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Hyper-realistic silicone masks provide a viable route to identity fraud. Over the last decade, more than 40 known criminal acts have been committed by perpetrators using this type of disguise. With the increasing availability and bespoke sophistication of these masks, research must now focus on ways to enhance their detection. In this study, we investigate whether super-recognisers (SRs), people who excel at identity recognition, are more likely to detect this type of fraud, in comparison to typical-recogniser controls. Across three tasks, we examined mask detection rates in the absence of a pre-task prompt (covert task), and again after making participants aware of their use in criminal settings (explicit task). Finally, participants were asked to indicate which aspects of the masks could support their detection (regions of interest task). The findings show an SR advantage for the detection of hyper-realistic masks across the covert and explicit mask detection tasks. In addition, the eye, mouth, and nose regions appear to be particularly indicative of the presence of a mask. The lack of natural skin texture, proportional features, expressiveness, and asymmetry are also salient cues. The theoretical and applied implications of these findings are discussed.

Background: A volitional help sheet (VHS) is an intervention for promoting implementation intentions. This study was the first to test the effectiveness of a VHS for increasing university students' lecture attendance. Aims: To develop a VHS to increase university students' lecture attendance and test its effectiveness at increasing the proportion of lectures attended, and promoting the maintenance of lecture attendance, over an 11-week teaching semester. Sample and Method: One hundred and seventy-eight undergraduate students enrolled in a psychology degree programme were allocated at random to a VHS or active control condition. Prior to intervention, measures of goal intention to attend lectures and trait conscientiousness were collected using self-report, online questionnaires. Over the following 11-week teaching semester, attendance at synchronous (live) online lectures was measured. Results: The VHS condition attended a greater proportion of lectures and maintained their lecture attendance for longer than did the active control condition. These effects were not sensitive to underlying goal intentions, although the sample means on the measures of goal intention were approaching ceiling. Trait conscientiousness increased the effects of the VHS on the proportion of lectures attended. Conclusions: VHSs constitute useful interventions for increasing and maintaining university students' lecture attendance.

Abstract Highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b viruses were first detected in St. John’s, Canada in late 2021. To investigate the patterns of avian influenza virus (AIV) infection and immune responses subsequent to the arrival of H5N1, we sampled the wild urban duck population in this area for a period of 16 months after the start of the outbreak and compared these findings to those from archived samples. Antibody seroprevalence was relatively stable before the outbreak (2011–2014) at 27.6% and 3.9% for anti-AIV (i.e., NP) and H5-specific antibodies, respectively. During the winter of 2022, AIV-NP and H5-specific antibody seroprevalence both reached 100%, signifying a population-wide infection event, which was observed again in late February 2023 following a second H5N1 incursion from Eurasia. As expected, population-level immunity waned over time, with ducks seropositive for anti-AIV-NP antibodies for approximately twice as long as for H5-specific antibodies, with the population seronegative to the latter after approximately six months. We observed a clear relationship of increasing antibody levels with decreasing viral RNA loads that allowed for interpretation of the course of infection and immune response in infected individuals and applied these findings to two cases of resampled ducks to infer infection history. Our study highlights the value of applying both AIV surveillance and seroprevalence monitoring to provide a better understanding of AIV dynamics in wild populations, which may be crucial following the global dissemination of clade 2.3.4.4b H5Nx subtypes to assess the threats they pose to both wild and domestic animals, and to humans.

Abstract Background Pain is common in the genetic skin fragility disorder epidermolysis bullosa (EB), from skin and mucosal injury and inflammation as well as extra-mucocutaneous sites. Individuals living with EB have identified pain as a priority for better treatments. Objectives The Prospective EB Longitudinal Evaluation Study (PEBLES) is a prospective register study exploring the natural history of RDEB across all ages from birth to death. Here, we investigated the characteristics and treatment of pain in different RDEB subtypes. Methods Information was collected from individuals with different RDEB subtypes over an 8-year period. Data included visual analogue scale (VAS) ratings of background and procedural pain, its location, intensity and impact on sleep, as well as pain medication. Disease severity scores and quality of life measures were correlated to pain scores. Results Sixty-one participants (13 children, 48 adults) completed a total of 361 reviews. Pain was common, experienced by 93% of participants at index review, with 80% suffering both background and procedural pain. Across all RDEB patients, the median VAS for background pain was 40 (out of 100) [interquartile range 20,60] and for those having regular dressing changes, median procedural pain was 52 [40,80]. Severe (RDEB-S) and pruriginosa (RDEB-Pru) groups had the greatest increase in procedural compared to background pain of 20 and 22 VAS points, respectively. Correlations between disease severity and quality of life impairment were observed across most groups, particularly RDEB-S. Over half of those studied experienced pain frequently or constantly, and in one third pain disturbed sleep at least 4 nights per week. Skin was the commonest source of pain in all subtypes except inversa RDEB where the mouth was the main site. Despite frequent and severe pain, one third of participants used no medication for pain and, in those that did, pain levels remained high suggesting ineffectiveness of current pain management approaches and a significant unmet need in RDEB. Conclusion The frequency, severity, and impact of pain in all RDEB patients is significant, particularly in RDEB-S and RDEB-Pru. Our findings highlight that current RDEB pain management is poorly effective and that further research is needed to address this symptom.

Abstract Seabird colonies with long-term monitoring records, i.e., > 50 years, are rare. The population data for northern gannets (Morus bassanus) in Cape St. Mary’s (CSM) Ecological Reserve (Newfoundland and Labrador, Canada) is robust, extending back to 1883 when the colony was presumed established. We inferred the colony’s historical population shifts by measuring ornithogenic proxies in a dated sediment record collected from a nearby pond. Our record extended to the early eighteenth century, but the proxy data only began to show significant signs of seabird presence between ca. 1832 and 1910, aligning with the period gannets were first observed at CSM. Through the twentieth century, we observed significant increases in δ15N, P, Zn, Cd, and chlorophyll a, coeval with a shift in the dominant diatom species, indicating rapid colony growth. The proxies were overall highest in ca. 2005, corresponding to the reported historical maximum of the gannet colony in 2009. Our results validate that paleo-reconstructions using ornithogenic proxies can accurately reflect population trends and provide a stronger understanding of the colony’s establishment and growth. This study highlights the value of applying paleolimnological methods in seabird population studies to frame the history of a colony’s dynamics and inform conservation efforts.

