No barrier breakdown between human and cattle schistosome species in the Senegal River Basin in the face of hybridisation

Schistosomiasis is widely distributed along the Senegal River Basin (SRB), affecting both the human population and their livestock. Damming of the Senegal River for irrigation purposes in the 1980s induced ecological changes that resulted in a large outbreak of Schistosoma mansoni, followed a few years later by an increase and spread of Schistosoma haematobium infections. The presence of hybrid crosses between the human and cattle schistosomes, S. haematobium and Schistosoma bovis, respectively, is adding complexity to the disease epidemiology in this area, and questions the strength of the species boundary between these two species. This study aimed to investigate the epidemiology of S. haematobium, S. bovis and their hybrids along the Senegal River basin using both microsatellite genetic markers and analysis of mitochondrial and nuclear DNA markers. Human schistosome populations with a S. haematobium cox1 mtDNA profile and those with a S. bovis cox1 mtDNA profile (the so-called hybrids) appear to belong to a single randomly mating population, strongly differentiated from the pure S. bovis found in cattle. These results suggest that, in northern Senegal, a strong species boundary persists between human and cattle schistosome species and there is no prolific admixing of the populations. In addition, we found that in the SRB S. haematobium was spatially more differentiated in comparison to S. mansoni. This may be related either to the presence and susceptibility of the intermediate snail hosts, or to the colonisation history of the parasite.     

Signal strength controls the rate of polarization within CTLs during killing

Cytotoxic T lymphocytes (CTLs) are key effector cells in the immune response against viruses and cancers, killing targets with high precision. Target cell recognition by CTL triggers rapid polarization of intracellular organelles toward the synapse formed with the target cell, delivering cytolytic granules to the immune synapse. Single amino acid changes within peptides binding MHC class I (pMHCs) are sufficient to modulate the degree of killing, but exactly how this impacts the choreography of centrosome polarization and granule delivery to the target cell remains poorly characterized. Here we use 4D imaging and find that the pathways orchestrating killing within CTL are conserved irrespective of the signal strength. However, the rate of initiation along these pathways varies with signal strength. We find that increased strength of signal leads to an increased proportion of CTLs with prolonged dwell times, initial Ca²⁺ fluxes, centrosome docking, and granule polarization. Hence, TCR signal strength modulates the rate but not organization of effector CTL responses.     

Differences in Time until Dispersal between Cryptic Species of a Marine Nematode Species Complex

Co-occurrence of closely related species may be achieved in environments with fluctuating dynamics, where competitively inferior species can avoid competition through dispersal. Here we present an experiment in which we compared active dispersal abilities (time until first dispersal, number and gender of dispersive adults, and nematode densities at time of dispersal) in Litoditis marina, a common bacterivorous nematode species complex comprising four often co-occurring cryptic species, Pm I, II, III, and IV, as a function of salinity and food distribution. The experiment was conducted in microcosms consisting of an inoculation plate, connection tube, and dispersal plate. Results show species-specific dispersal abilities with Pm I dispersing almost one week later than Pm III. The number of dispersive adults at time of first dispersal was species-specific, with one dispersive female in Pm I and Pm III and a higher, gender-balanced, number in Pm II and Pm IV. Food distribution affected dispersal: in absence of food in the inoculation plate, all species dispersed after ca four days. When food was available Pm I dispersed later, and at the same time and densities irrespective of food conditions in the dispersal plate (food vs no food), suggesting density-dependent dispersal. Pm III dispersed faster and at a lower population density. Salinity affected dispersal, with slower dispersal at higher salinity. These results suggest that active dispersal in Litoditis marina is common, density-dependent, and with species, gender- and environment-specific dispersal abilities. These differences can lead to differential responses under suboptimal conditions and may help to explain temporary coexistence at local scales.     

A role for PP1/NIPP1 in steering migration of human cancer cells

Electrical gradients are present in many developing and regenerating tissues and around tumours. Mimicking endogenous electric fields in vitro has profound effects on the behaviour of many cell types. Intriguingly, specific cell types migrate cathodally, others anodally and some polarise with their long axis perpendicular to the electric vector. These striking phenomena are likely to have in vivo relevance since one of the determining factors during cancer metastasis is the ability to switch between attractive and repulsive migration in response to extracellular guidance stimuli. We present evidence that the cervical cancer cell line HeLa migrates cathodally in a direct current electric field of physiological intensity, while the strongly metastatic prostate cancer cell line PC-3-M migrates anodally. Notably, genetic disruption of protein serine/threonine phosphatase-1 (PP1) and its regulator NIPP1 decrease directional migration in these cell lines. Conversely, the inducible expression of NIPP1 switched the directional response of HeLa cells from cathodal to slightly anodal in a PP1-dependent manner. Remarkably, induction of a hyperactive PP1/NIPP1 holoenzyme, further shifted directional migration towards the anode. We show that PP1 association with NIPP1 upregulates signalling by the GTPase Cdc42 and demonstrate that pharmacological inhibition of Cdc42 in cells overexpressing NIPP1 recovered cathodal migration. Taken together, we provide the first evidence for regulation of directional cell migration by NIPP1. In addition, we identify PP1/NIPP1 as a novel molecular compass that controls directed cell migration via upregulation of Cdc42 signalling and suggest a way by which PP1/NIPP1 may contribute to the migratory properties of cancer cells.     

Study of oxidative stress related responses induced in Arabidopsis thaliana following mixed exposure to uranium and cadmium

In this study, toxicity effects in plants of uranium in a binary pollution condition were investigated by studying biological responses and unraveling oxidative stress related mechanisms in Arabidopsis thaliana seedlings, grown on hydroponics and exposed for 3 days to 10 μM uranium in combination with 5 μM cadmium. While uranium mostly accumulated in the roots with very low root-to-shoot transport, cadmium was taken up less by the roots but showed higher translocation to the shoots. Under mixed exposure, cadmium influenced uranium uptake highly but not the other way round resulting in a doubled uranium concentration in the roots. Under our mixed exposure conditions, it is clear that micronutrient concentrations in the roots are strongly influenced by addition of cadmium as a second stressor, while leaf macronutrient concentrations are mostly influenced by uranium. Oxidative stress related responses are highly affected by cadmium while uranium influence is more limited. Hereby, an important role was attributed to the ascorbate redox balance together with glutathione as both metabolites, but more explicitly for ascorbate, increased their reduced form, indicating an important defense and regulatory function. While for roots, based on an increase in FSD1 gene expression, oxidative stress was suggested to be superoxide induced, in leaves on the other hand, hydrogen peroxide related genes were mostly altered.     

Identification and characterization of novel factors that act in the nonsense‐mediated mRNA decay pathway in nematodes,flies and mammals

Nonsense‐mediated mRNA decay (NMD) is a surveillance mechanism that degrades mRNAs harboring premature termination codons (PTCs). We have conducted a genome‐wide RNAi screen in Caenorhabditis elegans that resulted in the identification of five novel NMD genes that are conserved throughout evolution. Two of their human homologs, GNL2 (ngp‐1) and SEC13 (npp‐20), are also required for NMD in human cells. We also show that the C. elegans gene noah‐2, which is present in Drosophila melanogaster but absent in humans, is an NMD factor in fruit flies. Altogether, these data identify novel NMD factors that are conserved throughout evolution, highlighting the complexity of the NMD pathway and suggesting that yet uncovered novel factors may act to regulate this process.