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The nuclear dependence of the inclusive inelastic electron scattering cross section (the EMC effect) has been measured for the first time in B10 and B11. Previous measurements of the EMC effect in A≤12 nuclei showed an unexpected nuclear dependence; B10 and B11 were measured to explore the EMC effect in this region in more detail. Results are presented for Be9, B10, B11, and C12 at an incident beam energy of 10.6 GeV. The EMC effect in the boron isotopes was found to be similar to that for Be9 and C12, yielding almost no nuclear dependence in the EMC effect in the range A=4-12. This represents important new data supporting the hypothesis that the EMC effect depends primarily on the local nuclear environment due to the cluster structure of these nuclei.

Inclusive electron scattering from nuclear targets has been measured to extract the nuclear dependence of the inelastic cross section (σA) in Hall C at the Thomas Jefferson National Accelerator facility. Results are presented for H2, He3, He4, B9, C12, Cu63, and Au197 at an incident electron beam energy of 5.77 GeV for a range of momentum transfer from Q2 = 2 to 7 (GeV/c)2. These data improve the precision of the existing measurements of the EMC effect in the nuclear targets at large x and allow for more detailed examinations of the A dependence of the EMC effect.

We report measurements of the parity-conserving beam-normal single-spinelastic scattering asymmetries $B_n$ on $^{12}$C and $^{27}$Al, obtained withan electron beam polarized transverse to its momentum direction. Thesemeasurements add an additional kinematic point to a series of previousmeasurements of $B_n$ on $^{12}$C and provide a first measurement on $^{27}$Al.The experiment utilized the Qweak apparatus at Jefferson Lab with a beam energyof 1.158 GeV. The average lab scattering angle for both targets was 7.7degrees, and the average $Q^2$ for both targets was 0.02437 GeV$^2$ (Q=0.1561GeV). The asymmetries are $B_n$ = -10.68 $\pm$ 0.90 stat) $\pm$ 0.57 (syst) ppmfor $^{12}$C and $B_n$ = -12.16 $\pm$ 0.58 (stat) $\pm$ 0.62 (syst) ppm for$^{27}$Al. The results are consistent with theoretical predictions, and arecompared to existing data. When scaled by Z/A, the Q-dependence of all thefar-forward angle (theta < 10 degrees) data from $^{1}$H to $^{27}$Al can bedescribed by the same slope out to $Q \approx 0.35$ GeV. Larger-angle data fromother experiments in the same Q range are consistent with a slope about twiceas steep.

We report measurements of the parity-conserving beam-normal single-spinelastic scattering asymmetries $B_n$ on $^{12}$C and $^{27}$Al, obtained withan electron beam polarized transverse to its momentum direction. Thesemeasurements add an additional kinematic point to a series of previousmeasurements of $B_n$ on $^{12}$C and provide a first measurement on $^{27}$Al.The experiment utilized the Qweak apparatus at Jefferson Lab with a beam energyof 1.158 GeV. The average lab scattering angle for both targets was 7.7degrees, and the average $Q^2$ for both targets was 0.02437 GeV$^2$ (Q=0.1561GeV). The asymmetries are $B_n$ = -10.68 $\pm$ 0.90 stat) $\pm$ 0.57 (syst) ppmfor $^{12}$C and $B_n$ = -12.16 $\pm$ 0.58 (stat) $\pm$ 0.62 (syst) ppm for$^{27}$Al. The results are consistent with theoretical predictions, and arecompared to existing data. When scaled by Z/A, the Q-dependence of all thefar-forward angle (theta < 10 degrees) data from $^{1}$H to $^{27}$Al can bedescribed by the same slope out to $Q \approx 0.35$ GeV. Larger-angle data fromother experiments in the same Q range are consistent with a slope about twiceas steep.

Background: Measurements of exclusive meson production are a useful tool in the study of hadronic structure. In particular, one can discern the relevant degrees of freedom at different distance scales through these studies. Purpose: To study the transition between nonperturbative and perturbative quantum chromodynamics as the square of four-momentum transfer to the struck proton, -t, is increased. Method: Cross sections for the H1(e,e′π+)n reaction were measured over the -t range of 0.272 to 2.127 GeV2 with limited azimuthal coverage at fixed beam energy of 4.709 GeV, Q2 of 2.4 GeV2, and W of 2.0 GeV at the Thomas Jefferson National Accelerator Facility (JLab) Hall C. Results: The -t dependence of the measured π+ electroproduction cross section generally agrees with prior data from JLab Halls B and C. The data are consistent with a Regge amplitude-based theoretical model but show poor agreement with a generalized parton distribution-based model. Conclusion: The agreement of cross sections with prior data implies small contribution from the interference terms, and the confirmation of the change in t slopes between the low- and high - t regions previously observed in photoproduction indicates the changing nature of the electroproduction reaction in our kinematic regime.

