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Becker, J. M.

Publications and source records attributed to Becker, J. M..

3 recordsLinked to original sources

Measurement force, speed and post-mortem time affect the ratio of CNS grey to white matter elasticity

For several decades, many attempts have been made to characterise the mechanical properties of grey and white matter, which constitute the two main compartments of the central nervous system (CNS), with various methods and contradictory results. In particular, the ratio of grey-to-white-matter elasticity is sometimes larger than 1 and sometimes smaller; the reason for this apparent discrepancy is currently unknown. Here, we exploited atomic force microscopy (AFM)-based indentation measurements to systematically investigate how the measurement force, measurement speed, post-mortem interval and temperature affect the measured elasticity of spinal cord tissue, and in particular the ratio of grey-to-white-matter elasticity (Kg/Kw). Within the explored parameter space, increasing measurement force and speed increased the measured elasticity of both grey and white matter. However, Kg/Kw declined from values as high as [~]5 at low forces and speeds to [~]1 for high forces and speeds. Kg/Kw also strongly depended on the anatomical plane in which the measurements were conducted and was considerably higher in transverse sections compared to longitudinal sections. Furthermore, the post-mortem interval impacted both the absolute measured tissue elasticity and Kg/Kw. Grey matter elasticity started decreasing [~]3 hours post-mortem until reaching a plateau after [~]6 hours. In contrast, white matter elasticity started declining from the beginning of the measurements until [~]6 hours post-mortem, when it also levelled off. As a result, Kg/Kw increased until [~]6 hours post-mortem before stabilising. Between 20{degrees}C and 38{degrees}C, both grey and white matter elasticity decreased at a similar rate, without affecting Kg/Kw. We have thus identified differences in the response of grey and white matter to varying strains and strain rates, and the post-mortem interval, and excluded temperature as a factor affecting Kg/Kw. These differential responses likely contribute to the contradictory results obtained with different methods working in different strain regimes. Statement of significanceWe here showed that the mechanical response of CNS grey and white matter to an applied force differentially depends on measurement parameters such as the speed and magnitude of the applied forces, the post-mortem interval, as well as the anatomical axis along which measurements are conducted. These results broaden our understanding of CNS mechanics and pave the way for better and more targeted experimental design of future experiments. Ultimately, they may help to reconcile seemingly contradictory results in the literature concerning the ratio of grey-to-white-matter elasticity.

biophysics↗

Agricultural pesticides do not suppress infection of Biomphalaria (Gastropoda) by Schistosoma mansoni (Trematoda)

BackgroundSchistosomiasis is a neglected tropical disease caused by trematodes of the genus Schistosoma. The pathogen is transmitted via freshwater snails. These snails indirectly benefit from agricultural pesticides which affect their enemy species. Pesticide exposure of surface waters may thus increase the risk of schistosomiasis transmission unless it also affects the pathogen. MethodologyWe tested the tolerance of the free-swimming infective life stages (miracidia and cercariae) of Schistosoma mansoni to the commonly applied insecticides diazinon and imidacloprid. Additionally, we investigated whether these pesticides decrease the ability of miracidia to infect and further develop as sporocysts within the host snail Biomphalaria pfeifferi. Principal findingsExposure to imidacloprid for 6 and 12 hours immobilized 50% of miracidia at 150 and 16 g/L, respectively (nominal EC50); 50% of cercariae were immobilized at 403 and 284 g/L. Diazinon immobilized 50% of miracidia at 51 and 21 g/L after 6 and 12 hours; 50% of cercariae were immobilized at 25 and 13 g/L. This insecticide tolerance is lower than those of the host snail B. pfeifferi but comparable to those of other commonly tested freshwater invertebrates. Exposure for up to 6 hours decreased the infectivity of miracidia at high sublethal concentrations (48.8 g imidacloprid/L and 10.5 g diazinon/L, i.e. 20 - 33 % of EC50) but not at lower concentrations commonly observed in the field (4.88 g imidacloprid/L and 1.05 g diazinon/L). The development of sporocysts within the snail host was not affected at any of these test concentrations. ConclusionsInsecticides did not affect the performance of S. mansoni at environmentally relevant concentrations. Accordingly, pesticide exposure is likely to increase the risk of schistosomiasis transmission by increasing host snail abundance without affecting the pathogen. Our results illustrate how the ecological side effects of pesticides are linked to human health, emphasizing the need for appropriate mitigation measures. Author summarySchistosomiasis is a major public health problem in 51 countries worldwide. Transmission requires human contact with freshwater snails that act as intermediate hosts, releasing free-swimming life stages of the trematodes. The host snails are highly tolerant to agricultural pesticides used in plant protection products. Pesticides enter freshwaters via drift and runoff, and indirectly foster the spread of host snails via adverse effects on more sensitive competitor and predator species in the water. Increasing the abundance of intermediate hosts raises potential contact with the human definitive host while transmission of the pathogen is not affected. Here we show that pesticides do not affect the ability of the trematode Schistosoma mansoni to infect and develop within its host snail Biomphalaria pfeifferi at environmentally relevant concentrations. Consequently, risk of schistosomiasis increases when pesticide pollution favours the proliferation of snail hosts whilst not negatively affecting the free-living parasites nor their development in their snail hosts. Measures to mitigate pesticide pollution of freshwaters should be a concern in public health programs to sustainably roll back schistosomiasis. Intersectional collaborations are required to bridge the gap between the agricultural and the public health sector in search of sustainable and safe methods of crop production.

systems biology↗

POMC neurons functional heterogeneity relies on mTORC1 signaling

Hypothalamic Pro-opiomelanocortin (POMC) neurons are classically known to trigger satiety. However, they encompass heterogeneous subpopulations whose functions are unknown. Here we show that POMC neurons releasing GABA, glutamate or both neurotransmitters possess distinct spatial distribution, molecular signatures and functions. Functional specificity of these subpopulations relies on the energy sensor mechanistic Target of Rapamycin Complex 1 (mTORC1), since pharmacological blockade of mTORC1, by mimicking a cellular negative energy state, simultaneously inhibited POMC/glutamatergic and activated POMC/GABAergic neurons. Chemogenetics and conditional deletion of mTORC1 then demonstrated that mTORC1 blockade in POMC neurons causes hyperphagia. This is due to decreased POMC-derived anorexigenic -melanocyte-stimulating hormone and the recruitment of POMC/GABAergic neurotransmission, which is restrained by cannabinoid type 1 receptor signaling. Genetic inhibition of glutamate release from POMC neurons also produced hyperphagia, recapitulating the phenotype caused by mTORC1 blockade. Altogether, these findings pinpoint the molecular mechanisms engaged by POMC neurons to oppositely control feeding, thereby challenging conventional views about their functions.

neuroscience↗