Between 1963 and 1968, Pierre Mulele led a rebellion in Kwilu province against the Congolese government. The uprising ended in a heavy defeat for the rebel forces. Every political regime in Congo ...from the late 1960s up to the present has differently dealt with the memory of this rebellion. Through fragments of stories, this article looks deeply into this history in order to understand the ways in which the politics of forgetting has been constructed since the late 1960s. During the Mobutu regime, this politics was incredibly violent. The regime distinguished itself by its ability to configure a set of strategies to enforce silence and create a public forgetting about Mulele. The result of this new form of control and surveillance was that people were doomed to fall back on themselves as fragmented “bodies” and live piecemeal between the corporeal world (the body) and the incorporeal world (the world of memory). But this new form of discipline and control also proved to be “partially” a failure, given the fact that memories of Mulele merely became private (or secret) and that the potential (re)publicizing of these remained, in particular via a ghostly avatar. The advent of Laurent Désiré Kabila in 1997, as well as the inversion of the injunction to forget Mulele after he came to power, left Mulele’s victims feeling equally and mentally “colonized” by the political memory-work of the new regime.
Elevated postprandial triacylglycerols (TAG) are an important risk factor for cardiovascular disease. Men have higher plasma TAG and impaired TAG clearance compared to women, which may contribute to ...sex differences in risk of cardiovascular disease. Understanding mechanisms of sex differences in TAG metabolism may yield novel therapeutic targets to prevent cardiovascular disease. Cholesteryl ester transfer protein (CETP) is a lipid shuttling protein known for its effects on high‐density lipoprotein (HDL) cholesterol levels. Although mice lack CETP, we previously demonstrated that transgenic CETP expression in female mice alters TAG metabolism. The impact of CETP on TAG metabolism in males, however, is not well understood. Here, we demonstrate that CETP expression increases plasma TAG in males, especially in very‐low density lipoprotein (VLDL), by impairing postprandial plasma TAG clearance compared to wild‐type (WT) males. Gonadal hormones were required for CETP to impair TAG clearance, suggesting a role for sex hormones for this effect. Testosterone replacement in the setting of gonadectomy was sufficient to restore the effect of CETP on TAG. Lastly, liver androgen receptor (AR) was required for CETP to increase plasma TAG. Thus, expression of CETP in males raises plasma TAG by impairing TAG clearance via testosterone signaling to AR. Further understanding of how CETP and androgen signaling impair TAG clearance may lead to novel approaches to reduce TAG and mitigate risk of cardiovascular disease.
The stochastic collocation (SC) and stochastic Galerkin (SG) methods are two well-established and successful approaches for solving general stochastic problems. A recently developed method based on ...stochastic reduced order models (SROMs) can also be used. Herein we provide a comparison of the three methods for some numerical examples; our evaluation only holds for the examples considered in the paper. The purpose of the comparisons is not to criticize the SC or SG methods, which have proven very useful for a broad range of applications, nor is it to provide overall ratings of these methods as compared to the SROM method. Rather, our objectives are to present the SROM method as an alternative approach to solving stochastic problems and provide information on the computational effort required by the implementation of each method, while simultaneously assessing their performance for a collection of specific problems.
Schistosomiasis is an important neglected tropical disease caused by digenean helminth parasites of the genus Schistosoma. Schistosomes are unusual in that they are dioecious and the adult worms live ...in the blood system. MicroRNAs play crucial roles during gene regulation and are likely to be important in sex differentiation in dioecious species. Here we characterize 112 microRNAs from adult Schistosoma mansoni individuals, including 84 novel microRNA families, and investigate the expression pattern in different sexes. By deep sequencing, we measured the relative expression levels of conserved and newly identified microRNAs between male and female samples. We observed that 13 microRNAs exhibited sex-biased expression, 10 of which are more abundant in females than in males. Sex chromosomes showed a paucity of female-biased genes, as predicted by theoretical evolutionary models. We propose that the recent emergence of separate sexes in Schistosoma had an effect on the chromosomal distribution and evolution of microRNAs, and that microRNAs are likely to participate in the sex differentiation/maintenance process.
