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Hypophosphatasia (HPP) is an inborn disease that causes a rare form of osteomalacia, a mineralization disorder affecting mineralized tissues. Identification of patients at high risk for fractures or other skeletal manifestations (such as insufficiency fractures or excessive bone marrow edema) by bone densitometry and laboratory tests remains clinically challenging. Therefore, we examined two cohorts of patients with variants in the ALPL gene grouped by bone manifestations. These groups were compared by means of bone microarchitecture using high-resolution peripheral quantitative computed tomography (HR-pQCT) and simulated mechanical performance utilizing finite element analysis (FEA). Whereas the incidence of skeletal manifestations among the patients could not be determined by dual energy X-ray absorptiometry (DXA) or laboratory assessment, HR-pQCT evaluation showed a distinct pattern of HPP patients with such manifestations. Specifically, these patients had a pronounced loss of trabecular bone mineral density, increased trabecular spacing, and decreased ultimate force at the distal radius. Interestingly, the derived results indicate that the non-weight-bearing radius is superior to the weight-bearing tibia in identifying deteriorated skeletal patterns. Overall, the assessment by HR-pQCT appears to be of high clinical relevance due to the improved identification of HPP patients with an increased risk for fractures or other skeletal manifestations, especially at the distal radius.

Planktic foraminifera are major marine calcifiers in the modern ocean regulating the marine inorganic carbon pump and generating marine fossil archives of past climate change. Some planktic foraminifera evolved spine and symbiosis, increasing functional trait diversity and expanded their ecological niches. Here we incorporate symbiosis and spine traits into the ForamEcoGENIE model, a trait-based model focusing on functional trait rather than individual species, to enable us to study the importance of foraminifera biodiversity in the palaeoceanographic environment. We calibrated the modelled new traits using Latin Hypercube Sampling. We identified the best model run from an ensemble of 1200 runs compared with observations from global core-top, sediment trap, and plankton nets. The model successfully captures the global distribution and seasonal variation of the 4 major functional groups including dominance of the symbiont-obligate type in subtropical gyres and the symbiont-barren type in the productive subpolar oceans. The carbon export rate is correctly predicted for spinose foraminifera, but the model overestimates the global mean biomass of each group by 8 times and global export rate of non-spinose foraminifera by 4 times. Both the observational bias and the model's limitation in linking biomass to export production likely contributes to the discrepancy. Our model approximates a 3.05 g m-2 yr-1 global mean foraminifer-derived calcite flux and 1.1 Gt yr-1 total calcite export, account for 19 % of the global pelagic marine calcite budget within the lower range of modern calcite estimates. The calcite export is mostly derived from the symbiont-barren non-spinose group (39 %) and the symbiont-obligate spinose group (13 %). Our model overcomes the lack of biodiversity in previous version and offers the potential to explore foraminifera ecology dynamics and its impact on biogeochemistry in modern, future and paleogeographic environments.

Optical interconnects (OIs) based on vertical-cavity surface-emitting lasers (VCSELs) are the main workhorse within data centers, supercomputers, and even vehicles, providing low-cost, high-rate connectivity. VCSELs must operate under extremely harsh and time-varying conditions, thus requiring adaptive and flexible designs of the communication chain. Such designs can be built based on mathematical models (model-based design) or learned from data (machine learning (ML) based design). Various ML techniques have recently come to the forefront, replacing individual components in the transmitters and receivers with deep neural networks. Beyond such component-wise learning, end-to-end (E2E) autoencoder approaches can reach the ultimate performance through co-optimizing entire parameterized transmitters and receivers. This tutorial paper aims to provide an overview of ML for VCSEL-based OIs, with a focus on E2E approaches, dealing specifically with the unique challenges facing VCSELs, such as the wide temperature variations and complex models.

Interactions between glycan-binding proteins (GBPs) and glycosphingolipids (GSLs) are involved in numerous physiological and pathophysiological processes. Many model membrane systems are available for studying GBP-GSL interactions, but a systematic investigation has not been carried out on how the nature of the model membrane affects binding. In this work, we use electrospray ionization mass spectrometry (ESI-MS), both direct and competitive assays, to measure the binding of cholera toxin B subunit homopentamer (CTB

Diabetes mellitus (DM) is an emerging metabolic disease, and the management of diabetic bone disease poses a serious challenge worldwide. Understanding the underlying mechanisms leading to high fracture risk in DM is hence of particular interest and urgently needed to allow for diagnosis and treatment optimization. In a case-control postmortem study, the whole 12th thoracic vertebra and cortical bone from the mid-diaphysis of the femur from male individuals with type 1 diabetes mellitus (T1DM) (n = 6; 61.3 ± 14.6 years), type 2 diabetes mellitus (T2DM) (n = 11; 74.3 ± 7.9 years), and nondiabetic controls (n = 18; 69.3 ± 11.5) were analyzed with clinical and ex situ imaging techniques to explore various bone quality indices. Cortical collagen fibril deformation was measured in a synchrotron setup to assess changes at the nanoscale during tensile testing until failure. In addition, matrix composition was analyzed including determination of cross-linking and non-crosslinking advanced glycation end-products like pentosidine and carboxymethyl-lysine. In T1DM, lower fibril deformation was accompanied by lower mineralization and more mature crystalline apatite. In T2DM, lower fibril deformation concurred with a lower elastic modulus and tendency to higher accumulation of non-crosslinking advanced glycation end-products. The observed lower collagen fibril deformation in diabetic bone may be linked to altered patterns mineral characteristics in T1DM and higher advanced glycation end-product accumulation in T2DM. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Variation in breeding systems between species of the same taxonomic group complicates the consistent application of species concepts, and perhaps even the logically consistent circumscription of species. Several genera of arid-zone ephemerals in the Angianthus clade (Asteraceae: Gnaphalieae: Gnaphaliinae) contain both outcrossing and non-outcrossing species. The latter are recognised by producing an order of magnitude fewer pollen grains per anther and an often reduced number of corolla lobes, and they are frequently more widespread than are the former. In its current taxonomy, the genus Pogonolepis comprises an otherwise morphologically indistinguishable pair of one outcrossing and one non-outcrossing species. I generated sequence capture data to test the genetic segregation of P. stricta and P. muelleriana and the utility of sequence capture data for species circumscription and diagnostics. Phylogenetic analysis showed the two species to form two specimen clades, supporting the current taxonomy. Contrary to expectations, non-outcrossing P. muelleriana exhibited lower gene concordance, in line with values expected from recombination, as well as higher heterozygosity than its outcrossing sister species. More research on the breeding system and population structure of the two species may be required to explain these results.

