The Antiparkinsonian and Antidyskinetic Mechanisms of Mucuna pruriens

Chronic treatment with levodopa (LD) in Parkinson's disease (PD) can cause drug induced dyskinesias. Mucuna pruriens endocarp powder (MPEP) contains several compounds including natural LD and has been reported to not cause drug-induced dyskinesias. We evaluated the effects of Mucuna pruriens to determine if its underlying mechanistic actions are exclusively due to LD. We first compared MPEP with and without carbidopa (CD), and LD+CD in hemiparkinsonian (HP) monkeys. Each treatment ameliorated parkinsonism. We then compared the neuronal firing properties of the substantia nigra reticulata (SNR) and subthalamic nucleus (STN) in HP monkeys with MPEP+CD and LD+CD to evaluate basal ganglia circuitry alterations. Both treatments decreased SNR firing rate compared to HP state. However, LD+CD treatments significantly increased SNR bursting firing patterns that were not seen with MPEP+CD treatments. No significant changes were seen in STN firing properties. We then evaluated the effects of a water extract of MPEP. Oral MPWE ameliorated parkinsonism without causing drug-induced dyskinesias. The distinctive neurophysiological findings in the basal ganglia and the ability to ameliorate parkinsonism without causing dyskinesias strongly suggest that Mucuna pruriens acts through a novel mechanism that is different from that of LD

Melanoma cells break down LPA to establish local gradients that drive chemotactic dispersal.

The high mortality of melanoma is caused by rapid spread of cancer cells, which occurs unusually early in tumour evolution. Unlike most solid tumours, thickness rather than cytological markers or differentiation is the best guide to metastatic potential. Multiple stimuli that drive melanoma cell migration have been described, but it is not clear which are responsible for invasion, nor if chemotactic gradients exist in real tumours. In a chamber-based assay for melanoma dispersal, we find that cells migrate efficiently away from one another, even in initially homogeneous medium. This dispersal is driven by positive chemotaxis rather than chemorepulsion or contact inhibition. The principal chemoattractant, unexpectedly active across all tumour stages, is the lipid agonist lysophosphatidic acid (LPA) acting through the LPA receptor LPAR1. LPA induces chemotaxis of remarkable accuracy, and is both necessary and sufficient for chemotaxis and invasion in 2-D and 3-D assays. Growth factors, often described as tumour attractants, cause negligible chemotaxis themselves, but potentiate chemotaxis to LPA. Cells rapidly break down LPA present at substantial levels in culture medium and normal skin to generate outward-facing gradients. We measure LPA gradients across the margins of melanomas in vivo, confirming the physiological importance of our results. We conclude that LPA chemotaxis provides a strong drive for melanoma cells to invade outwards. Cells create their own gradients by acting as a sink, breaking down locally present LPA, and thus forming a gradient that is low in the tumour and high in the surrounding areas. The key step is not acquisition of sensitivity to the chemoattractant, but rather the tumour growing to break down enough LPA to form a gradient. Thus the stimulus that drives cell dispersal is not the presence of LPA itself, but the self-generated, outward-directed gradient

Differences in ebullitive methane release from small, shallow ponds present challenges for scaling

Small, shallow waterbodies are potentially important sites of greenhouse gas release to the atmosphere. The role of ebullition may be enhanced here relative to larger and deeper systems, due to their shallow water, but these features remain relatively infrequently studied in comparison to larger systems.Herein,we quantify ebullitive release ofmethane (CH4) in small shallow ponds in three regions of North America and investigate the role of potential drivers. Shallow ponds exhibited open-water season ebullitive CH4 release rates as high as 40 mmol m–2 d–1, higher than previously reported for similar systems. Ebullitive release of CH4 varied by four orders of magnitude across our 15 study sites, with differences in flux rates both within and between regions. What is less clear are the drivers responsible for these differences. There were few relationships between open water–season ebullitive flux and physicochemical characteristics, including organic matter, temperature, and sulphate. Temperature was only weakly related to ebullitive CH4 release across the studywhen considering all observation intervals. Only four individual sites exhibited significant relationships between temperature and ebullitive CH4 release. Other sites were unresponsive to temperature, and region-specific factors may play a role. There is some evidence that where surface water sulphate concentrations are high, CH4 production and release may be suppressed. Missouri sites (n = 5) had characteristically low ebullitive CH4 release; here bioturbation could be important. While this work greatly expands the number of open-water season ebullition rates for small and shallow ponds, more research is needed to disentangle the role of different drivers. Further investigation of the potential thresholding behaviour of sulphate as a control on ebullitive CH4 release in lentic systems is one such opportunity. What is clear, however, is that efforts to scale emissions (e.g., as a function of temperature) must be undertaken with caution."Fieldwork at US and GHG analyses for the project were funded through an NSERC-DG awarded to CJW. Fieldwork and analysis at UW were funded through an NSERC-DG awarded to NJC. Fieldwork and nutrient analysis atMUwere funded by the Prairie Fork Charitable Endowment Trust to RLN."https://www.sciencedirect.com/science/article/pii/S004896972104760