The abiotic environment can dictate the relative costs and benefits of plant-arbuscular mycorrhizal fungi (AMF) symbioses. While the effects of varying light or soil nutrient conditions are well ...studied, outcomes of plant-AMF interactions along soil moisture gradients are not fully understood. It is predicted that mycorrhizal associations may become parasitic in extreme soil moisture conditions. Under low soil moisture stress, costs of maintaining a mycorrhizal symbiont may outweigh benefits for the host plant, whereas under high soil moisture stress, the host plant may not need the symbiont. In a factorial growth chamber study, we investigated the effects of a plant-arbuscular mycorrhizal fungus symbiosis along a soil moisture gradient on growth, cell wall chemistry, and root architecture of a biofuel crop,
Panicum virgatum
(switchgrass). Regardless of soil moisture conditions, we found an increase in the number of tillers, number of leaves, root biomass, and amount of cellulose and hemicellulose in response to root colonization by the arbuscular mycorrhizal fungus. The fungus also increased aboveground biomass and changed several root architectural traits, but only under low soil moisture conditions, indicating a reduction in benefits of the mycorrhizal association under high soil moisture. Results from this study indicate that an arbuscular mycorrhizal fungus can increase some key measures of plant growth and cell wall chemistry regardless of soil moisture conditions but is most beneficial in low soil moisture conditions.
Despite successful control efforts in China over the past 60 years, zoonotic schistosomiasis caused by Schistosoma japonicum remains a threat with transmission ongoing and the risk of localised ...resurgences prompting calls for a novel integrated control strategy, with an anti-schistosome vaccine as a core element. Anti-schistosome vaccine development and immunisation attempts in non-human mammalian host species, intended to interrupt transmission, and utilising various antigen targets, have yielded mixed success, with some studies highlighting variation in schistosome antigen coding genes (ACGs) as possible confounders of vaccine efficacy. Thus, robust selection of target ACGs, including assessment of their genetic diversity and antigenic variability, is paramount. Tetraspanins (TSPs), a family of tegument-surface antigens in schistosomes, interact directly with the host's immune system and are promising vaccine candidates. Here, for the first time to our knowledge, diversity in S. japonicum TSPs (SjTSPs) and the impact of diversifying selection and sequence variation on immunogenicity in these protiens were evaluated.
SjTSP sequences, representing parasite populations from seven provinces across China, were gathered by baiting published short-read NGS data and were analysed using in silico methods to measure sequence variation and selection pressures and predict the impact of selection on variation in antigen protein structure, function and antigenic propensity.
Here, 27 SjTSPs were identified across three subfamilies, highlighting the diversity of TSPs in S. japonicum. Considerable variation was demonstrated for several SjTSPs between geographical regions/provinces, revealing that episodic, diversifying positive selection pressures promote amino acid variation/variability in the large extracellular loop (LEL) domain of certain SjTSPs. Accumulating polymorphisms in the LEL domain of SjTSP-2, -8 and -23 led to altered structural, functional and antibody binding characteristics, which are predicted to impact antibody recognition and possibly blunt the host's ability to respond to infection. Such changes, therefore, appear to represent a mechanism utilised by S. japonicum to evade the host's immune system.
Whilst the genetic and antigenic geographic variability observed amongst certain SjTSPs could present challenges to vaccine development, here we demonstrate conservation amongst SjTSP-1, -13 and -14, revealing their likely improved utility as efficacious vaccine candidates. Importantly, our data highlight that robust evaluation of vaccine target variability in natural parasite populations should be a prerequisite for anti-schistosome vaccine development.
