Search Results (30)

The canonical function of caspase-8 is to control timely cellular apoptosis to maintain tissue homeostasis and clear dysfunctional cells; however, emerging findings reveal novel, non-canonical roles of caspase in addition to regulating cellular apoptosis, including inflammatory response regulation, immune function, and cell differentiation. Furthermore, the functional versatility of caspase-8 is reported to be contingent on the presence and dimerization of various isoforms, which are produced through alternative splicing, altering its function and protein–protein interactions. Equally important are post-translational modifications, including phosphorylation and ubiquitination, which can act as a nexus to control caspase-8 activity and cellular localization. Here, we review the alternative splicing and post-translational modifications made to caspase-8 and discuss their influence on its canonical and non-canonical roles. Full article

The Australian lungfish, Neoceratodus forsteri, is one of the world’s oldest vertebrate lineages, with a slow life-history and threatened status, requiring immediate conservation efforts. The main threats to lungfish populations are degradation and availability of key macrophyte habitats, water regulation and flow modification. As this long-lived species (at least 77 years) has delayed maturity (mature at 10 years), field monitoring alone will not be enough to inform the challenge of ensuring sustainable populations. A stochastic metapopulation model was developed for the Burnett River (Southeast Queensland, Australia), an important habitat for the lungfish that is a highly regulated system with extensive water infrastructure. The model consists of three interacting populations, where the ecology and biology of the species were translated into an 80-year-class population projection matrix for each population, each with post-development streamflow, habitat and movement rules. The model highlights the longer-term interaction between dams and stream flows on habitat availability and subsequent recruitment. Through a pre-development streamflow, we quantify the impact of high regulation and development on the lungfish population in the Burnett River: a minor decline in the upstream population (e.g., 9.8% decline), a large decline in the middle population (64.2% decline), virtually no change in the downstream population (e.g., 1.2% decline) and a moderate decline in the overall metapopulation (e.g., 22.3% decline). The loss of spawning and feeding habitat remains the main reason for population decline, with implications that the loss will lead to greater pressure on remaining downstream habitat due to combined flow and dam effects and, in turn, to extended periods of recovery of spawning habitat. Our modeling approach substantially advances conservation management of this species, as it can be adapted to suit other populations in other river systems and used to test sensitivity to recovery actions. Full article

Background/Objectives: Influenza vaccination is recommended for pregnant women, offering the dual benefit of protecting pregnant women and their newborn infants against influenza. This study aimed to investigate the impact of body mass index (BMI) on influenza vaccine responses in pregnant women and their newborns. Methods: Participants included pregnant women attending the Women’s and Children’s Hospital in South Australia between 2018 and 2021. Maternal blood samples were collected prior to and at 1 and 6 months post-influenza vaccination to measure antibody responses by hemagglutination inhibition (HI) assay. Cord blood samples were also collected. The percentages of participants achieving HI titre ≥40 were compared between obese and non-obese groups. Results: A total of 73 women were enrolled and received quadrivalent influenza vaccination at a mean age of 32 years (range 21–44 y) and median gestation of 24 weeks (range 11–37 weeks). BMI at vaccination was ≥30 kg/m² for 21/73 women (29%). Most pregnant women demonstrated antibody titres ≥ 40 to all four influenza vaccine strains at 1 month post-vaccination regardless of BMI category (BMI ≥ 30 kg/m²: 19/20; 95% vs. BMI < 30 kg/m²: 47/49; 96%). At 6 months post-vaccination, 12/17 (71%) obese women compared to 36/43 (84%) non-obese women (p = 0.25) maintained HI titres ≥ 40. Cord blood serology showed HI titres ≥ 40 for 11/17 (65%) infants born to mothers with BMI ≥ 30 compared to 30/35 (86%) infants delivered by mothers with BMI < 30 kg/m². Conclusions: A high BMI did not impair influenza vaccine antibody responses in pregnant women at 1 month post-vaccination. However, at 6 months post-vaccination, and in the cord blood samples, the percentages maintaining HI titre ≥ 40 were lower for obese women than for non-obese pregnant women. Full article

