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Abstract Background Maternal diet quality and quantity have significant impacts on both maternal and fetal health and development. The composition and function of the maternal gut microbiome is also significantly influenced by diet; however, little is known about the impact of gestational nutrient restriction on the bovine maternal microbiome during early gestation, which is a critical stage for maternal microbiome-mediated fetal programming to take place. The objective of the present study was to evaluate the impacts of diet restriction and one-carbon metabolite (OCM) supplementation during early gestation on maternal ruminal, vaginal, and blood microbiota in cattle. Thirty-three beef heifers (approx. 14 months old) were used in a 2 × 2 factorial experiment with main factors of target gain (control [CON]; targeted 0.45 kg/d gain vs restricted [RES]; targeted − 0.23 kg/d gain), and OCM supplementation (+ OCM vs − OCM; n = 8/treatment; except n = 9 for RES–OCM). Heifers were individually fed, starting treatment at breeding (d 0) and concluding at d 63 of gestation. Ruminal fluid and vaginal swabs were collected on d − 2, d 35, and d 63 (at necropsy) and whole blood was collected on d 63 (necropsy). Bacterial microbiota was assessed using 16S rRNA gene (V3–V4) sequencing. Results Overall ruminal microbiota structure was affected by gain, OCM, time, and their interactions. The RES heifers had greater microbial richness (observed ASVs) but neither Shannon nor Inverse Simpson diversity was significantly influenced by gain or OCM supplementation; however, on d 63, 34 bacterial genera showed differential abundance in the ruminal fluid, with 25 genera enriched in RES heifers as compared to CON heifers. In addition, the overall interaction network structure of the ruminal microbiota changed due to diet restriction. The vaginal microbiota community structure was influenced by gain and time. Overall microbial richness and diversity of the vaginal microbiota steadily increased as pregnancy progressed. The vaginal ecological network structure was distinctive between RES and CON heifers with genera-genera interactions being intensified in RES heifers. A relatively diverse bacterial community was detected in blood samples, and the composition of the blood microbiota differed from that of ruminal and vaginal microbiota. Conclusion Restricted dietary intake during early gestation induced significant alterations in the ruminal microbiota which also extended to the vaginal microbiota. The composition of these two microbial communities was largely unaffected by OCM supplementation. Blood associated microbiota was largely distinctive from the ruminal and vaginal microbiota.

Solving the momentum balance is the computationally expensive part of simulating the evolution of ice sheets. The momentum balance is described by the nonlinear full-Stokes equations, which are solved iteratively. We use the Picard iteration and Newton's method combined with Armijo step sizes and approximately exact step sizes, respectively, to solve these equations. The Picard iteration uses either no step size control or the approximately exact step sizes. We compare the variants of Newton's method and the Picard iteration in benchmark experiments, called ISMIP-HOM experiments A, B, E1, and E2. The ISMIP-HOM experiments consist of a more realistic domain and are designed to test the quality of ice models. For an even more realistic test case, we simulate the experiments E1 and E2 with a time-dependent surface. We obtain that approximately exact step sizes greatly reduce the necessary number of iterations for the Picard iteration and Newton's method with nearly no increase in the computation time for each iteration.

Abstract Immune checkpoint blockade has yet to produce robust anti-cancer responses for prostate cancer. Sialyltransferases have been shown across several solid tumours, including breast, melanoma, colorectal and prostate to promote immune suppression by synthesising sialoglycans, which act as ligands for Siglec receptors. We report that ST3 beta-galactoside alpha-2,3-sialyltransferase 1 (ST3Gal1) levels negatively correlate with androgen signalling in prostate tumours. We demonstrate that ST3Gal1 plays an important role in modulating tumour immune evasion through the synthesises of sialoglycans with the capacity to engage the Siglec-7 and Siglec-9 immunoreceptors preventing immune clearance of cancer cells. Here, we provide evidence of the expression of Siglec-7/9 ligands and their respective immunoreceptors in prostate tumours. These interactions can be modulated by enzalutamide and may maintain immune suppression in enzalutamide treated tumours. We conclude that the activity of ST3Gal1 is critical to prostate cancer anti-tumour immunity and provide rationale for the use of glyco-immune checkpoint targeting therapies in advanced prostate cancer.

Background: Local authorities have a crucial role in building community resilience to the health effects of a changing climate. Support in achieving local action can be provided through improving available public health intelligence to inform decision making. We aimed to co-develop with a local authority a tool mapping vulnerability to climate related hazards. Methods: We conducted a feasibility study, exploring through stakeholder engagement local priorities and levers for action in adaptation that could be informed by provision of increased intelligence. This informed co-development of a proof-of-concept tool. Results: Stakeholders reported needs in better understanding the intersection between vulnerability and hazard to facilitate partnership working, decision making, and targeting of interventions. We developed a mapping tool, using nationally available data, overlaying a vulnerability index with hazard (heat and flooding) exposure. Conclusions: Mapping tools are feasible methods by which public health intelligence to support climate change adaptation planning can be shared. Barriers to action may result from the complexity of vulnerability, concerns of unintended consequences, and resource constraints. Co-development with local expertise is necessary to ensure that outputs add value to local response. This tool will now be piloted to gather feedback on useability, usefulness, and potential improvements.

A concern in weed biological control research is the potential for candidate biocontrol agents to impact not only the target weed but also native or economically important flora. The degree of evolutionary relatedness between the target weed species and a non-target species is a key predictor of the susceptibility of the non-target to the biocontrol agent. To manage this risk, biocontrol practitioners need to understand the phylogenetic position of the host weed relative to non-target plant species. However, comprehensively sampled phylogenetic trees are often unavailable, with incomplete information scattered across multiple publications. Further, older published phylogenies based on Sanger sequence data often lack branch resolution and support, which increases uncertainty in biocontrol decision making. Decreasing sequencing cost and technological advances have led to phylogenomic approaches being more widely used to understand evolutionary relationships between species. For example, target capture sequencing methods using bait kits such as Angiosperms353 enable cost-effective and timely phylogenomic-level analysis of flowering plant groups at different scales. Here, we introduce a workflow to embed a comprehensive understanding of evolutionary relationships into the efficient development of host test lists in weed biological control. We demonstrate the effectiveness of the workflow through a case study on the major crop weed flaxleaf fleabane (Erigeron bonariensis). Phylogenomic analysis was conducted on 280 species of the tribe Astereae (family Asteraceae) occurring in Australia and New Zealand, clarifying relationships between the target species and related clades of native and non-native Astereae. We consider the phylogenetic tree in the context of a previously proposed host test list and discuss taxonomic implications, highlighting avenues of future molecular-based work to uncover the origin of Australian fleabanes. This study provides a workflow and demonstrates the practical application of target sequence capture for phylogenomic inference to support risk analysis and decision making in classical weed biological control.

