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Why did the World not learn lessons from South Ossetia and Abkhazia: Russia’s push into Ukraine?
No full textSince wars begin in the minds of men, it is in the minds of men that the defences of peace must be constructed.
(UNESCO Constitution, 1945
Antisense oligonucleotide induction of the hnRNPA1b isoform affects pre-mRNA splicing of SMN2 in SMA type I fibroblasts
Get PDFSpinal muscular atrophy (SMA) is a severe, debilitating neuromuscular condition characterised by loss of motor neurons and progressive muscle wasting. SMA is caused by a loss of expression of SMN1 that encodes the survival motor neuron (SMN) protein necessary for the survival of motor neurons. Restoration of SMN expression through increased inclusion of SMN2 exon 7 is known to ameliorate symptoms in SMA patients. As a consequence, regulation of pre-mRNA splicing of SMN2 could provide a potential molecular therapy for SMA. In this study, we explored if splice switching antisense oligonucleotides could redirect the splicing repressor hnRNPA1 to the hnRNPA1b isoform and restore SMN expression in fibroblasts from a type I SMA patient. Antisense oligonucleotides (AOs) were designed to promote exon 7b retention in the mature mRNA and induce the hnRNPA1b isoform. RT-PCR and western blot analysis were used to assess and monitor the efficiency of different AO combinations. A combination of AOs targeting multiple silencing motifs in hnRNPA1 pre-mRNA led to robust hnRNPA1b induction, which, in turn, significantly increased expression of full-length SMN (FL-SMN) protein. A combination of PMOs targeting the same motifs also strongly induced hnRNPA1b isoform, but surprisingly SMN2 exon 5 skipping was detected, and the PMO cocktail did not lead to a significant increase in expression of FL-SMN protein. We further performed RNA sequencing to assess the genome-wide effects of hnRNPA1b induction. Some 3244 genes were differentially expressed between the hnRNPA1b-induced and untreated SMA fibroblasts, which are functionally enriched in cell cycle and chromosome segregation processes. RT-PCR analysis demonstrated that expression of the master regulator of these enrichment pathways, MYBL2 and FOXM1B, were reduced in response to PMO treatment. These findings suggested that induction of hnRNPA1b can promote SMN protein expression, but not at sufficient levels to be clinically relevant
Common data elements to standardize genomics studies in cerebral palsy
Get PDFAim
To define clinical common data elements (CDEs) and a mandatory minimum data set (MDS) for genomic studies of cerebral palsy (CP).
Method
Candidate data elements were collated following a review of the literature and existing CDEs. An online, three-round Delphi survey was used to rate each data element as either ‘core’, ‘recommended’, ‘exploratory’, or ‘not required’. Members of the International Cerebral Palsy Genomics Consortium (ICPGC) rated the core CDEs as either mandatory or not, to form the MDS. For both the CDEs and the MDS, a data element was considered to have reached consensus if more than 75% of respondents agreed.
Results
Forty-six individuals from around the world formed the Delphi panel: consumers (n=2), scientists/researchers (n=17), medical (n=19), and allied health professionals (n=8). The CDEs include 107 data elements across six categories: demographics, diagnostics, family history, antenatal and neonatal details, clinical traits, and CP-specific assessments. Of these, 10 are mandatory, 42 core, 41 recommended, and 14 are exploratory.
Interpretation
The ICPGC CDEs provide a foundation for the standardization of phenotype data captured in CP genomic studies and will benefit international collaborations and pooling of data, particularly in rare conditions
Breeding Drought-Tolerant Pearl Millet using conventional and genomic approaches: Achievements and prospects
Get PDFPearl millet [Pennisetum glaucum (L.) R. Br.] is a C4 crop cultivated for its grain and stover in crop-livestock-based rain-fed farming systems of tropics and subtropics in the Indian subcontinent and sub-Saharan Africa. The intensity of drought is predicted to further exacerbate because of looming climate change, necessitating greater focus on pearl millet breeding for drought tolerance. The nature of drought in different target populations of pearl millet-growing environments (TPEs) is highly variable in its timing, intensity, and duration. Pearl millet response to drought in various growth stages has been studied comprehensively. Dissection of drought tolerance physiology and phenology has helped in understanding the yield formation process under drought conditions. The overall understanding of TPEs and differential sensitivity of various growth stages to water stress helped to identify target traits for manipulation through breeding for drought tolerance. Recent advancement in high-throughput phenotyping platforms has made it more realistic to screen large populations/germplasm for drought-adaptive traits. The role of adapted germplasm has been emphasized for drought breeding, as the measured performance under drought stress is largely an outcome of adaptation to stress environments. Hybridization of adapted landraces with selected elite genetic material has been stated to amalgamate adaptation and productivity. Substantial progress has been made in the development of genomic resources that have been used to explore genetic diversity, linkage mapping (QTLs), marker-trait association (MTA), and genomic selection (GS) in pearl millet. High-throughput genotyping (HTPG) platforms are now available at a low cost, offering enormous opportunities to apply markers assisted selection (MAS) in conventional breeding programs targeting drought tolerance. Next-generation sequencing (NGS) technology, micro-environmental modeling, and pearl millet whole genome re-sequence information covering circa 1,000 wild and cultivated accessions have helped to greater understand germplasm, genomes, candidate genes, and markers. Their application in molecular breeding would lead to the development of high-yielding and drought-tolerant pearl millet cultivars. This review examines how the strategic use of genetic resources, modern genomics, molecular biology, and shuttle breeding can further enhance the development and delivery of drought-tolerant cultivars