Background: Novel vaccines targeting the world’s deadliest pathogen Mycobacterium tuberculosis (Mtb) are urgently needed as the efficacy of the Bacillus Calmette–Guérin (BCG) vaccine in its current use is limited. HLA-E is a virtually monomorphic unconventional antigen presentation molecule, and HLA-E-restricted Mtb-specific CD8⁺ T cells can control intracellular Mtb growth, making HLA-E a promising vaccine target for Mtb. Methods: In this study, we evaluated the frequency and phenotype of HLA-E-restricted Mtb-specific CD4⁺/CD8⁺ T cells in the circulation and bronchoalveolar lavage fluid of two independent non-human primate (NHP) studies and from humans receiving BCG either intradermally or mucosally. Results: BCG vaccination followed by Mtb challenge in NHPs did not affect the frequency of circulating and local HLA-E–Mtb CD4⁺ and CD8⁺ T cells, and we saw the same in humans receiving BCG. HLA-E–Mtb T cell frequencies were significantly increased after Mtb challenge in unvaccinated NHPs, which was correlated with higher TB pathology. Conclusions: Together, HLA-E–Mtb-restricted T cells are minimally induced by BCG in humans and rhesus macaques (RMs) but can be elicited after Mtb infection in unvaccinated RMs. These results give new insights into targeting HLA-E as a potential immune mechanism against TB. Full article

The Module-0 Demonstrator is a single-phase 600 kg liquid argon time projection chamber operated as a prototype for the DUNE liquid argon near detector. Based on the ArgonCube design concept, Module-0 features a novel 80k-channel pixelated charge readout and advanced high-coverage photon detection system. In this paper, we present an analysis of an eight-day data set consisting of 25 million cosmic ray events collected in the spring of 2021. We use this sample to demonstrate the imaging performance of the charge and light readout systems as well as the signal correlations between the two. We also report argon purity and detector uniformity measurements and provide comparisons to detector simulations. Full article

Boreal and Arctic regions have warmed up to four times quicker than the rest of the planet since the 1970s. As a result, boreal and tundra ecosystems are experiencing more frequent and higher intensity extreme weather events and disturbances, such as wildfires. Yet limitations in ground and satellite data across the Arctic and boreal regions have challenged efforts to track these disturbances at regional scales. In order to effectively monitor the progression and extent of wildfires in the Arctic-boreal zone, it is essential to determine whether burned area (BA) products are accurate representations of BA. Here, we use 12 different datasets together with MODIS active fire data to determine the total yearly BA and seasonal patterns of fires in Arctic-boreal North America and Russia for the years 2001–2020. We found relatively little variability between the datasets in North America, both in terms of total BA and seasonality, with an average BA of 2.55 ± 1.24 (standard deviation) Mha/year for our analysis period, the majority (ca. 41%) of which occurs in July. In contrast, in Russia, there are large disparities between the products—GFED5 produces over four times more BA than GFED4s in southern Siberia. These disparities occur due to the different methodologies used; dNBR (differenced Normalized Burn Ratio) of short-term composites from Landsat images used alongside hotspot data was the most consistently successful in representing BA. We stress caution using GABAM in these regions, especially for the years 2001–2013, as Landsat-7 ETM+ scan lines are mistaken as burnt patches, increasing errors of commission. On the other hand, we highlight using regional products where possible, such as ABoVE-FED or ABBA in North America, and the Talucci et al. fire perimeter product in Russia, due to their detection of smaller fires which are often missed by global products. Full article