Abstract A fifteen-month-old Pembroke Welsh corgi with respiratory distress, exercise intolerance, and moderate regenerative anemia was referred to The Norwegian University of Life Sciences, Small Animal Hospital. Hematology revealed moderate regenerative anemia without evidence of hemolysis. Thoracic radiographs showed a generalized mixed interstitial to alveolar lung pattern and enlarged pulmonary arteries. Changes suggestive of moderate pulmonary hypertension were noted on echocardiography. Baermann fecal diagnostic flotation identified large numbers of Angiostrongylus vasorum larvae, and the AngioDetect serological antigen test was positive. The dog was treated with a two-week course with fenbendazole (51 mg/kg q24h po) and topical imidacloprid/moxidectin (250 mg/62.5 mg) and a one-week course with sildenafil (0.45 mg/kg q12h po). Complete clinical, clinicopathological and echocardiographic resolution was observed after only four weeks. Rapid improvement of echocardiographic abnormalities in cases with suspected pulmonary hypertension is not usually reported in cases with angiostrongylosis. Infection with A. vasorum should be considered in dogs with respiratory signs and bleeding tendencies, even in countries with no endemic history or reported cases.

Abstract Background Stalk lodging (the premature breaking of plant stalks or stems prior to harvest) is a persistent agricultural problem that causes billions of dollars in lost yield every year. Three-point bending tests, and rind puncture tests are common biomechanical measurements utilized to investigate crops susceptibility to lodging. However, the effect of testing rate on these biomechanical measurements is not well understood. In general, biological specimens (including plant stems) are well known to exhibit viscoelastic mechanical properties, thus their mechanical response is dependent upon the rate at which they are deflected. However, there is very little information in the literature regarding the effect of testing rate (aka displacement rate) on flexural stiffness, bending strength and rind puncture measurements of plant stems. Results Fully mature and senesced maize stems and wheat stems were tested in three-point bending at various rates. Maize stems were also subjected to rind penetration tests at various rates. Testing rate had a small effect on flexural stiffness and bending strength calculations obtained from three-point bending tests. Rind puncture measurements exhibited strong rate dependent effects. As puncture rate increased, puncture force decreased. This was unexpected as viscoelastic materials typically show an increase in resistive force when rate is increased. Conclusions Testing rate influenced three-point bending test results and rind puncture measurements of fully mature and dry plant stems. In green stems these effects are expected to be even larger. When conducting biomechanical tests of plant stems it is important to utilize consistent span lengths and displacement rates within a study. Ideally samples should be tested at a rate similar to what they would experience in-vivo.

PCR-based diagnostics has revealed the previously largely unknown Cryptosporidium transmission and infections in high-income countries. This study aimed to determine domestic and imported subtypes of Cryptosporidium species in Norway, evaluate their demographic distribution, and identify potential small outbreaks. Cryptosporidium-positive human faecal samples were obtained from six medical microbiology laboratories between February 2022 and January 2024, together with 22 Cryptosporidium-positive animal samples. Species and subtypes were identified by sequencing PCR products from gp60 and SSU rRNA genes. Most cryptosporidiosis cases occurred during late summer/early autumn, primarily in children and young adults. Of 550 human samples, 359 were successfully characterized molecularly (65%), revealing infection with 10 different Cryptosporidium species. C. parvum occurred in 245 (68%) human isolates with IIa and IId being major allele families, with distinct regional distribution patterns of common subtypes. A kindergarten outbreak with 5 cases was due to C. parvum IIaA14G1R1. C. mortiferum was identified in 33 (9.2%) human cases of which 24 were known to be of domestic origin, making it the second most common species in human autochthonous cases in Norway. All C. mortiferum isolates were of the same genotype; XIVaA20G2T1, including 13 cases from a suspected small outbreak in Trøndelag. C. hominis occurred in 68 typed cases (19%), but mostly in infections acquired abroad, with allele families Ib and If occurring most often. In conclusion, this study of recent Cryptosporidium spp. and subtypes in Norway, highlights the predominance of C. parvum and the emergence of C. mortiferum among autochthonous cases.

Wild and semi-domesticated reindeer graze freely on natural pastures in Norway, often sharing these with domestic sheep and other domestic and wild ruminants. In this study, faecal samples from wild reindeer and domestic sheep were collected from two areas in southern Norway and analysed to assess the occurrence and assemblage of Giardia duodenalis. Among 162 wild reindeer samples, 25 (15%) were positive for Giardia, showing high infection intensities, with most of the samples belonging to sub-assemblage AI, which has zoonotic potential. Interestingly, this study did not detect subassemblage AIII, known to be found in wild ruminants. Among 45 sheep samples, 13 (29%) were Giardia-positive, with most belonging to assemblage E.The finding of predominantly assemblage AI in the reindeer was surprising, particularly given the large proportion of sheep shedding assemblage E Giardia cysts. As the number of sheep on these natural pastures far outnumbers the wild reindeer, it is intriguing that they do not seem to share Giardia assemblages.

Abstract CRISPR-Cas9 technology has facilitated development of strategies that can potentially provide more humane and effective methods to control invasive vertebrate species, such as mice. One promising strategy is X chromosome shredding which aims to bias offspring towards males, resulting in a gradual and unsustainable decline of females. This method has been explored in insects with encouraging results. Here, we investigated this strategy in Mus musculus by targeting repeat DNA sequences on the X chromosome with the aim of inducing sufficient DNA damage to specifically eliminate X chromosome-bearing sperm during gametogenesis. We tested three different guide RNAs (gRNAs) targeting different repeats on the X chromosome, together with three male germline-specific promoters for inducing Cas9 expression at different stages of spermatogenesis. A modest bias towards mature Y-bearing sperm was detected in some transgenic males, although this did not translate into significant male-biasing of offspring. Instead, cleavage of the X chromosome during meiosis typically resulted in a spermatogenic block, manifest as small testes volume, empty tubules, low sperm concentration, and sub/infertility. Our study highlights the importance of controlling the timing of CRISPR-Cas9 activity during mammalian spermatogenesis and the sensitivity of spermatocytes to X chromosome disruption.

