Mutations in the Amyloid-β Protein Precursor Reduce Mitochondrial Function and Alter Gene Expression Independent of 42-Residue Amyloid-β Peptide

Background:Dominant missense mutations in the amyloid-β protein precursor (AβPP) cause early-onset familial Alzheimer’s disease (FAD) and are associated with changes in the production or properties of the amyloid-β peptide (Aβ), particularly of the 42-residue variant (Aβ42) that deposits in the Alzheimer’s disease (AD) brain. Recent findings, however, show that FAD mutations in AβPP also lead to increased production of longer Aβ variants of 45–49 residues in length. Objective:We aimed to test neurotoxicity of Aβ42 vis-á-vis longer variants, focusing specifically on mitochondrial function, as dysfunctional mitochondria are implicated in the pathogenesis of AD. Methods:We generated SH-SY5Y human neuroblastoma cells stably expressing AβPP mutations that lead to increased production of long Aβ peptides with or without Aβ42. These AβPP-expressing cells were tested for oxygen consumption rates (OCR) under different conditions designed to interrogate mitochondrial function. These cell lines were also examined for expression of genes important for mitochondrial or neuronal structure and function. Results:The mutant AβPP-expressing cells showed decreased basal OCRs as well as decreased OCRs associated with mitochondrial ATP production, even more so in the absence of Aβ42 production. Moreover, mutant AβPP-expressing cells producing longer forms of Aβ displayed altered expression of certain mitochondrial- and neuronal-associated genes, whether or not Aβ42 was produced. Conclusion:These findings suggest that mutant AβPP can cause mitochondrial dysfunction that is associated with long Aβ but not with Aβ42

Volleyball Overhead Swing Volume and Injury Frequency over the Course of a Season

Background: Overuse injuries are common in volleyball; however, few studies exist that quantify the workload of a volleyball athlete in a season. The relationship between workload and shoulder injury has not been extensively studied in women\u27s collegiate volleyball athletes. Hypothesis/Purpose: This study aims to quantify shoulder workloads by counting overhead swings during practice and matches. The purpose of the current study is to provide a complete depiction of typical overhead swings, serves, and hits, which occur in both practices and matches. The primary hypothesis was that significantly more swings will occur in practices compared to matches. The secondary hypothesis was that greater swing volume and greater musculoskeletal injury frequency will occur in the pre-season than during the season. Study Design: Prospective cohort. Methods: Researchers observed practice and match videos and counted overhead serves and attacks of 19 women\u27s collegiate volleyball players for two seasons. Serves, overhead hits, and total swings (serves + hits) were the dependent variables; event (matches and practice) along with position (defensive specialists, setter, outside hitter, and middle blocker) were the independent variables. Musculoskeletal injury frequency and swing volume workload were compared across pre-season and competitive season time periods. Results: Across all positions except outside hitters twice as many total swings occurred in practices compared to matches (p = .002) resulting in an average of 19 (CI95 16.5, 21.5) more swings in practice than in matches. The average number of total swings during the pre-season 47.1 (CI95 44.1, 50.1) was significantly greater than average swings per session during the competitive season 37.7 (CI95 36.4, 38.9) (p \u3c 0.001) resulting in a mean difference of 9.4 (CI95 6.1, 12.7) swings. The number of athletes limited in participation or out due to a musculoskeletal injury during the pre-season (2.9%) was greater than during the season (1.1%) (p = 0.042). Conclusion: These findings support the primary hypothesis that women\u27s collegiate volleyball athletes swing more during practices than in matches. The higher average number of serves in the pre-season and the greater frequency of musculoskeletal injuries requiring participation restriction or removal from participation suggest that a concordant relationship may exist between workload and injury variables. Level of Evidence: 2

Magnetic and Transport Properties of Co2MnSnxSb1−x Heusler Alloys

We present the magnetic, structural, and transport properties of the quaternary Heusler alloys Co2MnSnxSb1−x (x = 0, 0.25, 0.50, 0.75, and 1.0), which have been theoretically predicted to be half-metallic. Magnetization measurements as a function of applied field show that the saturation moment for x = 1 (Co2MnSn) is near the Slater–Pauling value of 5μB; however, the moment for x = 0 (Co2MnSb) falls far short of its predicted value of 6μB. Resistivity as a function of temperature was measured from 5 to 400 K, and a phase transition from a half-metallic ferromagnetic phase to a normal ferromagnetic phase was observed between 50 and 80 K for all of the alloys. At low temperature (10 K\u3cT\u3c40 K), the resistivity ratio was found to vary as R(T)/R(T = 5 K) = A+BT2+CT9/2, where the T2 term results from electron-electron scattering, whereas the T9/2 term is a consequence of double magnon scattering