Summary: Background: Bone metastasis is a common consequence of advanced prostate cancer. Bisphosphonates can be used to manage symptoms, but there are currently no curative treatments available. Altered tumour cell glycosylation is a hallmark of cancer and is an important driver of a malignant phenotype. In prostate cancer, the sialyltransferase ST6GAL1 is upregulated, and studies show ST6GAL1-mediated aberrant sialylation of N-glycans promotes prostate tumour growth and disease progression. Methods: Here, we monitor ST6GAL1 in tumour and serum samples from men with aggressive prostate cancer and using in vitro and in vivo models we investigate the role of ST6GAL1 in prostate cancer bone metastasis. Findings: ST6GAL1 is upregulated in patients with prostate cancer with tumours that have spread to the bone and can promote prostate cancer bone metastasis in vivo. The mechanisms involved are multi-faceted and involve modification of the pre-metastatic niche towards bone resorption to promote the vicious cycle, promoting the development of M2 like macrophages, and the regulation of immunosuppressive sialoglycans. Furthermore, using syngeneic mouse models, we show that inhibiting sialylation can block the spread of prostate tumours to bone. Interpretation: Our study identifies an important role for ST6GAL1 and α2-6 sialylated N-glycans in prostate cancer bone metastasis, provides proof-of-concept data to show that inhibiting sialylation can suppress the spread of prostate tumours to bone, and highlights sialic acid blockade as an exciting new strategy to develop new therapies for patients with advanced prostate cancer. Funding: Prostate Cancer Research and the Mark Foundation For Cancer Research, the Medical Research Council and Prostate Cancer UK.

The impacts of climate change on marine organisms have been increasingly documented in laboratory and experimental studies. However, the use of different taxonomic groupings and the assessment of a range of processes make identifying overall trends challenging. Meta-analysis has been used to determine general trends, but coarse taxonomic granularity may mask phylogenetically specific responses. Bivalve molluscs are a data-rich clade of ecologically and economically important calcifying marine taxa that allow for the assessment of species-specific vulnerability across developmental stages. Drawing on the large body of available literature, we conduct a meta-analysis of 203 unique experimental set-ups in order to examine how bivalve growth responds to increased water temperature, acidity, deoxygenation, and changes in salinity in 10 climate change stressor combinations. This is the most complete examination of bivalve responses to date and shows that anthropogenic climate change will disproportionally affect particular families, suggesting taxonomic differentiation in climate change response. Specifically, Mytilidae, Ostreidae, and Pectinidae (67 % of experiments) respond with negative effect sizes for all individual stressors, whereas responses in Pinnidae, Tellinidae, and Veneridae are more complex. Our analysis shows that earlier studies reporting negative impacts on bivalves are driven by only three or four well-studied, commercially important families. Despite the taxonomic differentiation, almost all drivers and their combinations have significant negative effects on growth. The synergistic impacts of deoxygenation, acidification, and temperature result in the largest negative effect size. Infaunal taxa, including Tellinidae and Veneridae, appear more resistant to warming and oxygen reduction than epifaunal or motile taxa, but this difference between the two taxa is also based on a small number of data points. The current focus of experimental set-ups on commercially important taxa and families within a small geographic range creates gaps in the understanding of global impacts on these economically important foundation organisms.

Abstract Five essential oils (EOs) were previously characterized in vitro and identified as candidate EOs for the development of an intranasal EO spray to mitigate bovine respiratory disease (BRD) pathogens. In the present study, these EOs were evaluated for their potential to (i) reduce BRD pathogens, (ii) modulate nasopharyngeal microbiota, and (iii) influence animal performance, feeding behavior and immune response when a single dose administered intranasally to feedlot cattle. Forty beef steer calves (7–8 months old, Initial body weight = 284 ± 5 kg [SE]) received either an intranasal EO spray (ajowan, thyme, fennel, cinnamon leaf, and citronella) or PBS (Control; n = 20/group) on day 0. Deep nasopharyngeal swabs were collected on days (d) -1, 1, 2, 7, 14, 28, and 42 and processed for 16S rRNA gene sequencing, qPCR, and culturing. Significant effects of EO on community structure (d1), microbial richness and diversity, relative abundance of some dominant phyla (d1, d2, and d14), and the overall interaction network structure of the nasopharyngeal microbiota were detected. The relative abundance of Mannheimia was lower in the EO calves (4.34%) than in Control calves (10.4%) on d2, and M. haemolytica prevalence on d7 as compared to control calves. Feed intake, average daily gain, feeding behavior, and blood cell counts were not affected by EO treatment. Overall, a single intranasal dose of EO spray resulted in moderate modulation of nasopharyngeal microbiota and short-term inhibition of Mannheimia while not influencing animal performance, feeding behavior or immune response. Our study, for the first time, shows the potential use of intranasal EO to mitigate BRD in feedlot cattle.

Climate change is predicted to negatively impact calcification and change the structural integrity of biogenic carbonates, influencing their protective function. We assess the impacts of warming on the morphology and crystallography of Amphistegina lobifera, an abundant benthic foraminifera species in shallow environments. Specimens from a thermally disturbed field area, mimicking future warming, are about 50% smaller compared with a control location. Differences in the position of the ν1 Raman mode of shells between the sites, which serves as a proxy for Mg content and calcification temperature, indicate that calcification is negatively impacted when temperatures are below the thermal range facilitating calcification. To test the impact of thermal stress on the Young's modulus of calcite which contributes to structural integrity, we quantify elasticity changes in large benthic foraminifera by applying atomic force microscopy to a different genus, Operculina ammonoides, cultured under optimal and high temperatures. Building on these observations of size and the sensitivity analysis for temperature-induced change in elasticity, we used finite element analysis to show that structural integrity is increased with reduced size and is largely insensitive to calcite elasticity. Our results indicate that warming-induced dwarfism creates shells that are more resistant to fracture because they are smaller.