Abstract In 2022, a severe outbreak of disease caused by clade 2.3.4.4b Highly Pathogenic Avian Influenza (HPAI) H5N1 virus resulted in unprecedented mortality among wild birds in eastern Canada. Tens of thousands of birds were reported sick or dead, prompting a comprehensive assessment of mortality spanning the breeding season between April 1 and September 30, 2022. Mortality reports were collated from federal, Indigenous, provincial, and municipal agencies, the Canadian Wildlife Health Cooperative, and other nongovernmental organizations, universities, and citizen science platforms. A scenario analysis was conducted to refine mortality estimates, accounting for potential double counts from multiple sources under a range of spatial and temporal overlaps. Correcting for double counting, HPAI is estimated to have caused 40,391 wild bird mortalities in eastern Canada during the spring and summer of 2022; however, this figure underestimates total mortality as it excludes unreported deaths on land and at sea. Seabirds and sea ducks, long‐lived species that are slow to recover from perturbations, accounted for 98.7% of estimated mortalities. Our study provides estimates of bird mortality, with Northern Gannets (Morus bassanus; 25,669), Common Murres (Uria aalge; 8133), and American Common Eiders (Somateria mollissima dresseri; 1894) exhibiting the highest mortality figures. We then compare these mortality estimates with recent population estimates and trends and make an initial assessment of whether biologically meaningful population‐level impacts are possible. Specifically, we focus on the Northern Gannet, a species that has suffered significant global mortality, and two harvested species, Common Murre and American Common Eider, to inform management decisions. Our analysis suggests population‐level impacts in eastern Canada are possible for Northern Gannets and American Common Eiders, but are unlikely for Common Murres. This study demonstrates a comprehensive approach to assessing mortality and underscores the urgent need for further research to understand the broader ecological ramifications of the HPAI outbreak on wild bird populations.

ABSTRACT Following the detection of novel highly pathogenic avian influenza virus (HPAIV) H5N1 clade 2.3.4.4b in Newfoundland, Canada, in late 2021, avian influenza virus (AIV) surveillance in wild birds was scaled up across Canada. Herein, we present the results of Canada’s Interagency Surveillance Program for Avian Influenza in Wild Birds during the first year (November 2021–November 2022) following the incursions of HPAIV from Eurasia. The key objectives of the surveillance program were to (i) identify the presence, distribution, and spread of HPAIV and other AIVs; (ii) identify wild bird morbidity and mortality associated with HPAIV; (iii) identify the range of wild bird species infected by HPAIV; and (iv) genetically characterize detected AIV. A total of 6,246 sick and dead wild birds were tested, of which 27.4% were HPAIV positive across 12 taxonomic orders and 80 species. Geographically, HPAIV detections occurred in all Canadian provinces and territories, with the highest numbers in the Atlantic and Central Flyways. Temporally, peak detections differed across flyways, though the national peak occurred in April 2022. In an additional 11,295 asymptomatic harvested or live-captured wild birds, 5.2% were HPAIV positive across 3 taxonomic orders and 19 species. Whole-genome sequencing identified HPAIV of Eurasian origin as most prevalent in the Atlantic Flyway, along with multiple reassortants of mixed Eurasian and North American origins distributed across Canada, with moderate structuring at the flyway scale. Wild birds were victims and reservoirs of HPAIV H5N1 2.3.4.4b, underscoring the importance of surveillance encompassing samples from sick and dead, as well as live and harvested birds, to provide insights into the dynamics and potential impacts of the HPAIV H5N1 outbreak. This dramatic shift in the presence and distribution of HPAIV in wild birds in Canada highlights a need for sustained investment in wild bird surveillance and collaboration across interagency partners.IMPORTANCEWe present the results of Canada’s Interagency Surveillance Program for Avian Influenza in Wild Birds in the year following the first detection of highly pathogenic avian influenza virus (HPAIV) H5N1 on the continent. The surveillance program tested over 17,000 wild birds, both sick and apparently healthy, which revealed spatiotemporal and taxonomic patterns in HPAIV prevalence and mortality across Canada. The significant shift in the presence and distribution of HPAIV in Canada’s wild birds underscores the need for sustained investment in wild bird surveillance and collaboration across One Health partners.

Abstract Despite the significant advances in understanding the genetic architecture of epilepsy, many patients do not receive a molecular diagnosis after genomic testing. Re-analysing existing genomic data has emerged as a potent method to increase diagnostic yields—providing the benefits of genomic-enabled medicine to more individuals afflicted with a range of different conditions. The primary drivers for these new diagnoses are the discovery of novel gene-disease and variants-disease relationships; however, most decisions to trigger re-analysis are based on the passage of time rather than the accumulation of new knowledge. To explore how our understanding of a specific condition changes and how this impacts re-analysis of genomic data from epilepsy patients, we developed Vigelint. This approach combines the information from PanelApp and ClinVar to characterise how the clinically relevant genes and causative variants available to laboratories change over time, and this approach to five clinical-grade epilepsy panels. Applying the Vigelint pipeline to these panels revealed highly variable patterns in new, clinically relevant knowledge becoming publicly available. This variability indicates that a more dynamic approach to re-analysis may benefit the diagnosis and treatment of epilepsy patients. Moreover, this work suggests that Vigelint can provide empirical data to guide more nuanced, condition-specific approaches to re-analysis.

Abstract Background Despite the increasing focus on strengthening One Health capacity building on global level, challenges remain in devising and implementing real-world interventions particularly in the Asia-Pacific region. Recognizing these gaps, the One Health Action Commission (OHAC) was established as an academic community for One Health action with an emphasis on research agenda setting to identify actions for highest impact. Main text This viewpoint describes the agenda of, and motivation for, the recently formed OHAC. Recognizing the urgent need for evidence to support the formulation of necessary action plans, OHAC advocates the adoption of both bottom-up and top-down approaches to identify the current gaps in combating zoonoses, antimicrobial resistance, addressing food safety, and to enhance capacity building for context-sensitive One Health implementation. Conclusions By promoting broader engagement and connection of multidisciplinary stakeholders, OHAC envisions a collaborative global platform for the generation of innovative One Health knowledge, distilled practical experience and actionable policy advice, guided by strong ethical principles of One Health. Graphical Abstract

Based on 12 months of ethnographic fieldwork I conducted at an anal cancer prevention clinic in Chicago, USA, this article considers queer camp humour as a care practice to better understand how providers and patients navigate clinical interactions centred around a stigmatised disease in a taboo body part. Humorous moments infused daily life at the clinic, and I came to see them as a critical feature of the clinic’s uniquely queer environment and a central aspect of the staff’s queer care practices. I argue the campy queer style of humour in the clinic was a vital tool for providing culturally appropriate care, and describe how humour mediated patient-provider interactions, had palliative effects, and managed dirt and bodily excess. The article concludes with a brief discussion of the importance of anthropological attention to humour and joking as forms of care.

Abstract Objective The aim of this study is to report the updated 2‐year results of the intervention arm of the ROBUST III randomized trial evaluating the safety and efficacy of the Optilume drug‐coated balloon (DCB) versus standard endoscopic management of recurrent male anterior urethral stricture. Materials and Methods Eligible patients included men with recurrent anterior urethral stricture ≤3 cm in length and ≤12Fr in diameter, International Prostate Symptom Score (IPSS) ≥11 and peak flow rate (Qmax)

The authors wish to make a correction to the published paper [...]

