61871 research outputs found
Sort by
The role of glucose in cognition, risk of dementia, and related biomarkers in individuals without type 2 diabetes mellitus or the metabolic syndrome: A systematic review of observational studies
No full textBackground
Excessive blood glucose promotes neuropathological cognitive decline in individuals with type 2 diabetes mellitus and the metabolic syndrome, but no systematic synthesis of the evidence for the same association exists in individuals without these conditions.
Objectives
To systematically review studies exploring the role of glucose on cognition, dementia risk, and related biomarkers in adults without diabetes or metabolic syndrome.
Data sources
We searched databases from inception until July 2021 and manually searched the reference lists of included studies. Risk of bias was assessed using the Joanna Briggs Institute tool.
Results
We found 46 observational studies including approximately 98,216 participants. Substantial heterogeneity in study results precluded drawing definitive conclusion whether blood glucose levels are associated with cognition or dementia risk. Higher blood glucose, however, was associated with greater amyloid burden, brain atrophy, and reduced cortical thickness.
Conclusions and implications
High glucose concentrations in blood may exacerbate dementia-related neuropathology but whether this translates into pathological cognitive decline or elevate dementia risk later in life remains unclear
Analysis of pathogenic pseudoexons reveals novel mechanisms driving cryptic splicing
Get PDFUnderstanding pre-mRNA splicing is crucial to accurately diagnosing and treating genetic diseases. However, mutations that alter splicing can exert highly diverse effects. Of all the known types of splicing mutations, perhaps the rarest and most difficult to predict are those that activate pseudoexons, sometimes also called cryptic exons. Unlike other splicing mutations that either destroy or redirect existing splice events, pseudoexon mutations appear to create entirely new exons within introns. Since exon definition in vertebrates requires coordinated arrangements of numerous RNA motifs, one might expect that pseudoexons would only arise when rearrangements of intronic DNA create novel exons by chance. Surprisingly, although such mutations do occur, a far more common cause of pseudoexons is deep-intronic single nucleotide variants, raising the question of why these latent exon-like tracts near the mutation sites have not already been purged from the genome by the evolutionary advantage of more efficient splicing. Possible answers may lie in deep intronic splicing processes such as recursive splicing or poison exon splicing. Because these processes utilize intronic motifs that benignly engage with the spliceosome, the regions involved may be more susceptible to exonization than other intronic regions would be. We speculated that a comprehensive study of reported pseudoexons might detect alignments with known deep intronic splice sites and could also permit the characterisation of novel pseudoexon categories. In this report, we present and analyse a catalogue of over 400 published pseudoexon splice events. In addition to confirming prior observations of the most common pseudoexon mutation types, the size of this catalogue also enabled us to suggest new categories for some of the rarer types of pseudoexon mutation. By comparing our catalogue against published datasets of non-canonical splice events, we also found that 15.7% of pseudoexons exhibit some splicing activity at one or both of their splice sites in non-mutant cells. Importantly, this included seven examples of experimentally confirmed recursive splice sites, confirming for the first time a long-suspected link between these two splicing phenomena. These findings have the potential to improve the fidelity of genetic diagnostics and reveal new targets for splice-modulating therapies
Karyotype differentiation in cultivated chickpea revealed by Oligopainting fluorescence in situ hybridization
Get PDFChickpea (Cicer arietinum L.) is one of the main sources of plant proteins in the Indian subcontinent and West Asia, where two different morphotypes, desi and kabuli, are grown. Despite the progress in genome mapping and sequencing, the knowledge of the chickpea genome at the chromosomal level, including the long-range molecular chromosome organization, is limited. Earlier cytogenetic studies in chickpea suffered from a limited number of cytogenetic landmarks and did not permit to identify individual chromosomes in the metaphase spreads or to anchor pseudomolecules to chromosomes in situ. In this study, we developed a system for fast molecular karyotyping for both morphotypes of cultivated chickpea. We demonstrate that even draft genome sequences are adequate to develop oligo-fluorescence in situ hybridization (FISH) barcodes for the identification of chromosomes and comparative analysis among closely related chickpea genotypes. Our results show the potential of oligo-FISH barcoding for the identification of structural changes in chromosomes, which accompanied genome diversification among chickpea cultivars. Moreover, oligo-FISH barcoding in chickpea pointed out some problematic, most probably wrongly assembled regions of the pseudomolecules of both kabuli and desi reference genomes. Thus, oligo-FISH appears as a powerful tool not only for comparative karyotyping but also for the validation of genome assemblies
Linkage study of surveillance and hospital admission data to investigate Clostridium difficile infection in hospital patients in Perth, Western Australia
No full textObjectives
Increasing incidence rates of Clostridium difficile infection (CDI) and outbreaks of emerging strains have highlighted the need for continuous monitoring and surveillance of CDI in Australia. Active surveillance captures all hospital-identified CDI cases in Western Australia (WA), where all C. difficile isolates recovered are routinely PCR ribotyped. The aim of this study was to determine incidence rates and descriptive and molecular epidemiology of CDI among patients in Perth, WA using linkage of surveillance and hospital administrative records.
