition.

Methods and Findings

To compare the incidence of wasting, stunting and mortality between children aged 6 to 23 mo participating and not participating in distributions of RUSF, we implemented two exhaustive prospective cohorts including all children 60 cm to 80 cm, resident in villages of two districts of Maradi region in Niger (n = 2238). Villages (20) were selected to be representative of the population. All registered children were eligible for the monthly distributions between July and October 2010. Age, sex, height, weight, and Mid-Upper Arm Circumference (MUAC) were measured at baseline and two weeks after each distribution; the amount and type of distribution and the amount shared and remaining were also assessed. We compared the incidence of wasting, stunting, and mortality among children participating in the distribution (intervention) of RUSF versus children not participating in the distribution (comparison). The absolute rate of wasting was 4.71 events per child-year (503 events/106.59 child-year) in the intervention group and 4.98 events per child-year (322 events/64.54 child-year) in the comparison group. The intervention group had a small but higher weight-for-length Z-score gain (−0.2z vs. −0.3z) and less loss of MUAC than the comparison group (−2.8 vs. −4.0 mm). There was no difference in length gain (2.7 vs. 2.8 cm). Mortality was lower for children whose households received the intervention than those who did not (adjusted HR 0.55, 95% CI: 0.32–0.98).

Conclusions

Short-term distribution with RUSF for children 6 to 23 months improve the nutritional status of children at risk for malnutrition. Fewer children who participated in the RUSF distribution died than those who did not.     

Equilibration kinetics in isolated and membrane-bound photosynthetic reaction centers upon illumination: a method to determine the photoexcitation rate

Kinetics of electron transfer, following variation of actinic light intensity, for photosynthetic reaction centers (RCs) of purple bacteria (isolated and membrane-bound) were analyzed by measuring absorbance changes in the primary photoelectron donor absorption band at 865 nm. The bleaching of the primary photoelectron donor absorption band in RCs, following a sudden increase of illumination from the dark to an actinic light intensity of I _exp, obeys a simple exponential law with the rate constant , in which α is a parameter relating the light intensity, measured in mW/cm², to a corresponding theoretical rate in units of reciprocal seconds, and k _rec is the effective rate constant of the charge recombination in the photosynthetic RCs. In this work, a method for determining the α parameter value is developed and experimentally verified for isolated and membrane-bound RCs, allowing for rigorous modeling of RC macromolecule dynamics under varied photoexcitation conditions. Such modeling is necessary for RCs due to alterations of the forward photoexcitation rates and relaxation rates caused by illumination history and intramolecular structural dynamics effects. It is demonstrated that the classical Bouguer–Lambert–Beer formalism can be applied for the samples with relatively low scattering, which is not necessarily the case with strongly scattering media or high light intensity excitation. An erratum to this article can be found at