Preparing athletes for competition requires the diagnosis and monitoring of relevant physical qualities (e.g., strength, power, speed, endurance characteristics). Decisions regarding test selection that attempt to measure these physical attributes are fundamental to the training process yet are complicated by the myriad of tests and measurements available. This article presents an evidenced based process to inform test measurement selection for the physical preparation of athletes. We describe a method for incorporating multiple layers of validity to link test measurement to competition outcome. This is followed by a framework by which to evaluate the suitability of test measurements based on contemporary validity theory that considers technical, decision-making, and organisational factors. Example applications of the framework are described to demonstrate its utility in different settings. The systems presented here will assist in distilling the range of measurements available into those most likely to have the greatest impact on competition performance.

Stalk lodging (structural failure crops prior to harvest) significantly reduces annual yields of vital grain crops. The lack of standardized, high throughput phenotyping methods capable of quantifying biomechanical plant traits prevents comprehensive understanding of the genetic architecture of stalk lodging resistance. A phenotyping pipeline developed to enable higher throughput biomechanical measurements of plant traits related to stalk lodging is presented. The methods were developed using principles from the fields of engineering mechanics and metrology and they enable retention of plant-specific data instead of averaging data across plots as is typical in most phenotyping studies. This pipeline was specifically designed to be implemented in large experimental studies and has been used to phenotype over 40,000 maize stalks. The pipeline includes both lab- and field-based phenotyping methodologies and enables the collection of metadata. Best practices learned by implementing this pipeline over the past three years are presented. The specific instruments (including model numbers and manufacturers) that work well for these methods are presented, however comparable instruments may be used in conjunction with these methods as seen fit. • Efficient methods to measure biomechanical traits and record metadata related to stalk lodging. • Can be used in studies with large sample sizes (i.e., > 1,000).

Health care is at a turning point. We are shifting from protocolized medicine to precision medicine, and digital health systems are facilitating this shift. By providing clinicians with detailed information for each patient and analytic support for decision-making at the point of care, digital health technologies are enabling a new era of precision medicine. Genomic data also provide clinicians with information that can improve the accuracy and timeliness of diagnosis, optimize prescribing, and target risk reduction strategies, all of which are key elements for precision medicine. However, genomic data are predominantly seen as diagnostic information and are not routinely integrated into the clinical workflows of electronic medical records. The use of genomic data holds significant potential for precision medicine; however, as genomic data are fundamentally different from the information collected during routine practice, special considerations are needed to use this information in a digital health setting. This paper outlines the potential of genomic data integration with electronic records, and how these data can enable precision medicine.

Abstract Understanding the factors that drive spatial synchrony among populations or species is important for management and recovery of populations. The range‐wide declines in Atlantic salmon (Salmo salar) populations may be the result of broad‐scale changes in the marine environment. Salmon undergo rapid growth in the ocean; therefore changing marine conditions may affect body size and fecundity estimates used to evaluate whether stock reference points are met. Using a dataset that spanned five decades, 172,268 individuals, and 19 rivers throughout Eastern Canada, we investigated the occurrence of spatial synchrony in changes in the body size of returning wild adult Atlantic salmon. Body size was then related to conditions in the marine environment (i.e., climate indices, thermal habitat availability, food availability, density‐dependence, and fisheries exploitation rates) that may act on all populations during the ocean feeding phase of their life cycle. Body size increased during the 1980s and 1990s for salmon that returned to rivers after one (1SW) or two winters at sea (2SW); however, significant changes were only observed for 1SW and/or 2SW in some mid‐latitude and northern rivers (10/13 rivers with 10 of more years of data during these decades) and not in southern rivers (0/2), suggesting weak spatial synchrony across Eastern Canada. For 1SW salmon in nine rivers, body size was longer when fisheries exploitation rates were lower. For 2SW salmon, body size was longer when suitable thermal habitat was more abundant (significant for 3/8 rivers) and the Atlantic Multidecadal Oscillation was higher (i.e., warmer sea surface temperatures; significant for 4/8 rivers). Overall, the weak spatial synchrony and variable effects of covariates on body size across rivers suggest that changes in Atlantic salmon body size may not be solely driven by shared conditions in the marine environment. Regardless, body size changes may have consequences for population management and recovery through the relationship between size and fecundity.

Environmental air irritants including nanosized carbon black (nCB) can drive systemic inflammation, promoting chronic obstructive pulmonary disease (COPD) and emphysema development. The let-7 microRNA (Mirlet7 miRNA) family is associated with IL-17-driven T cell inflammation, a canonical signature of lung inflammation. Recent evidence suggests the Mirlet7 family is downregulated in patients with COPD, however, whether this repression conveys a functional consequence on emphysema pathology has not been elucidated. Here, we show that overall expression of the Mirlet7 clusters, Mirlet7b/Mirlet7c2 and Mirlet7a1/Mirlet7f1/Mirlet7d, are reduced in the lungs and T cells of smokers with emphysema as well as in mice with cigarette smoke (CS)- or nCB-elicited emphysema. We demonstrate that loss of the Mirlet7b/Mirlet7c2 cluster in T cells predisposed mice to exaggerated CS- or nCB-elicited emphysema. Furthermore, ablation of the Mirlet7b/Mirlet7c2 cluster enhanced CD8+IL17a+ T cells (Tc17) formation in emphysema development in mice. Additionally, transgenic mice overexpressing Mirlet7g in T cells are resistant to Tc17 and CD4+IL17a+ T cells (Th17) development when exposed to nCB. Mechanistically, our findings reveal the master regulator of Tc17/Th17 differentiation, RAR-related orphan receptor gamma t (RORγt), as a direct target of Mirlet7 in T cells. Overall, our findings shed light on the Mirlet7/RORγt axis with Mirlet7 acting as a molecular brake in the generation of Tc17 cells and suggest a novel therapeutic approach for tempering the augmented IL-17-mediated response in emphysema.