Legume based plant mixtures for delivery of multiple ecosystem services: An overview of benefits

As costs for mineral fertilizers rise, legume-based leys are recognised as a potential alternative nitrogen source for crops. Here we demonstrate that including species-rich legume-based leys in the rotation helps to maximize synergies between agricultural productivity and other ecosystem services. By using functionally diverse plant species mixtures these services can be optimised and fine-tuned to regional and farm-specific needs. Field experiments run over three years at multiple locations showed that the stability of ley performance was greater in multi-species mixtures than in legume monocultures. In addition, mixing different legume species in the ley helps to suppress both early and late weeds. Further, combining complementary phenologies of different legume species extended forage availability for key pollinator species. Finally, widening the range of legume species increases opportunities to build short term leys into rotations on conventional farms via cover cropping or undersowing

Numbers and narratives: How qualitative methods can strengthen the science of paediatric antimicrobial stewardship

Antimicrobial and diagnostic stewardship initiatives have become increasingly important in paediatric settings. The value of qualitative approaches to conduct stewardship work in paediatric patients is being increasingly recognized. This article seeks to provide an introduction to basic elements of qualitative study designs and provide an overview of how these methods have successfully been applied to both antimicrobial and diagnostic stewardship work in paediatric patients. A multidisciplinary team of experts in paediatric infectious diseases, paediatric critical care and qualitative methods has written a perspective piece introducing readers to qualitative stewardship work in children, intended as an overview to highlight the importance of such methods and as a starting point for further work. We describe key differences between qualitative and quantitative methods, and the potential benefits of qualitative approaches. We present examples of qualitative research in five discrete topic areas of high relevance for paediatric stewardship work: provider attitudes; provider prescribing behaviours; stewardship in low-resource settings; parents\u27 perspectives on stewardship; and stewardship work focusing on select high-risk patients. Finally, we explore the opportunities for multidisciplinary academic collaboration, incorporation of innovative scientific disciplines and young investigator growth through the use of qualitative research in paediatric stewardship. Qualitative approaches can bring rich insights and critically needed new information to antimicrobial and diagnostic stewardship efforts in children. Such methods are an important tool in the armamentarium against worsening antimicrobial resistance, and a major opportunity for investigators interested in moving the needle forward for stewardship in paediatric patients

Melting Alpine Glaciers Enrich High-Elevation Lakes with Reactive Nitrogen

Alpine glaciers have receded substantially over the last century in many regions of the world. Resulting changes in glacial runoff not only affect the hydrological cycle, but can also alter the physical (i.e., turbidity from glacial flour) and biogeochemical properties of downstream ecosystems. Here we compare nutrient concentrations, transparency gradients, algal biomass, and fossil diatom species richness in two sets of high-elevation lakes: those fed by snowpack melt alone (SF lakes) and those fed by both glacial and snowpack meltwaters (GSF lakes). We found that nitrate (NO3-) concentrations in the GSF lakes were 1-2 orders of magnitude higher than in SF lakes. Although nitrogen (N) limitation is common in alpine lakes, algal biomass was lower in highly N-enriched GSF lakes than in the N-poor SF lakes. Contrary to expectations, GSF lakes were more transparent than SF lakes to ultraviolet and equally transparent to photosynthetically active radiation.Sediment diatom assemblages had lower taxonomic richness in the GSF lakes, a feature that has persisted over the last century. Our results demonstrate that the presence of glaciers on alpine watersheds more strongly influences NO3- concentrations in high-elevation lake ecosystems than any other geomorphic or biogeographic characteristic