Abstract Background Preterm birth is the leading cause of neonatal and under-five mortality worldwide. It is a complex syndrome characterized by numerous etiologic pathways shaped by both maternal and fetal factors. To better understand preterm birth trends, the Global Alliance to Prevent Prematurity and Stillbirth published the preterm birth phenotyping framework in 2012 followed by an application of the model to a global dataset in 2015 by Barros, et al. Our objective was to adapt the preterm birth phenotyping framework to retrospective data from a low-resource, rural setting and then apply the adapted framework to a cohort of women from Migori, Kenya. Methods This was a single centre, observational, retrospective chart review of eligible births from November 2015 – March 2017 at Migori County Referral Hospital. Adaptations were made to accommodate limited diagnostic capabilities and data accuracy concerns. Prevalence of the phenotyping conditions were calculated as well as odds of adverse outcomes. Results Three hundred eighty-seven eligible births were included in our study. The largest phenotype group was none (no phenotype could be identified; 41.1%), followed by extrauterine infection (25.1%), and antepartum stillbirth (16.7%). Extrauterine infections included HIV (75.3%), urinary tract infections (24.7%), malaria (4.1%), syphilis (3.1%), and general infection (3.1%). Severe maternal condition was ranked fourth (15.6%) and included anaemia (69.5%), chronic respiratory distress (22.0%), chronic hypertension prior to pregnancy (5.1%), diabetes (3.4%), epilepsy (3.4%), and sickle cell disease (1.7%). Fetal anaemia cases were the most likely to transfer to the newborn unit (OR 5.1, 95% CI 0.8, 30.9) and fetal anomaly cases were the most likely to result in a pre-discharge mortality (OR 3.9, 95% CI 0.8, 19.2). Conclusions Using routine data sources allowed for a retrospective analysis of an existing dataset, requiring less time and fewer resources than a prospective study and demonstrating a feasible approach to preterm phenotyping for use in low-resource settings to inform local prevention strategies.

The Parallel Factor Analysis 2 (PARAFAC2) is a multimodal factor analysis model suitable for analyzing multi-way data when one of the modes has incomparable observation units, for example, because of differences in signal sampling or batch sizes. A fully probabilistic treatment of the PARAFAC2 is desirable to improve robustness to noise and provide a principled approach for determining the number of factors, but challenging because direct model fitting requires that factor loadings be decomposed into a shared matrix specifying how the components are consistently co-expressed across samples and sample-specific orthogonality-constrained component profiles. We develop two probabilistic formulations of the PARAFAC2 model along with variational Bayesian procedures for inference: In the first approach, the mean values of the factor loadings are orthogonal leading to closed form variational updates, and in the second, the factor loadings themselves are orthogonal using a matrix Von Mises–Fisher distribution. We contrast our probabilistic formulations to the conventional direct fitting algorithm based on maximum likelihood on synthetic data and real fluorescence spectroscopy and gas chromatography–mass spectrometry data showing that the probabilistic formulations are more robust to noise and model order misspecification. The probabilistic PARAFAC2, thus, forms a promising framework for modeling multi-way data accounting for uncertainty.

Abstract Coralline algae form complex habitats which are biodiversity hotspots. Experimental studies suggest that climate change will decrease coralline algal structural integrity. These experiments, however, lack information on local morphological variability and how much structural change would be needed to threaten habitat formation. Here, using finite element modelling, we assess variability in cellular structure and chemical composition of the carbonate skeleton of four coralline algal species from Britain in contemporary and historical specimens collected over the last 130 years. Cellular and mineral properties are highly variable within species, between sites and through time, with structurally weaker cells in the southern species and contemporary material compared to northern taxa and historical material. Yet, temporal differences in strength were smaller than spatial differences. Our work supports long term experiments which show the adaptation potential of this group. Our results suggest that future anthropogenic climate change may lead to loss of habitat complexity in the south and expansion of structurally weaker southern species into northern sites.

IntroductionThe rise in antibiotic resistant pathogens associated with bovine respiratory disease (BRD) poses a serious challenge, particularly to the beef feedlot industry, as they currently depend on antibiotics to prevent BRD to mitigate the financial burden (approx. $1 billion annual loss) inflicted by BRD-associated high mortality and morbidity in feedlot cattle. Thus, there is an impetus need for the development of antimicrobial alternative strategies against BRD. This study aimed to screen and select candidate essential oils (EOs) for the development of an intranasal EO spray that can inhibit BRD pathogens and promote microbiota-mediated respiratory health.MethodsThe effects of selected EOs (ajowan, cinnamon leaf, citronella, grapefruit, fennel, and thyme) on a bovine nasopharyngeal microbiota culture were evaluated using 16S rRNA gene sequencing. The microbiota culture was enriched by incubating nasopharyngeal swabs obtained from finishing beef heifers in brain heart infusion broth with and without EOs (0.025%, v/v). These EOs were then also evaluated for their immunomodulatory effects on bovine turbinate (BT) cells by analyzing the concentrations of 15 cytokines and chemokines in cell culture after 24 h incubation. The crystal violet assay was done to assess the antibiofilm activity of EOs against Escherichia coli UMN026 strain. Finally, 15 EOs were screened for their antiviral activity against the bovine viral diarrhea virus 1 (BVDV-1) using BT cells and a fluorescence-based method.ResultsAjowan, fennel, and thyme resulted in a moderate reduction of overall nasopharyngeal microbiota growth with significant alterations of both alpha and beta diversity, and the relative abundance of predominant bacterial families (e.g., increasing Enterobacteriaceae and decreasing Moraxellaceae) compared to the control (p 0.05). Ajowan, thyme, fennel, and cinnamon leaf exhibited antibiofilm activity at concentrations of 0.025 and 0.05%. Reduction of BVDV-1 replication in BT cells was observed with thyme (strong), and ajowan and citronella (moderate) at 0.0125% concentration.DiscussionAccordingly, ajowan, thyme, fennel, cinnamon leaf, and citronella EOs were selected for further development as an intranasal EO spray to prevent and control of BRD pathogens in feedlot cattle.