Migratory seabirds move across ocean basins and are one of the primary reservoirs of low pathogenic avian influenza virus (LPAIV). This includes the millions of thick-billed murres (Uria lomvia) and common murres (Uria aalge) that are distributed across northern hemisphere oceans. In response to increasingly frequent detections of highly pathogenic avian influenza virus (HPAIV) in Europe in 2020–2021, avian influenza virus (AIV) monitoring in wildlife has increased. We compiled data from murres tested for AIV in Canada between 2007 and 2022 to quantify spatiotemporal variation in the prevalence of LPAIV and HPAIV in these birds. No HPAIV was detected in murres prior to 2022, but HPAIV was present in 46% of both live/harvested and found dead murres in the northwestern Atlantic in 2022 with prevalence peaking at 63% among live birds in the summer. In the eastern Canadian Arctic, HPAIV prevalence in 2022 was

Abstract Among the causative agents of neonatal diarrhoea in calves, two of the most prevalent are bovine coronavirus (BCoV) and the intracellular parasite Cryptosporidium parvum. Although several studies indicate that co-infections are associated with greater symptom severity, the host–pathogen interplay remains unresolved. Here, our main objective was to investigate the modulation of the transcriptome of HCT-8 cells during single and co-infections with BCoV and C. parvum. For this, HCT-8 cells were inoculated with (1) BCoV alone, (2) C. parvum alone, (3) BCoV and C. parvum simultaneously. After 24 and 72 h, cells were harvested and analyzed using high-throughput RNA sequencing. Following differential expression analysis, over 6000 differentially expressed genes (DEGs) were identified in virus-infected and co-exposed cells at 72 hpi, whereas only 52 DEGs were found in C. parvum-infected cells at the same time point. Pathway (KEGG) and gene ontology (GO) analysis showed that DEGs in the virus-infected and co-exposed cells were mostly associated with immune pathways (such as NF-κB, TNF-α or, IL-17), apoptosis and regulation of transcription, with a more limited effect exerted by C. parvum. Although the modulation observed in the co-infection was apparently dominated by the virus, over 800 DEGs were uniquely expressed in co-exposed cells at 72 hpi. Our findings provide insights on possible biomarkers associated with co-infection, which could be further explored using in vivo models.

Bilateral synchronous renal cell carcinoma (RCC) is rare, especially in sporadic rather than familial cases. While immunotherapy has improved prognosis, RCC remains a diagnosis with significant morbidity and mortality, particularly pronounced in patients with sarcomatoid RCC (sRCC). We describe a case of a patient with bilateral, synchronous, nonfamilial RCC, with and without sarcomatoid features and differing genetic markers, who demonstrated a pathologic response after neoadjuvant nivolumab and ipilimumab. The patient then had radical left nephrectomy and partial right nephrectomy followed by adjuvant nivolumab and cabozantinib, after which the patient had no evidence of disease. Our patient’s illustrative case shows the potential therapeutic value of immunotherapy even in sRCC, the disease’s most aggressive clinical subtype.

The waters of Aotearoa New Zealand span over 4.2 million km2 of the South Pacific Ocean and harbour a rich diversity of seafloor-associated taxa. Due to the immensity and remoteness of the area, there are significant gaps in the availability of data that can be used to quantify and map the distribution of seafloor and demersal biodiversity, limiting effective management. In this study, we describe the development and accessibility of an online atlas of seabed biodiversity that aims to fill these gaps. Species distribution models were developed for 579 taxa across four taxonomic groups: demersal fish, reef fish, subtidal invertebrates and macroalgae. Spatial layers for taxa distribution based on habitat suitability were statistically validated and then, as a further check, evaluated by taxonomic experts to provide measures of confidence to guide the future use of these layers. Spatially explicit uncertainty (SD) layers were also developed for each taxon distribution. We generated layer-specific metadata, including statistical and expert evaluation scores, which were uploaded alongside the accompanying spatial layers to the open access database Zenodo. This database provides the most comprehensive source of information on the distribution of seafloor taxa for Aotearoa New Zealand and is thus a valuable resource for managers, researchers and the public that will guide the management and conservation of seafloor communities. The atlas of seabed biodiversity for Aotearoa New Zealand is freely accessible via the open-access database Zenodo under https://doi.org/10.5281/zenodo.7083642 (Stephenson et al., 2022).

Abstract Background Itch is common and distressing in epidermolysis bullosa (EB) but has not previously been studied in depth in different recessive dystrophic EB (RDEB) subtypes. Objectives As part of a prospective register study of the natural history of RDEB we explored features of itch, medications used, and correlation with disease severity and quality of life. Methods Fifty individuals with RDEB aged 8 years and above completed the Leuven Itch Scale (LIS) (total 243 reviews over a 7-year period). Data included itch frequency, severity, duration, distress, circumstances, consequences, itch surface area and medications for itch. The iscorEB disease severity score and the validated EB quality of life tool, QOLEB, were compared to LIS domains and analysed by RDEB subtype. Results Itch was frequent, present in the preceding month in 93% of reviews. Itch severity and distress were significantly greater in severe (RDEB-S) and pruriginosa (RDEB-Pru) subtypes compared to intermediate RDEB (RDEB-I). Itch medications were reported in just over half of reviews including emollients, topical corticosteroids and antihistamines; the proportion of participants not using medication despite frequent pruritus suggests limited efficacy. In inversa RDEB (RDEB-Inv) and RDEB-I, LIS domains correlated with iscorEB and QOLEB. In contrast to previous studies, correlations were lacking in RDEB-S suggesting that global disease burden relatively reduces the contribution of itch. Conclusions This comprehensive study of RDEB-associated itch highlights differences between RDEB subtypes, suggests an unmet need for effective treatments and could serve as control data for future clinical trials incorporating itch as an endpoint.

Abstract Complex traits often exhibit complex underlying genetic architectures resulting from a combination of evolution from standing variation, hard and soft sweeps, and alleles of varying effect size. Increasingly, studies implicate both large‐effect loci and polygenic patterns underpinning adaptation, but the extent that common genetic architectures are utilized during repeated adaptation is not well understood. Sea age or age at maturation represents a significant life history trait in Atlantic Salmon (Salmo salar), the genetic basis of which has been studied extensively in European Atlantic populations, with repeated identification of large‐effect loci. However, the genetic basis of sea age within North American Atlantic Salmon populations remains unclear, as does the potential for a parallel trans‐Atlantic genomic basis to sea age. Here, we used a large single‐nucleotide polymorphism (SNP) array and low‐coverage whole‐genome resequencing to explore the genomic basis of sea age variation in North American Atlantic Salmon. We found significant associations at the gene and SNP level with a large‐effect locus (vgll3) previously identified in European populations, indicating genetic parallelism, but found that this pattern varied based on both sex and geographic region. We also identified nonrepeated sets of highly predictive loci associated with sea age among populations and sexes within North America, indicating polygenicity and low rates of genomic parallelism. Despite low genome‐wide parallelism, we uncovered a set of conserved molecular pathways associated with sea age that were consistently enriched among comparisons, including calcium signaling, MapK signaling, focal adhesion, and phosphatidylinositol signaling. Together, our results indicate parallelism of the molecular basis of sea age in North American Atlantic Salmon across large‐effect genes and molecular pathways despite population‐specific patterns of polygenicity. These findings reveal roles for both contingency and repeated adaptation at the molecular level in the evolution of life history variation.