Developmental plasticity, where traits change state in response to environmental cues, is well studied in modern populations. It is also suspected to play a role in macroevolutionary dynamics, but due to a lack of long-term records, the frequency of plasticity-led evolution in deep time remains unknown. Populations are dynamic entities, yet their representation in the fossil record is a static snapshot of often isolated individuals. Here, we apply for the first time contemporary integral projection models (IPMs) to fossil data to link individual development with expected population variation. IPMs describe the effects of individual growth in discrete steps on long-term population dynamics. We parameterize the models using modern and fossil data of the planktonic foraminifer Trilobatus sacculifer. Foraminifera grow by adding chambers in discrete stages and die at reproduction, making them excellent case studies for IPMs. Our results predict that somatic growth rates have almost twice as much influence on population dynamics than survival and more than eight times more influence than reproduction, suggesting that selection would primarily target somatic growth as the major determinant of fitness. As numerous paleobiological systems record growth rate increments in single genetic individuals and imaging technologies are increasingly available, our results open up the possibility of evidence-based inference of developmental plasticity spanning macroevolutionary dynamics. Given the centrality of ecology in paleobiological thinking, our model is one approach to help bridge eco-evolutionary scales while directing attention toward the most relevant life-history traits to measure.

Golden everlasting paper daisies in the genus Xerochrysum Tzvelev are iconic Australian native plants grown worldwide. The X. bracteatum species complex has been regarded as taxonomically confusing and in need of revision for over 60 years. We applied morphological and molecular analyses to delimit species, detect common ancestry among populations, and identify putative hybrids in the genus Xerochrysum (Asteraceae: Gnaphalieae). Multiple lines of evidence provided strong support for the recognition of new taxa. Here we describe the following 11 new species: X. andrewiae T.L.Collins & J.J.Bruhl, X. berarngutta T.L.Collins & I.Telford, X. copelandii J.J.Bruhl & I.Telford, X. frutescens J.J.Bruhl & I.Telford, X. gudang T.L.Collins & J.J.Bruhl, X. hispidum T.L.Collins & I.Telford, X. macsweeneyorum T.L.Collins, X. murapan T.L.Collins & I.Telford, X. neoanglicum J.J.Bruhl & I.Telford, X. strictum T.L.Collins, and X. wilsonii T.L.Collins, reinstate Helichrysum banksii A.Cunn. ex DC. (as X. banksii (A.Cunn. ex DC.) T.L.Collins & I.Telford), lectotypify X. banksii and X. papillosum (Labill.) R.J.Bayer, and recircumscribe X. bicolor (Lindl.) R.J.Bayer to include X. halmaturorum Paul G.Wilson and some populations of X. bracteatum sens. lat. from mainland South Australia and Victoria. We also provide revised descriptions of all taxa in the genus, their conservation status, a dichotomous key, tables distinguishing closely related taxa and distribution maps.

A growing number of studies have investigated the feasibility of utilizing hemp by-products as livestock feedstuffs; however, their impact on livestock microbiomes remains unexplored. Here, we evaluated the effects of feeding hempseed cake on the gastrointestinal, respiratory, and reproductive microbiota in beef heifers. Angus-crossbred heifers (19-months old, initial body weight = 494 ± 10 kg [SE]) were fed a corn-based finishing diet containing 20% hempseed cake as a substitute for 20% corn dried distillers’ grains with solubles (DM basis; Control; n = 16/group) for 111 days until slaughter. Ruminal fluid and deep nasopharyngeal swabs (days 0, 7, 42, 70 and 98), and vaginal and uterine swabs (at slaughter) were collected, and the microbiota assessed using 16S rRNA gene sequencing. Diet affected the community structure of the ruminal (d 7−98; 0.06 ≤ R2 ≤ 0.12; P 2 = 0.18; P 2 = 0.06; P

