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Systemic perturbations of the kynurenine pathway precede progression to dementia independently of amyloid-β
Full text linkIncreasing evidence suggests that kynurenine pathway (KP) dyshomeostasis may promote disease progression in dementia. Studies in Alzheimer's disease (AD) patients confirm KP dyshomeostasis in plasma and cerebrospinal fluid (CSF) which correlates with amyloid-β and tau pathology. Herein, we performed the first comprehensive study assessing baseline levels of KP metabolites in participants enrolling in the Australian Imaging Biomarkers Flagship Study of Aging. Our purpose was to test the hypothesis that changes in KP metabolites may be biomarkers of dementia processes that are largely silent. We used a cross-sectional analytical approach to assess non-progressors (N = 73); cognitively normal (CN) or mild cognitive impairment (MCI) participants at baseline and throughout the study, and progressors (N = 166); CN or MCI at baseline but progressing to either MCI or AD during the study. Significant KP changes in progressors included increased 3-hydroxyanthranilic acid (3-HAA) and 3-hydroxyanthranilic acid/anthranilic acid (3-HAA/AA) ratio, the latter having the largest effect on the odds of an individual being a progressor (OR 35.3; 95% CI between 14 and 104). 3-HAA levels were hence surprisingly bi-phasic, high in progressors but low in non-progressors or participants who had already transitioned to MCI or dementia. This is a new, unexpected and interesting result, as most studies of the KP in neurodegenerative disease show reduced 3-HAA/AA ratio after diagnosis. The neuroprotective metabolite picolinic acid was also significantly decreased while the neurotoxic metabolite 3-hydroxykynurenine increased in progressors. These results were significant even after adjustment for confounders. Considering the magnitude of the OR to predict change in cognition, it is important that these findings are replicated in other populations. Independent validation of our findings may confirm the utility of 3-HAA/AA ratio to predict change in cognition leading to dementia in clinical settings
Evolutionary history of grazing and resources determine herbivore exclusion effects on plant diversity
No full textEcological models predict that the effects of mammalian herbivore exclusion on plant diversity depend on resource availability and plant exposure to ungulate grazing over evolutionary time. Using an experiment replicated in 57 grasslands on six continents, with contrasting evolutionary history of grazing, we tested how resources (mean annual precipitation and soil nutrients) determine herbivore exclusion effects on plant diversity, richness and evenness. Here we show that at sites with a long history of ungulate grazing, herbivore exclusion reduced plant diversity by reducing both richness and evenness and the responses of richness and diversity to herbivore exclusion decreased with mean annual precipitation. At sites with a short history of grazing, the effects of herbivore exclusion were not related to precipitation but differed for native and exotic plant richness. Thus, plant species’ evolutionary history of grazing continues to shape the response of the world’s grasslands to changing mammalian herbivory
Redactable blockchain-enabled hierarchical access control framework for data sharing in electronic medical records
No full textThe application of blockchain to data sharing in an untrusted environment has received widespread industry attention in recent years. However, the tamper-proof property of blockchain brings protection for sharing data and also leads to a new limitation for the deletion of malicious data. Nowadays, many methods based on redactable blockchain with a chameleon hash is proposed to attempt to solve the above problem, but loss of effective access control to the modifiers can easily lead to breaking the positive characteristics of the blockchain. To address the aforementioned problem, a hierarchical access control redactable blockchain model for data sharing through attribute-based encryption and a chameleon hash is introduced. Under this model, the data owner can specify who can modify their data by setting an access policy and authenticating the modifier with a digital signature. The data owner's full control over rights is guaranteed, while the modifier's behavior is regulated. In addition, the hierarchical access control decentralized technique solves the overpowerful problem of center authority and single-point-of-failure problems in the existing works. The security analysis indicates that the proposed scheme achieves indistinguishable chosen plaintext attack security as well as collision resistance security. Performance analysis shows that the proposed scheme is more complete and has better efficiency compared with other schemes