The intestinal protozoan parasites, Cryptosporidium and Giardia, are known to have a global distribution, infecting and causing disease in a range of hosts, including people, livestock, pets, and wildlife. However, data from some regions is very sparse. In Armenia, in the Caucasus region of West Asia, only scanty data are available, with just a few surveys on Cryptosporidium infections in livestock, and no available data on human infections or environmental contamination. As part of implementation of water analysis methods for these parasites in Armenia, 24 raw water samples and two sediment samples were analysed for these parasites using a range of approaches, including modified Ziehl-Neelsen, Lugol stain, immunofluorescent antibody test (IFAT), qPCR and, on sediment samples, immunomagnetic separation and IFAT. Results suggest substantial contamination of raw water sources and indicate the need for further targeted studies using appropriate methods and collecting data on host infections in catchment areas.

Background: South African legislation advocates for equitable access to mental healthcare services integrated into general healthcare settings. Mental, neurological, and substance use (MNS) disorders are often comorbid. Pharmacoepidemiology provides indirect evidence of service provision for conditions amenable to medicine treatment. Aim: The study aims to evaluate medicine procurement for MNS disorders at different service levels in the health system. Setting: The Public health sector, Gauteng province formed the setting for the study. Method: A secondary analysis of the Gauteng pharmaceutical database was conducted using Anatomic Therapeutic Chemical (ATC) and defined daily dose (DDD) methodology. Anatomic Therapeutic Chemical classes of medicines for MNS disorders were included. Defined daily doses and costs were calculated per 1000 population served by each facility and service level. Statistical comparisons were made using chi-square testing. Results: General healthcare settings accounted for 90% (R118 638 248) and specialised hospitals for 10% (R13 685 032) of expenditure on medicines for MNS disorders, procuring 94% (n = 49 442 474) and 6% (n = 3 311 528) of DDDs, respectively. Although district clinics procured 60% of DDDs, they procured the least per 1000 population served, whereas district hospitals procured the most. For almost all ATC classes, procurement differed significantly between municipalities at every service level and between specialised hospitals. Conclusion: In Gauteng province, most medicines for MNS disorders are procured by general healthcare services, but access to care may not be equitable. While population coverage at district clinics appears low, district hospitals may experience the greatest care burden. Research regarding quality of care at each service level is recommended. Contribution: This study provides insight into service provision for MNS disorders.

Abstract Plastic pollution is distributed patchily around the world’s oceans. Likewise, marine organisms that are vulnerable to plastic ingestion or entanglement have uneven distributions. Understanding where wildlife encounters plastic is crucial for targeting research and mitigation. Oceanic seabirds, particularly petrels, frequently ingest plastic, are highly threatened, and cover vast distances during foraging and migration. However, the spatial overlap between petrels and plastics is poorly understood. Here we combine marine plastic density estimates with individual movement data for 7137 birds of 77 petrel species to estimate relative exposure risk. We identify high exposure risk areas in the Mediterranean and Black seas, and the northeast Pacific, northwest Pacific, South Atlantic and southwest Indian oceans. Plastic exposure risk varies greatly among species and populations, and between breeding and non-breeding seasons. Exposure risk is disproportionately high for Threatened species. Outside the Mediterranean and Black seas, exposure risk is highest in the high seas and Exclusive Economic Zones (EEZs) of the USA, Japan, and the UK. Birds generally had higher plastic exposure risk outside the EEZ of the country where they breed. We identify conservation and research priorities, and highlight that international collaboration is key to addressing the impacts of marine plastic on wide-ranging species.

Abstract Inflammation in response to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection drives severity of coronavirus disease 2019 (COVID-19) and is influenced by host genetics. To understand mechanisms of inflammation, animal models that reflect genetic diversity and clinical outcomes observed in humans are needed. We report a mouse panel comprising the genetically diverse Collaborative Cross (CC) founder strains crossed to human ACE2 transgenic mice (K18-hACE2) that confers susceptibility to SARS-CoV-2. Infection of CC x K18-hACE2 resulted in a spectrum of survival, viral replication kinetics, and immune profiles. Importantly, in contrast to the K18-hACE2 model, early type I interferon (IFN-I) and regulated proinflammatory responses were required for control of SARS-CoV-2 replication in PWK x K18-hACE2 mice that were highly resistant to disease. Thus, virus dynamics and inflammation observed in COVID-19 can be modeled in diverse mouse strains that provide a genetically tractable platform for understanding anti-coronavirus immunity.

Abstract Intrapartum hypoxia–ischemia leading to neonatal encephalopathy (NE) results in significant neonatal mortality and morbidity worldwide, with > 85% of cases occurring in low- and middle-income countries (LMIC). Therapeutic hypothermia (HT) is currently the only available safe and effective treatment of HIE in high-income countries (HIC); however, it has shown limited safety or efficacy in LMIC. Therefore, other therapies are urgently required. We aimed to compare the treatment effects of putative neuroprotective drug candidates following neonatal hypoxic-ischemic (HI) brain injury in an established P7 rat Vannucci model. We conducted the first multi-drug randomized controlled preclinical screening trial, investigating 25 potential therapeutic agents using a standardized experimental setting in which P7 rat pups were exposed to unilateral HI brain injury. The brains were analysed for unilateral hemispheric brain area loss after 7 days survival. Twenty animal experiments were performed. Eight of the 25 therapeutic agents significantly reduced brain area loss with the strongest treatment effect for Caffeine, Sonic Hedgehog Agonist (SAG) and Allopurinol, followed by Melatonin, Clemastine, ß-Hydroxybutyrate, Omegaven, and Iodide. The probability of efficacy was superior to that of HT for Caffeine, SAG, Allopurinol, Melatonin, Clemastine, ß-hydroxybutyrate, and Omegaven. We provide the results of the first systematic preclinical screening of potential neuroprotective treatments and present alternative single therapies that may be promising treatment options for HT in LMIC.

Abstract Endocannabinoids (eCBs) are endogenous ligands of the cannabinoid receptor 1 (CB1), a G protein-coupled receptor that regulates a number of therapeutically relevant physiological responses. Hence, understanding the structural and functional consequences of eCB-CB1 interactions has important implications for designing effective drugs targeting this receptor. To characterize the molecular details of eCB interaction with CB1, we utilized AMG315, an analog of the eCB anandamide to determine the structure of the AMG315-bound CB1 signaling complex. Compared to previous structures, the ligand binding pocket shows some differences. Using docking, molecular dynamics simulations, and signaling assays we investigated the functional consequences of ligand interactions with the “toggle switch” residues F2003.36 and W3566.48. Further, we show that ligand-TM2 interactions drive changes to residues on the intracellular side of TM2 and are a determinant of efficacy in activating G protein. These intracellular TM2 rearrangements are unique to CB1 and are exploited by a CB1-specific allosteric modulator.