The Paleocene encompasses a series of hyperthamls including the Paleocene–Eocene Thermal Maximum (PETM) and the ETM2 which represent severe disturbances of global carbon cycling and the Earth system. Responses of marine organisms included extinction, migration and evolutionary turnover, but the role of ocean acidification on deep-sea foraminiferal calcification has not yet been quantified. Using computed tomography (CT) we investigate morphological (surface area, test volume, calcite volume, chamber number) and hence calcification response in two benthic foraminiferal species, at central Pacific Site 1210 (PaleoDepth 2100m), and Southern Ocean Maud Rise Site 690 (PD 1900m), Walvis Ridge Site 1264, and Kerguelen Plateau Site 1135 (PD ~800m) for the PETM and ETM2.The relative warming during the event was the same at all sites, suggesting that biotic differences are not likely related to differential warming. The environmental change led to reduction of test volume of both species, negatively impacting their potential ability to generate gametes. Epifaunal Nuttallides truempyi increased its surface area relative to volume in the Southern Ocean, potentially increasing its ability to forage and take up oxygen. In contrast, there is no clear pattern of change in shallow infaunal Oridorsalis umbonatus which, given sufficient food, can thrive at lower oxygen conditions. Calcite volume/test volume ratio decreased in both species during the PETM in the Southern Ocean, with the lack of response at upper abyssal depth in the Pacific possibly driven by severe oligotrophy even before the excursion. Therefore, changes in food supply during hyperthermals might have been less pronounced at upper abyssal depths in the Pacific than at the other two sites. These results contrast with published results from Walvis Ridge which showed an increase in calcification in small specimens of O. umbonatus. Food availability at the Southern Ocean sites may have supported growth as indicated by test volumes, but did not supply enough energy for calcification to mitigate against lower carbonate ion saturation during the PETM CIE.

The phosphoregulation of proteins with multiple phosphorylation sites is governed by biochemical reaction networks that can exhibit multistable behavior. However, the behavior of such networks is typically studied in a single reaction volume, while cells are spatially organized into compartments that can exchange proteins. In this work, we use stochastic simulations to study the impact of compartmentalization on a two-site phosphorylation network. We characterize steady states and fluctuation-driven transitions between them as a function of the rate of protein exchange between two compartments. Surprisingly, the rate of stochastic switching between states depends nonmonotonically on the protein exchange rate, with the highest rate of switching occurring at intermediate exchange rates. At sufficiently small exchange rates, the state of the system and rate of switching are controlled largely by fluctuations in the balance of enzymes in each compartment. This leads to negatively correlated states in the compartments. For large exchange rates, the two compartments behave as a single effective compartment. However, when the compartmental volumes are unequal, the behavior differs from a single compartment with the same total volume. These results demonstrate that exchange of proteins between distinct compartments can regulate the emergent behavior of a common signaling motif.

Increasing evidence from human and other animal species supports the existence of a commensal microbiota in semen and that this seminal microbiota may influence not only sperm quality and fertility but also female reproduction. Seminal microbiota in bulls and its evolution and factors shaping this community, however, remain largely underexplored.

The version of this article on this repository is an arXiv preprint (arXiv:2208.14575v2 [physics.ins-det] Mon, 6 Mar 2023 19:46:42 UTC (39,794 KB)) submitted to Elsevier and is not the final, peer reviewed, corrected article. It is made available under a Creative Commons (CC BY 4.0) Attribution License. This article presents a collection of simulation studies using the ECCE detector concept in the context of the EIC's exclusive, diffractive, and tagging physics program, which aims to further explore the rich quark–gluon structure of nucleons and nuclei. To successfully execute the program, ECCE proposed to utilize the detector system close to the beamline to ensure exclusivity and tag ion beam/fragments for a particular reaction of interest. Preliminary studies confirm the proposed technology and design satisfy the requirements. The projected physics impact results are based on the projected detector performance from the simulation at 10 or 100 fb−1 of integrated luminosity. Additionally, insights related to a potential second EIC detector are documented, which could serve as a guidepost for future development. Office of Nuclear Physics in the Office of Science in the Department of Energy, the National Science Foundation, USA, the Los Alamos National Laboratory Directed Research and Development (LDRD), USA 20200022DR, the Natural Sciences and Engineering Research Council of Canada (NSERC), and the UK Research and Innovation Science and Technology Facilities Council; This research used resources from the Compute and Data Environment for Science (CADES) at the Oak Ridge National Laboratory, which is supported by the Office of Science of the U.S. Department of Energy under Contract No. DE-AC05-00OR22725; Brookhaven National Lab and the Thomas Jefferson National Accelerator Facility which are operated under contracts DE-SC0012704 and DE-AC05-06OR23177 respectively.

Immune checkpoint blockade trials have yet to produce a robust anti-cancer response in prostate cancer patients as a monotherapy due to the immunosuppressed prostate cancer tumour immune microenvironment. ST3Gal1 and other sialyltransferases are implicated in cancer and immune suppression by synthesizing sialoglycans, which act as ligands for Siglec receptors. These checkpoints are important for the immune response. However, it’s unclear how the synthesis of Siglec ligands is regulated, and little is known about the role of sialoglycan-Siglec-axis in prostate cancer’s evasion of anti-tumour immunity. We report that ST3Gal1 levels negatively correlate with androgen signalling in prostate tumours. Utilising syngeneic mouse models, we demonstrate that ST3Gal1 plays an important role in modulating tumour immune evasion. Using mouse models, patient samples andin vitromodels we show that ST3Gal1 synthesises sialoglycans with the capacity to engage the Siglec-7 and Siglec-9 immunoreceptors preventing immune clearance of cancer cells. For the first time we provide evidence of the expression of Siglec-7/9 ligands and their respective immunoreceptors in prostate tumours. Importantly, we show that these interactions can be modulated by enzalutamide and may maintain immune suppression in enzalutamide treated tumours. We conclude that the activity of ST3Gal1 is critical to prostate cancer anti-tumour immunity and provide rationale for the use of glyco-immune checkpoint targeting therapies in advanced prostate cancer.

