Calmodulin Activation by Calcium Transients in the Postsynaptic Density of Dendritic Spines

The entry of calcium into dendritic spines can trigger a sequence of biochemical reactions that begins with the activation of calmodulin (CaM) and ends with long-term changes to synaptic strengths. The degree of activation of CaM can depend on highly local elevations in the concentration of calcium and the duration of transient increases in calcium concentration. Accurate measurement of these local changes in calcium is difficult because the spaces are so small and the numbers of molecules are so low. We have therefore developed a Monte Carlo model of intracellular calcium dynamics within the spine that included calcium binding proteins, calcium transporters and ion channels activated by voltage and glutamate binding. The model reproduced optical recordings using calcium indicator dyes and showed that without the dye the free intracellular calcium concentration transient was much higher than predicted from the fluorescent signal. Excitatory postsynaptic potentials induced large, long-lasting calcium gradients across the postsynaptic density, which activated CaM. When glutamate was released at the synapse 10 ms before an action potential occurred, simulating activity patterns that strengthen hippocampal synapses, the calcium gradient and activation of CaM in the postsynaptic density were much greater than when the order was reversed, a condition that decreases synaptic strengths, suggesting a possible mechanism underlying the induction of long-term changes in synaptic strength. The spatial and temporal mechanisms for selectivity in CaM activation demonstrated here could be used in other signaling pathways

Large-Scale Selective Sweep among Segregation Distorter Chromosomes in African Populations of Drosophila melanogaster

Segregation Distorter (SD) is a selfish, coadapted gene complex on chromosome 2 of Drosophila melanogaster that strongly distorts Mendelian transmission; heterozygous SD/SD+ males sire almost exclusively SD-bearing progeny. Fifty years of genetic, molecular, and theory work have made SD one of the best-characterized meiotic drive systems, but surprisingly the details of its evolutionary origins and population dynamics remain unclear. Earlier analyses suggested that the SD system arose recently in the Mediterranean basin and then spread to a low, stable equilibrium frequency (1–5%) in most natural populations worldwide. In this report, we show, first, that SD chromosomes occur in populations in sub-Saharan Africa, the ancestral range of D. melanogaster, at a similarly low frequency (∼2%), providing evidence for the robustness of its equilibrium frequency but raising doubts about the Mediterranean-origins hypothesis. Second, our genetic analyses reveal two kinds of SD chromosomes in Africa: inversion-free SD chromosomes with little or no transmission advantage; and an African-endemic inversion-bearing SD chromosome, SD-Mal, with a perfect transmission advantage. Third, our population genetic analyses show that SD-Mal chromosomes swept across the African continent very recently, causing linkage disequilibrium and an absence of variability over 39% of the length of the second chromosome. Thus, despite a seemingly stable equilibrium frequency, SD chromosomes continue to evolve, to compete with one another, or evade suppressors in the genome

CD8α Dendritic Cells Drive Establishment of HSV-1 Latency

It is generally accepted that CD8 T cells play the key role to maintain HSV-1 latency in trigeminal ganglia of ocularly infected mice. Yet, comparably little is known about the role of innate immunity in establishment of viral latency. In the current study, we investigated whether CD8α DCs impact HSV-1 latency by examining latency in the trigeminal ganglia (TG) of wildtype (WT) C57BL/6 versus CD8α‒/‒ (lack functional CD8 T cells and CD8α+ DCs), CD8β‒/‒ (have functional CD8α+ T cells and CD8α+ DCs), and β2m‒/‒ (lack functional CD8 T cells but have CD8α+ DCs) mice as well as BXH2 (have functional CD8 T cells but lack CD8α+ DCs) versus WT C3H (have functional CD8α T cells and CD8α+ DCs) mice. We also determined whether the phenotype of CD8α‒/‒ and BXH2 mice could be restored to that of WT mice by adoptive transfer of WT CD8+ T cells or bone marrow (BM) derived CD8α+ DCs. Our results clearly demonstrate that CD8α DCs, rather than CD8 T cells, are responsible for enhanced viral latency and recurrences

Coping with Natural Hazards in a Conservation Context: Resource-Use Decisions of Maasai Households During Recent and Historical Droughts

Analyzing people’s decisions can reveal key variables that affect their behaviors. Despite the demonstrated utility of this approach, it has not been applied to livelihood decisions in the context of conservation initiatives. We used ethnographic decision modeling in combination with qualitative comparative analysis (QCA) to examine the herding decisions of Maasai households living near Tarangire National Park (TNP) during recent and historical droughts. The effects of the establishment of TNP on herding practices during drought were different than anticipated based on the size and reliability of several prominent resource areas that are now within the park. We found little evidence of people relying on these swamps and rivers for watering cattle during historical droughts; rather, these sites were more commonly used as grazing areas for small stock and wet-season grazing areas for cattle to avoid disease carried by calving wildebeest. Yet during the 2009 drought, many herders moved their livestock – especially cattle from outside of the study area – toward TNP in search of grazing. Our analysis of herding decisions demonstrates that resource-use decisions are complex and incorporate a variety of information beyond the size or reliability of a given resource area, including contextual factors (e.g., disease, conflict, grazing) and household factors (e.g., social capital, labor, herd size). More broadly, this research illustrates that pairing decision modeling with QCA is a structured approach to identifying these factors and understanding how opportunities, constraints, and perceptions influence how people respond to changes in resource access