Pituitary carcinoma (PC) is a rare, aggressive malignancy that comprises 0.1–0.2% of all pituitary tumors. PC is defined anatomically as a pituitary tumor that metastasizes outside the primary intrasellar location as noncontiguous lesions in the central nervous system or as metastases to other organs. Similar to pituitary adenoma, PC originates from various cell types of the pituitary gland and can be functioning or nonfunctioning, with the former constituting the majority of the cases. Compression of intricate skull-based structures, excessive hormonal secretion, impaired pituitary function from therapy, and systemic metastases lead to debilitating symptoms and a poor survival outcome in most cases. PC frequently recurs despite multimodality treatments, including surgical resection, radiotherapy, and biochemical and cytotoxic treatments. There is an unmet need to better understand the pathogenesis and molecular characterization of PC to improve therapeutic strategies. As our understanding of the role of signaling pathways in the tumorigenesis of and malignant transformation of PC evolves, efforts have focused on targeted therapy. In addition, recent advances in the use of immune checkpoint inhibitors to treat various solid cancers have led to an interest in exploring the role of immunotherapy for the treatment of aggressive refractory pituitary tumors. Here, we review our current understanding of the pathogenesis, molecular characterization, and treatment of PC. Particular attention is given to emerging treatment options, including targeted therapy, immunotherapy, and peptide receptor radionuclide therapy.

Sperm DNA integrity is increasingly considered a useful measure of semen quality in mammalian reproduction. However, the definition of DNA integrity, the ideal means by which it should be measured, and its predictive value for fertility remain a topic of much discussion. With an emphasis on livestock species, this review discusses the assays that have been developed to measure DNA integrity as well as their correlation with in vitro and in vivo fertility.

This study sought to better understand how time of day (ToD) or turgor pressure might affect the flexural stiffness of sweet sorghum stalks and potentially regulate stalk lodging resistance. Stalk flexural stiffness measured across a 48 h period in 2019 showed a significant diurnal association with leaf water potential and stalk flexural stiffness. While the correlation between stalk flexural stiffness and this proxy for internal turgor status was statistically significant, it only accounted for roughly 2% of the overall variance in stiffness. Given that turgor status is a dynamic rather than fixed physiological variable like the cellular structure, these data suggest that internal turgor plays a small yet significant role in influencing the flexural stiffness of fully mature stalks prior to a stalk lodging event. The association was assessed at earlier developmental stages across three distinct cultivars and found not to be significant. Panicle weight and stalk basal weight, but not stalk Brix or water content, were found to be better predictors of stalk flexural stiffness than either ToD or turgor status. Observation across three cultivars and four distinct developmental stages ranging from the vegetative to the hard-dough stages suggests that stalk flexural stiffness changes significantly as a function of time. However, neither ToD nor turgor status appear to meaningfully contribute to observed variations in stalk flexural stiffness in either individual stalks or across larger populations. As turgor status was not found to meaningfully influence stalk strength or flexural stiffness at any developmental time point examined in any of the three sweet sorghum cultivars under study, turgor pressure likely offers only inconsequential contributions to the biomechanics underlying sweet sorghum stalk lodging resistance.

In 2021, the Norwegian Scientific Committee for Food and Environment published a multi-criteria risk ranking of 20 potentially food-borne pathogens in Norway. The pathogens ranked included five parasite taxa (3 species, one genus, one family): Toxoplasma gondii, Echinococcus multilocularis, Giardia duodenalis, Cryptosporidium spp., and Anisakidae. Two of these, T. gondii and E. multilocularis, scored very highly (1st and 3rd place, respectively), Cryptosporidium was about midway (9th place), and G. duodenalis and Anisakidae ranked relatively low (15th and 20th place, respectively). Parasites were found, on average, more likely to present an increasing food-borne disease burden in the future than the other pathogens. Here, we review the current impact of these five potentially food-borne parasites in Norway, and factors of potential importance in increasing their future food-borne disease burden. Climate change may affect the contamination of water and fresh produce with transmission stages of the first four parasites, potentially leading to increased infection risk. Alterations in host distribution (potentially due to climate change, but also other factors) may affect the occurrence and distribution of Toxoplasma, Echinococcus, and Anisakidae, and these, coupled with changes in food consumption patterns, could also affect infection likelihood. Transmission of food-borne pathogens is complex, and the relative importance of different pathogens is affected by many factors and will not remain static. Further investigation in, for example, ten-years’ time, could provide a different picture of the relative importance of different pathogens. Nevertheless, there is clearly the potential for parasites to exert a greater risk to public health in Norway than currently occurs.

The common snipe (Gallinago gallinago) is a wader that breeds in subarctic regions from Iceland to Russia, and for which global populations are in decline. We studied snipe breeding in western Iceland between 1998 and 2020, locating nests and ringing birds annually. In 2019 and 2020, we deployed geolocators on nesting adults to estimate the timing of their annual migration and the location of overwintering areas. Birds moved principally between breeding locations in Iceland to wintering areas in Ireland, although some birds may winter farther north. We also found that apparent annual adult survival averaged 66%, but was higher in years with warmer, wetter winters. Given the similarity of our survival estimates to those from snipe elsewhere, we suggest that adult survival is unlikely a major contributor to declining populations, and other factors like habitat loss may be of more concern.

Abstract This study presents a methodology for a high-throughput digitization and quantification process of plant cell walls characterization, including the automated development of two-dimensional finite element models. Custom algorithms based on machine learning can also analyze the cellular microstructure for phenotypes such as cell size, cell wall curvature, and cell wall orientation. To demonstrate the utility of these models, a series of compound microscope images of both herbaceous and woody representatives were observed and processed. In addition, parametric analyses were performed on the resulting finite element models. Sensitivity analyses of the structural stiffness of the resulting tissue based on the cell wall elastic modulus and the cell wall thickness; demonstrated that the cell wall thickness has a three-fold larger impact of tissue stiffness than cell wall elastic modulus.