Here, we investigated whether initial microbial colonization at seven different anatomical locations in newborn calves and their blood cytokines are influenced by prenatal vitamin and mineral (VTM) supplementation. Samples were collected from the hoof, liver, lung, nasal cavity, eye, rumen (tissue and fluid), and vagina of beef calves that were born from dams that received diets with or without VTM supplementation throughout gestation (n=7/group). Calves were separated from their dams immediately after birth and fed colostrum and milk replacer until euthanasia at 30 h post-initial colostrum feeding. The microbiota of all samples was assessed using 16S rRNA gene sequencing and qPCR. 15 cytokines and chemokines were quantified in their serum. The hoof, ocular, liver, respiratory, and reproductive sites of newborn calves were colonized by site-specific microbiota that differed from that of the rumen (0.64 ≥ R2≥ 0.12,P≤ 0.003). Only the ruminal fluid microbiota was differed by on prenatal VTM supplementation (P<0.01 Differences (PP=0.02) in VTM calves. Overall, our results suggest that despite immediate separation from the dam upon birth, whole-body of 32-h old calves are colonized by relatively rich, diverse and site-specific bacterial communities, and that initial microbial colonization of the rumen, vagina and oculus seem to be influenced by the prenatal VTM supplementation.IMPORTANCEIncreased appreciation of maternal nutrition and microbiome’s involvement in developmental programming and evidence supportingin uteromicrobial colonization highlight that maternal nutrition factors could impact offspring microbial colonization. Here, we investigated whether initial microbial colonization in any of 7 different anatomical sites of newborn calves was influenced by maternal vitamin and mineral (VTM) supplementation. We identified changes in ruminal, vaginal, and ocular microbiota in newborn calves in response to prenatal VTM supplementation. We provided a “holistic” view on the whole-body calf microbiota. Our data was obtained from calves of the same sex and age, and who were immediately separated from dams, and hence provides novel insights on taxonomic composition of initial bacterial microbiota colonization in those anatomical sites examined. Combined, this study provides direction for future work targeting the manipulation of early life microbiome via alteration of maternal nutrition and harnessing early life microbiota for improved cattle health and production.

Acknowledgements: We sincerely thank the professional support of the captain and crew of the R/V Maria S. Merian as well as the scientific team on the expedition MSM12/2. We also thank W. Luttmer for technical assistance with the measurement at AWI. Many thanks to G. Mollenhauer, the AWI MICADAS lab, and S. Morton (SUERC) for radiocarbon measurement. Thanks to C. Vogt for XRD analysis. This project was supported by the Deutsche Forschungsgemeinschaft (DFG) through the International Research Training Group IRTG 1904 ArcTrain. Grant NE/I020261/1 from NERC in the ocean acidification program to D.N.S. is also gratefully acknowledged. Furthermore, we acknowledge support by the Open Access Publication Funds of AWI., Funder: Deutsche Forschungsgemeinschaft through "ArcTrain" (GRK1904), Freshwater perturbations are often thought to be associated with abrupt climate changes during the last deglaciation, while many uncertainties remain regarding the exact timing, pathway, mechanism, and influence of meltwater release. Here, we present very well-dated and high-resolution records from the eastern Labrador Sea representing the last 19.000 years, which demonstrate abrupt changes in sea surface characteristics. Four millennial-scale meltwater events have been identified between the last 14.000 and 8.200 years based on independent biomarker proxies and X-ray fluorescence scanning data. These events are characterized by increased sea ice formation and decreased sea surface temperatures which might have occurred within a few decades. We propose these abrupt changes were triggered by meltwater pulsing into the Labrador Sea periodically, resulting from collapse of the Laurentide-Greenland Ice Sheets caused by (sub-)surface ocean warming in the Labrador Sea. Our findings provide more precise information about impact of freshwater forcing on abrupt climate changes, which may help to improve simulations for past and future changes in ocean circulation and climate.

Here, we present the first draft genome sequences of 10 bacterial strains that were isolated from the rumen, nasopharynx, vagina, or uterus of healthy beef cattle. These genomes are from one Alkalihalobacillus clausii isolate, three Bacillus safensis isolates, five Escherichia coli isolates, and one Pasteurella multocida isolate.

Impacts of a range of climate change on marine organisms have been analysed in laboratory and experimental studies. The use of different taxonomic groupings, and assessment of different processes, though, makes identifying overall trends challenging, and may mask phylogenetically different responses. Bivalve molluscs are an ecologically and economically important data-rich clade, allowing for assessment of individual vulnerability and across developmental stages. We use meta-analysis of 203 unique experimental setups to examine how bivalve growth rates respond to increased water temperature, acidity, deoxygenation, changes to salinity, and combinations of these drivers. Results show that anthropogenic climate change will affect different families of bivalves disproportionally but almost unanimously negatively. Almost all drivers and their combinations have significant negative effects on growth. Combined deoxygenation, acidification, and temperature shows the largest negative effect size. Eggs/larval bivalves are more vulnerable overall than either juveniles or adults. Infaunal taxa, including Tellinidae and Veneridae, appear more resistant to warming and oxygen reduction than epifaunal or free-swimming taxa but this assessment is based on a small number of datapoints. The current focus of experimental set-ups on commercially important taxa and families within a small range of habitats creates gaps in understanding of global impacts on these economically important foundation organisms.

