19683 research outputs found
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Archetypal clustering reveals physiological mechanisms linking milk yield and fertility in dairy cattle
No full textFertility in dairy cattle has declined as an unintended consequence of single-trait selection for high milk yield. The unfavorable genetic correlation between milk yield and fertility is now well documented; however, the underlying physiological mechanisms are still uncertain. To understand the relationship between these traits, we developed a method that clusters variants with similar patterns of effects and, after the integration of gene expression data, identifies the genes through which they are likely to act. Biological processes that are enriched in the genes of each cluster were then identified. We identified several clusters with unique patterns of effects. One of the clusters included variants associated with increased milk yield and decreased fertility, where the “archetypal” variant (i.e., the one with the largest effect) was associated with the GC gene, whereas others were associated with TRIM32, LRRK2, and U6-associated snRNA. These genes have been linked to transcription and alternative splicing, suggesting that these processes are likely contributors to the unfavorable relationship between the 2 traits. Another cluster, with archetypal variant near DGAT1 and including variants associated with CDH2, BTRC, SFRP2, ZFHX3, and SLITRK5, appeared to affect milk yield but have little effect on fertility. These genes have been linked to insulin, adipose tissue, and energy metabolism. A third cluster with archetypal variant near ZNF613 and including variants associated with ROBO1, EFNA5, PALLD, GPC6, and PTPRT were associated with fertility but not milk yield. These genes have been linked to GnRH neuronal migration, embryonic development, or ovarian function. The use of archetypal clustering to group variants with similar patterns of effects may assist in identifying the biological processes underlying correlated traits. The method is hypothesis generating and requires experimental confirmation. However, we have uncovered several novel mechanisms potentially affecting milk production and fertility such as GnRH neuronal migration. We anticipate our method to be a starting point for experimental research into novel pathways, which have been previously unexplored within the context of dairy production
Using major ions and stable isotopes to improve conceptualisation of a spring-aquifer system in the Galilee Basin, Australia
No full textDeveloping conceptual models is a critical step in hydrogeological studies that should utilise multiple lines of evidence and data types to minimise conceptual uncertainty, particularly in data-sparse systems. This study used new and existing major ion and isotope (O, H, Sr, C) data sets to refine a previous hydraulic-head-based conceptual model of the Galilee Basin (Australia). The analyses provide evidence for the locations of recharge and discharge areas and determine hydrochemical processes along flow paths to improve understanding of potential source waters to the Doongmabulla Springs Complex (DSC) and to infer mixing within, or exchange between aquifer units. There was good agreement between previously inferred recharge and discharge areas defined using hydraulic head data and interpretations from hydrochemical evolution along groundwater flow pathways, at least where data were available. Major ion and isotope data suggest that the DSC likely receives water from both a relatively shallow, local flow path and a deeper regional flow path. This observation is relevant to previous concerns about threats to the DSC, as mine-induced drawdown may impact the relative contributions to spring discharge from different recharge sources and aquifers. Silicate weathering in the deeper Clematis Formation and Dunda Beds, and evapotranspiration in the overlying Moolayember Formation have strong control on the total dissolved solids content. These findings suggest that the Clematis Formation and Dunda Beds are hydrochemically distinct from the Moolayember Formation, with limited exchange between these aquifers, which has important implications for model conceptualisation and ongoing monitoring of mining activities in the Galilee Basin
Harm from the drinking of people you know: A range of effects from different relationships
No full textAims: To describe the range of effects experienced due to the drinking of people respondents know and analyze risk and protective factors for harm from the drinking of partners and household members, other relatives and friends and co-workers. Design, setting and participants: Surveys of 2574 participants' experiences were obtained from two samples: 1000 people responded to random digitally dialled Australian mobile calls and 1574 participants responded from the Life in AustraliaTM panel survey. Measurements: Respondents were asked whether they had been negatively affected in the previous 12 months by the drinking of persons they knew who were ‘a heavy drinker or drank a lot sometimes’ and the nature of these harms. Weighted logistic regressions were used to analyze differences in rates of key negative outcomes from known others' drinking by gender, age and socio-economic status. Findings: Almost two thirds [60.2%; 95% confidence interval (CI) = 57.7%–62.7%] of participants reported having heavy drinkers in their lives and 21.8% (95% CI = 19.8%–23.9%) reported being negatively affected by the drinking of people they knew well in some way. Participants reported a gamut of effects, including, most commonly, adverse social effects: having to transport relatives and friends who had been drinking, role failure and faults, being emotionally hurt or neglected, serious arguments, family problems, having to care for drinkers and verbal abuse. Less commonly, respondents reported physical or sexual harm, property damage, financial stress and threats from others' drinking. Women (odds ratio = 1.49; 95% CI = 1.13–1.95), younger people, rural, Australian-born (vs. respondents born overseas in non-English speaking countries) and more frequent drinkers were more likely to report harm from a drinker they knew than their counterparts after adjusting for other variables in the model. Conclusions: Australians appear to be commonly adversely affected by the drinking of people they know. Harms from known drinkers are more likely to be experienced by women than men, particularly from the people they live with and other relatives
The cytopathological mechanisms caused by DJ-1 loss in the D. discoideum Parkinson’s disease model
No full textA thesis submitted in total fulfillment of the requirements for the degree of Doctor of Philosophy to the School of Agriculture, Biomedicine and Environment, La Trobe University, Victoria, Australia.</p
Combination of bazedoxifene with chemotherapy and SMAC-mimetics for the treatment of colorectal cancer