Successional patterns in lacustrine sand dunes along Lake Superior begin with grass-dominated plant communities leading to the establishment of Pinus banksiana Lamb. as initial forests. Using maximum entropy models, we predicted P. banksiana seedling and sapling patterns within the Grand Sable Dunes, Pictured Rocks National Lakeshore, USA, based on slope, aspect, forest basal area, and vegetation types. Across the different vegetation types, there were variable probabilities of seedling and sapling occurrence. For both seedlings and saplings, the higher likelihoods of occurrence were observed in coastal pine barrens vegetation types. P. banksiana regeneration is occurring in the Grand Sable Dunes in the absence of fire, with seedlings establishing and saplings being recruited in a variety of vegetation types. With the greatest probabilities in barrens, there is likely a relationship with seed source and canopy density. Understanding regeneration patterns in dune ecosystems is necessary to predict the future forest arrangement and colonization of P. banksiana into the dunes. These results contribute insights into the dynamics of plant communities in lacustrine dune systems, specifically the establishment of P. banksiana seedlings in various vegetation types. Continued forest establishment and increasing P. banksiana density will influence endangered species and non-native species management strategies for Pictured Rocks National Lakeshore. Full article

Background: Post-cardiotomy cardiogenic shock (PCCS) remains a life-threatening complication after cardiac surgery. Extracorporeal membrane oxygenation (ECMO) represents the mainstay of mechanical circulatory support for PCCS; however, its availability is limited to larger experienced centers, leading to a mismatch between centers performing cardiac surgery and hospitals offering ECMO management beyond cannulation. We sought to evaluate the outcomes and complications of PCCS patients requiring veno-arterial (V-A) ECMO cannulated at our hospital compared to those cannulated at referral hospitals. Methods: A retrospective analysis of PCCS patients requiring V-A ECMO was conducted between October 2014 to December 2022. Results: A total of 121 PCCS patients required V-A ECMO support, of which 62 (51%) patients were cannulated at the referring institutions and retrieved (retrieved group), and 59 (49%) were cannulated at our hospital (on-site group). The baseline demographics and pre-ECMO variables were similar between groups, except retrieved patients had higher lactic acid levels (retrieved group: 8.5 mmol/L ± 5.8 vs. on-site group: 6.6 ± 5; p = 0.04). Coronary artery bypass graft was the most common surgical intervention (51% in the retrieved group vs. 47% in the on-site group). There was no difference in survival-to-discharge rates between the groups (45% in the retrieved group vs. 51% in the on-site group; p = 0.53) or in the rate of patient-related complications. Conclusions: PCCS patients retrieved on V-A ECMO can achieve similar outcomes as those cannulated at experienced centers. An established network in a hub-and-spoke model is critical for the PCCS patients managed at hospitals without ECMO abilities to improve outcomes. Full article

Long COVID (LongC) is associated with a myriad of symptoms including cognitive impairment. We reported at the beginning of the COVID-19 pandemic that neuronal-enriched or L1CAM+ extracellular vesicles (nEVs) from people with LongC contained proteins associated with Alzheimer’s disease (AD). Since that time, a subset of people with prior COVID infection continue to report neurological problems more than three months after infection. Blood markers to better characterize LongC are elusive. To further identify neuronal proteins associated with LongC, we maximized the number of nEVs isolated from plasma by developing a hybrid EV Microfluidic Affinity Purification (EV-MAP) technique. We isolated nEVs from people with LongC and neurological complaints, AD, and HIV infection with mild cognitive impairment. Using the OLINK platform that assesses 384 neurological proteins, we identified 11 significant proteins increased in LongC and 2 decreased (BST1, GGT1). Fourteen proteins were increased in AD and forty proteins associated with HIV cognitive impairment were elevated with one decreased (IVD). One common protein (BST1) was decreased in LongC and increased in HIV. Six proteins (MIF, ENO1, MESD, NUDT5, TNFSF14 and FYB1) were expressed in both LongC and AD and no proteins were common to HIV and AD. This study begins to identify differences and similarities in the neuronal response to LongC versus AD and HIV infection. Full article