Dropout has recently emerged as a powerful and simple method for training neural networks preventing co-adaptation by stochastically omitting neurons. Dropout is currently not grounded in explicit modelling assumptions which so far has precluded its adoption in Bayesian modelling. Using Bayesian entropic reasoning we show that dropout can be interpreted as optimal inference under constraints. We demonstrate this on an analytically tractable regression model providing a Bayesian interpretation of its mechanism for regularizing and preventing co-adaptation as well as its connection to other Bayesian techniques. We also discuss two general approximate techniques for applying Bayesian dropout for general models, one based on an analytical approximation and the other on stochastic variational techniques. These techniques are then applied to a Baysian logistic regression problem and are shown to improve performance as the model become more misspecified. Our framework roots dropout as a theoretically justified and practical tool for statistical modelling allowing Bayesians to tap into the benefits of dropout training., 21 pages, 3 figures. Manuscript prepared 2014 and awaiting submission

BackgroundGangliosides are glycosphingolipids highly enriched in the brain, with important roles in cell signaling, cell-to-cell communication, and immunomodulation. Genetic defects in the ganglioside biosynthetic pathway result in severe neurodegenerative diseases, while a partial decrease in the levels of specific gangliosides was reported in Parkinson’s disease and Huntington’s disease. In models of both diseases and other conditions, administration of GM1—one of the most abundant gangliosides in the brain—provides neuroprotection. Most studies have focused on the direct neuroprotective effects of gangliosides on neurons, but their role in other brain cells, in particular microglia, is not known. In this study we investigated the effects of exogenous ganglioside administration and modulation of endogenous ganglioside levels on the response of microglia to inflammatory stimuli, which often contributes to initiation or exacerbation of neurodegeneration.MethodsIn vitro studies were performed using BV2 cells, mouse, rat, and human primary microglia cultures. Modulation of microglial ganglioside levels was achieved by administration of exogenous gangliosides, or by treatment with GENZ-123346 and L–t-PDMP, an inhibitor and an activator of glycolipid biosynthesis, respectively. Response of microglia to inflammatory stimuli (LPS, IL-1β, phagocytosis of latex beads) was measured by analysis of gene expression and/or secretion of pro-inflammatory cytokines. The effects of GM1 administration on microglia activation were also assessed in vivo in C57Bl/6 mice, following intraperitoneal injection of LPS.ResultsGM1 decreased inflammatory microglia responses in vitro and in vivo, even when administered after microglia activation. These anti-inflammatory effects depended on the presence of the sialic acid residue in the GM1 glycan headgroup and the presence of a lipid tail. Other gangliosides shared similar anti-inflammatory effects in in vitro models, including GD3, GD1a, GD1b, and GT1b. Conversely, GM3 and GQ1b displayed pro-inflammatory activity. The anti-inflammatory effects of GM1 and other gangliosides were partially reproduced by increasing endogenous ganglioside levels with L–t-PDMP, whereas inhibition of glycolipid biosynthesis exacerbated microglial activation in response to LPS stimulation.ConclusionsOur data suggest that gangliosides are important modulators of microglia inflammatory responses and reveal that administration of GM1 and other complex gangliosides exerts anti-inflammatory effects on microglia that could be exploited therapeutically.

Raman spectroscopy is an effective, low-cost, non-intrusive technique often used for chemical identification. Typical approaches are based on matching observations to a reference database, which requires careful preprocessing, or supervised machine learning, which requires a fairly large number of training observations from each class. We propose a new machine learning technique for Raman spectrum matching, based on contrastive representation learning, that requires no preprocessing and works with as little as a single reference spectrum from each class. On three datasets we demonstrate that our approach significantly improves or is on par with the state of the art in prediction accuracy, and we show how to compute conformal prediction sets with specified frequentist coverage. Based on our findings, we believe contrastive representation learning is a promising alternative to existing methods for Raman spectrum matching., Under review at Analytical Chemistry

During the Pliocene the planktic ecosystem, for the first time in its evolutionary history, experienced a separation of the tropical seaways. At the same time, low latitude planktic foraminifers reached sizes not seen for millions of years. We set out to examine whether the closure of the Central American Seaway (CAS) led to the reorganisation of the planktic food web and enabled this growth. As many plankton are not well preserved in the fossil record, we applied a trait-based ecosystem model for plankton – ForamEcoGEnIE – to an open and closed CAS Pliocene environment. ForamEcoGEnIE is an extension of the size-structured 3-D plankton ecosystem model, “EcoGEnIE” that includes non-spinose planktic foraminifers as a new functional group based on the costs and benefits of key traits (e.g. growth, grazing, calcification). We test whether the planktic food web and planktic foraminiferal physiology responded to this change in paleogeography by quantifying changes in plankton biomass and size. In large regions of the ocean, we observe no change in phytoplankton, zooplankton, or foraminiferal biomass in response to a closed CAS. However, we note an increase in biomass at the eastern equatorial Pacific and a decrease in the North Atlantic in response to the closure of the CAS. ForamEcoGEnIE predicts an increase in non-spinose foraminiferal body size at the eastern equatorial Pacific and a small decrease in the North Atlantic. We attribute the Pacific response to increased upwelling due to the closure of the CAS and in the North Atlantic we suggest the reduction in biomass and size is linked with the reorganisation of surface ocean currents. As much of the ocean shows no response, we tentatively conclude that the closure of the CAS did not induce a major reorganisation of the planktic ecosystem.