ABSTRACT Type 2 diabetes mellitus (T2DM) is a metabolic disease affecting bone tissue and leading to increased fracture risk in men and women, independent of bone mineral density (BMD). Thus, bone material quality (i.e., properties that contribute to bone toughness but are not attributed to bone mass or quantity) is suggested to contribute to higher fracture risk in diabetic patients and has been shown to be altered. Fracture toughness properties are assumed to decline with aging and age‐related disease, while toughness of human T2DM bone is mostly determined from compression testing of trabecular bone. In this case‐control study, we determined fracture resistance in T2DM cortical bone tissue from male individuals in combination with a multiscale approach to assess bone material quality indices. All cortical bone samples stem from male nonosteoporotic individuals and show no significant differences in microstructure in both groups, control and T2DM. Bone material quality analyses reveal that both control and T2DM groups exhibit no significant differences in bone matrix composition assessed with Raman spectroscopy, in BMD distribution determined with quantitative back‐scattered electron imaging, and in nanoscale local biomechanical properties assessed via nanoindentation. Finally, notched three‐point bending tests revealed that the fracture resistance (measured from the total, elastic, and plastic J‐integral) does not significantly differ in T2DM and control group, when both groups exhibit no significant differences in bone microstructure and material quality. This supports recent studies suggesting that not all T2DM patients are affected by a higher fracture risk but that individual risk profiles contribute to fracture susceptibility, which should spur further research on improving bone material quality assessment in vivo and identifying risk factors that increase bone fragility in T2DM. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

ABSTRACT In this study, we evaluated the vaginal and uterine microbiota between beef cattle that became pregnant via artificial insemination (AI) and those that remained open to identify microbial signatures associated with fertility. We also characterized the culturable fraction of these microbiota and screened certain vaginal and uterine bacterial isolates for antimicrobial resistance. For this, vaginal and uterine swabs were collected before AI from two cohorts of Angus-crossbred cattle: mature cows (vaginal and uterine: 27 open and 31 pregnant) and heifers (vaginal: 26 open and 33 pregnant). The microbiota of these samples were assessed using 16S rRNA gene sequencing and culturing. Twenty-nine vaginal and uterine bacterial isolates were screened for resistance against 41 antibiotics. Within the vaginal microbiota, 11 amplicon sequence variants (ASVs) were more relatively abundant in the open heifers compared with the pregnant heifers. No differentially abundant ASVs were detected in the vaginal samples from pregnant versus open cows. Pregnant cows had a distinct uterine microbiota community structure (P = 0.008) and interaction network structure compared with open cows. Twenty-eight differentially abundant uterine ASVs were observed between the pregnant and open cows. Community structure and diversity were different between the cow’s vagina and uterus. A total of 733 bacterial isolates were recovered from vaginal (512) and uterine (221) swabs under aerobic (83 different species) and anaerobic (69 species) culturing. Among these isolates were pathogenic species and those mostly susceptible to tested antibiotics. Overall, our results indicate that fertility-associated taxonomic signatures are present in the bovine uterine and vaginal microbiota. IMPORTANCE Emerging evidence suggests that microbiome-targeted approaches may provide a novel opportunity to reduce the incidence of reproductive failures in cattle. To develop such microbiome-based strategies, one of the first logical steps is to identify reproductive microbiome features related to fertility and to isolate the fertility-associated microbial species for developing a future bacterial consortium that could be administered before breeding to enhance pregnancy outcomes. Here, we characterized the vaginal and uterine microbiota in beef cattle that became pregnant or remained open via artificial insemination and identified microbiota features associated with fertility. We compared similarities between vaginal and uterine microbiota and between heifers and cows. Using culturing, we provided new insights into the culturable fraction of the vaginal and uterine microbiota and their antimicrobial resistance. Overall, our findings will serve as an important basis for future research aimed at harnessing the vaginal and uterine microbiome for improved cattle fertility.

Abstract A growing number of studies have investigated the feasibility of utilizing hemp by-products as livestock feedstuffs; however, their impact on livestock microbiomes remains unexplored. Here, we evaluated the effects of feeding hempseed cake on the gastrointestinal, respiratory, and reproductive microbiota in beef heifers. Angus-crossbred heifers (19-months old, initial body weight = 494 ± 10 kg [SE]) were fed a corn-based finishing diet containing 20% hempseed cake as a substitute for 20% corn dried distillers’ grains with solubles (DM basis; Control; n = 16/group) for 111 days until slaughter. Ruminal fluid and deep nasopharyngeal swabs (days 0, 7, 42, 70 and 98), and vaginal and uterine swabs (at slaughter) were collected, and the microbiota assessed using 16S rRNA gene sequencing. Diet affected the community structure of the ruminal (d 7−98; 0.06 ≤ R2 ≤ 0.12; P

Abstract Immunomodulatory Siglecs are controlled by their glycoprotein and glycolipid ligands. Siglec-glycolipid interactions are often studied outside the context of a lipid bilayer, missing the complex behaviors of glycolipids in a membrane. Through optimizing a liposomal formulation to dissect Siglec–glycolipid interactions, it is shown that Siglec-6 can recognize glycolipids independent of its canonical binding pocket, suggesting that Siglec-6 possesses a secondary binding pocket tailored for recognizing glycolipids in a bilayer. A panel of synthetic neoglycolipids is used to probe the specificity of this glycolipid binding pocket on Siglec-6, leading to the development of a neoglycolipid with higher avidity for Siglec-6 compared to natural glycolipids. This neoglycolipid facilitates the delivery of liposomes to Siglec-6 on human mast cells, memory B-cells and placental syncytiotrophoblasts. A physiological relevance for glycolipid recognition by Siglec-6 is revealed for the binding and internalization of extracellular vesicles. These results demonstrate a unique and physiologically relevant ability of Siglec-6 to recognize glycolipids in a membrane.

Periodic meltwater pulses from the Laurentide-Greenland Ice Sheets during the last deglaciation drove abrupt changes in sea surface temperature and sea ice extent, according to sediment core biomarker proxy records from the Eirik Drift, eastern Labrador Sea

Background Cystic fibrosis (CF) lung disease starts in infancy and can be assessed for structural lung abnormalities using computed tomography or magnetic resonance scans, or for lung function impairment using multiple breath washout (MBW). However, in infancy these two methods are not well correlated. Trajectories of CF lung disease assessed by MBW in infants and toddlers remain poorly described, which is why we aimed to 1) describe the trajectory of lung function, 2) explore risk factors for progression and 3) explore the real-life effect of lumacaftor/ivacaftor. Methods This was a nationwide observational cohort study (2018–2021) using data collected as part of the routine clinical surveillance programme (including MBW and monthly endo-laryngeal suction sampling for bacterial pathogens) in children born after implementation of newborn screening for CF (May 2016). Lumacaftor/ivacaftor commenced from age 2 years in children homozygous for F508del. Ventilation distribution efficiency (VDE), recently described to have advantages over lung clearance index (LCI), was reported as the primary MBW outcome after z-score calculations based on published reference data. Mixed effect linear regression models were the main statistical analyses performed in this study. Results 59 children, aged 2–45 months, contributed with 211 MBW occasions (median (interquartile range (IQR)) 3 (2–5) MBW occasions per child) with a median (IQR) follow-up time of 10.8 (5.2–22.3) months. An overall mean annual deterioration rate of −0.50 (95% CI −0.78– −0.22) z-VDE was observed, starting from an estimated mean z-VDE of −1.68 (95% CI −2.15– −1.22) at age 0.0 years (intercept). Pseudomonas aeruginosa “ever” (n=14, MBWs 50) had a significantly worse z-VDE trajectory versus P. aeruginosa “never” (mean difference 0.53 (95% CI 0.16–0.89) per year; p=0.0047) and lumacaftor/ivacaftor treatment (n=22, MBWs 46) significantly improved the trajectory of z-VDE (mean difference 1.72 (95% CI 0.79–2.66) per year; p=0.0004), leading to a stable mean z-VDE trajectory after start of treatment. Conclusions Infants and toddlers with CF demonstrated progressive deterioration in z-VDE over the first years of life. P. aeruginosa isolation “ever” was associated with an accelerated deterioration in lung function, while lumacaftor/ivacaftor therapy significantly improved and stabilised the trajectory.

