Sex and gender analysis improves science and engineering.

The goal of sex and gender analysis is to promote rigorous, reproducible and responsible science. Incorporating sex and gender analysis into experimental design has enabled advancements across many disciplines, such as improved treatment of heart disease and insights into the societal impact of algorithmic bias. Here we discuss the potential for sex and gender analysis to foster scientific discovery, improve experimental efficiency and enable social equality. We provide a roadmap for sex and gender analysis across scientific disciplines and call on researchers, funding agencies, peer-reviewed journals and universities to coordinate efforts to implement robust methods of sex and gender analysis.

Identifying biochemical changes in the kidney using proton nuclear magnetic resonance in an adenine diet chronic kidney disease mouse model.

This study aimed to investigate the metabolic changes in the kidneys in a murine adenine-diet model of chronic kidney disease (CKD). Kidney fibrosis is the common pathological manifestation across CKD aetiologies. Sustained inflammation and fibrosis cause changes in preferred energy metabolic pathways in the cells of the kidney. Kidney cortical tissue from mice receiving a control or adenine-supplemented diet for 8 weeks (late inflammation and fibrosis) and 12 weeks (8 weeks of treatment followed by 4 weeks recovery) were analysed by 2D-correlated nuclear magnetic resonance spectroscopy and compared with histopathology and biomarkers of kidney damage. Tissue metabolite and lipid levels were assessed using the MestreNova software. Expression of genes related to inflammation, fibrosis, and metabolism were measured using quantitative polymerase chain reaction. Animals showed indicators of severely impaired kidney function at 8 and 12 weeks. Significantly increased fibrosis was present at 8 weeks but not in the recovery group suggesting some reversal of fibrosis and amelioration of inflammation. At 8 weeks, metabolites associated with glycolysis were increased, while lipid signatures were decreased. Genes involved in fatty acid oxidation were decreased at 8 weeks but not 12 weeks while genes associated with glycolysis were significantly increased at 8 weeks but not at 12 weeks. In this murine model of CKD, kidney fibrosis was associated with the accumulation of triglyceride and free lactate. There was an up-regulation of glycolytic enzymes and down-regulation of lipolytic enzymes. These metabolic changes reflect the energy demands associated with progressive kidney disease where there is a switch from fatty acid oxidation to that of glycolysis.

Heat hardening improves thermal tolerance in abalone, without the trade-offs associated with chronic heat exposure.

Marine animals are challenged by chronically raised temperatures alongside an increased frequency of discrete, severe warming events. Exposure to repeated heat shocks could result in heat hardening, where sub-lethal exposure to thermal stress temporarily enhances thermotolerance, and may be an important mechanism by which marine species will cope with future thermal challenges. However, we have relatively little understanding of the effects of heat hardening in comparison to chronic exposure to elevated temperatures. Therefore, we compared the effects of heat hardening from repeated exposure to acute heat shocks and chronic exposure to elevated temperatures on thermal tolerance in the European abalone, Haliotis tuberculata. Adult abalones were exposed to either control temperature (15 °C), chronic warming (20 °C) or a regime of two events of repeated acute heat shock cycles (23-25 °C) during six months, and their thermal tolerance and performance, based upon cardiac activity, compared using a dynamic ramping assay. The cost associated with each treatment was also estimated via measurements of condition index (CI). Abalone exposed to both temperature treatments had higher upper thermal limits than the control, but heat-hardened individuals had significantly higher CI values, indicating an enhancement in condition status. Differences in the shape of the thermal performance curve suggest different mechanisms may be at play under different temperature exposure treatments. We conclude that heat hardening can boost thermal tolerance in this species, without performance trade-offs associated with chronic warming.

Factors associated with hospitalisations and deaths of residential aged care residents with COVID-19 during the Omicron (BA.1) wave in Queensland.

