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Abstract Cotton is the most common natural fibre used in textile manufacture, used alone or with other fibres to create a wide range of fashion clothing and household textiles. Most of these textiles are cleaned using detergents and domestic or commercial washing machines using processes that require many chemicals and large quantities of water and energy. Enzymes can reduce this environmental footprint by enabling effective detergency at reduced temperatures, mostly by directly attacking substrates present in the soils. In the present study, we report the contribution of a cleaning cellulase enzyme based on the family 44 glycoside hydrolase (GH) endo-beta-1,4-glucanase from Paenibacillus polymyxa. The action of this enzyme on textile fibres improves laundry detergent performance in several vectors including soil anti-redeposition, dye transfer inhibition and stain removal. Molecular probes are used to study how this enzyme is targeting both amorphous cellulose and xyloglucan on textile fibres and the relationship between textile surface effects and observed performance benefits.

Abstract The ongoing evolution of the SARS-CoV-2 virus has led to a move to update vaccine antigens in 2022 and 2023. These updated antigens were chosen and approved based largely on in vitro neutralisation titres against recent SARS-CoV-2 variants. However, unavoidable delays in vaccine manufacture and distribution meant that the updated booster vaccine was no longer well-matched to the circulating SARS-CoV-2 variant by the time of its deployment. Understanding whether the updating of booster vaccine antigens improves immune responses to subsequent SARS-CoV-2 circulating variants is a major priority in justifying future vaccine updates. Here we analyse all available data on the immunogenicity of variants containing SARS-CoV-2 vaccines and their ability to neutralise later circulating SARS-CoV-2 variants. We find that updated booster antigens give a 1.4-fold [95% CI: 1.07–1.82] greater increase in neutralising antibody levels when compared with a historical vaccine immunogen. We then use this to predict the relative protection that can be expected from an updated vaccine even when the circulating variant has evolved away from the updated vaccine immunogen. These findings help inform the rollout of future booster vaccination programmes.

ABSTRACTIntroduction Influenza B viruses (IBV) cause a significant health and economic burden annually. Due to lower antigenic drift rate, less extensive antigenic diversity, and lack of animal reservoirs, the development of highly effective universal vaccines against IBV might be in reach. Current seasonal influenza vaccines are formulated to induce antibodies against the Hemagglutinin (HA) protein, but their effectiveness is reduced by mismatch between vaccine and circulating strains.Areas covered Given antibodies against the Neuraminidase (NA) have been associated with protection during influenza infection, there is considerable interest in the development of NA-based influenza vaccines. This review summarizes insights into the role of NA-based immunity against IBV and highlights knowledge gaps that should be addressed to inform the design of next-generation influenza B vaccines. We discuss how antibodies recognize broadly cross-reactive epitopes on the NA and the lack of understanding of IBV NA antigenic evolution which would benefit vaccine development in the future.Expert opinion Demonstrating NA antibodies as correlates of protection for IBV in humans would be paramount. Determining the extent of IBV NA antigenic evolution will be informative. Finally, it will be critical to determine optimal strategies for incorporating the appropriate NA antigens in existing clinically approved vaccine formulations.

Distributed energy resources and the number of relays are expected to rise in modern electrical grids; consequently, relay misoperations are also expected to grow. Relays can detect electrical fault types using an internal algorithm and can display the result using light indicators on the front of the relay. However, some relays’ internal algorithms for predicting types of electrical faults could be improved. This study assesses a relay’s external and internal algorithms with an Advanced Synchronized Time Digital Grid Twin (ASTDGT) testbed with paired relays. A misoperation relay analysis focused on measuring the accuracy of using the boundary admittance (the external algorithm) versus the set-default (the internal algorithm) relay method to determine the electrical fault types was performed. In this study, the internal and external relay algorithms were assessed with a synchronized time digital grid twin testbed using a real-time simulator. This testbed evaluated two sets of logic at the same time with the digital grid twin and paired relays in the loop. Different types of electrical faults were simulated, and the relays’ recorded events and electrical fault light indicator states were collected from the human–machine interfaces. This ASTDGT testbed with paired relays successfully evaluated the relay algorithm misoperations. The boundary admittance method had an accuracy of 100% for line-to-line, line-to-ground, and line-to-line ground faults.

Abstract In this paper, we investigate the heavy quark (HQ) mass effects on the transverse momentum dependent fragmentation function (TMDFF). We first calculate the one-loop TMDFF initiated by a heavy quark. We then investigate the HQ TMDFF in the limit where the transverse momentum, q ⊥ is small compared to the heavy quark mass, q ⊥ ≪ m and also in the opposite limit where q ⊥ ≫ m. As applications of the HQ TMDFF, we study the HQ transverse momentum dependent jet fragmentation function, where the heavy quark fragments into a jet containing a heavy hadron, and we investigate a heavy hadron’s transverse momentum dependent distribution with respect to the thrust axis in e + e − collisions.

Therocephalia are an important clade of non-mammalian therapsids that evolved a diverse array of morphotypes and body sizes throughout their evolutionary history. The postcranial anatomy of therocephalians has largely been overlooked, but remains important towards understanding aspects of their palaeobiology and phylogenetic relationships. Here, we provide the first postcranial description of the large akidnognathid eutherocephalian Moschorhinus kitchingi by examining multiple specimens from fossil collections in South Africa. We also compare the postcranial anatomy with previously described therocephalian postcranial material and provide an updated literature review to ensure a reliable foundation of comparison for future descriptive work. Moschorhinus shares all the postcranial features of eutherocephalians that differentiate them from early-diverging therocephalians, but is differentiated from other eutherocephalian taxa by aspects concerning the scapula, interclavicle, sternum, manus, and femur. The novel anatomical data from this contribution shows that Moschorhinus possessed a stocky bauplan with a particularly robust scapula, humerus, and femur. These attributes, coupled with the short and robust skull bearing enlarged conical canines imply that Moschorhinus was well equipped to grapple with and subdue prey items. Additionally, the combination of these attributes differ from those of similarly sized coeval gorgonopsians, which would have occupied a similar niche in late Permian ecosystems. Moreover, Moschorhinus was the only large carnivore known to have survived the Permo-Triassic mass extinction. Thus, the subtle but important postcranial differences may suggest a type of niche partitioning in the predator guild during the Permo-Triassic mass extinction interval.

Abstract Understanding the mechanisms that drive TDP-43 pathology is integral to combating amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD) and other neurodegenerative diseases. Here we generated a longitudinal quantitative proteomic map of the cortex from the cytoplasmic TDP-43 rNLS8 mouse model of ALS and FTLD, and developed a complementary open-access webtool, TDP-map ( https://shiny.rcc.uq.edu.au/TDP-map/ ). We identified distinct protein subsets enriched for diverse biological pathways with temporal alterations in protein abundance, including increases in protein folding factors prior to disease onset. This included increased levels of DnaJ homolog subfamily B member 5, DNAJB5, which also co-localized with TDP-43 pathology in diseased human motor cortex. DNAJB5 over-expression decreased TDP-43 aggregation in cell and cortical neuron cultures, and knockout of Dnajb5 exacerbated motor impairments caused by AAV-mediated cytoplasmic TDP-43 expression in mice. Together, these findings reveal molecular mechanisms at distinct stages of ALS and FTLD progression and suggest that protein folding factors could be protective in neurodegenerative diseases.

