Project description:Fire disturbances are becoming more common, more intense, and further-reaching across the globe, with consequences for ecosystem functioning. Importantly, fire can have strong effects on the soil microbiome, including community and functional changes after fire, but surprisingly little is known regarding the role of soil fire legacy in shaping responses to recent fire. To address this gap, we conducted a manipulative field experiment administering fire across 32 soils with varying fire legacies, including combinations of 1-7 historic fires and 1-33 years since most recent fire. We analyzed soil metatranscriptomes, determining for the first time how fire and fire legacy interactively affect metabolically-active soil taxa, the microbial regulation of important carbon (C), nitrogen (N) and phosphorus (P) cycling, expression of carbohydrate-cycling enzyme pathways, and functional gene co-expression networks. Experimental fire strongly downregulated fungal activity while upregulating many bacterial and archaeal phyla. Further, fire decreased soil capacity for microbial C and N cycling and P transport, and drastically rewired functional gene co-expression. Perhaps most importantly, we highlight a novel role of soil fire legacy in regulation of microbial C, N, and P responses to recent fire. We observed a greater number of functional genes responsive to the interactive effects of fire and fire legacy than those affected solely by recent fire, indicating that many functional genes respond to fire only under certain fire legacy contexts. Therefore, without incorporating fire legacy of soils, studies will miss important ways that fire shapes microbial roles in ecosystem functioning. Finally, we showed that fire caused significant downregulation of carbon metabolism and nutrient cycling genes in microbiomes under abnormal soil fire histories, producing a novel warning for the future: human manipulation of fire legacies, either indirectly through global change-induced fire intensification or directly through fire suppression, can negatively impact soil microbiome functional responses to new fires.
Project description:During S-phase of the eukaryotic cell cycle, controls exist to ensure that replication origins fire only once and become inactivated after traverse of a replication fork. Failure of these controls results in local amplification of the genome which can lead to gene copy increases important for both evolutionary change and for somatic genetic diseases such as cancer. It is not known what characteristics of replication origins might predispose them to escape from these controls. We have investigated this problem in the fission yeast Schizosaccharomyces pombe by characterizing regions of the genome which become amplified when the DNA synthesis initiation factors cdc18 (cdc6) and cdt1 are co-overexpressed and by defining origins of replication responsible for local amplification. We find that a single origin can be necessary but not sufficient to induce ectopic local amplification and that origins likely to escape the regulation of one firing per cell cycle are among the most AT-rich, efficient and early firing in the genome, and are embedded in long intergenes. Replication origins with these features may be more prone to re-fire within a round of replication potentiating genome instability.
Project description:The emergence and fast global spread of COVID-19 has presented one of the greatest public health challenges in modern times with no proven cure or vaccine. Africa is still early in this epidemic, therefore the extent of disease severity is not yet clear. We used a mathematical model to fit to the observed cases of COVID-19 in South Africa to estimate the basic reproductive number and critical vaccination coverage to control the disease for different hypothetical vaccine efficacy scenarios. We also estimated the percentage reduction in effective contacts due to the social distancing measures implemented. Early model estimates show that COVID-19 outbreak in South Africa had a basic reproductive number of 2.95 (95% credible interval [CrI] 2.83–3.33). A vaccine with 70% efficacy had the capacity to contain COVID-19 outbreak but at very higher vaccination coverage 94.44% (95% Crl 92.44–99.92%) with a vaccine of 100% efficacy requiring 66.10% (95% Crl 64.72–69.95%) coverage. Social distancing measures put in place have so far reduced the number of social contacts by 80.31% (95% Crl 79.76–80.85%). These findings suggest that a highly efficacious vaccine would have been required to contain COVID-19 in South Africa. Therefore, the current social distancing measures to reduce contacts will remain key in controlling the infection in the absence of vaccines and other therapeutics.