Editorial
Get PDF‘A new spring, and a new sound’, so begins a famous Dutch poem. Will the birds sing differently, as the poet wishes in the next line? BKI, now 178 years old—surely one of the longest-running journals of Southeast Asian studies in the world, and known around its original home, the KITLV (Royal Institute), as ‘the Old Dame’—starts 2022 with a remarkable new development. For this reason, the first issue of the year opens with an Editorial. After generations of sound and steady editing under the direction of two scholars, one in the role of Chief Editor and one as Managing Editor, from now on, BKI will be run by an expanded editorial team of seven scholars drawn both from the geographical region, Southeast Asia, and the disciplines in the humanities and social sciences that BKI is dedicated to examining..
The association between Alzheimer's Disease-Related markers and physical activity in cognitively normal older adults
Get PDFPrevious studies have indicated that physical activity may be beneficial in reducing the risk for Alzheimer's disease (AD), although the underlying mechanisms are not fully understood. The goal of this study was to evaluate the relationship between habitual physical activity levels and brain amyloid deposition and AD-related blood biomarkers (i.e., measured using a novel high-performance mass spectrometry-based assay), in apolipoprotein E (APOE) ε4 carriers and noncarriers. We evaluated 143 cognitively normal older adults, all of whom had brain amyloid deposition assessed using positron emission tomography and had their physical activity levels measured using the International Physical Activity Questionnaire (IPAQ). We observed an inverse correlation between brain amyloidosis and plasma beta-amyloid (Aβ)1−42 but found no association between brain amyloid and plasma Aβ1−40 and amyloid precursor protein (APP)669−711. Additionally, higher levels of physical activity were associated with lower plasma Aβ1−40, Aβ1−42, and APP669−711 levels in APOE ε4 noncarriers. The ratios of Aβ1−40/Aβ1−42 and APP669−711/Aβ1−42, which have been associated with higher brain amyloidosis in previous studies, differed between APOE ε4 carriers and non-carriers. Taken together, these data indicate a complex relationship between physical activity and brain amyloid deposition and potential blood-based AD biomarkers in cognitively normal older adults. In addition, the role of APOE ε4 is still unclear, and more studies are necessary to bring further clarification
Gut microbiota-testis axis: FMT improves systemic and testicular micro-environment to increase semen quality in type 1 diabetes
Get PDFBackground
Clinical data suggest that male reproductive dysfunction especially infertility is a critical issue for type 1 diabetic patient (T1D) because most of them are at the reproductive age. Gut dysbiosis is involved in T1D related male infertility. However, the improved gut microbiota can be used to boost spermatogenesis and male fertility in T1D remains incompletely understood.
Methods
T1D was established in ICR (CD1) mice with streptozotocin. Alginate oligosaccharide (AOS) improved gut microbiota (fecal microbiota transplantation (FMT) from AOS improved gut microbiota; A10-FMT) was transplanted into the T1D mice by oral administration. Semen quality, gut microbiota, blood metabolism, liver, and spleen tissues were determined to investigate the beneficial effects of A10-FMT on spermatogenesis and underlying mechanisms.
Results
We found that A10-FMT significantly decreased blood glucose and glycogen, and increased semen quality in streptozotocin-induced T1D subjects. A10-FMT improved T1D-disturbed gut microbiota, especially the increase in small intestinal lactobacillus, and blood and testicular metabolome to produce n-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) to ameliorate spermatogenesis and semen quality. Moreover, A10-FMT can improve spleen and liver functions to strengthen the systemic environment for sperm development. FMT from gut microbiota of control animals (Con-FMT) produced some beneficial effects; however, to a smaller extent.
Conclusions
AOS-improved gut microbiota (specific microbes) may serve as a novel, promising therapeutic approach for the improvement of semen quality and male fertility in T1D patients via gut microbiota-testis axis
The impact of occupancy on baseline building energy modelling performance
Get PDFFor promoting energy efficiency practices in the building sector, energy conservation measures are of utmost importance. The energy conservation measures implemented through Energy performance contracting (EPC) are predominantly linked with the performance of baseline building energy models. While occupants are recognized as one of the most important driving factors of energy use in buildings, current research has failed to identify if building occupancy rate can be an influential independent variable to predict baseline energy use in buildings. This research aims to identify the influence of considering occupancy rate as an explanatory variable on the modelling performance of baseline building energy.