When testing the virucidal activity of biocides, the non-inactivated residual virus is titrated on cell cultures by the end point dilution method on 96-well tissue culture plates. However, residues of the biocide to be tested also come into contact with the cell cultures in varying concentrations and thus can lead to cytotoxic effects even at high levels of dilution. In the European standards for testing biocides, in particular disinfectants, methods such as Large-Volume-Plating (LVP) method and, in some guidelines, gel filtration procedures are described for reducing cytotoxic effects in the case of highly cytotoxic products, if the classical dilution method proves to be impractical.In order to enable the testing of highly cytotoxic biocides for their activity against viruses, an alternative method for reducing cytotoxicity is introduced, which is based on a procedure of isolating infectious viruses from cytotoxic patients’ materials such as stool and can be applied when the other methods fail.

Planktic foraminifera are major marine calcifiers in the modern ocean, regulating the marine inorganic carbon pump, and generating marine fossil archives of past climate change. The foraminifera contain ecogroups with and without spines and algal symbionts, creating functional trait diversity which expands their ecological niches. Here, we incorporate symbiosis and spine traits into the symbiont-barren non-spinose foraminifer functional type in EcoGEnIE to represent all the extant foraminifera species. We calibrated the modelled new traits using Latin hypercube sampling (LHS) and identified the optimal model parameters from an ensemble of 1200 runs compared with global observations from core-top sediment samples, sediment traps, and plankton nets. The model successfully describes the global distribution and seasonal abundance variation of the four major foraminiferal functional groups. The model reproduces the dominance of the symbiont-obligate group in subtropical gyres and of the symbiont-barren types in the productive subpolar oceans. Global annual mean biomass and foraminifer-derived carbon export rate are correctly predicted compared to data, with biomass ranging from 0.001 to 0.010 mmol C m−3 and organic carbon export 0.002–0.031 mmol C m−2 d−1. The model captures the seasonal peak time of biomass and organic carbon export but struggles to reproduce the amplitude of both in productive areas. The sparseness and uneven distribution of observations and the model's limitation in upwelling regions likely contribute to this discrepancy. Our model overcomes the lack of major groups in the previous ForamEcoGEnIE 1.0 version and offers the potential to explore foraminiferal ecology dynamics and its impact on biogeochemistry in modern, future, and paleogeographic environments.

Abstract Background A lack of undergraduate medical curricula on providing healthcare to transgender and gender diverse (TGD) patients has contributed to significant health disparities for TGD communities. To address this gap, we designed and evaluated a novel curriculum to train Obstetrics and Gynecology (OB/GYN) clerkship students in caring for TGD patients. Methods Following Kern’s 6-step method for curriculum development, we created a two-part curriculum on TGD healthcare topics – an online module on gender-affirming care, followed by a series of interactive cases on TGD-specific health topics. Undergraduate medical students completing their core OB/GYN clerkships at a university academic medical center (January-December 2021) were invited to complete this curriculum. Participants completed pre/post assessment surveys to assess their experience caring for TGD patients, as well as a scored knowledge assessment before and after completing the curriculum. Results Sixty-five students participated in this curricular assessment. Prior to completing the module, 45% agreed that they had received adequate TGD health training. Following module completion, students reported increased comfort in caring for transgender patients (49.2% vs. 81.5%; p

Abstract Background It is well known that skeletal integrity is influenced by the musculature. Poor muscle strength (i.e. sarcopenia) is considered a major predictor of fragility fractures. While this observation appears particularly relevant for older women with increased risk of osteoporosis, there has been no comprehensive investigation to determine the influence of muscle performance on compartment‐specific bone microarchitecture in multiple body regions. Methods We retrospectively analysed data from different muscle performance and bone microarchitecture assessments in 230 women (aged 21 to 87 years) at high risk of osteoporosis. Muscle performance tests included grip strength and chair rising test (CRT) combined with mechanography. Balance was determined by Romberg posturography. Areal bone mineral density (BMD) was measured by dual‐energy X‐ray absorptiometry (DXA) at the hip and lumbar spine. Compartment‐specific volumetric BMD, microarchitecture, and geometry were assessed by second‐generation high‐resolution peripheral quantitative computed tomography (HR‐pQCT) at multiple skeletal sites (distal radius, tibia, and fibula). Regression models were applied to test for interactions between muscle and bone parameters. Subgroups were defined to compare women with osteoporosis and osteosarcopenia regarding BMD and microarchitecture. Results While osteoporosis was diagnosed in 115/230 (50.0%) women, sarcopenia was detected in 38/230 (16.5%). Positive associations of both grip strength and CRT maximum force with cortical geometric and microarchitectural parameters were detected at all measured sites, with the strongest effect applying to CRT maximum force and tibial parameters (e.g. tibial cortical area R2 = 0.36, P

Abstract Premise The HybPiper pipeline has become one of the most widely used tools for the assembly of target capture data for phylogenomic analysis. After the production of locus sequences and before phylogenetic analysis, the identification of paralogs is a critical step for ensuring the accurate inference of evolutionary relationships. Algorithmic approaches using gene tree topologies for the inference of ortholog groups are computationally efficient and broadly applicable to non‐model organisms, especially in the absence of a known species tree. Methods and Results We containerized and expanded the functionality of both HybPiper and a pipeline for the inference of ortholog groups, providing novel options for the treatment of target capture sequence data, and allowing seamless use of the outputs of the former as inputs for the latter. The Singularity container presented here includes all dependencies, and the corresponding pipelines (hybpiper‐nf and paragone‐nf, respectively) are implemented via two Nextflow scripts for easier deployment and to vastly reduce the number of commands required for their use. Conclusions The hybpiper‐nf and paragone‐nf pipelines are easily installed and provide a user‐friendly experience and robust results to the phylogenetic community. They are used by the Australian Angiosperm Tree of Life project. The pipelines are available at https://github.com/chrisjackson-pellicle/hybpiper-nf and https://github.com/chrisjackson-pellicle/paragone-nf.