Emerging research suggests that body dissatisfaction (BD) is prevalent among midlife and older women (i.e., upwards of 70%). Cross-sectionally, BD is associated with myriad poor health and wellness outcomes (e.g., depression, disordered eating, bad nutrition) in midlife/older women. However, relatively few studies have examined the longitudinal relations between BD and health outcomes in this population. This preliminary study investigated the longitudinal associations of BD with wellbeing and health-related quality of life (QOL) among midlife/older adult women over one year. Participants (n = 86, women aged 40–72 years, M = 51.49, SD = 7.34, 86% white) completed self-report measures of BD, psychosocial impairment, health behaviors, and QOL at baseline (T1) and 12-month follow-up (T2). A series of multiple linear regression models included T1 BD as the predictor variable of health outcomes at T2, covarying for T1 BMI and age in all models. BD was associated with greater negative emotions and psychosocial impairment, less physical activity enjoyment, and poorer physical, psychological, and social QOL one year later. Findings suggest that BD is associated with negative consequences for women across the lifespan (ƒ² ranges = 0.06–0.60). Future research investigating BD as a unique, modifiable risk factor for health outcomes among diverse samples of midlife/older women is warranted. Targeting BD in interventions may improve health indices beyond eating disorders for this population. Full article

While traditional multivitamin and mineral (MVM) supplements generally come in tablet form, new powder forms of MVM supplements are available with theoretically higher bioavailability relative to tablet MVM supplements. The purpose of this study was to assess the bioaccessibility and bioavailability of minerals (magnesium (Mg), zinc (Zn), calcium (Ca), and potassium (K)) in a tablet MVM supplement compared to a novel powder Foundational Nutrition supplement (AG1^®), containing minerals, vitamins, phytochemicals, and pre-/probiotics, in the upper gastrointestinal tract. The tablet MVM supplement was specifically formulated for this study, with matched mineral contents and identical chemical structures. The adapted Simulator of the Human Intestinal Microbial Ecosystem (SHIME^®) model was used to assess the bioaccessibility and bioavailability of soluble minerals using a simulated upper gastrointestinal tract and dialysis membrane to mimic human digestion and absorption. The bioaccessibility was assessed at the end of the stomach and duodenum. The bioaccessibility and bioavailability were assessed at 1, 2, and 3 h following dialysis. The preliminary soluble mineral analysis of the tablet (crushed to a powder) and AG1 powder demonstrated significantly higher (p < 0.05) soluble fractions of Zn and Ca, but lower Mg in the AG1 powder vs. the tablet. The total soluble mineral percentages at the stomach and duodenum end were all significantly higher for the AG1 powder vs. the tablet (p < 0.05). Mg, Ca, and Zn were more (p < 0.05) bioaccessible and bioavailable in the powder compared to the tablet during the small intestine simulation. The bioaccessible fraction of K was higher (p < 0.05) only at 3 h for the tablet vs. the powder. These preclinical data demonstrate that the AG1 powder has superior dissolution and disintegration characteristics compared to the tablet, leading to increased bioaccessibility and bioavailability in vitro. Full article

Bacterial and fungal co-infections are reported complications of coronavirus disease 2019 (COVID-19) in critically ill patients but may go unrecognized premortem due to diagnostic limitations. We compared the premortem with the postmortem detection of pulmonary co-infections in 55 fatal COVID-19 cases from March 2020 to March 2021. The concordance in the premortem versus the postmortem diagnoses and the pathogen identification were evaluated. Premortem pulmonary co-infections were extracted from medical charts while applying standard diagnostic definitions. Postmortem co-infection was defined by compatible lung histopathology with or without the detection of an organism in tissue by bacterial or fungal staining, or polymerase chain reaction (PCR) with broad-range bacterial and fungal primers. Pulmonary co-infection was detected premortem in significantly fewer cases (15/55, 27%) than were detected postmortem (36/55, 65%; p < 0.0001). Among cases in which co-infection was detected postmortem by histopathology, an organism was identified in 27/36 (75%) of cases. Pseudomonas, Enterobacterales, and Staphylococcus aureus were the most frequently identified bacteria both premortem and postmortem. Invasive pulmonary fungal infection was detected in five cases postmortem, but in no cases premortem. According to the univariate analyses, the patients with undiagnosed pulmonary co-infection had significantly shorter hospital (p = 0.0012) and intensive care unit (p = 0.0006) stays and significantly fewer extra-pulmonary infections (p = 0.0021). Bacterial and fungal pulmonary co-infection are under-recognized complications in critically ill patients with COVID-19. Full article