ABSTRACTPrecision engineering of the gut microbiome holds promise as an effective therapeutic approach for diseases associated with a disruption in this microbial community. Engrafting a live biotherapeutic product (LBP) in a predictable, controllable manner is key to the consistent success of this approach and has remained a challenge for most LBPs under development. We recently demonstrated high-level engraftment of Bifidobacterium longum subsp. infantis (B. infantis) in adults when co-dosed with a specific prebiotic, human milk oligosaccharides (HMO). Here, we present a cellular kinetic-pharmacodynamic approach, analogous to pharmacokinetic-pharmacodynamic-based analyses of small molecule- and biologic-based drugs, to establish how HMO controls expansion, abundance, and metabolic output of B. infantis in a human microbiota-based model in gnotobiotic mice. Our data demonstrate that the HMO dose controls steady-state abundance of B. infantis in the microbiome, and that B. infantis together with HMO impacts gut metabolite levels in a targeted, HMO-dependent manner. We also found that HMO creates a privileged niche for B. infantis expansion across a 5-log range of bacterial inocula. These results demonstrate remarkable control of both B. infantis levels and the microbiome community metabolic outputs using this synbiotic approach, and pave the way for precision engineering of desirable microbes and metabolites to treat a range of diseases.

ABSTRACT: The consumption of poultry products contaminated with Salmonella species is one of the most common causes of Salmonella infections. In vivo studies demonstrated the potential application of peanut skins (PS) as an antimicrobial poultry feed additive to help mitigate the proliferation of Salmonella in poultry environments. Tons of PS, a waste by-product of the peanut industry, are generated and disposed in U.S. landfills annually. Peanut skins and extracts have been shown to possess antimicrobial and antioxidant properties. Hence, we aimed to determine the effect of PS as a feed additive on the gut microbiota of broilers fed a control or PS supplemented (4% inclusion) diet and inoculated with or without Salmonella enterica Enteritidis (SE). At hatch 160 male broilers were randomly assigned to 4 treatments: 1) CON-control diet without SE, 2) PS-PS diet without SE, 3) CONSE-control diet with SE, 4) PSSE-PS diet with SE. On d 3, birds from CONSE and PSSE treatments were inoculated with 4.2 × 109 CFU/mL SE. At termination (4 wk), 10 birds/treatment were euthanized and ileal and cecal contents were collected for 16S rRNA analysis using standard methodologies. Sequencing data were analyzed using QIIME2. No effect of PS or SE was observed on ileal alpha and beta diversity, while evenness, richness, number of amplicon sequence variants (ASV) and Shannon, as well as beta diversity were significantly (P < 0.05) affected in ceca. Similarly, more differentially abundant taxa between treatment groups were identified in ceca than in ileum. However, more microbiota functional changes, based on the PICRUST2 prediction, were observed in ileum. Overall, relatively minor changes in microbiota were observed during SE infection and PS treatment, suggesting that PS addition may not attenuate the SE proliferation, as shown previously, through modulation of microbiota in gastrointestinal tract. However, while further studies are warranted, these results suggest that PS may potentially serve as a functional feed additive for poultry for improvement of animal health.

Abstract Background Gastrointestinal symptoms and inflammatory gastrointestinal diseases exist at higher rates in the autistic population. It is not clear however whether autism is associated with elevated gastrointestinal inflammation as studies examining non-invasive faecal biomarkers report conflicting findings. To understand the research landscape and identify gaps, we performed a systematic review and meta-analysis of studies measuring non-invasive markers of gastrointestinal inflammation in autistic and non-autistic samples. Our examination focused on faecal biomarkers as sampling is non-invasive and these markers are a direct reflection of inflammatory processes in the gastrointestinal tract. Methods We extracted data from case–control studies examining faecal markers of gastrointestinal inflammation. We searched PubMed, Embase, Cochrane CENTRAL, CINAHL, PsycINFO, Web of Science Core Collection and Epistemonikos and forward and backwards citations of included studies published up to April 14, 2023 (PROSPERO CRD42022369279). Results There were few studies examining faecal markers of gastrointestinal inflammation in the autistic population, and many established markers have not been studied. Meta-analyses of studies examining calprotectin (n = 9) and lactoferrin (n = 3) were carried out. A total of 508 autistic children and adolescents and 397 non-autistic children and adolescents were included in the meta-analysis of calprotectin studies which found no significant group differences (ROM: 1.30 [0.91, 1.86]). Estimated differences in calprotectin were lower in studies with siblings and studies which did not exclude non-autistic controls with gastrointestinal symptoms. A total of 139 autistic participants and 75 non-autistic controls were included in the meta-analysis of lactoferrin studies which found no significant group differences (ROM: 1.27 [0.79, 2.04]). Limitations All studies included in this systematic review and meta-analysis examined children and adolescents. Many studies included non-autistic controls with gastrointestinal symptoms which limit the validity of their findings. The majority of studies of gastrointestinal inflammation focused on children under 12 with few studies including adolescent participants. Most studies that included participants aged four or under did not account for the impact of age on calprotectin levels. Future studies should screen for relevant confounders, include larger samples and explore gastrointestinal inflammation in autistic adolescents and adults. Conclusions There is no evidence to suggest higher levels of gastrointestinal inflammation as measured by calprotectin and lactoferrin are present in autistic children and adolescents at the population level. Preliminary evidence suggests however that higher calprotectin levels may be present in a subset of autistic participants, who may be clinically characterised by more severe gastrointestinal symptoms and higher levels of autistic traits.

Abstract Serotonergic psychedelics possess considerable therapeutic potential. Although 5-HT2A receptor activation mediates psychedelic effects, prototypical psychedelics activate both 5-HT2A-Gq/11 and β-arrestin2 transducers, making their respective roles unclear. To elucidate this, we develop a series of 5-HT2A-selective ligands with varying Gq efficacies, including β-arrestin-biased ligands. We show that 5-HT2A-Gq but not 5-HT2A-β-arrestin2 recruitment efficacy predicts psychedelic potential, assessed using head-twitch response (HTR) magnitude in male mice. We further show that disrupting Gq-PLC signaling attenuates the HTR and a threshold level of Gq activation is required to induce psychedelic-like effects, consistent with the fact that certain 5-HT2A partial agonists (e.g., lisuride) are non-psychedelic. Understanding the role of 5-HT2A Gq-efficacy in psychedelic-like psychopharmacology permits rational development of non-psychedelic 5-HT2A agonists. We also demonstrate that β-arrestin-biased 5-HT2A receptor agonists block psychedelic effects and induce receptor downregulation and tachyphylaxis. Overall, 5-HT2A receptor Gq-signaling can be fine-tuned to generate ligands distinct from classical psychedelics.