Methods
All CDI cases (confirmed by tcdB PCR) from July 2012 to June 2014 captured in the Hospital Infection Surveillance WA dataset for three hospitals were linked with hospital admission records from the Patient Administration System and ribotyping data to calculate incidence rates of CDI and the distribution of various ribotypes (RTs).
Results
There were 381 individual cases of CDI identified among 354 hospital patients (including outpatients and ED) who experienced ≥1 CDI episode during the study period. CDI was hospital-associated in 62.7% of cases and community-associated (CA)-CDI in 31.2%. The overall incidence rate was 4.40/10,000 patient days (PD, 95% CI 3.98–4.86), females across all age groups experienced higher incidence (risk ratio 1.29, p < 0.05). The risk ratio for CA-CDI was highest (7.76, p < 0.01) for females vs males aged 15–29 years. Overall, 10.8% of cases were admitted to ICU, 15.2% had a recurrent infection and the mortality rate was 7.2%. C. difficile RT 014/020 predominated (34.9%) among 339 isolates of 71 different RTs.
Conclusions
The incidence of CDI in WA is high and RT 014/020 continues to be the dominant molecular type in an otherwise diverse array of strains. High strain diversity suggests CDI cases arise from exposure to many different reservoirs
Assessing changes in static and dynamic postural stability in youth football players following the FIFA 11+ injury prevention program
No full textObjective
To examine the effect of FIFA 11+ warm-up program on static and dynamic postural stability in football players. Equipment and methods: Thirty young male football players (mean ± SD; age: 14.96 ± 0.76 years were recruited and divided into two groups (FIFA 11+ exercise group, n = 15 and control group, n = 15). The exercise group performed the FIFA 11+ injury prevention exercises as part of their warm-up and the control group continued their traditional warm up routines. The FIFA 11+ exercises were performed three times a week, for eight weeks. A single leg test with eyes closed, on a force platform, was used to measure static postural stability measurement, and time to stability after single leg drop-landing test was used for dynamic postural stability measurement.
Results
The repeated measures (Anova) showed that the experimental group performed significantly better (adjusted mean difference [95% CI] or percentage %) in static postural stability (center of pressure displacement in the anterior-posterior direction [0.03 (95% CI 0.003 to 0.06), 8.56%] and medial-lateral [0.05 (95% CI 0.02 to 0.08), 9.19%]), and in dynamic postural stability (time to stability in the anterior-posterior direction [0.64 (95% CI 0.09 to 1.2), 15.82%] and medial-lateral [0.6 (95% CI 0.01 to 1.2), 18.92%]), compared with the control group. In conclusion, The FIFA 11+ injury prevention program may improve static and dynamic postural stability
Microalgal dewatering with focus on filtration and antifouling strategies: A review
No full textDewatering constitutes a major drawback in terms of cost and energy required to concentrate a highly diluted microalgal culture. This has hampered the economic viability of microalgal products. To this end, several technologies have been developed for harvesting microalgal biomass. Membrane technology emerges as one of the preferred harvesting and dewatering technologies in terms of low cost, simplicity of operation, energy demand and biomass recovery rate and efficiency. However, membrane fouling impedes the development and large-scale application of membrane technology. Here, we systematically reviewed and discussed the fouling phenomenon in the microalgal membrane filtration, considering the types and characteristics of foulants, the mechanism of fouling and the factors influencing membrane fouling. The state-of-the art strategies for mitigating membrane fouling are discussed, including cleaning of the fouled membrane, pretreatment of feed solution, optimization of membrane configuration and membrane surface modification. Since membrane fouling is the ultimate barrier in membrane filtration process, enhancing the fouling resistance characteristics of the membrane surface is identified and highlighted as the most promising fouling control strategy. However, more research is needed to develop durable fouling resistant membranes with enhanced stability over a long period of operation
Microbial inoculation to improve plant performance in mine‐waste substrates: A test using pigeon pea (Cajanus cajan)