Early life microbial colonization and factors affecting colonization patterns are gaining interest due to recent developments suggesting that early life microbiome may play a role in Developmental Origins of Health and Disease. In cattle, limited information exists on the early microbial colonization of anatomical sites involved in bovine health beyond the gastrointestinal tract. Here, we investigated 1) the initial microbial colonization of seven different anatomical locations in newborn calves and 2) whether these early life microbial communities and 3) serum cytokine profiles are influenced by prenatal vitamin and mineral (VTM) supplementation. Samples were collected from the hoof, liver, lung, nasal cavity, eye, rumen (tissue and fluid), and vagina of beef calves that were born from dams that either received or did not receive VTM supplementation throughout gestation (n = 7/group). Calves were separated from dams immediately after birth and fed commercial colostrum and milk replacer until euthanasia at 30 h post-initial colostrum feeding. The microbiota of all samples was assessed using 16S rRNA gene sequencing and qPCR. Calf serum was subjected to multiplex quantification of 15 bovine cytokines and chemokines. Our results indicated that the hoof, eye, liver, lung, nasal cavity, and vagina of newborn calves were colonized by site-specific microbiota, whose community structure differed from the ruminal-associated communities (0.64 ≥ R2 ≥ 0.12, p ≤ 0.003). The ruminal fluid microbial community was the only one that differed by treatment (p < 0.01). However, differences (p < 0.05) by treatment were detected in microbial richness (vagina); diversity (ruminal tissue, fluid, and eye); composition at the phylum and genus level (ruminal tissue, fluid, and vagina); and in total bacterial abundance (eye and vagina). From serum cytokines evaluated, concentration of chemokine IP-10 was greater (p = 0.02) in VTM calves compared to control calves. Overall, our results suggest that upon birth, the whole-body of newborn calves are colonized by relatively rich, diverse, and site-specific bacterial communities. Noticeable differences were observed in ruminal, vaginal, and ocular microbiota of newborn calves in response to prenatal VTM supplementation. These findings can derive future hypotheses regarding the initial microbial colonization of different body sites, and on maternal micronutrient consumption as a factor that may influence early life microbial colonization.

Abstract A passive‐adaptive slat concept was designed to avoid separation in the root region of a horizontal‐axis wind turbine blade. This concept incorporates an autonomously moveable slat device only driven by the aerodynamic forces acting on it without the need for mechanical or electrical actuation. It opens at high local angles of attack to delay the stall angle and closes for small angles of attack to increase the lift to drag ratio of the blade segment. This article describes the development of a passive‐adaptive slat for a DU‐91‐W2‐250 airfoil, which is a segment of the reference rotor blade in the project SmartBlades 2.0. In the course of the passive‐adaptive slat design, the optimization of the slat and its extended position is presented. This is followed by the development of two passive‐adaptive slat kinematics, which are opening and closing the slat passively at different angles of attack. With the designed passive‐adaptive slat the stall of the airfoil is delayed by 20° in incidence and the maximum lift of the airfoil is increased by about 130% at the same time in comparison to the original airfoil. Furthermore, the DU‐91‐W2‐250 airfoil with moveable passive‐adaptive slat has in most conditions a higher climb index and therefore a better aerodynamic performance than the same airfoil with a fixed integrated slat.

Abstract Background Gangliosides are glycosphingolipids highly enriched in the brain, with important roles in cell signaling, cell-to-cell communication, and immunomodulation. Genetic defects in the ganglioside biosynthetic pathway result in severe neurodegenerative diseases, while a partial decrease in the levels of specific gangliosides was reported in Parkinson’s disease and Huntington’s disease. In models of both diseases and other conditions, administration of GM1—one of the most abundant gangliosides in the brain—provides neuroprotection. Most studies have focused on the direct neuroprotective effects of gangliosides on neurons, but their role in other brain cells, in particular microglia, is not known. In this study we investigated the effects of exogenous ganglioside administration and modulation of endogenous ganglioside levels on the response of microglia to inflammatory stimuli, which often contributes to initiation or exacerbation of neurodegeneration. Methods In vitro studies were performed using BV2 cells, mouse, rat, and human primary microglia cultures. Modulation of microglial ganglioside levels was achieved by administration of exogenous gangliosides, or by treatment with GENZ-123346 and L–t-PDMP, an inhibitor and an activator of glycolipid biosynthesis, respectively. Response of microglia to inflammatory stimuli (LPS, IL-1β, phagocytosis of latex beads) was measured by analysis of gene expression and/or secretion of pro-inflammatory cytokines. The effects of GM1 administration on microglia activation were also assessed in vivo in C57Bl/6 mice, following intraperitoneal injection of LPS. Results GM1 decreased inflammatory microglia responses in vitro and in vivo, even when administered after microglia activation. These anti-inflammatory effects depended on the presence of the sialic acid residue in the GM1 glycan headgroup and the presence of a lipid tail. Other gangliosides shared similar anti-inflammatory effects in in vitro models, including GD3, GD1a, GD1b, and GT1b. Conversely, GM3 and GQ1b displayed pro-inflammatory activity. The anti-inflammatory effects of GM1 and other gangliosides were partially reproduced by increasing endogenous ganglioside levels with L–t-PDMP, whereas inhibition of glycolipid biosynthesis exacerbated microglial activation in response to LPS stimulation. Conclusions Our data suggest that gangliosides are important modulators of microglia inflammatory responses and reveal that administration of GM1 and other complex gangliosides exerts anti-inflammatory effects on microglia that could be exploited therapeutically.