OBJECTIVE: To identify characteristics associated with the hospitalisation and death of people with COVID-19 living in residential aged care facilities (RACFs). DESIGN: Retrospective cohort study. SETTING, PARTICIPANTS: All confirmed (polymerase chain reaction testing) or probable SARS-CoV-2 infections (rapid antigen tests) in residents of the 86 RACFs in the Metro South Hospital and Health Service area (southeast Queensland), 13 December 2021 - 24 January 2022. MAIN OUTCOME MEASURES: Hospitalisation within 14 days or death within 28 days of COVID-19 diagnosis. RESULTS: Of 1071 RACF residents with COVID-19, 151 were hospitalised within 14 days and 126 died within 28 days of diagnosis. Likelihood of death increased with age (per five years: adjusted odds ratio [aOR], 1.38; 95% confidence interval [CI], 1.21-1.57), but not that of hospitalisation. Men were more likely to be hospitalised (aOR, 1.7; 95% CI, 1.2-2.4) or die (aOR, 2.5; 95% CI, 1.7-3.6) than women. The likelihood of hospitalisation was greater for those with dementia (aOR, 1.9; 95% CI, 1.2-3.0), heart failure (aOR, 1.7; 95% CI, 1.1-2.7), chronic kidney disease (aOR, 1.7; 95% CI, 1.1-2.5), or asthma (aOR, 2.2; 95% CI, 1.2-3.8). The likelihood of death was greater for residents with dementia (aOR, 2.2; 95% CI, 1.3-3.7), diabetes mellitus (aOR, 1.9; 95% CI, 1.3-3.0), heart failure (aOR, 2.0; 95% CI, 1.1-3.3), or chronic lung disease (aOR, 1.7; 95% CI, 1.1-2.7). The likelihood of hospitalisation and death were each higher for residents who had received two or fewer vaccine doses than for those who had received three doses. CONCLUSIONS: Most characteristics that influenced the likelihood of hospitalisation or death of RACF residents with COVID-19 were non-modifiable factors linked with frailty and general health status. Having received three COVID-19 vaccine doses was associated with much lower likelihood of hospitalisation or death.

Relationship between cortical and medullary thickness and glomerular filtration rate among living kidney donors.

The relationship between the kidney cortex and medulla is not well understood in healthy populations. This study characterised the relationship between cortical/medullary thickness and measured glomerular filtration rate (GFR) in 390 living kidney donors. A positive relationship was observed between medullary, but not cortical, thickness and GFR. We propose that this reflects a correlation between juxtamedullary nephron number and GFR.

Self-reported and digital-trace measures of computer science students' self-regulated learning in blended course designs.

This study investigated the extent to which self-report and digital-trace measures of students' self-regulated learning in blended course designs align with each other amongst 145 first-year computer science students in a blended "computer systems" course. A self-reported Motivated Strategies for Learning Questionnaire was used to measure students' self-efficacy, intrinsic motivation, test anxiety, and use of self-regulated learning strategies. Frequencies of interactions with six different online learning activities were digital-trace measures of students' online learning interactions. Students' course marks were used to represent their academic performance. SPSS 28 was used to analyse the data. A hierarchical cluster analysis using self-reported measures categorized students as better or poorer self-regulated learners; whereas a hierarchical cluster analysis using digital-trace measures clustered students as more active or less active online learners. One-way ANOVAs showed that: 1) better self-regulated learners had higher frequencies of interactions with three out of six online learning activities than poorer self-regulated learners. 2) More active online learners reported higher self-efficacy, higher intrinsic motivation, and more frequent use of positive self-regulated learning strategies, than less active online learners. Furthermore, a cross-tabulation showed significant (p < .01) but weak association between student clusters identified by self-reported and digital-trace measures, demonstrating self-reported and digital-trace descriptions of students' self-regulated learning experiences were consistent to a limited extent. To help poorer self-regulated learners improve their learning experiences in blended course designs, teachers may invite better self-regulated learners to share how they approach learning in class.

Explaining medical students' learning outcomes in blended course designs: combining self-reported and observational learning experiences.