Within the marine fossil record, size is a fundamental trait providing information on both assemblages and individual species. Changes in size within an assemblage are largely driven by species composition typically related to environmental conditions. Changes in size of an individual species can be an indicator of health and whether optimal growth conditions (i.e. temperature, salinity and food availability) prevail. Over evolutionary timescales, individuals tend to increase in size (Cope’s rule) also altering the average size of the population.The Pliocene provides an excellent opportunity to look at environmental drivers and ecological responses to a warmer world, at high resolution and with extant species. A short glaciation phase, during marine isotope stage (MIS) M2, interrupted the Pliocene global warming between ~ 3.31 – 3.26 Ma. This event provides the ideal framework to quantify how biota, already adapted to warming conditions, respond to a short, but substantial cooling event. We analysed the size and species composition of samples collected as part of the Pliocene Research, Interpretation and Synoptic Mapping (PRISM) Project from a variety of locations around the globe. The samples cover the Atlantic, Indian and Pacific oceans at a range of latitudes (e.g. DSDP Site 521, 586, 607 and ODP Site 716, 754, 887). We measured the maximum diameter of planktonic foraminifera tests with a fully automated light microscope, enabling high resolution sampling at a multitude of sites, before, during and after the MIS M2 glaciation event. On average 2000 specimens were measured per sample, resulting in over a million analyses in total. Changes in planktonic foraminiferal assemblage composition were characterised by quantifying relative species abundances and augmented by determining the largest species.Planktonic foraminiferal assemblage size shows a general increase during the Pliocene likely related to warming temperatures. What is unclear is if this change is driven by changes in diversity due to extinction and origination, responses to environmental change or a general increase in size of species found through the record. Here we discuss reactions of species and (or) ecological groups to environmental change and determine the individual drivers of size change across the world’s oceans.

We performed feasibility studies for various single transverse spin measurements that are related to the Sivers effect, transversity and the tensor charge, and the Collins fragmentation function. The processes studied include semi-inclusive deep inelastic scattering (SIDIS) where single hadrons (pions and kaons) were detected in addition to the scattered DIS lepton. The data were obtained in {\sc pythia}6 and {\sc geant}4 simulated e+p collisions at 18 GeV on 275 GeV, 18 on 100, 10 on 100, and 5 on 41 that use the ECCE detector configuration. Typical DIS kinematics were selected, most notably $Q^2 > 1 $ GeV$^2$, and cover the $x$ range from $10^{-4}$ to $1$. The single spin asymmetries were extracted as a function of $x$ and $Q^2$, as well as the semi-inclusive variables $z$, and $P_T$. They are obtained in azimuthal moments in combinations of the azimuthal angles of the hadron transverse momentum and transverse spin of the nucleon relative to the lepton scattering plane. The initially unpolarized MonteCarlo was re-weighted in the true kinematic variables, hadron types and parton flavors based on global fits of fixed target SIDIS experiments and $e^+e^-$ annihilation data. The expected statistical precision of such measurements is extrapolated to 10 fb$^{-1}$ and potential systematic uncertainties are approximated given the deviations between true and reconstructed yields. The impact on the knowledge of the Sivers functions, transversity and tensor charges, and the Collins function has then been evaluated in the same phenomenological extractions as in the Yellow Report. The impact is found to be comparable to that obtained with the parameterized Yellow Report detector and shows that the ECCE detector configuration can fulfill the physics goals on these quantities., 22 pages, 22 figures, to be submitted to joint ECCE proposal NIM-A volume

Families of newborns are frequently referred to child protection systems because of parental substance use, yet many families face barriers to accessing prenatal care and substance use treatment services. Although federal legislation requires states to develop Plans of Safe Care to address families' health and substance use treatment needs, few have developed comprehensive and systematic approaches to provide perinatal support to parents and infants. In this commentary, we describe the development and initial testing of a Plan of Safe Care that engages patients and their providers in perinatal care coordination. Developed out of an in-depth analysis of current care workflows at an urban safety net health system, the Plan of Safe Care facilitates conversations with clients around delivery planning and aligns resources to support families with substance use disorders.

Prescribed fires often stimulate short-term productivity of grasslands that influences use by large, grazing herbivores. But studies examining burning effects on large herbivore population dynamics while simultaneously considering other environmental factors that might also influence population dynamics are lacking. We examined the influences of burned area, precipitation during the growing season, and possible distributional shifts from a nearby public hunt on maximum intrinsic rate of population growth (rmax) and environmental carrying capacity (K). We examined the influences of these predictors in a Roosevelt elk (Cervus elaphus roosevelti) population studied across 43 years where abundances ranged from 4 to 322 animals and prescribed fires ranged from 14 to 891 ha of burned area in Redwood National and State Parks, California, USA. The highest count across surveys conducted in a year was our index of elk (females, juveniles, subadult males) abundance. We estimated Ricker type models in a hierarchical, state-space formulation that separated observer error from process variation. We found a slight influence from burned area on both rmax and K but a stronger influence from precipitation during the growing season. The lack of a substantial effect from burned area on elk population parameters might be from a variety of factors such as spatial and temporal variation in intensity of prescribed fires and weak density dependence. Nonetheless, one positive benefit to elk population processes was that the patchwork of burning retarded encroachment of woody plants into forage habitat and, thus, maintained a constant area of forage habitat across 43 years.

Topical 17-beta-estradiol (E2) regulates the hair cycle, hair shaft differentiation, and sebum production. Vitamin A also regulates sebum production. Vitamin A metabolism proteins localized to the pilosebaceous unit (PSU; hair follicle and sebaceous gland); and were regulated by E2 in other tissues. This study tests the hypothesis that E2 also regulates vitamin A metabolism in the PSU. First, aromatase and estrogen receptors localized to similar sites as retinoid metabolism proteins during mid-anagen. Next, female and male wax stripped C57BL/6J mice were topically treated with E2, the estrogen receptor antagonist ICI 182,780 (ICI), letrozole, E2 plus letrozole, or vehicle control (acetone) during mid-anagen. E2 or one of its inhibitors regulated most of the vitamin A metabolism genes and proteins examined in a sex-dependent manner. Most components were higher in females and reduced with ICI in females. ICI reductions occurred in the premedulla, sebaceous gland, and epidermis. Reduced E2 also reduced RA receptors in the sebaceous gland and bulge in females. However, reduced E2 increased the number of retinal dehydrogenase 2 positive hair follicle associated dermal dendritic cells in males. These results suggest that estrogen regulates vitamin A metabolism in the skin. Interactions between E2 and vitamin A have implications in acne treatment, hair loss, and skin immunity.