Atomic structures of amyloid oligomers that capture the neurodegenerative disease pathology are essential to understand disease‐state causes and finding cures. Here we investigate the G6W mutation of ...the cytotoxic, hexameric amyloid model KV11. The mutation results into an asymmetric dodecamer composed of a pair of 30° twisted antiparallel β‐sheets. The complete break between adjacent β‐strands is unprecedented among amyloid fibril crystal structures and supports that our structure is an oligomer. The poor shape complementarity between mated sheets reveals an interior channel for binding lipids, suggesting that the toxicity may be due to a perturbation of lipid transport rather than a direct disruption of membrane integrity. Viability assays on mouse suprachiasmatic nucleus, anterior hypothalamus, and cerebral cortex demonstrated selective regional vulnerability consistent with Alzheimer's disease. Neuropeptides released from the brain slices may provide clues to how G6W initiates cellular injury.
PDB Code(s): 7ROL and 7ROJ;
While there has been extensive interest in understanding the relationship between diversity and invasibility of communities, most studies have only focused on one component of diversity: species ...richness. Although the number of species can affect community invasibility, other aspects of diversity, including species identity and community evenness, may be equally important. While several field studies have examined how invasibility varies with diversity by manipulating species identity or evenness, the results are often confunded by resource heterogeneity, site history, or disturbance. We designed a mesocosm experiment to examine explicitly the role of dominant species identity and evenness on the invasibility of grassland plant communities. We found that the identity of the dominant plant species, but not community evenness, significantly impacted invasibility. Using path analysis, we found that community composition (dominant species identity) reduced invasion by reducing early-season light availability and increasing late-season plant community biomass. Nitrogen availability was an important factor for the survival of invaders in the second year of the experiment. We also found significant direct effects of certain dominant species on invasion, although the mechanisms driving these effects remain unclear. The magnitude of dominant species effects on invasibility we observed are comparable to species richness effects observed in other studies, showing that species composition and dominant species can have strong effects on the invasibility of a community.
Repurposing of existing cancer drugs to overcome their physical limitations, such as insolubility, represents an attractive strategy to achieve enhanced therapeutic efficacy and broaden the range of ...clinical applications. Such an approach also promises to offer substantial cost savings in drug development efforts. Here we repurposed FDA-approved topical agent bexarotene (Targretin), currently in limited use for cutaneous manifestations of T-cell lymphomas, and re-engineer it for use in solid tumor applications by forming self-assembling nanobubbles. Physico-chemical characterization studies of the novel prodrug nanobubbles demonstrated their stability, enhanced target cell internalization capability, and highly controlled release profile in response to application of focused ultrasound energy. Using an in vitro model of hepatocellular carcinoma and an in vivo large animal model of liver ablation, we demonstrate the effectiveness of bexarotene prodrug nanobubbles when used in conjunction with catheter-based ultrasound, thereby highlighting the therapeutic promise of this trimodal approach.
The outcome of infection in the host snail Biomphalaria glabrata with the digenean parasite Schistosoma mansoni is determined by the initial molecular interplay occurring between them. The mechanisms ...by which schistosomes evade snail immune recognition to ensure survival are not fully understood, but one possibility is that the snail internal defence system is manipulated by the schistosome enabling the parasite to establish infection. This study provides novel insights into the nature of schistosome resistance and susceptibility in B. glabrata at the transcriptomic level by simultaneously comparing gene expression in haemocytes from parasite-exposed and control groups of both schistosome-resistant and schistosome-susceptible strains, 2 h post exposure to S. mansoni miracidia, using an novel 5K cDNA microarray. Differences in gene expression, including those for immune/stress response, signal transduction and matrix/adhesion genes were identified between the two snail strains and tests for asymmetric distributions of gene function also identified immune-related gene expression in resistant snails, but not in susceptible. Gene set enrichment analysis revealed that genes involved in mitochondrial electron transport, ubiquinone biosynthesis and electron carrier activity were consistently up-regulated in resistant snails but down-regulated in susceptible. This supports the hypothesis that schistosome-resistant snails recognize schistosomes and mount an appropriate defence response, while in schistosome-susceptible snails the parasite suppresses this defence response, early in infection.
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