Background: Women experiencing homelessness with substance use disorders face unique and intersecting barriers to realizing their reproductive goals. Objective: This study explored the reproductive aspirations of this population, as well as the barriers to accessing reproductive services from the perspectives of affected individuals, and the healthcare providers who serve them. Design: This mixed-methods study included surveys and interviews with women experiencing homelessness with substance use disorders and healthcare providers. Methods: We conducted surveys and semi-structured interviews with women recruited from opiate treatment programs and homeless encampments in San Francisco, California in 2018. We also conducted interviews and focus groups with healthcare providers in reproductive health and substance use treatment settings. Interviews were recorded, transcribed, and coded. Descriptive statistics of survey results were performed. Results: Twenty-eight women completed surveys, 96% of whom reported current substance use. Ten women participated in interviews. One-third (9/28) reported desiring pregnancy in the next year; over half (16/28) reported they would be somewhat or very happy to learn they were pregnant. A majority used no contraception at last intercourse (14/28). Twenty-six healthcare providers participated in interviews (n = 15) and focus groups (n = 2). Patients and providers identified similar barriers to care access, including discrimination, logistical and financial challenges, and delayed pregnancy awareness. While providers proposed solutions focused on overcoming logistical challenges, patients emphasized the importance of transforming the healthcare environment to treat patients affected by substance use and homelessness with dignity and respect. Conclusion: Women experiencing homelessness with substance use disorders face intersecting and compounding barriers to accessing reproductive health services. For patients, the impact of stigma and bias on treatment experiences are particularly salient, in contrast to logistical barriers emphasized by providers. Improving access will require structural and individual-level solutions to address stigma and create person-centered, trauma-informed, and respectful care environments.

Climate change is impacting marine seascapes against a backdrop of multiple anthropogenic stressors. These current impacts are projected to increase in the future with increasing warming, acidification, oxygen loss, and sea level rise. Marine Protected Areas (MPAs) have been established to protect features in the ocean, traditionally with a focus to reduce fishing pressures and infrastructure placements. These MPAs are static in nature and are rarely considering climate change; therefore, their potential adaptation effectiveness as local adaptation measures for conservation in response to climate change are not clear. Here we discuss the challenges to Marine Protected Areas as conservation tools and for adaptation to climate change threats. We use two case studies from the UK to ask how climate change resilience could be included in MPA management to future-proof these conservation measures. We conclude that the resilience of MPAs to climate change would be better supported when adaptive management measures and an ecosystem-based approaches are adopted. We emphasise the need to increase the recognition in the primary legislation of MPAs and the monitoring of sites to better understand climate change as it becomes more pronounced, and impacts emerge.

Abstract We build random forests models to predict elastic properties and mechanical hardness of a compound, using only its chemical formula as input. The model training uses over 10,000 target compounds and 60 features based on stoichiometric attributes, elemental properties, orbital occupations, and ionic bonding levels. Using the models, we construct triangular graphs for B-C-N compounds to map out their bulk and shear moduli, as well as hardness values. The graphs indicate that a 1:1 B-N ratio can lead to various superhard compositions. We also validate the machine learning results by evolutionary structure prediction and density functional theory. Our study shows that BC10N, B4C5N3, and B2C3N exhibit dynamically stable phases with hardness values >40 GPa, which are superhard materials that potentially could be synthesized by low-temperature plasma methods.

Latent Profile Analysis (LPA) is a method to extract homogeneous clusters characterized by a common response profile. Previous works employing LPA to human value segmentation tend to select a small number of moderately homogeneous clusters based on model selection criteria such as Akaike information criterion, Bayesian information criterion and Entropy. The question is whether a small number of clusters is all that can be gleaned from the data. While some studies have carefully compared different statistical model selection criteria, there is currently no established criteria to assess if an increased number of clusters generates meaningful theoretical insights. This article examines the content and meaningfulness of the clusters extracted using two algorithms: Variational Bayesian LPA and Maximum Likelihood LPA. For both methods, our results point towards eight as the optimal number of clusters for characterizing distinctive Schwartz value typologies that generate meaningful insights and predict several external variables.

Climate change is impacting organisms in every region of the world ocean by acting though on individuals in response to their local environments. Given projected future risks derived from these changes, it is becoming increasingly important to understand regional signals of how organisms respond to facilitate their governance and protection. Benthic organisms structure ecological compositions and ecosystem dynamics, therefore not only providing insights into their own response to climate change but also how ecosystems might respond to future conditions. European seas are transitional areas including boreal, warm-temperate, and subarctic waters with organisms frequently at limits of their distributions. Here, we use a meta-analytical approach to assess how calcification, growth, metabolism, photosynthesis, reproduction, and survival in European benthic organisms respond to ocean acidification and warming. Using meta-regression, we examine how study design factors influence effect-size outcomes. Longer experimental periods generally amplified the effects of climate change on taxonomic groupings and related physiological traits and against expectation do not result in acclimation. In agreement with global studies, we find that impacts vary considerably on different taxonomic groupings and their physiological traits. We found calcifying organisms are an at-risk taxon in European waters, with climate stressors decreasing growth rates, reproduction, and survival rates. Fleshy algal species demonstrate resilience to climate stressors, suggesting future European benthic ecosystems will undergo restructuring based on current climate emission pathways.

MAPM (Mapping Air Pollution eMissions) is a project whose goal is to develop a method to infer airborne particulate matter (PM) emissions maps from in situ PM concentration measurements. In support of MAPM, a winter field campaign was conducted in New Zealand in 2019 (June to September) to obtain the measurements required to test and validate the MAPM methodology. Two different types of instruments measuring PM were deployed: ES-642 remote dust monitors (17 instruments) and Outdoor Dust Information Nodes (ODINs; 50 instruments). The measurement campaign was bracketed by two intercomparisons where all instruments were co-located, with a permanently installed tapered element oscillating membrane (TEOM) instrument, to determine any instrument biases. Changes in biases between the pre- and post-campaign intercomparisons were used to determine instrument drift over the campaign period. Once deployed, each ES-642 was co-located with an ODIN. In addition to the PM measurements, meteorological variables (temperature, pressure, wind speed, and wind direction) were measured at three automatic weather station (AWS) sites established as part of the campaign, with additional data being sourced from 27 further AWSs operated by other agencies. Vertical profile measurements were made with 12 radiosondes during two 24 h periods and complimented measurements made with a mini micropulse lidar and ceilometer. Here we present the data collected during the campaign and discuss the correction of the measurements made by various PM instruments. We find that when compared to measurements made with a simple linear correction, a correction based on environmental conditions improves the quality of measurements retrieved from ODINs but results in over-fitting and increases the uncertainties when applied to the more sophisticated ES-642 instruments. We also compare PM2.5 and PM10 measured by ODINs which, in some cases, allows us to identify PM from natural and anthropogenic sources. The PM data collected during the campaign are publicly available from https://doi.org/10.5281/zenodo.4542559 (Dale et al., 2020b), and the data from other instruments are available from https://doi.org/10.5281/zenodo.4536640 (Dale et al., 2020a).