Concentrations of specific secondary metabolites can be higher in organically grown crops. This may be linked to organic nitrogen (N) nutrition that provides a gradual supply of N to crops over the growing season. This study examined whether organic N nutrition influenced the concentration of glucosinolates in broccoli crops. Nitrogen release patterns were determined from three synthetic (Rustica, 12% N; calcium nitrate, 15.5% N; urea, 46% N) and two organic fertilizers in an incubation experiment. Broccoli seedlings were then grown in two N dose response pot trials with different N source or application timing treatments to investigate growth and glucosinolate responses. Synthetic fertilizers released 84 to 89% of total N after 28 days, while chicken manure pellets and composted cow manure had only released 52% and 13% of total N, respectively, after 91 days. Broccoli yield and N content were generally higher in synthetic fertilizer treatments. Glucosinolate concentrations were generally higher in the synthetic fertilizer treatments, and only sinigrin and glucoiberin concentrations in the 800 kg ha−1 N application rate of organic fertilizer matched those in the corresponding synthetic fertilizer treatment. Broccoli head weight was reduced when N was applied fortnightly compared to basal and weekly N applications, but glucosinolate concentrations were not significantly different. Overall, there was no evidence that organic (chicken manure) N nutrition, or the rate of N supply to broccoli plants, affect glucosinolate concentrations.

The article presents the results of research on the impact of the use of an original, innovative method of deposition of Parylene C on the functional properties of fabrics with various potential applications (e.g., thermal and chemical protective clothing, packaging, covers and others). Verification of the effects of the method used was based on interdisciplinary research taking into account the impact of coating fabrics on changes in their structure (micro-CT), surface properties (contact angle), barrier properties (water and chemical liquid wetting), electrostatic properties (charge decay), biophysical properties describing heat and mass transfer (by the Alambeta system and thermal imaging) and flammable properties. Four fabrics made of synthetic organic fibres (meta-aramid, para-aramid) and natural inorganic fibres (basalt) were selected for testing. Given the complex structure of textile substrates, the results confirmed that the two assumed thicknesses of the Parylene C coating were consistent with the actual measurements. The findings indicated that the coatings significantly reduced water and acid absorption in the fabrics compared to unmodified ones. Thermal insulation property tests revealed that coated fabrics exhibited higher thermal conductivity than unmodified fabrics. Additionally, the presence of Parylene C on aramid fabrics resulted in a modest increase in their ignition resistance.

The PD-1/PD-L1 complex belongs to the group of inhibitory immune checkpoints and plays a critical role in immune regulation. The PD-1/PD-L1 axis is also responsible for immune evasion of cancer cells, and this complex is one of the main targets of immunotherapies used in oncology. Treatment using immune checkpoint inhibitors is mainly based on antibodies. This approach has great therapeutic potential; however, it also has major drawbacks and can induce immune-related adverse events. Thus, there is a strong need for alternative, non-antibody-based therapies using small molecules, peptides, or peptidomimetics. In the present study, we designed, synthesized, and evaluated a set of PD-1-targeting peptides based on the sequence and structure of PD-L1. The binding of these peptides to PD-1 was investigated using SPR and ELISA. We also assessed their ability to compete with PD-L1 for binding to PD-1 and their inhibitory properties against the PD-1/PD-L1 complex at the cellular level. The best results were obtained for the peptide PD-L1(111–127)(Y112C-I126C), named (L11), which displaced PD-L1 from binding to PD-1 in the competitive assay and inhibited the formation of the PD-1/PD-L1 complex. The (L11) peptide also exhibited strong affinity for PD-1. NMR studies revealed that (L11) does not form a well-defined secondary structure; however, MD simulation indicated that (L11) binds to PD-1 at the same place as PD-L1. After further optimization of the structure, the peptide inhibitor obtained in this study could also be used as a potential therapeutic compound targeting the PD-1/PD-L1 axis.

Exhausted CD8 T cells (TEX) are associated with worse outcome in cancer yet better outcome in autoimmunity. Building on our past findings of increased TIGIT+KLRG1+ TEX with teplizumab therapy in type 1 diabetes (T1D), in the absence of treatment we found that the frequency of TIGIT+KLRG1+ TEX is stable within an individual but differs across individuals in both T1D and healthy control (HC) cohorts. This TIGIT+KLRG1+ CD8 TEX population shares an exhaustion-associated EOMES gene signature in HC, T1D, rheumatoid arthritis (RA), and cancer subjects, expresses multiple inhibitory receptors, and is hyporesponsive in vitro, together suggesting co-expression of TIGIT and KLRG1 may broadly define human peripheral exhausted cells. In HC and RA subjects, lower levels of EOMES transcriptional modules and frequency of TIGIT+KLRG1+ TEX were associated with RA HLA risk alleles (DR0401, 0404, 0405, 0408, 1001) even when considering disease status and cytomegalovirus (CMV) seropositivity. Moreover, the frequency of TIGIT+KLRG1+ TEX was significantly increased in RA HLA risk but not non-risk subjects treated with abatacept (CTLA4Ig). The DR4 association and selective modulation with abatacept suggests that therapeutic modulation of TEX may be more effective in DR4 subjects and TEX may be indirectly influenced by cellular interactions that are blocked by abatacept.

Vision is an effective sensor for robotics from which we can derive rich information about the environment: the geometry and semantics of the scene, as well as the age, identity, and activity of humans within that scene. This raises important questions about the reach, lifespan, and misuse of this information. This paper is a call to action to consider privacy in robotic vision. We propose a specific form of inherent privacy preservation in which no images are captured or could be reconstructed by an attacker, even with full remote access. We present a set of principles by which such systems could be designed, employing data-destroying operations and obfuscation in the optical and analogue domains. These cameras never see a full scene. Our localisation case study demonstrates in simulation four implementations that all fulfil this task. The design space of such systems is vast despite the constraints of optical-analogue processing. We hope to inspire future works that expand the range of applications open to sighted robotic systems.

The high ecological and economic value of seagrass has been long recognized, with these foundational habitats providing myriad ecosystem services. Yet through cumulative anthropogenic impacts, seagrasses are exhibiting extensive declines globally. A litany of studies and active restoration trials have demonstrated practical methodologies to restore seagrass habitats and effectively return critical habitat functions to degraded coastal zone systems worldwide. Seagrass loss along the U.S. West Coast has precipitated decades of seagrass protection, conservation, and restoration efforts. Yet, mitigation transplanting efforts have prioritized Zostera marina (narrow-leaved eelgrass) in shallow, protected environments, while a dearth of information is available on species inhabiting offshore islands and exposed mainland coasts. In this study, we conducted a novel transplant of Zostera pacifica, a wide-leaved species found in depths of 7 – 20 m along the offshore islands and mainland coast of California. Transplants were conducted at three geographically distinct sites in Santa Monica Bay, coupled with continuous monitoring of biophysical parameters providing insight into physical drivers at transplant and donor sites. Utilizing in situ data, and environmental thresholds adapted from the literature for Z. marina, we performed exposure analyses to evaluate factors influencing Z. pacifica transplant performance. Exceedances of threshold values for environmental parameters, specifically, wave exposure and near-bed flow speeds (Hrms > 0.59 m and Urms > 0.1 m s-1), photosynthetically active radiation (< 3 and > 5 mol m-2 day-1) and dissolved oxygen (< 3 mg O2 L-1) exposure impacted transplant survivorship. These results suggest Z. pacifica persist in biophysically dynamic conditions and are sensitive to exceedances of thresholds, underlining the importance of pre-transplant site-selection processes to this species. These data represent the first holistic study of Z. pacifica transplanting on an exposed mainland coast, which provides a view into the baseline environmental envelopes within existing Z. pacifica habitat, and further, may serve as a model for investigating scalable open coast seagrass restoration for temperate regions.