Blended course designs have been increasingly adopted in medical education. However, research on the relations between the key aspects of students' learning experience and their learning outcomes often only measures students' self-reported experience, neglecting what they actually do in learning. This study combined both self-reported and observational measures of students' learning experiences and examined the relations between the two sets of measures and their contributions to learning outcomes. Australian medical students were asked to report their approaches to, and perceptions of, learning. The frequency and duration of their interactions with both online formative and summative tasks were observed and recorded. Correlation analyses showed that the learning outcome was positively related to deep approaches to using online technologies and duration of interactions with online summative tasks. The hierarchical multiple regression analysis found that the self-reported approaches and duration of interactions jointly explained the learning outcomes, accounting for 6% of the variance. The study demonstrated the complementary nature of using both self-reported and observational measures of students' learning experiences to explain the learning outcomes in blended course designs.

Sensor Verification and Analytical Validation of Algorithms to Measure Gait and Balance and Pronation/Supination in Healthy Volunteers.

Numerous studies have sought to demonstrate the utility of digital measures of motor function in Parkinson's disease. Frameworks, such as V3, document digital measure development: technical verification, analytical and clinical validation. We present the results of a study to (1) technically verify accelerometers in an Apple iPhone 8 Plus and ActiGraph GT9X versus an oscillating table and (2) analytically validate software tasks for walking and pronation/supination on the iPhone plus passively detect walking measures with the ActiGraph in healthy volunteers versus human raters. In technical verification, 99.4% of iPhone and 91% of ActiGraph tests show good or excellent agreement versus the oscillating table as the gold standard. For the iPhone software task and algorithms, intraclass correlation coefficients (ICCs) > 0.75 are achieved versus the human raters for measures when walking distance is >10 s and pronation/supination when the arm is rotated more than two times. Passively detected walking start and end time was accurate to approx. 1 s and walking measures were accurate to one unit, e.g., one step. The results suggest that the Apple iPhone and ActiGraph GT9X accelerometers are fit for purpose and that task and passively collected measures are sufficiently analytically valid to assess usability and clinical validity in Parkinson's patients.

Allograft failure in kidney transplant recipients who developed kidney failure secondary to ANCA-associated vasculitis.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides are uncommon causes of kidney failure. In kidney transplant recipients who developed kidney failure secondary to ANCA-associated vasculitis, disease recurrence is unlikely due to ongoing immunosuppression, and patients generally have good immunological outcomes. This study compared transplant outcomes between ANCA-associated vasculitis and other etiologies of kidney disease. All 18 901 adult kidney transplant recipients (1990-2018) were ascertained from the ANZDATA Registry. Cox proportional hazards models were used to compare allograft failure between etiologies of kidney disease. Of 254 participants whose primary disease was ANCA-associated vasculitis, 95 (37%) developed allograft failure; of those who developed graft failure, 62 (65%) died with a functioning allograft. Compared with patients with IgA nephropathy, those with ANCA-associated vasculitis had higher rates of all-cause allograft failure (HR: 1.4, 95% CI: 1.2-1.7); however, rates of death-censored allograft failure were similar (HR: 1.0, 95% CI: 0.7-1.4). The most frequent causes of death in the ANCA-vasculitis group who died with a functioning graft were infection (23%) and malignancy (36%). Kidney transplant recipients who developed kidney failure secondary to ANCA-associated vasculitis may have had a higher risk of dying due to complications of immunosuppression compared with most other causes of kidney failure; however, they also had lower risks of disease recurrence and rejection.

Configurations of collaborations based on learning orientations amongst medical students.

While collaboration is an important and key attribute for medical students in order to prepare them to perform well in health care teams, how to effectively develop and assess such skills is challenging. The current widespread practice of using Likert-scale questionnaire only to measure the quantity of collaboration at course and/or program level appears to be insufficient to provide an evidence-base for what counts desirable collaborative learning experience. Drawing on research into student approaches to learning and social network analysis, this study investigates differences in collaborative learning configurations amongst 217 Australian medical students. Based on students' learning orientations (i.e., 'understanding' and 'reproducing') and their choice of collaborations (i.e., whether to collaborate or not, with whom to collaborate, and mode of collaboration), the analyses found five configurations of collaborations differing in a number of features. The most desirable collaborative experience was a configuration of collaborations formed by students with an 'understanding' orientation. This configuration revealed a strong tendency towards intensive pair work with measurable differences in how easy and effectively they collaborated. The results of the study not only have practical implications for teaching and curriculum design for collaborative learning, but also have significant implications for assessing students' collaborative learning experiences.