Objective Gastroschisis is a full-thickness congenital defect of the abdominal wall through which intestines and other organs may herniate. In a prior analysis, attempted vaginal delivery with fetal gastroschisis appeared to increase through 2013, although cesarean delivery remained common. The objective of this analysis was to update current trends in attempted vaginal birth among pregnancies complicated by gastroschisis. Study Design We performed an updated cross-sectional analysis of live births from 2014 and 2020 using data from the U.S. National Vital Statistics System and evaluated trends in attempted vaginal deliveries among births with gastroschisis. Trends were evaluated using joinpoint regression. We constructed logistic regression models to evaluate the association between demographic and clinical variables and attempted vaginal delivery in the setting of gastroschisis. Results Among 5,355 deliveries with gastroschisis meeting inclusion criteria, attempted vaginal delivery increased significantly from 68.9% to 75.1%, an average annual percent change of 1.7% (95% confidence interval [CI], 0.8–2.5). Among gastroschisis-complicated pregnancies, patients 35 to 39 years old (adjusted odds ratio [aOR], 0.53; 95% CI, 0.37–0.79) and Hispanic race/ethnicity (aOR, 0.69; 95% CI, 0.58–0.62) were at lower likelihood of attempted vaginal delivery in adjusted analyses. Conclusion These findings suggest that vaginal delivery continues to increase in the setting of gastroschisis. Further reduction of surgical delivery for this fetal defect may be possible. Key Points

Studies in extant populations have shown that plasticity in developmental trajectories can contribute to the origin of novel traits and species divergence via the expression of previously cryptic variation in response to environmental change. Finding evidence for plasticity-led evolution in the fossil record remains challenging due to the poor preservation of developmental stages in many organisms. Planktic foraminifera are ideally suited for addressing this knowledge gap, because adult organisms in species in which development has been studied retain information about all the ontogenetic stages they have undergone. Here we map changes in the developmental trajectories of 68 specimens in the Globorotalia plesiotumida–tumida lineage of planktic foraminifera from the late Miocene until Recent using high-resolution computer tomography techniques. Our unique dataset shows that the transition from the ancestral G. plesiotumida to the descendant G. tumida is preceded by an increased variability in total cumulative volume—an important indicator of reproductive success in this taxon. We also find that the transition interval is marked by a distinct shift in developmental trajectory, which supports a rapid lineage division rather than gradual change. We suggest that high levels of plasticity—particularly in the early stages of development—have contributed to divergence in the ancestral morphology when subjected to a global cooling trend in the late Miocene. The large variation in developmental trajectories that we uncover within our samples emphasizes the need for high-throughput approaches in studies of ontogenetic change in the fossil record.

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

ZUSAMMENFASSUNGFür junge Forscher*innen am Beginn des Karriereweges sind Instrumente der Nachwuchsförderung und -vernetzung von großer Bedeutung. Unterstützung ist hier in vielen Bereichen notwendig, vom Erwerb sogenannter Soft Skills, der Ausweitung von persönlichen Fähigkeiten und Fachkompetenz, dem Kontakt zu Kollegen*innen und dem Aufbau eines eigenen Netzwerkes bis hin zur Planung des Karriereweges. In einem breiten Themenbereich wie der muskuloskelettalen Forschung sind hier interdisziplinäre und Fachgesellschaften-übergreifende Angebote von großer Bedeutung. In diesem Artikel stellen wir Nachwuchsnetzwerke für den muskuloskelettalen Nachwuchs im deutschsprachigen Bereich vor, die ein breites Spektrum an Symposien, Forschungsförderung und Mentoring anbieten, vor allem aber eine Plattform zur Vernetzung junger Forscher darstellen. Dies sind insbesondere die MuSkITYR (Muskuloskeletal Interdisciplinary Translational Young Researcher), das Junge Forum O und U, die AGA-Studenten (Gesellschaft für Arthroskopie und Gelenkchirurgie) sowie das Junge Forum ÖGU (Österreichische Gesellschaft für Unfallchirurgie) und die SSB + RM (Swiss Society for Biomaterials and Regenerative Medicine) Young Scientists.

Golden everlasting paper daisies (Xerochrysum, Gnaphalieae, Asteraceae) were some of the earliest Australian native plants to be cultivated in Europe. Reputedly a favourite of Napoléon Bonaparte and Empress Joséphine, X. bracteatum is thought to have been introduced to the island of St Helena in the South Atlantic during Napoléon’s exile there. Colourful cultivars were developed in the 1850s, and there is a widely held view that these were produced by crossing Xerochrysum with African or Asian Helichrysum spp. Recent molecular phylogenetic analyses and subtribal classification of Gnaphalieae cast doubt on this idea. Using single-nucleotide polymorphism (SNP) data, we looked for evidence of gene flow between modern cultivars, naturalized paper daisies from St Helena and four Xerochrysum spp. recorded in Europe in the 1800s. There was strong support for gene flow between cultivars and X. macranthum. Paper daisies from St Helena were genotypically congruent with X. bracteatum and showed no indications of ancestry from other species or from the cultivars, consistent with the continuous occurrence of naturalized paper daisies introduced by Joséphine and Napoléon. We also present new evidence for the origin of colourful Xerochrysum cultivars and hybridization of congeners in Europe from Australian collections.