Get PDFMining activities alter soil physicochemical and biological properties that are critical for plant establishment. Revitalisation of soil biological properties via microbial inoculations can potentially be adopted to improve vegetation restoration. Here, we evaluate the feasibility of using beneficial microorganisms in the form of commercially available inoculants to enhance plant performance in a non-toxic and infertile mine-waste substrate, using pigeon pea [Cajanus cajan (L) Millsp.] as a test plant. Six treatments were established to investigate the effects of inoculants (Bradyrhizobium spp., microbial mix and uninoculated controls) and water availability (low and moderate) in a factorial design over 6 months. Plant performance was determined by physiological parameters (leaf gas exchange, leaf carbon, nitrogen and stable isotopes) and growth (height and biomass). Plant xylem sap phytohormones were measured to determine the plants' physiological status and effects of inoculation treatments. Results revealed that water had a greater effect on plant growth than inoculation treatments. Inoculation treatments, however, improved some physiological parameters. This study suggests that physical conditions such as soil moisture and nutrient availability may occlude more subtle (direct or interactive) effects of beneficial soil microbes on plant growth and plant condition. Prior knowledge on the biological and physicochemical properties of the soil to be amended, and on plant species-specific responses, would be needed to customise microbial inoculants for maximum benefits to ecological restoration, to support future adoption of this practice
Abacavir inhibits but does not cause self-reactivity to HLA-B*57:01-restricted EBV specific T cell receptors
Get PDFPre-existing pathogen-specific memory T cell responses can contribute to multiple adverse outcomes including autoimmunity and drug hypersensitivity. How the specificity of the T cell receptor (TCR) is subverted or seconded in many of these diseases remains unclear. Here, we apply abacavir hypersensitivity (AHS) as a model to address this question because the disease is linked to memory T cell responses and the HLA risk allele, HLA-B*57:01, and the initiating insult, abacavir, are known. To investigate the role of pathogen-specific TCR specificity in mediating AHS we performed a genome-wide screen for HLA-B*57:01 restricted T cell responses to Epstein-Barr virus (EBV), one of the most prevalent human pathogens. T cell epitope mapping revealed HLA-B*57:01 restricted responses to 17 EBV open reading frames and identified an epitope encoded by EBNA3C. Using these data, we cloned the dominant TCR for EBNA3C and a previously defined epitope within EBNA3B. TCR specificity to each epitope was confirmed, however, cloned TCRs did not cross-react with abacavir plus self-peptide. Nevertheless, abacavir inhibited TCR interactions with their cognate ligands, demonstrating that TCR specificity may be subverted by a drug molecule. These results provide an experimental road map for future studies addressing the heterologous immune responses of TCRs including T cell mediated adverse drug reactions
Sire breed, litter size, and environment influence genetic potential for lamb growth when using sire breeding values
Get PDFLamb growth can be optimised with genetic selection using sire Australian sheep breeding values, however, breeding value expression has been shown to be reduced with poor nutrition. It was therefore hypothesised that the genetic potential for lamb growth would also be reduced, where production factors such as multiple births limit growth. Live weights at birth, weaning, and post-weaning were collected from more than 18,000 lambs produced over five years and eight locations of the Sheep Cooperative Research Centre Information Nucleus Flock experiment, and the impact of environment, production factors, and genotype was determined using mixed effects regression. The genetic potential for lamb growth was moderated by environment, multiple births, and sire type (p < 0.05). Twin lambs achieved 76% of the expected weight gain at weaning and 58% post-weaning. For triplet lambs weight gains were drastically less at approximately 30% of the expected gain at the same time points. Lambs born to maternal sires consistently had the poorest response to genetic selection, achieving approximately half the expected weight gain. Hence, producers need to temper expectations for growth based on genetic selection, or employ mitigation strategies such as precision feeding, the use of alternate breeds, or place emphasis on the genetic merit of other desirable traits