Abstract Background Non‐small cell lung cancer (NSCLC) comprises the majority (~85%) of all lung tumors, with lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) being the most frequently diagnosed histological subtypes. Multi‐modal omics profiling has been carried out in NSCLC, but no studies have yet reported a unique metabolite‐related gene signature and altered metabolic pathways associated with LUAD and LUSC. Methods We integrated transcriptomics and metabolomics to analyze 30 human lung tumors and adjacent noncancerous tissues. Differential co‐expression was used to identify modules of metabolites that were altered between normal and tumor. Results We identified unique metabolite‐related gene signatures specific for LUAD and LUSC and key pathways aberrantly regulated at both transcriptional and metabolic levels. Differential co‐expression analysis revealed that loss of coherence between metabolites in tumors is a major characteristic in both LUAD and LUSC. We identified one metabolic onco‐module gained in LUAD, characterized by nine metabolites and 57 metabolic genes. Multi‐omics integrative analysis revealed a 28 metabolic gene signature associated with poor survival in LUAD, with six metabolite‐related genes as individual prognostic markers. Conclusions We demonstrated the clinical utility of this integrated metabolic gene signature in LUAD by using it to guide repurposing of AZD‐6482, a PI3Kβ inhibitor which significantly inhibited three genes from the 28‐gene signature. Overall, we have integrated metabolomics and transcriptomics analyses to show that LUAD and LUSC have distinct profiles, inferred gene signatures with prognostic value for patient survival, and identified therapeutic targets and repurposed drugs for potential use in NSCLC treatment.

Abstract Background Homeothermic marine animals in Polar Regions face an energetic bottleneck in winter. The challenges of short days and cold temperatures are exacerbated for flying seabirds with small body size and limited fat stores. We use biologging approaches to examine how habitat, weather, and moon illumination influence behaviour and energetics of a marine bird species, thick-billed murres (Uria lomvia). Methods We used temperature-depth-light recorders to examine strategies murres use to survive winter in the Northwest Atlantic, where contrasting currents create two distinct marine habitats: cold (−0.1 ± 1.2 °C), shallower water along the Labrador Shelf and warmer (3.1 ± 0.3 °C), deep water in the Labrador Basin. Results In the cold shelf water, murres used a high-energy strategy, with more flying and less diving each day, resulting in high daily energy expenditure and also high apparent energy intake; this strategy was most evident in early winter when day lengths were shortest. By contrast, murres in warmer basin water employed a low-energy strategy, with less time flying and more time diving under low light conditions (nautical twilight and night). In warmer basin water, murres increased diving at night when the moon was more illuminated, likely taking advantage of diel vertically migrating prey. In warmer basin water, murres dove more at night and foraging efficiency increased under negative North Atlantic Oscillation (calmer ocean conditions). Conclusions The proximity of two distinct marine habitats in this region allows individuals from a single species to use dual (low-energy/high-energy) strategies to overcome winter energy bottlenecks.

In terms of utility and technical quality, open-source software solutions have become a common option for many libraries. As barriers to adoption have been reduced and systems such as FOLIO appear poised to change the landscape of LIS technology, it is worth examining how the use of open source can support the normative core values of librarianship and to outline a strategy for critical engagement with the technology that is beneficial to patrons and libraries. Such a strategy will require further codification, institutionalization, and investigation of open source at many levels., INTRODUCTION Open-source software has continued to gain popularity among libraries in the past decade. It has moved from the periphery to become a major competitor with some of the most [...]

Failure times (tf) and brittle creep strain rates (ἑ) for static fatigue of Hi-Nicalon™-S fiber tows were measured at 500 and 600 °C. These measurements added to those done previously at 700–1100 °C. Subcritical crack growth (SCG) based models developed to predict tf and ἑ from the 700–1100 °C data were modified to include the additional data. Parameters for two SCG laws were determined for air and Si(OH)4 saturated steam environments, and an additional parameter for effective room-temperature residual stress (σRo) along the crack path was introduced. Tow failure was modelled as sequential filament failure by SCG from weakest to strongest in a Weibull distribution. The increase in stress on intact filaments as they oxidized and as other filaments failed caused brittle creep strain. SCG-based models for both surface and interior cracks were considered. Orthogonal direction regression (ODR) was used to find the best parameter fits to data. Faster numerical methods to find the global parameter-space minima and avoid local minima were developed. New model parameters were determined using the entire 500–1100 °C tf and ἑ data set, done at initial applied stresses from 260 to 1526 MPa. In air, measured tf and ἑ at 500 and 600 °C follow the trends previously observed for higher temperatures. However, beneath 700 °C in steam, tf are longer and ἑ are much slower than expected. They are similar to values measured for air, suggesting an SCG mechanism change between 700° and 600 °C in steam. An atomistic SCG law-based model with activation energy (Q) of 310 kJ/mol and σRo of ∼200 MPa compression is suggested to be appropriate for static fatigue in air. An atomistic SCG law-based model with Q of 360 kJ/mol and σRo of ∼0 MPa best fit data measured in steam. However, differences in data fit quality between models were small, so firm conclusions about the correct model, residual stress effects, and associated crack paths could not be made. As stress approaches zero, the model converges to tow failure times that are the times for complete fiber oxidation. As failure times approach zero and temperatures decrease, the model converges to tow strengths predicted by fiber bundle theory at room temperature. The sources of error in data fit, the merit of different SCG models, and the possible roles of residual stress in SCG for Hi-Nicalon™-S fibers are discussed.

Oxygen supplementation is life saving for premature infants and for COVID-19 patients but can induce long-term pulmonary injury by triggering inflammation, with xenobiotic-metabolizing CYP enzymes playing a critical role. Murine studies showed that CYP1B1 enhances, while CYP1A1 and CYP1A2 protect from, hyperoxic lung injury. In this study we tested the hypothesis that Cyp1b1-null mice would revert hyperoxia-induced transcriptomic changes observed in WT mice at the transcript and pathway level. Wild type (WT) C57BL/6J and Cyp1b1-null mice aged 8–10 weeks were maintained in room air (21% O2) or exposed to hyperoxia (>95% O2) for 48h. Transcriptomic profiling was conducted using the Illumina microarray platform. Hyperoxia exposure led to robust changes in gene expression and in the same direction in WT, Cyp1a1-, Cyp1a2-, and Cyp1b1-null mice, but to different extents for each mouse genotype. At the transcriptome level, all Cyp1-null murine models reversed hyperoxia effects. Gene Set Enrichment Analysis identified 118 hyperoxia-affected pathways mitigated only in Cyp1b1-null mice, including lipid, glutamate, and amino acid metabolism. Cell cycle genes Cdkn1a and Ccnd1 were induced by hyperoxia in both WT and Cyp1b1-null mice but mitigated in Cyp1b1-null O2 compared to WT O2 mice. Hyperoxia gene signatures associated positively with bronchopulmonary dysplasia (BPD), which occurs in premature infants (with supplemental oxygen being one of the risk factors), but only in the Cyp1b1-null mice did the gene profile after hyperoxia exposure show a partial rescue of BPD-associated transcriptome. Our study suggests that CYP1B1 plays a pro-oxidant role in hyperoxia-induced lung injury.

Detection of invading bacteria is key to immunity. Here, the authors report cryo-electron microscopy structures of agonist-bound formyl peptide receptor 1 (FPR1), that reveal structural basis for recognition of bacteria-derived formyl peptides.