Abstract Background Individuals with an increased body mass index (BMI) (≥ 30 kg/m2) experience higher rates of perinatal mental health disorders than individuals with BMI

The optimal approach to COVID-19 surveillance in congregate populations remains unclear. Our study at the US Naval Academy in Annapolis, Maryland, USA, assessed the concordance of antibody prevalence in longitudinally collected dried blood spots and saliva in a setting of frequent PCR-based testing. Our findings highlight the utility of salivary-based surveillance.

Abstract Human milk contains over 200 distinct oligosaccharides, which are critical to shaping the developing neonatal gut microbiome. To investigate whether a complex mixture of human milk oligosaccharides (HMOs) would similarly modulate the adult gut microbiome, HMO-Concentrate derived from pooled donor breast milk was administered orally to 32 healthy adults for 7 days followed by 21 days of monitoring. Fecal samples were collected for 16S rRNA gene sequencing, shotgun metagenomics, and metabolomics analyses. HMO-Concentrate induced dose-dependent Bifidobacterium expansion, reduced microbial diversity, and altered microbial gene content. Following HMO cessation, a microbial succession occurred with diverse taxonomic changes—including Bacteroides expansion—that persisted through day 28. This was associated with altered microbial gene content, shifts in serum metabolite levels, and increased circulating TGFβ and IL-10. Incubation of cultured adult microbiota with HMO-Concentrate induced dose-dependent compositional shifts that were not recapitulated by individual HMOs or defined mixtures of the 10 most abundant HMOs in HMO-Concentrate at their measured concentrations. These findings support that pooled donor HMOs can exert direct effects on adult gut microbiota and that complex mixtures including low abundance HMOs present in donor milk may be required for maximum effect. Registration: ClinicalTrials.gov NCT05516225

The levels of mercury (Hg) were examined in the leg muscle of the crab Grapsus grapsus from five sites on four islands within the Galápagos archipelago. Mercury values obtained using a Milestone DMA 80 evo direct mercury analyzer varied both within and among sites. Total mercury concentrations (mg kg−1 dry weight) ranged from the lowest at a protected location at Isabela Island (0.06 ± 0.02) to the highest at the San Cristóbal urban location (2.04 ± 0.069). Crabs from South Plaza Island also had surprisingly high levels of mercury with a mean of 1.2 ± 0.6. Values from urban sites at Isabela Island and Academy Bay, Santa Cruz, had intermediate values. When converted to wet weight, crabs from both San Cristóbal and South Plaza were within or above the levels (0.3–0.5 mg kg−1 wet weight set by various government agencies) considered potentially harmful to human health if ingested. A lesser number of both oysters and barnacles were also analyzed for mercury at South Plaza and Academy Bay, and while the values were lower compared to the crabs, they followed the same pattern of elevated levels at South Plaza compared to Academy Bay. It is unclear as to whether the mercury comes from natural sources, such as volcanism, or anthropogenic causes.

Electro-conductive fabrics are key materials for designing and developing wearable smart textiles. The properties of textile materials depend on the production method, the technique which leads to high conductivity, and the structure. The aim of the research work was to determine the factors affecting the electrical conductivity of woven fabrics and elucidate the mechanism of electric current conduction through this complex, aperiodic textile material. The chemical composition of the material surface was identified using scanning electron microscopy energy dispersion X-ray spectroscopy. The van der Pauw method was employed for multidirectional resistance measurements. The coefficient was determined for the assessment of the electrical anisotropy of woven fabrics. X-ray micro-computed tomography was used for 3D woven structure geometry analysis. The anisotropy coefficient enabled the classification of electro-conductive fabrics in terms of isotropic or anisotropic materials. It was found that the increase in weft density results in an increase in sample anisotropy. The rise in thread width can lead to smaller electrical in-plane anisotropy. The threads are unevenly distributed in woven fabric, and their widths are not constant, which is reflected in the anisotropy coefficient values depending on the electrode arrangement. The smaller the fabric area covered by four electrodes, the fewer factors leading to structure aperiodicity.

Dogtooth tuna, Gymnosarda unicolor were sampled off the east coast of Australia (southwest Pacific Ocean) from 2007 to 2012. Ages were determined by examining thin transverse sections of their sagittal otoliths and were based on counts of alternating opaque and translucent zones (annual growth increments). Growth was rapid during the first year of life, after which growth in length was much reduced. Parameters of the constrained von Bertalanffy growth function (fork length-at-age) were L∞ = 1164.77 (mm, FL) and K = 0.44 year−1. Preliminary estimates of longevity indicate a maximum observed age of at least 20 years. There was a high degree of variation in the observed length and age of sexual maturity for G. unicolor. Despite this variation, the size at 50% maturity for female G. unicolor estimated in this study was 713 mm FL (

We present a near-infrared (NIR) candidate star cluster catalog for the central kiloparsec of M82 based on new JWST NIRCam images. We identify star cluster candidates using the F250M filter, finding 1357 star cluster candidates with stellar masses >10 ^4 M _⊙ . Compared to previous optical catalogs, nearly all (87%) of the candidates we identify are new. The star cluster candidates have a median intrinsic cluster radius of ≈1 pc and stellar masses up to 10 ^6 M _⊙ . By comparing the color–color diagram to dust-free yggdrasil stellar population models, we estimate that the star cluster candidates have A _V ∼ 3−24 mag, corresponding to A _2.5 _μ _m ∼ 0.3−2.1 mag. There is still appreciable dust extinction toward these clusters into the NIR. We measure the stellar masses of the star cluster candidates, assuming ages of 0 and 8 Myr. The slope of the resulting cluster mass function is β = 1.9 ± 0.2, in excellent agreement with studies of star clusters in other galaxies.

Aims Some patients with cardiac dystrophinopathy die suddenly. Whether such deaths are preventable by specific antiarrhythmic management or simply indicate heart failure overwhelming medical therapies is uncertain. The aim of this prospective, cohort study was to describe the occurrence and nature of cardiac arrhythmias recorded during prolonged continuous ECG rhythm surveillance in patients with established cardiac dystrophinopathy and relate them to abnormalities on cardiac MRI.Methods and results A cohort of 10 patients (36.3 years; 3 female) with LVEF