Age-related somatic genomic alterations in hematopoietic cell lines have been well characterized in humans; however, this phenomenon has not been well studied in other species. Next-generation sequencing-based liquid biopsy testing for cancer detection was recently developed for dogs and has been used to study the genomic profiles of blood samples from thousands of canine patients since 2021. In this study, 4870 client-owned dogs with and without a diagnosis or suspicion of cancer underwent liquid biopsy testing by this method. Copy number variants detected exclusively in genomic DNA derived from white blood cells (WBC gDNA-specific CNVs) were observed in 126 dogs (2.6%; 95% CI: 2.2–3.1); these copy number variants were absent from matched plasma cell-free DNA, and from tumor tissue in dogs with concurrent cancer. These findings were more common in older dogs and were persistent in WBC gDNA in over 70% of patients, with little to no change in the amplitude of the signal across longitudinal samples. Many of these alterations were observed at recurrent locations in the genome across subjects; the most common finding was a partial loss on CFA25, typically accompanied by a partial gain on the same chromosome. These early findings suggest that age-related somatic alterations may be present at an appreciable frequency in the general canine population. Further research is needed to determine the clinical significance of these findings. Full article

Oxidative stress is considered one of the early underlying contributors of sepsis-induced myocardial depression. DJ-1, also known as PARK7, has a well-established role as an antioxidant. We have previously shown, in a clinically relevant model of polymicrobial sepsis, DJ-1 deficiency improved survival and bacterial clearance by decreasing ROS production. In the present study, we investigated the role of DJ-1 in sepsis-induced myocardial depression. Here we compared wildtype (WT) with DJ-1 deficient mice at 24 and 48 h after cecal ligation and puncture (CLP). In WT mice, DJ-1 was increased in the myocardium post-CLP. DJ-1 deficient mice, despite enhanced inflammatory and oxidative responses, had an attenuated hypertrophic phenotype, less apoptosis, improved mitochondrial function, and autophagy, that was associated with preservation of myocardial function and improved survival compared to WT mice post-CLP. Collectively, these results identify DJ-1 as a regulator of myocardial function and as such, makes it an attractive therapeutic target in the treatment of early sepsis-induced myocardial depression. Full article

The purpose of this study was to compare cardiac autonomic responses following bilateral and unilateral upper-body (UB) acute resistance exercise (ARE). In total, 14 individuals were assessed for markers of cardiac autonomic responses via heart rate variability (HRV) and baroreflex sensitivity (BRS) at rest and at 10- and 30-min following ARE. Logarithmically transformed (ln) HRV measures included: total power (ln TP), high-frequency power (ln HF power), low-frequency power (ln LF power), sympathovagal balance (ln LF: HF), and the square root of the mean squared differences of successive R-R intervals (ln RMSSD). BRS was assessed using the sequence method. Two-way repeated measures ANOVAs were used to analyze effects of UB ARE (bilateral, unilateral) across time (Rest, 10, and 30 min). There were no significant (p > 0.05) interactions. However, there were significant (p ≤ 0.05) main effects of time such that ln TP, ln HF power, ln RMSSD, and BRS decreased and did not recover within 30 min compared to Rest for both conditions. Collectively, this study suggests that bilateral and unilateral UB ARE yielded similar reductions, for at least 30 min, in respect to vagal measures of HRV and BRS. Full article