How do abiotic environmental conditions influence shrimp susceptibility to disease? A critical analysis focussed on White Spot Disease.

White Spot Syndrome Virus (WSSV) causes White Spot Disease (WSD) and is historically the most devastating disease in the shrimp industry. Global losses from this disease have previously exceeded $3 bn annually, having a major impact on a global industry worth US$19 bn per annum. Shrimp are cultured predominantly in enclosed ponds that are subject to considerable fluctuations in abiotic conditions and WSD outbreaks are increasingly linked to periods of extreme weather, which may cause major fluctuations in pond culture conditions. Combined with the intensity of production in these systems, the resulting suboptimal physicochemical conditions have a major bearing on the susceptibility of shrimp to infection and disease. Current knowledge indicates that pond temperature and salinity are major factors determining outbreak severity. WSSV appears to be most virulent in water temperatures between 25 and 28 °C and salinities far removed from the isoosmotic point of shrimp. Elevated temperatures (>30 °C) may protect against WSD, depending on the stage of infection, however the mechanisms mediating this effect have not been well established. Other factors relating to water quality that may play key roles in determining outbreak severity include dissolved oxygen concentration, nitrogenous compound concentration, partial pressure of carbon dioxide and pH, but data on their impacts on WSSV susceptibility in cultured shrimps is scarce. This illustrates a major research gap in our understanding of the influence of environmental conditions on disease. For example, it is not clear whether temperature manipulations can be used effectively to prevent or mitigate WSD in cultured shrimp. Therefore, developing our understanding of the impact of environmental conditions on shrimp susceptibility to WSSV may provide insight for WSD mitigation when, even after decades of research, there is no effective practical prophylaxis or treatment.

A Simple Clinical Tool for Stratifying Risk of Clinically Significant CKD after Nephrectomy: Development and Multinational Validation.

BACKGROUND: Clinically significant CKD following surgery for kidney cancer is associated with increased morbidity and mortality, but identifying patients at increased CKD risk remains difficult. Simple methods to stratify risk of clinically significant CKD after nephrectomy are needed. METHODS: To develop a tool for stratifying patients' risk of CKD arising after surgery for kidney cancer, we tested models in a population-based cohort of 699 patients with kidney cancer in Queensland, Australia (2012-2013). We validated these models in a population-based cohort of 423 patients from Victoria, Australia, and in patient cohorts from single centers in Queensland, Scotland, and England. Eligible patients had two functioning kidneys and a preoperative eGFR ≥60 ml/min per 1.73 m2. The main outcome was incident eGFR <45 ml/min per 1.73 m2 at 12 months postnephrectomy. We used prespecified predictors-age ≥65 years old, diabetes mellitus, preoperative eGFR, and nephrectomy type (partial/radical)-to fit logistic regression models and grouped patients according to degree of risk of clinically significant CKD (negligible, low, moderate, or high risk). RESULTS: Absolute risks of stage 3b or higher CKD were <2%, 3% to 14%, 21% to 26%, and 46% to 69% across the four strata of negligible, low, moderate, and high risk, respectively. The negative predictive value of the negligible risk category was 98.9% for clinically significant CKD. The c statistic for this score ranged from 0.84 to 0.88 across derivation and validation cohorts. CONCLUSIONS: Our simple scoring system can reproducibly stratify postnephrectomy CKD risk on the basis of readily available parameters. This clinical tool's quantitative assessment of CKD risk may be weighed against other considerations when planning management of kidney tumors and help inform shared decision making between clinicians and patients.

Haemodialysis withdrawal in Australia and New Zealand: a binational registry study.