No full textExcessive STAT3 signalling via gp130, the shared receptor subunit for IL-6 and IL-11, contributes to disease progression and poor survival outcomes in patients with colorectal cancer. Here, we provide evidence that bazedoxifene inhibits tumour growth via direct interaction with the gp130 receptor to suppress IL-6 and IL-11-mediated STAT3 signalling. Additionally, bazedoxifene combined with chemotherapy synergistically reduced cell proliferation and induced apoptosis in patient-derived colon cancer organoids. We elucidated that the primary mechanism of anti-tumour activity conferred by bazedoxifene treatment occurs via pro-apoptotic responses in tumour cells. Co-treatment with bazedoxifene and the SMAC-mimetics, LCL161 or Birinapant, that target the IAP family of proteins, demonstrated increased apoptosis and reduced proliferation in colorectal cancer cells. Our findings provide evidence that bazedoxifene treatment could be combined with SMAC-mimetics and chemotherapy to enhance tumour cell apoptosis in colorectal cancer, where gp130 receptor signalling promotes tumour growth and progression.</p
Epidemiology of time-loss injuries within an Australian male professional football club: A 5-year prospective observational study of 21,343 player hours
No full textThis study aimed to establish injury incidence rates (IIRs) and burden within an Australian male professional football club (n = 73) and to investigate longitudinal trends across five consecutive seasons (2016/17–2020/21). There was an overall IIR of 9.18 injuries per 1000 hours (h) (95% CI [7.89, 10.47]). The IIR was approximately seven times greater (rate ratio (RR): 6.85; 95% CI [5.13, 9.19]; p </p
Formation of Strong Boron Lewis Acid Sites on Silica
No full textBis(1-methyl-ortho-carboranyl)borane (HBMeoCb2) is a very strong Lewis acid that reacts with the isolated silanols present on silica partially dehydroxylated at 700 °C (SiO2‑700) to form the well-defined Lewis site MeoCb2B(OSi≡) (1) and H211B{1H} magic-angle spinning (MAS) nuclear magnetic resonance (NMR) data of 1 are consistent with that of a three-coordinate boron site. Contacting 1 with O͇PEt3 (triethylphosphine oxide TEPO) and measuring 31P{1H} MAS NMR spectra show that 1 preserves the strong Lewis acidity of HBMeoCb2. Hydride ion affinity and fluoride ion affinity calculations using small molecules analogs of 1 also support the strong Lewis acidity of the boron sites in this material. Reactions of 1 with Cp2Hf(13CH3)2 show that the Lewis sites are capable of abstracting methide groups from Hf to form [Cp2Hf−13CH3][H313C− B(MeoCb2)OSi≡], but with a low overall efficiency
Assessing infection prevention and control programs in residential aged care in Australia: A multi‐methods cross‐sectional study
No full textAim: To assess infection prevention and control programs in residential aged care facilities. Methods: A cross-sectional survey and structured interviews from 10 residential aged care facilities in Victoria, Australia, were used. Infection prevention and control nurse leads from each facility completed a purpose-built survey based on best practice infection prevention control program core components, including staff training, policies and procedures, governance, and surveillance. Follow-up interviews with residential aged care staff, residents and family visitors were carried out to elaborate and verify survey data. Results: Surveys from all 10 facilities were received and 75 interviews carried out. All facilities had an infection prevention and control lead nurse who had undergone additional training, and 60% of facilities had an infection prevention and control lead position description. All facilities had a committee to oversee their infection prevention and control program, and all had policies and procedures for standard and transmission-based precautions. One facility did not have a policy on healthcare-associated infection surveillance, and two facilities did not have an antimicrobial stewardship policy. All facilities provided staff training in hand hygiene and personal protective equipment use, but not all routinely assessed competency in these. Conclusions: The residential aged care facilities' infection prevention and control programs were generally in a strong position, although there were some areas that require improvement. Further assessment of the quality of infection prevention and control program components, such as content of education and training, and policies and procedures, and ongoing evaluation of programs is recommended. </p
An Actualistic Experimental Study of Giant Quartzite Core Reduction Strategies: Implications for Large Flake Blank Production and Handaxe Manufacture at Amanzi Springs, South Africa
No full textThe later Acheulian assemblages (ca. 534–</p
Evaluating models for estimating introduction rates of alien species from discovery records
No full textAim: Reducing the rate of alien species introductions is a major conservation aim. However, accurately quantifying the rate at which species are introduced into new regions remains a challenge due to the confounding effect of observation efforts on discovery records. Despite the recognition of this issue, most analyses are still based on raw discovery records, leading to biased inferences. In this study, we evaluate different models for estimating introduction rates, including new models that use auxiliary data on observation effort, and identify their strengths and weaknesses. Innovation: We compare four models: (1) a naïve model which assumes perfect detection; (2) a model proposed by Solow and Costello (the S&C model); (3) constant detection model: a modified version of the S&C model with constant detection probabilities and (4) a novel sampling proxy model: a model that uses external data on observation effort. We simulate discovery records of varying lengths, introduction rates and temporal patterns of detection probabilities to explore scenarios under which these models accurately estimate underlying introduction rates. (5) We also include code to perform a model based on Belmaker using independent data on the number of native species. Main conclusion: We found that the length of the discovery records and the annual number of recorded species play a crucial role in the performance of all models. Under simulated scenarios of high detection, the naïve model is usually the best-performing model, but it falls short when detection is low. Moreover, we find that in simulations which most likely mimic most real-world cases (i.e. non-monotonic probability of detection), incorporating external data on observation effort using the sampling proxy model, substantially improve estimates. This highlights the importance of considering observation effort when estimating introduction rates of alien species. To facilitate the use of these models, we provide a decision workflow and a dedicated R package (‘alien’).</p