Six multivariate machine learning approaches (e.g., linear regression, regression trees, ensembles of trees, Gaussian Process, support vector machine, nonlinear Autoregressive Exogenous model (NARX)) and one univariate (e.g., reformed ten-parameter change point model) inverse modelling approach were employed in the baseline model development process of building heating and cooling energy use and electricity. The specified multivariate baseline modelling approaches were investigated to better isolate the impact of occupancy on building energy performance. NARX outperformed other baseline modelling approaches in terms of model predictive accuracy and data fitting capabilities. On the contrary, the proposed adapted change point model demonstrates the capability of providing operational insight into the case study building.
The hourly fifteen-month worth of energy use data used in baseline models was extracted from the building management system (BMS) server of a real case study building. The prediction period was defined as the most recent six months of the available data representing the COVID lockdown period. The models were trained using the nine-month worth of data that immediately preceded the prediction period. The arrangement of different input parameters selected by a forward sequential feature selection approach was considered an important step to identify the influence of individual parameters on baseline energy use. The influence of occupancy on the accuracy of baseline models was quantitively evaluated from this analysis. The results show that baseline model performance slightly improves when occupancy data are considered as an explanatory variable. However, occupancy data can significantly influence the performance of a baseline energy use model in an occupant-centric building. The assessment of hourly energy data and associated occupancy data for the case study building indicates the necessity of implementing occupant-centric control strategies to improve its energy performance
Bayesian modelling reveals differences in long-term trends in the harvest of native and introduced species by recreational hunters in Australia
Get PDFContext: Little is known about wildlife harvesting by licensed recreational hunters in Australia, where both native and introduced species are hunted. It is important to understand harvest trends to assess sustainability for native species and implications for population control of introduced species.
Aim: The aim of this study was to analyse trends in hunter participation, activity and efficiency, and wildlife harvest, including effects of climate, in Victoria, Australia, for three game species groups: introduced deer, native waterfowl (ducks) and one native grassland species, stubble quail (Coturnix pectoralis).
Methods: Telephone surveys of a random sample of licenced Victorian hunters were performed annually from 2009 to 2019. Hunters were asked to quantify their hunting effort and the number of animals harvested. The respondents’ answers were analysed to estimate measures of hunter success, activity and efficiency. Bayesian modelling was applied to these data, accounting for changes over time, differences between survey periods for all licence types, and random effects for over-dispersion. The effect of climate on game bird hunter activity and harvest was estimated, as measured by the El Niño-Southern Oscillation (ENSO).
Results: Over 11 years, annual deer harvest (all species) increased exponentially, at a mean annual rate of 17% (95% credible interval: 14–21%), and the number of deer hunters increased at 8% (5–11%). In contrast, for ducks and stubble quail, hunter numbers remained relatively unchanged, with no evidence of consistent change to total harvests over time, unrelated to changes in environmental conditions or regulations. The annual duck harvest was influenced by ENSO and hunting regulations. The annual stubble quail harvest exhibited ‘boom-and-bust’ dynamics, with an exceptionally large harvest immediately after a La Niña season.
Conclusions: Long-term monitoring of harvest trends in south-eastern Australia revealed stark differences between introduced deer and native birds: harvest of deer increased rapidly whereas equivalent rates for game birds were either stable or declining. Seasonal effects had a strong influence on game bird harvest. Environmental and regulatory conditions were influential for harvest outcomes for ducks and stubble quail.
Implications: This study filled a key knowledge gap around managing harvesting of game species, but increased scrutiny is warranted in this field
Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume
Get PDFThe concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-β PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Significant associations were observed between age acceleration using the Hannum epigenetic clock and cross-sectional hippocampal volume in AIBL and replicated in ADNI. In AIBL, several other findings were observed cross-sectionally, including a significant association between hippocampal volume and the Hannum and Phenoage epigenetic clocks. Further, significant associations were also observed between hippocampal volume and the Zhang and Phenoage epigenetic clocks within Amyloid-β positive individuals. However, these were not validated within the ADNI cohort. No associations between age acceleration and other Alzheimer’s disease-related phenotypes, including measures of cognition or brain Amyloid-β burden, were observed, and there was no association with longitudinal change in any phenotype. This study presents a link between age acceleration, as determined using DNA methylation, and hippocampal volume that was statistically significant across two highly characterised cohorts. The results presented in this study contribute to a growing literature that supports the role of epigenetic modifications in ageing and AD-related phenotypes