Vehicloak: A blockchain-enabled privacy-preserving payment scheme for location-based vehicular services
No full textThe Internet of Vehicles (IoV) technology enables vehicles to communicate with each other, with pedestrians and with roadside infrastructures, to realize more efficient, safer and more environmentally friendly transportation. IoV also promises rich location-based services for vehicles, such as parking and toll highway. However, preserving privacy for location-based service payments emerges as a critical and challenging problem in IoV. Existing schemes rely on centralized banks for payment processing, resulting in location privacy leakage to centralized entities. In this paper, we propose a decentralized privacy-preserving payment scheme named Vehicloak for IoV based on the blockchain technology. The biggest challenge is to provide location privacy for vehicles while guaranteeing correct service payments using the transparent blockchain. To tackle this challenge, we introduce a new cryptographic technique called zk-GSigproof that integrates zero-knowledge proof with group signature. Vehicloak implements this technique in a smart contract to process payment, which verifies zero-knowledge proof and group signature without leaking location information. It is not limited to IoV and can be applied in many payment scenarios. To evaluate the performance of our scheme, we implement Vehicloak on a private blockchain of 100 nodes on Aliyun, and conduct a test with up to 4,000 transactions. The experimental results prove the feasibility of Vehicloak
Chemical evidence for the tradeoff-in-the-nephron hypothesis to explain secondary hyperparathyroidism
Full text linkBackground
Secondary hyperparathyroidism (SHPT) complicates advanced chronic kidney disease (CKD) and causes skeletal and other morbidity. In animal models of CKD, SHPT was prevented and reversed by reduction of dietary phosphate in proportion to GFR, but the phenomena underlying these observations are not understood. The tradeoff-in-the-nephron hypothesis states that as GFR falls, the phosphate concentration in the distal convoluted tubule ([P]DCT]) rises, reduces the ionized calcium concentration in that segment ([Ca++]DCT), and thereby induces increased secretion of parathyroid hormone (PTH) to maintain normal calcium reabsorption. In patients with CKD, we previously documented correlations between [PTH] and phosphate excreted per volume of filtrate (EP/Ccr), a surrogate for [P]DCT. In the present investigation, we estimated [P]DCT from physiologic considerations and measurements of phosphaturia, and sought evidence for a specific chemical phenomenon by which increased [P]DCT could lower [Ca++]DCT and raise [PTH].
Methods and findings
We studied 28 patients (“CKD”) with eGFR of 14–49 mL/min/1.73m2 (mean 29.9 ± 9.5) and 27 controls (“CTRL”) with eGFR > 60 mL/min/1.73m2 (mean 86.2 ± 10.2). In each subject, total [Ca]DCT and [P]DCT were deduced from relevant laboratory data. The Joint Expert Speciation System (JESS) was used to calculate [Ca++]DCT and concentrations of related chemical species under the assumption that a solid phase of amorphous calcium phosphate (Ca3(PO4)2 (am., s.)) could precipitate. Regressions of [PTH] on eGFR, [P]DCT, and [Ca++]DCT were then examined. At filtrate pH of 6.8 and 7.0, [P]DCT was found to be the sole determinant of [Ca++]DCT, and precipitation of Ca3(PO4)2 (am., s.) appeared to mediate this result. At pH 6.6, total [Ca]DCT was the principal determinant of [Ca++]DCT, [P]DCT was a minor determinant, and precipitation of Ca3(PO4)2 (am., s.) was predicted in no CKD and five CTRL. In CKD, at all three pH values, [PTH] varied directly with [P]DCT and inversely with [Ca++]DCT, and a reduced [Ca++]DCT was identified at which [PTH] rose unequivocally. Relationships of [PTH] to [Ca++]DCT and to eGFR resembled each other closely.