BACKGROUND: Withdrawal from dialysis is an increasingly common cause of death in patients with end-stage kidney disease (ESKD). As most published reports of dialysis withdrawal have been outside the Oceania region, the aims of this study were to determine the frequency, temporal pattern and predictors of dialysis withdrawal in Australian and New Zealand patients receiving chronic haemodialysis. METHODS: This study included all people with ESKD in Australia and New Zealand who commenced chronic haemodialysis between 1 January 1997 and 31 December 2016, using data from the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry. Competing risk regression models were used to identify predictors of dialysis withdrawal mortality, using non-withdrawal cause of death as the competing risk event. RESULTS: Among 40 447 people receiving chronic haemodialysis (median age 62 years, 61% male, 9% Indigenous), dialysis withdrawal mortality rates increased from 1.02 per 100 patient-years (11% of all deaths) during the period 1997-2000 to 2.20 per 100 patient-years (32% of all deaths) during 2013-16 (P < 0.001). Variables that were significantly associated with a higher likelihood of haemodialysis withdrawal were older age {≥70 years subdistribution hazard ratio [SHR] 1.77 [95% confidence interval (CI) 1.66-1.89]; reference 60-70 years}, female sex [SHR 1.14 (95% CI 1.09-1.21)], white race [Asian SHR 0.56 (95% CI 0.49-0.65), Aboriginal and Torres Strait Islander SHR 0.83 (95% CI 0.74-0.93), Pacific Islander SHR 0.47 (95% CI 0.39-0.68), reference white race], coronary artery disease [SHR 1.18 (95% CI 1.11-1.25)], cerebrovascular disease [SHR 1.15 (95% CI 1.08-1.23)], chronic lung disease [SHR 1.13 (95% CI 1.06-1.21)] and more recent era [2013-16 SHR 3.96 (95% CI 3.56-4.48); reference 1997-2000]. CONCLUSIONS: Death due to haemodialysis withdrawal has become increasingly common in Australia and New Zealand over time. Predictors of haemodialysis withdrawal include older age, female sex, white race and haemodialysis commencement in a more recent era.

High Failure Rates for Unicompartmental Knee Arthroplasty in Morbidly Obese Patients: A Two-Year Minimum Follow-Up Study.

BACKGROUND: Several recent studies have recommended offering unicompartmental knee arthroplasty (UKA) to all patients regardless of body mass index (BMI). The aim of this investigation was to evaluate the proposition that UKA can indeed be offered to the morbidly-obese and super-obese (morbidly-obese, BMI ≥ 40 kg/m2) without compromising results or survivorship. METHODS: We retrospectively reviewed mobile-bearing medial UKA procedures performed at our facility from January 2012 to May 2015 with a minimum of 2-year follow-up. The study cohort was divided into patients with morbid obesity (BMI ≥ 40 kg/m2) and those without morbid obesity (BMI < 40 kg/m2). A detailed medical record review was performed. Extracted outcome data included the frequency of (1) major revision procedures (components revised), (2) minor secondary procedures (components not revised), (3) infection procedures, and (4) recommendations for revision. RESULTS: We found 152 patients (190 knees) who met criteria for inclusion. Mean follow-up duration was 3.4 years (range: 2.0-6.8 years). Major revision surgery occurred more frequently in the morbid-obesity UKA group (15.7% vs 3.0%, P < .01). Rates of minor secondary surgery and infection were comparable for both groups. Most failures in the morbid-obesity UKA group (85.7%) were due to disease progression involving other compartments or mobile-bearing instability. CONCLUSION: We found the rate of early major revision surgery in morbidly-obese patients undergoing UKA to be over 5-times greater than that of other patients. Failure was predominantly due to disease progression in other compartments or mobile-bearing instability. Further study is warranted and needed before expanding UKA indications to the morbidly-obese population.

The myth of school shooters and psychotropic medications.

There has been an assertion in certain parts of the media, especially social media, that the majority of individuals who have engaged in a school shooting were prescribed psychotropic medications prior to the event. To determine if there is any validity to this assertion, the authors of this article reviewed publicly available information regarding individuals involved in "educational shootings" per FBI publications for active shooters from 2000 to 2017. Sources of information included news reports with official citations, official reports regarding events, available court records, and FBI Freedom of Information Act requests. Secondary data-points were also collected, such as location, number of weapons used, number of victims, legal outcome, and whether the shooter committed suicide. From the information obtained, it appears that most school shooters were not previously treated with psychotropic medications - and even when they were, no direct or causal association was found.