Melting Alpine Glaciers Enrich High-Elevation Lakes with Reactive Nitrogen

Alpine glaciers have receded substantially over the last century in many regions of the world. Resulting changes in glacial runoff not only affect the hydrological cycle, but can also alter the physical (i.e., turbidity from glacial flour) and biogeochemical properties of downstream ecosystems. Here we compare nutrient concentrations, transparency gradients, algal biomass, and fossil diatom species richness in two sets of high-elevation lakes: those fed by snowpack melt alone (SF lakes) and those fed by both glacial and snowpack meltwaters (GSF lakes). We found that nitrate (NO3-) concentrations in the GSF lakes were 1-2 orders of magnitude higher than in SF lakes. Although nitrogen (N) limitation is common in alpine lakes, algal biomass was lower in highly N-enriched GSF lakes than in the N-poor SF lakes. Contrary to expectations, GSF lakes were more transparent than SF lakes to ultraviolet and equally transparent to photosynthetically active radiation.Sediment diatom assemblages had lower taxonomic richness in the GSF lakes, a feature that has persisted over the last century. Our results demonstrate that the presence of glaciers on alpine watersheds more strongly influences NO3- concentrations in high-elevation lake ecosystems than any other geomorphic or biogeographic characteristic

Weeds in Organic Fertility-Building Leys: Aspects of Species Richness and Weed Management

Legume-based leys (perennial sod crops) are an important component of fertility management in organic rotations in many parts of Europe. Despite their importance, however, relatively little is known about how these leys affect weed communities or how the specific composition of leys may contribute to weed management. To determine whether the choice of plant species in the ley affects weeds, we conducted replicated field trials at six locations in the UK over 24 months, measuring weed cover and biomass in plots sown with monocultures of 12 legume and 4 grass species, and in plots sown with a mixture of 10 legume species and 4 grass species. Additionally, we monitored weed communities in leys on 21 organic farms across the UK either sown with a mixture of the project species or the farmers’ own species mix. In total, 63 weed species were found on the farms, with the annuals Stellaria media, Sonchus arvensis, and Veronica persica being the most frequent species in the first year after establishment of the ley, while Stellaria media and the two perennials Ranunculus repens and Taraxacum officinale dominated the weed spectrum in the second year. Our study shows that organic leys constitute an important element of farm biodiversity. In both replicated and on-farm trials, weed cover and species richness were significantly lower in the second year than in the first, owing to lower presence of annual weeds in year two. In monocultures, meadow pea (Lathyrus pratensis) was a poor competitor against weeds, and a significant increase in the proportion of weed biomass was observed over time, due to poor recovery of meadow pea after mowing. For red clover (Trifolium pratense), we observed the lowest proportion of weed biomass in total biomass among the tested legume species. Crop biomass and weed biomass were negatively correlated across species. Residuals from the linear regression between crop biomass and weed biomass indicated that at similar levels of crop biomass, grasses had lower weed levels than legumes. We conclude that choice of crop species is an important tool for weed management in leys

Weeds in organic fertility-building leys:aspects of species richness and weed management

Legume-based leys (perennial sod crops) are an important component of fertility management in organic rotations in many parts of Europe. Despite their importance, however, relatively little is known about how these leys affect weed communities or how the specific composition of leys may contribute to weed management. To determine whether the choice of plant species in the ley affects weeds, we conducted replicated field trials at six locations in the UK over 24 months, measuring weed cover and biomass in plots sown with monocultures of 12 legume and 4 grass species and in plots sown with a mixture of 10 legume species and 4 grass species. Additionally, we monitored weed communities in leys on 21 organic farms across the UK either sown with a mixture of the project species or the farmers? own species mix. In total, 63 weed species were found on the farms, with the annuals Stellaria media, Sonchus arvensis, and Veronica persica being the most frequent species in the first year after establishment of the ley, while Stellaria media and the two perennials Ranunculus repens and Taraxacum officinale dominated the weed spectrum in the second year. Our study shows that organic leys constitute an important element of farm biodiversity. In both replicated and on-farm trials, weed cover and species richness were significantly lower in the second than in the first year, owing to lower presence of annual weeds in year two. In monocultures, meadow pea (Lathyrus pratensis) was a poor competitor against weeds, and a significant increase in the proportion of weed biomass was observed over time, due to poor recovery of meadow pea after mowing. For red clover (Trifolium pratense), we observed the lowest proportion of weed biomass in total biomass among the tested legume species. Crop biomass and weed biomass were negatively correlated across species. Residuals from the linear regression between crop biomass and weed biomass indicated that at similar levels of crop biomass, grasses had lower weed levels than legumes. We conclude that choice of crop species is an important tool for weed management in leys.authorsversionPeer reviewe