Abstract The southern Great Plains of the USA has great potential to produce biofuel feedstock while minimizing the dual stresses of woody plant encroachment and climate change. Switchgrass (Panicum virgatum) cultivation, woody biomass captured during removal of the encroaching eastern redcedar (Juniperus virginiana) to restore grasslands and thinning of the native oak forest can provide an integrated source of feedstock and improve ecosystem services. In north‐central Oklahoma, we quantified productivity and ecosystem water use of switchgrass stands and degraded ecosystems encroached by eastern redcedar and compared these to native oak forest and tallgrass prairie ecosystems. We measured aboveground net primary productivity (ANPP) using allometric equations (trees) and clip plots (herbaceous), and evapotranspiration (ET) using a water balance approach from gauged watersheds, and calculated water use efficiency (WUE = ANPP/ET) from 2016 to 2019. Among vegetation cover types, ANPP averaged 5.1, 5.4, 6.0, and 7.8 Mg ha−1 year−1 for the prairie, oak, eastern redcedar, and switchgrass watersheds and was significantly greater for switchgrass in 2018 and 2019 (2 and 3 years post establishment) when it reached 8.6 Mg ha−1 year−1. Averaged across 2017–2019, ET was significantly greater in the forested watersheds than the grassland watersheds (1022 mm year−1 for eastern redcedar, 1025 mm year−1 for oak, 874 mm year−1 for prairie, and 828 mm year−1 for switchgrass). The mean WUE was significantly greater (9.47 kg ha−1 mm−1) for switchgrass than for the prairie, eastern redcedar, and oak cover types (6.03, 6.02, and 5.31 kg ha−1 mm−1). Switchgrass offered benefits of greater ANPP, less ET, and greater WUE. Our findings indicate that an integrated biofuel feedstock system that includes converting eastern redcedar encroached areas to switchgrass and thinning the oak forest can increase productivity, increase runoff to streams, and improve ecosystem services.

Modern diffusion and functional magnetic resonance imaging (dMRI/fMRI) provide non-invasive high-resolution images from which multi-layered networks of whole-brain structural and functional connectivity can be derived. Unfortunately, the lack of observed correspondence between the connectivity profiles of the two modalities challenges the understanding of the relationship between the functional and structural connectome. Rather than focusing on correspondence at the level of connections we presently investigate correspondence in terms of modular organization according to shared canonical processing units. We use a stochastic block-model (SBM) as a data-driven approach for clustering high-resolution multi-layer whole-brain connectivity networks and use prediction to quantify the extent to which a given clustering accounts for the connectome within a modality. The employed SBM assumes a single underlying parcellation exists across modalities whilst permitting each modality to possess an independent connectivity structure between parcels thereby imposing concurrent functional and structural units but different structural and functional connectivity profiles. We contrast the joint processing units to their modality specific counterparts and find that even though data-driven structural and functional parcellations exhibit substantial differences, attributed to modality specific biases, the joint model is able to achieve a consensus representation that well accounts for both the functional and structural connectome providing improved representations of functional connectivity compared to using functional data alone. This implies that a representation persists in the consensus model that is shared by the individual modalities. We find additional support for this viewpoint when the anatomical correspondence between modalities is removed from the joint modeling. The resultant drop in predictive performance is in general substantial, confirming that the anatomical correspondence of processing units is indeed present between the two modalities. Our findings illustrate how multi-modal integration admits consensus representations well-characterizing each individual modality despite their biases and points to the importance of multi-layered connectomes as providing supplementary information regarding the brain's canonical processing units.

Sialic acid-binding immunoglobulin-type lectins (Siglecs) are a family of immunomodulatory receptors expressed on cells of the hematopoietic lineage. Here the authors demonstrate an approach for the identification of the glycan ligands of Siglecs, which is also applicable to other families of glycan-binding proteins.

Changes in morphology during ontogeny can have profound impacts on the physiology and biology of a species. Studies of ontogenetic disparity through time are rare because of the lack of preservation of developmental stages in the fossil record. As they grow by incremental chamber accretion and retain evidence of growth in their shell, planktic foraminifera are an ideal group for the study ontogenetic disparity through the evolution of a higher taxon. Here, we quantify different developmental stages in Jurassic foraminifers and infer the evolutionary implications of the shape of these earliest representatives of the group. Using a Zeiss Xradia micro-CT scanner, the development of Globuligerina bathoniana and Globuligerina oxfordiana from the Bathonian sediments of Gnaszyn, Poland, and Globuligerina balakhmatovae and Globuligerina tojeiraensis from the Kimmeridgian Tojeira Formation of Portugal was reconstructed. Disparity is low through the early evolution of planktic foraminifers. The number of chambers and range in surface area per unit volume are lower than in modern specimens. We interpret this morphology as an indication of opportunistic behaviour. The low morphological plasticity during the juvenile stage suggests that strong constraints on the juveniles, described in the modern ocean, were already acting on Jurassic specimens. The high surface area per unit volume in these developmental stages points towards the need to satisfy a higher metabolic demand than in the adult specimens. We are interpreting the lower chamber numbers as indicative of short life cycles and potentially rapid reproduction, both of which may have allowed these species to exploit the nutrient-rich waters of the Jurassic Tethys Ocean.

Doses of irradiation above 25 ​kGy are known to cause irreversible mechanical decay in bone tissue. However, the impact of irradiation doses absorbed in a clinical setting on the mechanical properties of bone remains unclear. In daily clinical practice and research, patients and specimens are exposed to irradiation due to diagnostic imaging tools, with doses ranging from milligray to Gray. The aim of this study was to investigate the influence of irradiation at these doses ranges on the mechanical performance of bone independent of inter-individual bone quality indices.Therefore, cortical bone specimens (n ​= ​10 per group) from a selected organ donor were irradiated at doses of milligray, Gray and kilogray (graft tissue sterilization) at five different irradiation doses. Three-point bending was performed to assess mechanical properties in the study groups.Our results show a severe reduction in mechanical performance (work to fracture: 50.29 ​± ​11.49 Nmm in control, 14.73 ​± ​1.84 Nmm at 31.2 ​kGy p ​≤ ​0.05) at high irradiation doses of 31.2 ​kGy, which correspond to graft tissue sterilization or synchrotron imaging. In contrast, no reduction in mechanical properties were detected for doses below 30 ​Gy. These findings are further supported by fracture surface texture imaging (i.e. more brittle fracture textures above 31.2 ​kGy).Our findings show that high radiation doses (≥31.2 ​kGy) severely alter the mechanical properties of bone. Thus, irradiation of this order of magnitude should be taken into account when mechanical analyses are planned after irradiation. However, doses of 30 ​Gy and below, which are common for clinical and experimental imaging (e.g., radiation therapy, DVT imaging, CT imaging, HR-pQCT imaging, DXA measurements, etc.), do not alter the mechanical bending-behavior of bone.