Conclusions
As [P]DCT increases, chemical speciation calculations predict reduction of [Ca++]DCT through precipitation of Ca3(PO4)2 (am., s.). [PTH] appears to rise unequivocally if [Ca++]DCT falls sufficiently. These results support the tradeoff-in-the-nephron hypothesis, and they explain why proportional phosphate restriction prevented and reversed SHPT in experimental CKD. Whether equally stringent treatment can be as efficacious in humans warrants investigation
Exploiting the potential of bioreactors for creating spatial organization in the soil microbiome: A strategy for increasing sustainable agricultural practices
Full text linkIndustrial production of synthetic nitrogen fertilizers and their crop application have caused considerable environmental impacts. Some eco-friendly alternatives try to solve them but raise some restrictions. We tested a novel method to produce a nitrogen bioinoculant by enriching a soil microbial community in bioreactors supplying N2 by air pumping. The biomass enriched with diazotrophic bacteria was diluted and applied to N-depleted and sterilized soil of tomato plants. We estimated microbial composition and diversity by 16S rRNA metabarcoding from soil and bioreactors at different run times and during plant uprooting. Bioreactors promoted the N-fixing microbial community and revealed a hided diversity. One hundred twenty-four (124) operational taxonomic units (OTUs) were assigned to bacteria with a greater Shannon diversity during the reactor’s steady state. A total of 753 OTUs were found in the rhizospheres with higher biodiversity when the lowest concentration of bacteria was applied. The apparent bacterial abundance in the batch and continuous bioreactors suggested a more specific functional ecological organization. We demonstrate the usefulness of bioreactors to evidence hidden diversity in the soil when it passes through bioreactors. By obtaining the same growth of inoculated plants and the control with chemical synthesis fertilizers, we evidence the potential of the methodology that we have called directed bioprospecting to grow a complex nitrogen-fixing microbial community. The simplicity of the reactor’s operation makes its application promising for developing countries with low technological progress
Correcting magnification error in foveal avascular zone area measurements of optical coherence tomography angiography images with estimated axial length
Full text linkBackground
To generate and validate a method to estimate axial length estimated (ALest) from spherical equivalent (SE) and corneal curvature [keratometry (K)], and to determine if this ALest can replace actual axial length (ALact) for correcting transverse magnification error in optical coherence tomography angiography (OCTA) images using the Littmann-Bennett formula.
Methods
Data from 1301 participants of the Raine Study Gen2-20 year follow-up were divided into two datasets to generate (n = 650) and validate (n = 651) a relationship between AL, SE, and K. The developed formula was then applied to a separate dataset of 46 participants with AL, SE, and K measurements and OCTA images to estimate and compare the performance of ALest against ALact in correcting transverse magnification error in OCTA images when measuring the foveal avascular zone area (FAZA).
Results
The formula for ALest yielded the equation: ALest = 2.102K − 0.4125SE + 7.268, R2 = 0.794. There was good agreement between ALest and ALact for both study cohorts. The mean difference [standard deviation (SD)] between FAZA corrected with ALest and ALact was 0.002 (0.015) mm2 with the 95% limits of agreement (LoA) of − 0.027 to 0.031 mm2. In comparison, mean difference (SD) between FAZA uncorrected and corrected with ALact was − 0.005 (0.030) mm2, with 95% LoA of − 0.064 to 0.054 mm2.
Conclusions
ALact is more accurate than ALest and hence should be used preferentially in magnification error correction in the clinical setting. FAZA corrected with ALest is comparable to FAZA corrected with ALact, while FAZA measurements using images corrected with ALest have a greater accuracy than measurements on uncorrected images. Hence, in the absence of ALact, clinicians should use ALest to correct for magnification error as this provides for more accurate measurements of fundus parameters than uncorrected images
Risk management and organisational performance in the Indonesian public sector: An empirical study
Full text linkIssues surrounding the real benefits of risk management and the factors that can support successful risk management systems in the public sector are still relevant topics discussed by accounting scholars. However, most risk management research in the public sector focuses on the experiences of developed countries. To fill this gap in the literature, this quantitative study uses a survey to investigate the relationship between risk management systems and organisational performance in public sector organisations in Indonesia, a developing country. It concurrently explores transformational leadership, internal audit activities, public service motivation and business process improvement as elements that may influence the original relationship between risk management systems and organisational performance on these organisations. A final sample of 202 usable questionnaires was obtained and analysed using Partial least squares (PLS) path modelling to test the hypotheses using SmartPLS 3.0 software. PLS path analysis involved a main analysis of all usable samples and an additional multigroup analysis.