Age-related differences in binaural masking level differences: behavioral and electrophysiological evidence.

The effects of aging and stimulus configuration on binaural masking level differences (BMLDs) were measured behaviorally and electrophysiologically, using the frequency-following response (FFR) to target brainstem/midbrain encoding. The tests were performed in 15 younger normal-hearing (<30 yr) and 15 older normal-hearing (>60 yr) participants. The stimuli consisted of a 500-Hz target tone embedded in a narrowband (50-Hz bandwidth) or wideband (1,500-Hz bandwidth) noise masker. The interaural phase conditions included NoSo (tone and noise presented interaurally in-phase), NoSπ (noise presented interaurally in-phase and tone presented out-of-phase), and NπSo (noise presented interaurally out-of-phase and tone presented in-phase) configurations. In the behavioral experiment, aging reduced the magnitude of the BMLD. The magnitude of the BMLD was smaller for the NoSo-NπSo threshold difference compared with the NoSo-NoSπ threshold difference, and it was also smaller in narrowband compared with wideband conditions, consistent with previous measurements. In the electrophysiology experiment, older participants had reduced FFR magnitudes and smaller differences between configurations. There were significant changes in FFR magnitude between the NoSo to NoSπ configurations but not between the NoSo to NπSo configurations. The age-related reduction in FFR magnitudes suggests a temporal processing deficit, but no correlation was found between FFR magnitudes and behavioral BMLDs. Therefore, independent mechanisms may be contributing to the behavioral and neural deficits. Specifically, older participants had higher behavioral thresholds than younger participants for the NoSπ and NπSo configurations but had equivalent thresholds for the NoSo configuration. However, FFR magnitudes were reduced in older participants across all configurations. NEW & NOTEWORTHY Behavioral and electrophysiological testing reveal an aging effect for stimuli presented in wideband and narrowband noise conditions, such that behavioral binaural masking level differences and subcortical spectral magnitudes are reduced in older compared with younger participants. These deficits in binaural processing may limit the older participant's ability to use spatial cues to understand speech in environments containing competing sound sources.

Predictors of new-onset chronic kidney disease in patients managed surgically for T1a renal cell carcinoma: An Australian population-based analysis.

BACKGROUND: New-onset chronic kidney disease (CKD) following surgical management of kidney tumors is common. This study evaluated risk factors for new-onset CKD after nephrectomy for T1a renal cell carcinoma (RCC) in an Australian population-based cohort. METHODS: There were 551 RCC patients from the Australian states of Queensland and Victoria included in this study. The primary outcome was new-onset CKD (eGFR <60 mL/min per 1.73 m2 ) and the secondary outcome was new-onset moderate-severe CKD (<45 mL/min per 1.73 m2 ). Multivariable logistic regression was used to evaluate associations between patient, tumor and health-service characteristics and these outcomes. RESULTS: Forty percent (219/551) of patients developed new-onset CKD, and 12% (68/551) experienced new-onset moderate-severe CKD. Risk factors for new-onset CKD were age, lower preoperative eGFR, tumor size >20 mm, radical nephrectomy, lower hospital caseloads (<20 cases/year), and rural place of residence. The associations between rural place of residence and low center volume were a consequence of higher radical nephrectomy rates. CONCLUSION: Risk factors for CKD after nephrectomy generally relate to worse baseline health, or likelihood of undergoing radical nephrectomy. Surgeons in rural centres and hospitals with low caseloads may benefit from formalized integration with specialist centers for continued professional development and case-conferencing, to assist in management decisions.

Indoxyl Sulfate Induces Apoptosis and Hypertrophy in Human Kidney Proximal Tubular Cells.