Abstract Objectives Amino acid variations across more than 30 immunoglobulin (Ig) allotypes may introduce structural changes that influence recognition by anti‐Ig detection reagents, consequently confounding interpretation of antibody responses, particularly in genetically diverse cohorts. Here, we assessed a panel of commercial monoclonal anti‐IgG1 clones for capacity to universally recognise two dominant IgG1 haplotypes (G1m‐1,3 and G1m1,17). Methods Four commercial monoclonal anti‐human IgG1 clones were assessed via ELISAs and multiplex bead‐based assays for their ability to bind G1m‐1,3 and G1m1,17 IgG1 variants. Detection antibodies were validated against monoclonal IgG1 allotype standards and tested for capacity to recognise antigen‐specific plasma IgG1 from G1m‐1,3 and G1m1,17 homozygous and heterozygous SARS‐CoV‐2 BNT162b2 vaccinated (n = 28) and COVID‐19 convalescent (n = 44) individuals. An Fc‐specific pan‐IgG detection antibody corroborated differences between hinge‐ and Fc‐specific anti‐IgG1 responses. Results Hinge‐specific anti‐IgG1 clone 4E3 preferentially bound G1m1,17 compared to G1m‐1,3 IgG1. Consequently, SARS‐CoV‐2 Spike‐specific IgG1 levels detected in G1m1,17/G1m1,17 BNT162b2 vaccinees appeared 9‐ to 17‐fold higher than in G1m‐1,3/G1m‐1,3 vaccinees. Fc‐specific IgG1 and pan‐IgG detection antibodies equivalently bound G1m‐1,3 and G1m1,17 IgG1 variants, and detected comparable Spike‐specific IgG1 levels between haplotypes. IgG1 responses against other human coronaviruses and influenza were similarly poorly detected by 4E3 anti‐IgG1 in G1m‐1,3/G1m‐1,3 subjects. Conclusion Anti‐IgG1 clone 4E3 confounds assessment of antibody responses in clinical cohorts owing to bias towards detection of G1m1,17 IgG1 variants. Validation of anti‐Ig clones should include evaluation of binding to relevant antibody variants, particularly as the role of immunogenetics upon humoral immunity is increasingly explored in diverse populations.

This article’s emphasis is on the holistic care of women who are assessed as suitable for and amenable to vaginal birth after Caesarean section (VBAC) in the South African state health sector context. It is beyond its scope to deal with the minutiae of VBAC conduct, operative conduct of repeat Caesarean section (CS), or management of uterine rupture. It is also beyond the scope of the article to reflect on practices, which are accepted in other healthcare contexts. The intention is not to promote VBAC over elective repeat CS, but rather to assist healthcare workers with providing high-quality holistic care. The goal is that women with previous CS are given access to the mode of delivery, which is safest for them and their fetus, while minimising adverse psychological effects of previous and future negative birth experiences.

Herein, nitrogen-doped CDs (NCDs) were synthesized in a hydrothermal microwave-assisted pyrolysis using citric acid and urea. Differing carbon-to-urea molar ratios were used and the pH-dependent fluorescence and quantum yield (QY) at various pHs were measured. All NCDs demonstrated pH-dependent fluorescence with increased fluorescence from pH 1-13. Overall, the NCDs with a carbon-to-dopant molar ratio of 1:6 demonstrated the highest QY of 19% in pH 11. Additionally, high quantum yields were observed between pH 7-11. Therefore, NCDs, as prepared, may serve as cost-effective fluorescent pH sensors or in bioimaging applications.

Correctly initializing the fire within coupled fire-atmosphere models is critical for producing accurate forecasts of meteorology near the fire, as well as the fire growth, and plume evolution. Improperly initializing the fire in a coupled fire-atmosphere model can introduce forecast errors that can impact wind circulations surrounding the fire and updrafts along the fire front. A well-constructed fire initialization process must be integrated within coupled fire-atmosphere models to ensure that the atmospheric component of the model does not become numerically unstable due to excessive heat fluxes released during the ignition, and that realistic fire-induced atmospheric circulations are established at the model initialization time. The primary objective of this study is to establish an effective fire initialization method in a coupled fire-atmosphere model, based on the analysis of the impact of the initialization procedure on the model’s ability to resolve fire-atmosphere circulations and fire growth. Here, we test three different fire initialization approaches leveraging the FireFlux II experimental fire, which provides a comprehensive suite of observations of the pyroconvective column, local micrometeorology, and fire characteristics. The two most effective fire initialization methods identified using the FireFlux II case study are then tested on the 380,000-acre Creek Fire, which burned across the central Sierra Nevada mountains during the 2020 Western U.S. wildfire season. For this case study, simulated pyroconvection and fire progression are evaluated using plume top height observations from MISR and airborne fire perimeter data, to assess the effectiveness of different initialization methods in the context of establishing pyroconvection and resolving the fire growth. The analyses of both the experimental fire simulation and the wildfire simulation indicate that the spin-up initialization method based on historical fire progression that masks out inactive fire regions provides the best results in terms of resolving the fire-induced vertical circulation and fire progression.

Abstract BackgroundThe transition to parenthood is a period of major stressors and increased risk of anxiety for all parents. Though rates of perinatal anxiety are similar among women (4%-25%) and men (3%-25%), perinatal anxiety research on nonbirthing partners remains limited. ObjectiveWe aimed to examine whether demographic characteristics or digital perinatal support preferences differed among nonbirthing partners with compared to without self-reported high parenthood-related anxiety. MethodsIn this large cross-sectional study of nonbirthing partners using a digital perinatal health platform during their partner’s pregnancy, users reported their parenthood-related anxiety through a 5-item Likert scale in response to the prompt “On a scale of 1=None to 5=Extremely, how anxious are you feeling about parenthood?” High parenthood-related anxiety was defined as reporting being very or extremely anxious about parenthood. During the onboarding survey, in response to the question “Which areas are you most interested in receiving support in?” users selected as many support interests as they desired from a list of options. Chi-square ResultsAmong 2756 nonbirthing partners enrolled in the digital platform during their partner’s pregnancy, 2483 (90.1%) were men, 1668 (71.9%) were first-time parents, 1159 (42.1%) were non-Hispanic White, and 1652 (50.9%) endorsed an annual household income of >US $100,000. Overall, 2505 (91.9%) reported some amount of parenthood-related anxiety, and 437 (15.9%) had high parenthood-related anxiety. High parenthood-related anxiety was more common among non-White nonbirthing partners: compared to those who identified as non-Hispanic White, those who identified as Asian, Black, or Hispanic had 2.39 (95% CI 1.85-3.08), 2.01 (95% CI 1.20-3.23), and 1.68 (95% CI 1.15-2.41) times the odds of high parenthood-related anxiety, respectively. Lower household income was associated with increased odds of reporting high parenthood anxiety, with the greatest effect among those with annual incomes of US $100,000 (OR 2.13, 95% CI 1.32-3.34). In general, nonbirthing partners were interested in receiving digital support during their partner’s pregnancy, but those with high parenthood-related anxiety were more likely to desire digital support for all support interests compared to those without high parenthood anxiety. Those with high parenthood-related anxiety had more than 2 times higher odds of requesting digital education about their emotional health compared to those without high parenthood-related anxiety (OR 2.06, 95% CI 1.67-2.55). ConclusionsThese findings demonstrate the need for perinatal anxiety-related support for all nonbirthing partners and identify nonbirthing partners’ demographic characteristics that increase the odds of endorsing high parenthood-related anxiety. Additionally, these findings suggest that most nonbirthing partners using a digital health platform with high parenthood-related anxiety desire to receive perinatal mental health support.

