Avoiding ecosystem and social impacts of hydropower, wind, and solar in Southern Africa's low-carbon electricity system.

The scale at which low-carbon electricity will need to be deployed to meet economic growth, electrification, and climate goals in Africa is unprecedented, yet the potential land use and freshwater impacts from this massive build-out of energy infrastructure is poorly understood. In this study, we characterize low-impact onshore wind, solar photovoltaics, and hydropower potential in Southern Africa and identify the cost-optimal mix of electricity generation technologies under different sets of socio-environmental land use and freshwater constraints and carbon targets. We find substantial wind and solar potential after applying land use protections, but about 40% of planned or proposed hydropower projects face socio-environmental conflicts. Applying land and freshwater protections results in more wind, solar, and battery capacity and less hydropower capacity compared to scenarios without protections. While a carbon target favors hydropower, the amount of cost-competitively selected hydropower is at most 45% of planned or proposed hydropower capacity in any scenario-and is only 25% under socio-environmental protections. Achieving both carbon targets and socio-environmental protections results in system cost increases of 3-6%. In the absence of land and freshwater protections, environmental and social impacts from new hydropower development could be significant.

Structural biases in disordered proteins are prevalent in the cell.

Intrinsically disordered proteins and protein regions (IDPs) are prevalent in all proteomes and are essential to cellular function. Unlike folded proteins, IDPs exist in an ensemble of dissimilar conformations. Despite this structural plasticity, intramolecular interactions create sequence-specific structural biases that determine an IDP ensemble's three-dimensional shape. Such structural biases can be key to IDP function and are often measured in vitro, but whether those biases are preserved inside the cell is unclear. Here we show that structural biases in IDP ensembles found in vitro are recapitulated inside human-derived cells. We further reveal that structural biases can change in a sequence-dependent manner due to changes in the intracellular milieu, subcellular localization, and intramolecular interactions with tethered well-folded domains. We propose that the structural sensitivity of IDP ensembles can be leveraged for biological function, can be the underlying cause of IDP-driven pathology or can be used to design disorder-based biosensors and actuators.

The DizzyQuest Combined with Accelerometry: Daily Physical Activities and Limitations among Patients with Bilateral Vestibulopathy Due to DFNA9.

BACKGROUND: DFNA9 is a genetic disease of the inner ear, causing progressive bilateral sensorineural deafness and bilateral vestibulopathy (BV). In this study, DizzyQuest, a mobile vestibular diary, and the MOX accelerometer were combined to assess the daily life functional limitations and physical activity of patients with DFNA9 suffering from BV. These parameters might be appropriate as potential candidacy criteria and outcome measures for new therapeutic interventions for BV. METHODS: Fifteen DFNA9 patients with BV and twelve age-matched healthy controls were included. The DizzyQuest was applied for six consecutive days, which assessed the participants' extent of functional limitations, tiredness, types of activities performed during the day, and type of activity during which the participant felt most limited. The MOX accelerometer was worn during the same six days of DizzyQuest use, measuring the participants intensity and type of physical activity. Mixed-effects linear and logistic regression analyses were performed to compare the DFNA9 patients and control group. RESULTS: DFNA9 patients with BV felt significantly more limited in activities during the day compared to the age-matched controls, especially in social participation (p < 0.005). However, these reported limitations did not cause adjustment in the types of activities and did not reduce the intensity or type of physical activity measured with accelerometry. In addition, no relationships were found between self-reported functional limitations and physical activity. CONCLUSIONS: This study demonstrated that self-reported functional limitations are significantly higher among DFNA9 patients with BV. As a result, these limitations might be considered as part of the candidacy criteria or outcome measures for therapeutic interventions. In addition, the intensity or type of physical activity performed during the day need to be addressed more specifically in future research.

Effects of 3 months of 10-h per-day time-restricted eating and 3 months of follow-up on bodyweight and cardiometabolic health in Danish individuals at high risk of type 2 diabetes: the RESET single-centre, parallel, superiority, open-label, randomised controlled trial.

BACKGROUND: Time-restricted eating (TRE) has been suggested to be a simple, feasible, and effective dietary strategy for individuals with overweight or obesity. We aimed to investigate the effects of 3 months of 10-h per-day TRE and 3 months of follow-up on bodyweight and cardiometabolic risk factors in individuals at high risk of type 2 diabetes. METHODS: This was a single-centre, parallel, superiority, open-label randomised controlled clinical trial conducted at Steno Diabetes Center Copenhagen (Denmark). The inclusion criteria were age 30-70 years with either overweight (ie, BMI ≥25 kg/m2) and concomitant prediabetes (ie, glycated haemoglobin [HbA1c] 39-47 mmol/mol) or obesity (ie, BMI ≥30 kg/m2) with or without prediabetes and a habitual self-reported eating window (eating and drinking [except for water]) of 12 h per day or more every day and of 14 h per day or more at least 1 day per week. Individuals were randomly assigned 1:1 to 3 months of habitual living (hereafter referred to as the control group) or TRE, which was a self-selected 10-h per-day eating window placed between 0600 h and 2000 h. Randomisation was done in blocks varying in size and was open for participants and research staff, but outcome assessors were masked during statistical analyses. The randomisation list was generated by an external statistician. The primary outcome was change in bodyweight, assessed after 3 months (12 weeks) of the intervention and after 3 months (13 weeks) of follow-up. Adverse events were reported and registered at study visits or if participants contacted study staff to report events between visits. This trial is registered on ClinicalTrials.gov (NCT03854656). FINDINGS: Between March 12, 2019, and March 2, 2022, 100 participants (66 [66%] were female and 34 [34%] were male; median age 59 years [IQR 52-65]) were enrolled and randomly assigned (50 to each group). Of those 100, 46 (92%) in the TRE group and 46 (92%) in the control group completed the intervention period. After 3 months of the intervention, there was no difference in bodyweight between the TRE group and the control group (-0·8 kg, 95% CI -1·7 to 0·2; p=0·099). Being in the TRE group was not associated with a lower bodyweight compared with the control group after subsequent 3-month follow-up (-0·2 kg, -1·6 to 1·2). In the per-protocol analysis, participants who completed the intervention in the TRE group lost 1·0 kg (-1·9 to -0·0; p=0·040) bodyweight compared with the control group after 3 months of intervention, which was not maintained after the 3-month follow-up period (-0·4 kg, -1·8 to 1·0). During the trial and follow-up period, one participant in the TRE group reported a severe adverse event: development of a subcutaneous nodule and pain when the arm was in use. This side-effect was evaluated to be related to the trial procedures. INTERPRETATION: 3 months of 10-h per-day TRE did not lead to clinically relevant effects on bodyweight in middle-aged to older individuals at high risk of type 2 diabetes. FUNDING: Novo Nordisk Foundation, Aalborg University, Helsefonden, and Innovation Fund Denmark.