Project description:The aim of this study was to compare the transcriptomes of Plasmodium falciparum parasites sourced from high vs. low malaria transmission settings in east Africa in order to test the hypothesis that malaria parasites are locally adapted to their environment. In three separate experiments, parasites from ‘High’ vs. ‘Low’ transmission populations were taken from non-immune children and measured for gene expression levels by microarray against a reference genome. Two of these population comparisons were geographic in nature while the third was temporal, i.e., before and after a marked decline in malaria. This study is described in Rono MK, Nyonda MA, Simam JJ, Ngoi, JM et al. Nat Ecol Evol. PMID: .
Project description:The aim of this study was to describe gene copy number variation in Plasmodium falciparum parasites sourced from high vs. low malaria transmission settings in east Africa in order to test the hypothesis that malaria parasites are locally adapted to their environment. In three separate experiments, parasites from ‘High’ vs. ‘Low’ transmission populations were taken from non-immune children and evaluated for copy number variants by microarray against a reference genome. Two of these population comparisons were geographic in nature while the third was temporal, i.e., before and after a marked decline in malaria. This study is described in Simam et al. 2018 BMC Genomics.
Project description:Electrical excitability—the ability to fire and propagate action potentials—is a signature feature of neurons. How neurons become excitable during development and whether excitability is an intrinsic property of neurons or requires signaling from glial cells remain unclear. Here, we demonstrate that Schwann cells, the most abundant glia in the peripheral nervous system, promote somatosensory neuron excitability during development. We find that Schwann cells secrete prostaglandin E2, which is necessary and sufficient to induce developing somatosensory neurons to express normal levels of genes required for neuronal function, including voltage gated sodium channels, and to fire action potential trains. In this RNA-Seq study, we discovered that treating cultured DRG neurons with Schwann cell-conditioned media or PGE2 increased the expression of several genes required for neuronal maturation and excitability, including voltage-gated sodium channels.
Project description:Electrical excitability—the ability to fire and propagate action potentials—is a signature feature of neurons. How neurons become excitable during development and whether excitability is an intrinsic property of neurons or requires signaling from glial cells remain unclear. Here, we demonstrate that Schwann cells, the most abundant glia in the peripheral nervous system, promote somatosensory neuron excitability during development. We find that Schwann cells secrete prostaglandin E2, which is necessary and sufficient to induce developing somatosensory neurons to express normal levels of genes required for neuronal function, including voltage gated sodium channels, and to fire action potential trains. In this scRNAseq study, we found that inactivating PGE2 synthesis in Schwann cells, in vivo, impaired somatosensory neuron maturation, with the most dramatic effects on nociceptor and proprioceptor somatosensory neuron subtypes.
Project description:Electrical excitability—the ability to fire and propagate action potentials—is a signature feature of neurons. How neurons become excitable during development and whether excitability is an intrinsic property of neurons or requires signaling from glial cells remain unclear. Here, we demonstrate that Schwann cells, the most abundant glia in the peripheral nervous system, promote somatosensory neuron excitability during development. We find that Schwann cells secrete prostaglandin E2, which is necessary and sufficient to induce developing somatosensory neurons to express normal levels of genes required for neuronal function, including voltage gated sodium channels, and to fire action potential trains. In this scRNAseq study, we found that inactivating PGE2 synthesis in Schwann cells in vivo impaired somatosensory neuron maturation, with the most dramatic effects on nociceptor and proprioceptor somatosensory neuron subtypes.
Project description:Peripheral T cell lymphoma (PTCL) is a very aggressive disease which currently lacks efficient targeted therapy. New therapeutic strategies are needed to improve the very poor outcome of these patients. However, little is known about the molecular pathogenesis of this disease. In this study, we performed a gene expression profiling analysis of a series of 38 PTCL cases in order to find deregulated pathways or genes that could become therapeutic agents for PTCL patients. 38 PTCL cases and 6 reactive lymph nodes were hybridized with the Universal Human Reference RNA (Stratagene, La Jolla, CA), which served as the reference sample.