Abstract Microglia, the innate immune cells of the brain, are activated by damage or disease. In mouse models of amyotrophic lateral sclerosis (ALS), microglia shift from neurotrophic to neurotoxic states with disease progression. It remains unclear how human microglia change relative to the TAR DNA-binding protein 43 (TDP-43) aggregation that occurs in 97% of ALS cases. Here we examine spatial relationships between microglial activation and TDP-43 pathology in brain tissue from people with ALS and from a TDP-43-driven ALS mouse model. Post-mortem human brain tissue from the Neurological Foundation Human Brain Bank was obtained from 10 control and 10 ALS cases in parallel with brain tissue from a bigenic NEFH-tTA/tetO-hTDP-43∆NLS (rNLS) mouse model of ALS at disease onset, early disease, and late disease stages. The spatiotemporal relationship between microglial activation and ALS pathology was determined by investigating microglial functional marker expression in brain regions with low and high TDP-43 burden at end-stage human disease: hippocampus and motor cortex, respectively. Sections were immunohistochemically labelled with a two-round multiplexed antibody panel against; microglial functional markers (L-ferritin, HLA-DR, CD74, CD68, and Iba1), a neuronal marker, an astrocyte marker, and pathological phosphorylated TDP-43 (pTDP-43). Single-cell levels of microglial functional markers were quantified using custom analysis pipelines and mapped to anatomical regions and ALS pathology. We identified a significant increase in microglial Iba1 and CD68 expression in the human ALS motor cortex, with microglial CD68 being significantly correlated with pTDP-43 pathology load. We also identified two subpopulations of microglia enriched in the ALS motor cortex that were defined by high L-ferritin expression. A similar pattern of microglial changes was observed in the rNLS mouse, with an increase first in CD68 and then in L-ferritin expression, with both occurring only after pTDP-43 inclusions were detectable. Our data strongly suggest that microglia are phagocytic at early-stage ALS but transition to a dysfunctional state at end-stage disease, and that these functional states are driven by pTDP-43 aggregation. Overall, these findings enhance our understanding of microglial phenotypes and function in ALS.

The analysis of longitudinal bulk and single-cell multi-omics data is a highly complex task. Here, the authors introduce PALMO, a software platform with five modules to analyse longitudinal bulk and single-cell multi-omics data, which is extensively tested in external datasets that include multiple omics modalities.

Abstract Zanubrutinib‐treated and treatment‐naïve patients with chronic lymphocytic leukaemia (CLL) or Waldenstrom's macroglobulinaemia were recruited in this prospective study to comprehensively profile humoral and cellular immune responses to COVID‐19 vaccination. Overall, 45 patients (median 72 years old) were recruited; the majority were male (71%), had CLL (76%) and were on zanubrutinib (78%). Seroconversion rates were 65% and 77% following two and three doses, respectively. CD4+ and CD8+ T‐cell response rates increased with third dose. In zanubrutinib‐treated patients, 86% developed either a humoral or cellular response. Patients on zanubrutinib developed substantial immune responses following two COVID‐19 vaccine doses, which further improved following a third dose.

Fullerenes, particularly C60, exhibit unique properties that make them promising candidates for various applications, including drug delivery and nanomedicine. However, their interactions with biomolecules, especially proteins, remain not fully understood. This study implements both explicit and implicit C60 models into the UNRES coarse-grained force field, enabling the investigation of fullerene–protein interactions without the need for restraints to stabilize protein structures. The UNRES force field offers computational efficiency, allowing for longer timescale simulations while maintaining accuracy. Five model proteins were studied: FK506 binding protein, HIV-1 protease, intestinal fatty acid binding protein, PCB-binding protein, and hen egg-white lysozyme. Molecular dynamics simulations were performed with and without C60 to assess protein stability and investigate the impact of fullerene interactions. Analysis of contact probabilities reveals distinct interaction patterns for each protein. FK506 binding protein (1FKF) shows specific binding sites, while intestinal fatty acid binding protein (1ICN) and uteroglobin (1UTR) exhibit more generalized interactions. The explicit C60 model shows good agreement with all-atom simulations in predicting protein flexibility, the position of C60 in the binding pocket, and the estimation of effective binding energies. The integration of explicit and implicit C60 models into the UNRES force field, coupled with recent advances in coarse-grained modeling and multiscale approaches, provides a powerful framework for investigating protein–nanoparticle interactions at biologically relevant scales without the need to use restraints stabilizing the protein, thus allowing for large conformational changes to occur. These computational tools, in synergy with experimental techniques, can aid in understanding the mechanisms and consequences of nanoparticle–biomolecule interactions, guiding the design of nanomaterials for biomedical applications.

Background: The objective was to estimate the effect of intrapartum amnioinfusion (AI) for recurrent variable decelerations on neonatal morbidity. The primary outcome was composite neonatal neurologic morbidity assembled from individual neonatal outcomes used clinically with suspected hypoxic-ischemic encephalopathy (HIE). Secondary outcomes were composite neonatal morbidity not associated with HIE. Methods: Data Sources: A predefined, systematic search was conducted through Ovid Medline, Embase, CINAHL PLUS, Cochrane library (including CENTRAL), Scopus, and Clinicaltrials.gov and was used to identify studies assessing the relationship between intrapartum AI and neonatal morbidity yielding 345 unique citations from 1982 to 2018. Study Eligibility Criteria: Randomized control trials that compared intrapartum AI to no AI for recurrent variable decelerations and included neonatal outcomes were included. Randomized trials comparing AI for other indications (e.g., meconium aspiration syndrome) were excluded, as were studies on intrapartum AI that lacked a control group (i.e., no amnioinfusion). Results: A total of 3 randomized control trials met the selection criteria. Outcomes from 282 neonates exposed to intrapartum AI for recurrent variable decelerations were compared to those from 286 who had fetal monitoring with recurrent variable decelerations but did not receive AI. There were no data on neonatal neurologic morbidity outcomes related to HIE. Among the data available, composite neonatal morbidity was not significantly different with AI (28.7% vs. 59.1%, pooled risk ratio, –0.30; 95% CI (95% confidence interval) –0.99–0.40; I2 = 94.51%; p = 0.40). Separated by individual outcomes contributing to the composite, intensive care unit admissions (ICU) (1 study; 6.8% vs. 16.5%; risk ratio 0.45; 95% CI 0.25–0.83) were less likely in those receiving an intrapartum AI, compared to no intrapartum AI while there was no difference in umbilical cord pH

This article presents studies on the evaluation of the impact of surface modification of cotton, viscose, and polyester fabrics using three techniques (flocking, layer by layer, and screen printing) with materials with electrically conductive properties on their structural, biophysical, and conductive properties. Each tested fabric is characterized by specific biophysical properties. which can be disturbed by various modification methods, therefore, the following tests were carried out in the article: optical microscopy, micro-computed tomography, guarded perspiration heating plate, air permeability, sorption and electrical conductivity tester. The use of screen printing increased the thermal resistance of the cotton woven fabric by 119%, the polyester woven fabric by 156%, and the viscose fabric by 261%. The smallest changes in thermal resistance compared to unmodified textiles were observed in layer by layer modified fabrics and are as follows: −15% (cotton woven fabric), +77% (PES woven fabric), and +80% (viscose woven fabric).

