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Coastal ecosystems such as those in the Great Barrier Reef (GBR) lagoon, are exposed to stressors in flood plumes including low light (caused by increased turbidity) and agricultural pesticides. Photosystem II (PSII)-inhibiting herbicides are the most frequently detected pesticides in the GBR lagoon, but it is not clear how their toxicity to phototrophic species depends on light availability. This study investigated the individual and combined effects of PSII-inhibiting herbicide, diuron, and reduced light intensity (as a proxy for increased turbidity) on the marine diatom, Phaeodactylum tricornutum. Effective quantum yield (EQY) and cell density were measured to calculate responses relative to the controls over 72-h, in tests with varying stressor intensities. Individually, diuron concentrations (0.1–3 μg l−1) were not high enough to significantly reduce growth (cell density), but led to decreased EQY; while, low light generally led to increased EQY, but only reduced growth at the lowest tested light intensity (5 μmol photons m−2 s−1) after 48-hours. P. tricornutum was less affected by diuron when combined with low light scenarios, with increased EQY (up to 163% of the controls) that was likely due to increased electron transport per photon, despite lesser available photons at this low light intensity. In contrast, growth was completely inhibited relative to the controls when algae were simultaneously exposed to the highest stressor levels (3 μg l−1 diuron and 5 μmol photons m−2 s−1). This study highlights the importance of measuring more than one biological response variable to capture the combined effects of multiple stressors. Management of water quality stressors should consider combined impacts rather than just the impacts of individual stressors alone. Reducing suspended sediment and diuron concentrations in marine waters can decrease harmful effects and bring synergistic benefits to water quality.

Abstract Aggregation of α-synuclein, the hallmark of α-synucleinopathies such as Parkinson’s disease, occurs in various glycosphingolipidoses. Although α-synuclein aggregation correlates with deficiencies in the lysosomal degradation of glycosphingolipids (GSL), the mechanism(s) involved in this aggregation remains unclear. We previously described the aggregation of α-synuclein in Krabbe’s disease (KD), a neurodegenerative glycosphingolipidosis caused by lysosomal deficiency of galactosyl-ceramidase (GALC) and the accumulation of the GSL psychosine. Here, we used a multi-pronged approach including genetic, biophysical and biochemical techniques to determine the pathogenic contribution, reversibility, and molecular mechanism of aggregation of α-synuclein in KD. While genetic knock-out of α-synuclein reduces, but does not completely prevent, neurological signs in a mouse model of KD, genetic correction of GALC deficiency completely prevents α-synuclein aggregation. We show that psychosine forms hydrophilic clusters and binds the C-terminus of α-synuclein through its amino group and sugar moiety, suggesting that psychosine promotes an open/aggregation-prone conformation of α-synuclein. Dopamine and carbidopa reverse the structural changes of psychosine by mediating a closed/aggregation-resistant conformation of α-synuclein. Our results underscore the therapeutic potential of lysosomal correction and small molecules to reduce neuronal burden in α-synucleinopathies, and provide a mechanistic understanding of α-synuclein aggregation in glycosphingolipidoses.

AimYoung people with psychosis have higher rates of obesity, premature cardiovascular disease, and death compared to non-psychotic peers in the general population due to changes in metabolic regulation linked to antipsychotic medication and adverse health risk behaviors. The aim of this paper is to outline the development, implementation, and evaluation of a combined 12-week exercise and health behavior intervention delivered as part of an Early Intervention in Psychosis (EIP) routine service, within the UK.MethodsParticipants (n = 27) completed a 12-week combined intervention program, engaging in weekly, 90-min sessions comprising a healthy behavior education session (45 min), followed by a facilitated exercise session (45 min). Anthropometric data from participants (n = 26) were collected at baseline, 12 weeks, and 12 months post-intervention. Health behaviors and clinical measurements were assessed at baseline and 12 months.ResultsMean baseline data suggests participants were at an increased health risk on entry to the program, with elevated values in mean body mass index (BMI; 70% overweight/obese), waist circumference, resting heart rate, and triglycerides. Fifty percent reported smoking daily, 64% ate < 5 fruits/vegetables per day, and 52% of participants were prescribed highly obesogenic antipsychotic medications (i.e., Olanzapine). At 12 weeks and 12 months, no changes were observed in mean BMI, waist circumference or any other clinical variable (p > 0.05). At 12 months, participants reported a positive impact on health behaviors including improved diet, increased physical activity levels, and cessation of substance use (n = 2), alcohol use (n = 2), and smoking (n = 4). Focus groups captured participant experiences, engagement with and satisfaction with the program, including challenges/barriers to program adherence.ConclusionsThe 12-week exercise and health behaviors program supported participants to attenuate their physical health risk which was sustained at 12-month follow-up. Self-reported positive health behavior changes are likely to have contributed to the prevention of excessive weight gain in this high-risk period. The evaluation was designed to have validity for a “real world EIP setting” and reflect the complexity of delivery to this participant group. Evaluation findings influenced subsequent commissioning of the physical health intervention as an ongoing element of routine EIP care within the participant site.