Empirical evidence in this study suggests that transformational leadership and internal audit activities significantly influence risk management systems. Risk management system, in turn, significantly influences organisational performance through the mediating effect of business process improvement. Public service motivation serves as a mediator for the relationship between risk management system and business process improvement. However, the mediation effect of public service motivation is weak. The results of multigroup analysis revealed that organisation size does not moderate any paths in the model. Perceived risk management budget sufficiency significantly moderates the relationship between transformational leadership and risk management system and the relationship between risk management system and organisational performance. Perceived uncertainty level significantly moderates the relationship between risk management system and business process improvement.
Thus, this study expands the discussion related to the complex relationship between a risk management system and organisational performance in a developing country’s public sector. The findings of this study provide practical implications for leaders and risk management practitioners in the public sector, particularly in the Indonesian context. This study also measured the risk management system and public service motivation as second-order formative constructs; these are considered new to the existing literature.
However, the structured questionnaire used in this study restricted the depth of data collected; the use of a cross-sectional design limited the ability of this study to extensively examine the cause-and-effect relationships that can be identified in a longitudinal design. Nevertheless, these limitations are justifiable because the hypotheses of this study required answers for scope, rather than depth. Further, the use of moderating variables, which are examined in multigroup analysis, strengthened the cross-sectional design in this study
Non-Modifiable factors as moderators of the relationship between physical activity and brain volume: A Cross-Sectional UK Biobank Study
No full textBackground:Previous research suggests physical activity attenuates grey and white matter loss; however, there appears to be individual variability in this effect. Understanding factors that can influence the relationship between physical activity and brain volume may enable prediction of individual response. Objective:The current study examined the relationship between objectively-measured physical activity and brain volume; and whether this relationship is moderated by age, sex, or a priori candidate genetic factors, brain-derived neurotrophic factor (BDNF) Val66Met, or apolipoprotein (APOE) ɛ4 allele carriage. Methods:Data from 10,083 men and women (50 years and over) of the UK Biobank were used to examine the study objectives. All participants underwent a magnetic resonance imaging scan to quantify grey and white matter volumes, physical activity monitoring via actigraphy, and genotyping. Results:Physical activity was associated with total grey matter volume, total white matter volume, and right hippocampal volume. Only males had an association between higher physical activity levels and greater cortical grey matter volume, total grey matter volume, and right hippocampal volume. Age moderated the relationship between physical activity and white matter volume. Conclusion:Our results indicate that in males, but not females, an association exists between objectively-measured physical activity and grey matter volume. Age may also play a role in impacting the relationship between physical activity and brain volume. Future research should evaluate longitudinal brain volumetrics to better understand the nature of age and sex-effects on the physical activity and brain volume relationship
Organic carbon compounds associated with deep soil carbon stores
Full text linkAims
Organic carbon has been reported in deep regolithic profiles to depths of tens of metres, but the composition of the carbon compounds is unknown.
Methods
Residual carbon in the form of non-volatile low molecular weight compounds (LMWC) was characterised in three deep soil profiles to a depth of 19 m under farmland in south-western Australia following extraction with ethyl acetate and analysis by GC/MS. Pyrolysis and off-line thermochemolysis were used to characterise macromolecular organic carbon (MOC) to a depth of 29 m at a fourth site.
Results
Three compound classes occurred across the three different field locations: (1) terpenes, (2) fatty acids, amides and alcohols, and (3) plant steroids; indicating the influence of input of the past and present vegetation. Compounds related to fatty acids were the predominant residual carbon species in deep soils, and may be derived from plants and microorganisms. Biomarkers such as lignin, polysaccharides, proteins and terpenes at 0–0.1 m implied influences of vegetation, fire events and microorganisms. Pyrolysis found that polysaccharides were distributed mainly from 0 to 0.1 m, while aromatic compounds were consistently detected down to 29 m.
Conclusions
Carbon was stabilised in the form of aromatic compounds in deep soil, whereas other carbon sources such as cellulose, chitin, and N-containing compounds were confined to the surface soil. LMWC (Z)-docos-13-enamide and bis(6-methylheptyl) phthalate, were the main components throughout the soil profiles representing 53–81% of the LMWC, and were a greater proportion of the organic matter at depths of 18–19 m