Background High-resolution imaging receives increasing attention and leads to an improved understanding of skeletal diseases. Before the introduction of high-resolution peripheral quantitative computed tomography (HR-pQCT), the evaluation of bone microstructure was not feasible in vivo but required bone biopsies. Methods With HR-pQCT, it is possible to evaluate the bone microarchitecture three-dimensionally and with a high spatial resolution (60.7 μm voxel size). Results In multiple studies, relevant insights of bone microarchitecture have been revealed by HR-pQCT at the distal tibia and radius in both health and disease, accompanied by superior correlations with the incidence of fragility fractures compared to bone mineral density measurement by dual-energy X-ray absorptiometry. Conclusions Consequently, HR-pQCT offers great potential to improve the understanding of bone and joint diseases, especially in foot and ankle surgery, as it enables the evaluation of individualized bone regions at the microstructural level (e.g., bone erosion, fracture healing) within the clinical routine.

Background: Increasing evidence supports the existence of a microbial community in bovine semen, and that this seminal microbiota may influence not only the male fertility but also female reproduction. In this study, we evaluated the seminal and fecal microbiota in yearling beef bulls fed a common diet to achieve moderate (1.13 kg/d) or high (1.80 kg/d) rates of weight gain. Semen samples were collected on days 0 and 112 of dietary intervention (n = 19/group) as well as post-breeding (n = 6/group) using electroejaculation and the microbiota was assessed using 16S rRNA gene sequencing, qPCR, and culturing. The fecal microbiota was also evaluated and its similarity with seminal microbiota assessed. A subset of seminal bacterial isolates (n = 33) was screened for resistance against 28 antibiotics.Results: A complex and dynamic microbiota was detected in bovine semen, and the community structure was affected by sampling time (R2 = 0.16, P < 0.001). Microbial richness increased from d 0 (ASVs, 253 ± 12) to d 112 (293 ± 14) (P < 0.05). Microbial diversity did not change during pre-breeding but increased after breeding (P < 0.05). Fusobacteriota, Bacteroidota, Firmicutes and Actinobacteriota were dominant in the seminal microbiota, and their abundance changed over time and following breeding (P < 0.05). Seminal microbiota remained unaffected by the differential rate of gains, and its overall composition was distinct from fecal microbiota, with only 6% of the taxa shared between them. The fecal microbiota did not differ between the two dietary treatments at d 112 and post-breeding but changed over time from d 112 to post-breeding (P < 0.05). A total of 364 isolates from 49 different genera were recovered under aerobic and anaerobic culturing. Among these seminal isolates were pathogenic species associated with respiratory disease, liver abscesses and reproductive infections, as well as those resistant to several antibiotics. Conclusions: Our results suggest that bovine semen harbors a rich and complex microbiota which changes over time and in response to breeding activity but appears to be resilient to differential gains achieved via a common diet. Seminal microbiota is distinct from the fecal microbiota and harbors potentially pathogenic and antibiotic-resistant bacterial species.

Climate and ecological emergencies play out acutely in coastal systems with devastating impacts on biodiversity, and the livelihoods of communities and their cultural values. Marine Protected Areas (MPAs) are one of the key management and regulatory tools against biodiversity loss, playing a role in strengthening bio-cultural diversity and sustainability of coastal social-ecological systems. What is unclear though is the effectiveness of static protections under climate change as species move. Next to ecological uncertainty, regulatory uncertainty may play a role in weakening marine conservation. We asked whether MPAs are ecologically effective now and can sustain or improve to be so in the future while facing key climate and regulatory uncertainties. MPAs can support the protection of cultural values and have an impact on activities of sea-users and the sustainability of social-ecological systems. As such, questions surrounding their legitimacy under a changing climate and increased uncertainty are pertinent. We argue that MPA governance must be cognisant of the interdependency between natural and human systems and their joint reaction to climate change impacts based on an integrated, co-developed, and interdisciplinary approach. Focusing on the UK as a case study, we highlight some of the challenges to achieve effective, adaptive and legitimate governance of MPAs. This article is part of the theme issue ‘Nurturing resilient marine ecosystems’.

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

Australia’s 2019–2020 ‘Black Summer’ bushfires burnt more than 8 million hectares of vegetation across the south-east of the continent, an event unprecedented in the last 200 years. Here we report the impacts of these fires on vascular plant species and communities. Using a map of the fires generated from remotely sensed hotspot data we show that, across 11 Australian bioregions, 17 major native vegetation groups were severely burnt, and up to 67–83% of globally significant rainforests and eucalypt forests and woodlands. Based on geocoded species occurrence data we estimate that >50% of known populations or ranges of 816 native vascular plant species were burnt during the fires, including more than 100 species with geographic ranges more than 500 km across. Habitat and fire response data show that most affected species are resilient to fire. However, the massive biogeographic, demographic and taxonomic breadth of impacts of the 2019–2020 fires may leave some ecosystems, particularly relictual Gondwanan rainforests, susceptible to regeneration failure and landscape-scale decline., Fires triggered by climate change threaten plant diversity in many biomes. Here the authors investigate how the catastrophic fires of 2019–2020 affected the vascular flora of SE Australia. They report that 816 species were highly impacted, including taxa of biogeographic and conservation interest.