The application of biobased and biodegradable polymers, such as polylactide (PLA), in fused deposition modeling (FDM) 3D-printing technology creates a new prospect for rapid prototyping and other applications in the context of ecology. The popularity of the FDM method and its significance in material engineering not only creates new prospects for the development of technical sciences on an industrial scale, but also introduces new technologies into households. In this study, the kinetics of the hydrolytic degradation of samples obtained by the FDM method from commercially available PLA filaments under a thermally accelerated regime were analyzed. The investigation was conducted at the microstructural, supramolecular, and molecular levels by using methods such as micro-computed tomography (micro-CT), wide-angle X-ray diffraction (WAXD), viscosimetry, and mass erosion measurements. The obtained results clearly present the rapid structural changes in 3D-printed materials during degradation due to their amorphous initial structure. The complementary studies carried out at different scale levels allowed us to demonstrate the relationship between the observed structural changes in the samples and the hydrolytic decomposition of the polymer chains, which made it possible to scientifically understand the process and expand the knowledge on biodegradation.

Abstract INTRODUCTION The risk of developing Alzheimer's disease is associated with genes involved in microglial function. Inositol polyphosphate‐5‐phosphatase (INPP5D), which encodes Src homology 2 (SH2) domain–containing inositol polyphosphate 5‐phosphatase 1 (SHIP1), is a risk gene expressed in microglia. Because SHIP1 binds receptor immunoreceptor tyrosine‐based inhibitory motifs (ITIMs), competes with kinases, and converts PI(3,4,5)P3 to PI(3,4)P2, it is a negative regulator of microglia function. Validated inhibitors are needed to evaluate SHIP1 as a potential therapeutic target. METHODS We identified inhibitors and screened the enzymatic domain of SHIP1. A protein construct containing two domains was used to evaluate enzyme inhibitor potency and selectivity versus SHIP2. Inhibitors were tested against a construct containing all ordered domains of the human and mouse proteins. A cellular thermal shift assay (CETSA) provided evidence of target engagement in cells. Phospho‐AKT levels provided further evidence of on‐target pharmacology. A high‐content imaging assay was used to study the pharmacology of SHIP1 inhibition while monitoring cell health. Physicochemical and absorption, distribution, metabolism, and excretion (ADME) properties were evaluated to select a compound suitable for in vivo studies. RESULTS SHIP1 inhibitors displayed a remarkable array of activities and cellular pharmacology. Inhibitory potency was dependent on the protein construct used to assess enzymatic activity. Some inhibitors failed to engage the target in cells. Inhibitors that were active in the CETSA consistently destabilized the protein and reduced pAKT levels. Many SHIP1 inhibitors were cytotoxic either at high concentration due to cell stress or they potently induced cell death depending on the compound and cell type. One compound activated microglia, inducing phagocytosis at concentrations that did not result in significant cell death. A pharmacokinetic study demonstrated brain exposures in mice upon oral administration. DISCUSSION 3‐((2,4‐Dichlorobenzyl)oxy)‐5‐(1‐(piperidin‐4‐yl)‐1H‐pyrazol‐4‐yl) pyridine activated primary mouse microglia and demonstrated exposures in mouse brain upon oral dosing. Although this compound is our recommended chemical probe for investigating the pharmacology of SHIP1 inhibition at this time, further optimization is required for clinical studies. Highlights Cellular thermal shift assay (CETSA) and signaling (pAKT) assays were developed to provide evidence of src homology 2 (SH2) domain‐contaning inositol phosphatase 1 (SHIP1) target engagement and on‐target activity in cellular assays. A phenotypic high‐content imaging assay with simultaneous measures of phagocytosis, cell number, and nuclear intensity was developed to explore cellular pharmacology and monitor cell health. SHIP1 inhibitors demonstrate a wide range of activity and cellular pharmacology, and many reported inhibitors are cytotoxic. The chemical probe 3‐((2,4‐dichlorobenzyl)oxy)−5‐(1‐(piperidin‐4‐yl)−1H‐pyrazol‐4‐yl) pyridine is recommended to explore SHIP1 pharmacology.

Convolutional neural networks (CNN) have demonstrated good accuracy and speed in spatially registering high signal-to-noise ratio (SNR) structural magnetic resonance imaging (sMRI) images. However, some functional magnetic resonance imaging (fMRI) images, e.g., those acquired from arterial spin labeling (ASL) perfusion fMRI, are of intrinsically low SNR and therefore the quality of registering ASL images using CNN is not clear. In this work, we aimed to explore the feasibility of a CNN-based affine registration network (ARN) for registration of low-SNR three-dimensional ASL perfusion image time series and compare its performance with that from the state-of-the-art statistical parametric mapping (SPM) algorithm. The six affine parameters were learned from the ARN using both simulated motion and real acquisitions from ASL perfusion fMRI data and the registered images were generated by applying the transformation derived from the affine parameters. The speed and registration accuracy were compared between ARN and SPM. Several independent datasets, including meditation study (10 subjects × 2), bipolar disorder study (26 controls, 19 bipolar disorder subjects), and aging study (27 young subjects, 33 older subjects), were used to validate the generality of the trained ARN model. The ARN method achieves superior image affine registration accuracy (total translation/total rotation errors of ARN vs. SPM: 1.17 mm/1.23° vs. 6.09 mm/12.90° for simulated images and reduced MSE/L1/DSSIM/Total errors of 18.07% / 19.02% / 0.04% / 29.59% for real ASL test images) and 4.4 times (ARN vs. SPM: 0.50 s vs. 2.21 s) faster speed compared to SPM. The trained ARN can be generalized to align ASL perfusion image time series acquired with different scanners, and from different image resolutions, and from healthy or diseased populations. The results demonstrated that our ARN markedly outperforms the iteration-based SPM both for simulated motion and real acquisitions in terms of registration accuracy, speed, and generalization.

Understanding mucosal antibody responses from SARS-CoV-2 infection and/or vaccination is crucial to develop strategies for longer term immunity, especially against emerging viral variants. We profiled serial paired mucosal and plasma antibodies from COVID-19 vaccinated only vaccinees (vaccinated, uninfected), COVID-19–recovered vaccinees (recovered, vaccinated), and individuals with breakthrough Delta or Omicron BA.2 infections (vaccinated, infected). Saliva from COVID-19–recovered vaccinees displayed improved antibody-neutralizing activity, Fcγ receptor (FcγR) engagement, and IgA levels compared with COVID-19–uninfected vaccinees. Furthermore, repeated mRNA vaccination boosted SARS-CoV-2–specific IgG2 and IgG4 responses in both mucosa biofluids (saliva and tears) and plasma; however, these rises only negatively correlated with FcγR engagement in plasma. IgG and FcγR engagement, but not IgA, responses to breakthrough COVID-19 variants were dampened and narrowed by increased preexisting vaccine-induced immunity against the ancestral strain. Salivary antibodies delayed initiation following breakthrough COVID-19 infection, especially Omicron BA.2, but rose rapidly thereafter. Importantly, salivary antibody FcγR engagements were enhanced following breakthrough infections. Our data highlight how preexisting immunity shapes mucosal SARS-CoV-2–specific antibody responses and has implications for long-term protection from COVID-19.