Indoxyl sulfate (IS) is a protein-bound uremic toxin that accumulates in patients with declining kidney function. Although generally thought of as a consequence of declining kidney function, emerging evidence demonstrates direct cytotoxic role of IS on endothelial cells and cardiomyocytes, largely through the expression of pro-inflammatory and pro-fibrotic factors. The direct toxicity of IS on human kidney proximal tubular epithelial cells (PTECs) remains a matter of debate. The current study explored the effect of IS on primary cultures of human PTECs and HK-2, an immortalized human PTEC line. Pathologically relevant concentrations of IS induced apoptosis and increased the expression of the proapoptotic molecule Bax in both cell types. IS impaired mitochondrial metabolic activity and induced cellular hypertrophy. Furthermore, statistically significant upregulation of pro-fibrotic (transforming growth factor-ß, fibronectin) and pro-inflammatory molecules (interleukin-6, interleukin-8, and tumor necrosis factor-α) in response to IS was observed. Albumin had no influence on the toxicity of IS. The results of this study suggest that IS directly induced a pro-inflammatory and pro-fibrotic phenotype in proximal tubular cells. In light of the associated apoptosis, hypertrophy, and metabolic dysfunction, this study demonstrates that IS may play a role in the progression of chronic kidney disease.

Lessons from two high CO2 worlds - future oceans and intensive aquaculture.

Exponentially rising CO2 (currently ~400 µatm) is driving climate change and causing acidification of both marine and freshwater environments. Physiologists have long known that CO2 directly affects acid-base and ion regulation, respiratory function and aerobic performance in aquatic animals. More recently, many studies have demonstrated that elevated CO2 projected for end of this century (e.g. 800-1000 µatm) can also impact physiology, and have substantial effects on behaviours linked to sensory stimuli (smell, hearing and vision) both having negative implications for fitness and survival. In contrast, the aquaculture industry was farming aquatic animals at CO2 levels that far exceed end-of-century climate change projections (sometimes >10 000 µatm) long before the term 'ocean acidification' was coined, with limited detrimental effects reported. It is therefore vital to understand the reasons behind this apparent discrepancy. Potential explanations include 1) the use of 'control' CO2 levels in aquaculture studies that go beyond 2100 projections in an ocean acidification context; 2) the relatively benign environment in aquaculture (abundant food, disease protection, absence of predators) compared to the wild; 3) aquaculture species having been chosen due to their natural tolerance to the intensive conditions, including CO2 levels; or 4) the breeding of species within intensive aquaculture having further selected traits that confer tolerance to elevated CO2 . We highlight this issue and outline the insights that climate change and aquaculture science can offer for both marine and freshwater settings. Integrating these two fields will stimulate discussion on the direction of future cross-disciplinary research. In doing so, this article aimed to optimize future research efforts and elucidate effective mitigation strategies for managing the negative impacts of elevated CO2 on future aquatic ecosystems and the sustainability of fish and shellfish aquaculture.

Membrane and nuclear estrogen receptor α collaborate to suppress adipogenesis but not triglyceride content.

Estrogen and estrogen receptor (ER)-α suppress visceral fat development through actions in several organs via unclear mechanisms that we sought to identify. Using mice that express only nuclear ER-α [nuclear-only ER-α (NOER) mice] or plasma membrane ER-α [membrane-only ER-α (MOER) mice], we found that 10-wk-old mice that lacked either receptor pool showed extensive abdominal visceral fat deposition and weight gain compared with wild-type (WT) mice. Differentiation of cultured bone marrow stem cells (BMSCs) into the adipocyte lineage was suppressed by 17-ß-estradiol (E2) in WT female mice but not in NOER or MOER mice. This finding correlated with E2 inhibition of prominent differentiation genes in WT BMSCs. In contrast, triglyceride content in differentiated BMSCs or 3T3-L1 cells was suppressed as a result of membrane ER-α signaling through several kinases to inhibit carbohydrate response element-binding protein-α and -ß. We concluded that extranuclear and nuclear ER-α collaborate to suppress adipocyte development, but inhibition of lipid synthesis in mature cells does not involve nuclear ER-α.