LakeEnsemblR: an R package that facilitates ensemble modelling of lakes

Model ensembles have several benefits compared to single-model applications but are not frequently used within the lake modelling community. Setting up and running multiple lake models can be challenging and time consuming, despite the many similarities between the existing models (forcing data, hypsograph, etc.). Here we present an R package, LakeEnsemblR, that facilitates running ensembles of five different vertical one-dimensional hydrodynamic lake models (FLake, GLM, GOTM, Simstrat, MyLake). The package requires input in a standardised format and a single configuration file. LakeEnsemblR formats these files to the input required by each model, and provides functions to run and calibrate the models. The outputs of the different models are compiled into a single file, and several post-processing operations are supported. LakeEnsemblR's workflow standardisation can simplify model benchmarking and uncertainty quantification, and improve collaborations between scientists. We showcase the successful application of LakeEnsemblR for two different lakes

Global patterns of nitrate isotope composition in rivers and adjacent aquifers reveal reactive nitrogen cascading

Remediation of nitrate pollution of Earth’s rivers and aquifers is hampered by cumulative biogeochemical processes and nitrogen sources. Isotopes (δ15N, δ18O) help unravel spatiotemporal nitrogen(N)-cycling of aquatic nitrate (NO3−). We synthesized nitrate isotope data (n = ~5200) for global rivers and shallow aquifers for common patterns and processes. Rivers had lower median NO3− (0.3 ± 0.2 mg L−1, n = 2902) compared to aquifers (5.5 ± 5.1 mg L−1, n = 2291) and slightly lower δ15N values (+7.1 ± 3.8‰, n = 2902 vs +7.7 ± 4.5‰, n = 2291), but were indistinguishable in δ18O (+2.3 ± 6.2‰, n = 2790 vs +2.3 ± 5.4‰, n = 2235). The isotope composition of NO3− was correlated with water temperature revealing enhanced N-cascading in warmer climates. Seasonal analyses revealed higher δ15N and δ18O values in wintertime, suggesting waste-related N-source signals are better preserved in the cold seasons. Isotopic assays of nitrate biogeochemical transformations are key to understanding nitrate pollution and to inform beneficial agricultural and land management strategies

High burn-up issues in fast breeder reactor fuels and structural materials

Fast breeder reactors (FBR) are essential to enhance the share of nuclear power to meet the growing energy demands in India. For economic viability and sustainability of nuclear power, there is urgent need to achieve higher fuel burn-up so as to reduce the fuel cycle cost and supply power at competitive rates. Indian energy scenario demands development of high burn-up and high breeding capable fuels working with high safety and performance levels typical of FBRs. However, this poses many challenges in the development of advanced fuels as well as structural materials which can cope up with the rigorous environment in fast reactors. Prospective fuels for FBRs include mixed oxide, carbide, nitride and metallic fuels. Choice of core structural materials range from the conventional austenitic stainless steel to ferritic steels and oxide dispersion strengthened (ODS) steels. Various issues limiting the achievable burn-up in fuels and structural materials of fast breeder reactors are discussed in this paper

Characterization of mechanical properties and microstructure of highly irradiated SS 316

Cold worked austenitic stainless steel type AISI 316 is used as the material for fuel cladding and wrapper of the Fast Breeder Test Reactor (FBTR), India. The evaluation of mechanical properties of these core structurals is very essential to assess its integrity and ensure safe and productive operation of FBTR to very high burn-ups. The changes in the mechanical properties of these core structurals are associated with microstructural changes caused by high fluence neutron irradiation and temperatures of 673–823 K. Remote tensile testing has been used for evaluating the tensile properties of irradiated clad tubes and shear punch test using small disk specimens for evaluating the properties of irradiated hexagonal wrapper. This paper will highlight the methods employed for evaluating the mechanical properties of the irradiated cladding and wrapper and discuss the trends in properties as a function of dpa (displacement per atom) and irradiation temperature