Background The crown-of-thorns starfish (COTS; Acanthaster species) is a slow-moving corallivore protected by an extensive array of long, sharp toxic spines. Envenomation can result in nausea, numbness, vomiting, joint aches and sometimes paralysis. Small molecule saponins and the plancitoxin proteins have been implicated in COTS toxicity. Methods Brine shrimp lethality assays were used to confirm the secretion of spine toxin biomolecules. Histological analysis, followed by spine-derived proteomics helped to explain the source and identity of proteins, while quantitative RNA-sequencing and phylogeny confirmed target gene expression and relative conservation, respectively. Results We demonstrate the lethality of COTS spine secreted biomolecules on brine shrimp, including significant toxicity using aboral spine semi-purifications of >10 kDa (p > 0.05, 9.82 µg/ml), supporting the presence of secreted proteins as toxins. Ultrastructure observations of the COTS aboral spine showed the presence of pores that could facilitate the distribution of secreted proteins. Subsequent purification and mass spectrometry analysis of spine-derived proteins identified numerous secretory proteins, including plancitoxins, as well as those with relatively high gene expression in spines, including phospholipase A2, protease inhibitor 16-like protein, ependymin-related proteins and those uncharacterized. Some secretory proteins (e.g., vitellogenin and deleted in malignant brain tumor protein 1) were not highly expressed in spine tissue, yet the spine may serve as a storage or release site. This study contributes to our understanding of the COTS through functional, ultrastructural and proteomic analysis of aboral spines.

The deepening of the Drake Passage cooled Antarctic coasts and increased the temperature gradient between Australia and Antarctica which ultimately enhanced thermal isolation of the Antarctic Ice sheet, according to biomarker derived temperature records and simulation output.

Here, the enzymatic activity of APOBEC3G resulting in conversion of 2′-deoxy-zebularine into a hydration product allowed the authors to capture the transition state, which provides a blueprint for designing a new class of transition state-mimicking inhibitors for this class of enzyme.

Abstract We calculate the decay branching fractions of the Higgs boson to J/ψ and η c via the charm-quark fragmentation mechanism for the color-singlet and color-octet states in the framework of non-relativistic QCD. The decay rates are governed by the charm-quark Yukawa coupling, unlike the decay H → J/ψ + γ, which is dominated by the γ ∗-J/ψ mixing. We find that the decay branching fractions can be about 2×10 −5 for H → c c ¯ + J / ψ $$ H\to c\overline{c}+J/\psi $$ , and 6 × 10 −5 for H → c c ¯ + η c $$ H\to c\overline{c}+{\eta}_c $$ . We comment on the perspective of searching for the Higgs boson to J/ψ transition at the High-Luminosity LHC for testing the charm-quark Yukawa coupling.

In this study, observations of live fuel moisture content (LFMC) for predominantly sampled fuels in six distinct regions of California were examined from 2000 to 2021. To gather the necessary data, an open-access database called the Fuel Moisture Repository (FMR), was developed. By harnessing the extensive data aggregation and query capabilities of the FMR, which draws upon the National Fuel Moisture Database, valuable insights into the live fuel moisture seasonality were obtained. Specifically, our analysis revealed a distinct downtrend in LFMC across all regions, with the exception of the two Northernmost regions. The uptrends of LFMC seen in those regions are insignificant to the general downtrend seen across all of the regions. Although the regions do not share the same trends over the temporal span of the study, from 2017 to 2021, all the regions experienced a downtrend two times more severe than the general 22-year downtrend. Further analysis of the fuel types in each of the six regions, revealed significant variability in LFMC across different fuel types and regions. To understand potential drivers of this variability, the relationship between LFMC and drought conditions was investigated. This analysis found that LFMC fluctuations were closely linked to water deficits. However, the drought conditions varied across the examined regions, contributing to extreme LFMC variability. Notably, during prolonged drought periods of 2 or more years, fuels adapted to their environment by stabilizing or even increasing their maximum and minimum moisture values, contrary to the expected continual decrease. These LFMC trends have been found to correlate to wildfire activity and the specific LFMC threshold of 79% has been proposed as trigger of an increased likelihood of large fires. By analyzing the LFMC and fire activity data in each region, we found that more optimal local thresholds can be defined, highlighting the spatial variability of the fire response to the LFMC. This work expands on existing literature regarding the connections between drought and LFMC, as well as fire activity and LFMC. The study presents a 22-year dataset of LFMC spanning the entirety of California and analyses the LFMC trends in California that haven’t been rigorously studied before.

Summary: Background: The SARS-CoV-2 global pandemic has fuelled the generation of vaccines at an unprecedented pace and scale. However, many challenges remain, including: the emergence of vaccine-resistant mutant viruses, vaccine stability during storage and transport, waning vaccine-induced immunity, and concerns about infrequent adverse events associated with existing vaccines. Methods: We report on a protein subunit vaccine comprising the receptor-binding domain (RBD) of the ancestral SARS-CoV-2 spike protein, dimerised with an immunoglobulin IgG1 Fc domain. These were tested in conjunction with three different adjuvants: a TLR2 agonist R4-Pam2Cys, an NKT cell agonist glycolipid α-Galactosylceramide, or MF59® squalene oil-in-water adjuvant, using mice, rats and hamsters. We also developed an RBD-human IgG1 Fc vaccine with an RBD sequence of the immuno-evasive beta variant (N501Y, E484K, K417N). These vaccines were also tested as a heterologous third dose booster in mice, following priming with whole spike vaccine. Findings: Each formulation of the RBD-Fc vaccines drove strong neutralising antibody (nAb) responses and provided durable and highly protective immunity against lower and upper airway infection in mouse models of COVID-19. The ‘beta variant’ RBD vaccine, combined with MF59® adjuvant, induced strong protection in mice against the beta strain as well as the ancestral strain. Furthermore, when used as a heterologous third dose booster, the RBD-Fc vaccines combined with MF59® increased titres of nAb against other variants including alpha, delta, delta+, gamma, lambda, mu, and omicron BA.1, BA.2 and BA.5. Interpretation: These results demonstrated that an RBD-Fc protein subunit/MF59® adjuvanted vaccine can induce high levels of broadly reactive nAbs, including when used as a booster following prior immunisation of mice with whole ancestral-strain spike vaccines. This vaccine platform offers a potential approach to augment some of the currently approved vaccines in the face of emerging variants of concern, and it has now entered a phase I clinical trial. Funding: This work was supported by grants from the Medical Research Future Fund (MRFF) (2005846), The Jack Ma Foundation, National Health and Medical Research Council of Australia (NHMRC; 1113293) and Singapore National Medical Research Council (MOH-COVID19RF-003). Individual researchers were supported by an NHMRC Senior Principal Research Fellowship (1117766), NHMRC Investigator Awards (2008913 and 1173871), Australian Research Council Discovery Early Career Research Award (ARC DECRA; DE210100705) and philanthropic awards from IFM investors and the A2 Milk Company.

Summary: Currently approved COVID-19 vaccines administered parenterally induce robust systemic humoral and cellular responses. While highly effective against severe disease, there is reduced effectiveness of these vaccines in preventing breakthrough infection and/or onward transmission, likely due to poor immunity elicited at the respiratory mucosa. As such, there has been considerable interest in developing novel mucosal vaccines that engenders more localised immune responses to provide better protection and recall responses at the site of virus entry, in contrast to traditional vaccine approaches that focus on systemic immunity. In this review, we explore the adaptive components of mucosal immunity, evaluate epidemiological studies to dissect if mucosal immunity conferred by parenteral vaccination or respiratory infection drives differential efficacy against virus acquisition or transmission, discuss mucosal vaccines undergoing clinical trials and assess key challenges and prospects for mucosal vaccine development.