Background: Measurements of exclusive meson production are a useful tool in the study of hadronic structure. In particular, one can discern the relevant degrees of freedom at different distance scales through these studies. Purpose: To study the transition between nonperturbative and perturbative quantum chromodynamics as the square of four-momentum transfer to the struck proton, -t, is increased. Method: Cross sections for the H1(e,e′π+)n reaction were measured over the -t range of 0.272 to 2.127 GeV2 with limited azimuthal coverage at fixed beam energy of 4.709 GeV, Q2 of 2.4 GeV2, and W of 2.0 GeV at the Thomas Jefferson National Accelerator Facility (JLab) Hall C. Results: The -t dependence of the measured π+ electroproduction cross section generally agrees with prior data from JLab Halls B and C. The data are consistent with a Regge amplitude-based theoretical model but show poor agreement with a generalized parton distribution-based model. Conclusion: The agreement of cross sections with prior data implies small contribution from the interference terms, and the confirmation of the change in t slopes between the low- and high - t regions previously observed in photoproduction indicates the changing nature of the electroproduction reaction in our kinematic regime.

Backward-angle meson electroproduction above the resonance region, which was previously ignored, is anticipated to offer unique access to the three quark plus sea component of the nucleon wave function. In this Letter, we present the first complete separation of the four electromagnetic structure functions above the resonance region in exclusive ω electroproduction off the proton, ep→e^{'}pω, at central Q^{2} values of 1.60, 2.45  GeV^{2}, at W=2.21  GeV. The results of our pioneering -u≈-u_{min} study demonstrate the existence of a unanticipated backward-angle cross section peak and the feasibility of full L/T/LT/TT separations in this never explored kinematic territory. At Q^{2}=2.45  GeV^{2}, the observed dominance of σ_{T} over σ_{L}, is qualitatively consistent with the collinear QCD description in the near-backward regime, in which the scattering amplitude factorizes into a hard subprocess amplitude and baryon to meson transition distribution amplitudes: universal nonperturbative objects only accessible through backward-angle kinematics.

We present extractions of the nucleon nonsinglet moments utilizing new precision data on the deuteron F_{2} structure function at large Bjorken-x determined via the Rosenbluth separation technique at Jefferson Lab Experimental Hall C. These new data are combined with a complementary set of data on the proton previously measured in Hall C at similar kinematics and world datasets on the proton and deuteron at lower x measured at SLAC and CERN. The new Jefferson Lab data provide coverage of the upper third of the x range, crucial for precision determination of the higher moments. In contrast to previous extractions, these moments have been corrected for nuclear effects in the deuteron using a new global fit to the deuteron and proton data. The obtained experimental moments represent an order of magnitude improvement in precision over previous extractions using high x data. Moreover, recent exciting developments in lattice QCD calculations provide a first ever comparison of these new experimental results with calculations of moments carried out at the physical pion mass, as well as a new approach that first calculates the quark distributions directly before determining moments.

Structure functions, as measured in lepton-nucleon scattering, have proven to be very useful in studying the partonic dynamics within the nucleon. However, it is experimentally difficult to separately determine the longitudinal and transverse structure functions, and consequently there are substantially less data available in particular for the longitudinal structure function. Here, we present separated structure functions for hydrogen and deuterium at low four-momentum transfer squared, Q2

The H1(e,e′K+)Λ reaction was studied as a function of the Mandelstam variable -t using data from the E01-004 (FPI-2) and E93-018 experiments that were carried out in Hall C at the 6 GeV Jefferson Laboratory. The cross section was fully separated into longitudinal and transverse components, and two interference terms at four-momentum transfers Q2 of 1.00, 1.36, and 2.07GeV2. The kaon form factor was extracted from the longitudinal cross section using the Regge model by Vanderhaeghen et al. [Phys. Rev. C 57, 1454 (1998)PRVCAN0556-281310.1103/PhysRevC.57.1454]. The results establish the method, previously used successfully for pion analyses, for extracting the kaon form factor. Data from 12 GeV Jefferson Laboratory experiments are expected to have sufficient precision to distinguish between theoretical predictions, for example, recent perturbative QCD calculations with modern parton distribution amplitudes. The leading-twist behavior for light mesons is predicted to set in for values of Q2 between 5 and 10GeV2, which makes data in the few-GeV regime particularly interesting. The Q2 dependence at fixed x and -t of the longitudinal cross section that we extracted seems consistent with the QCD factorization prediction within the experimental uncertainty.

Conservation Science Education Online (CSEO) is a new online resource that shares strategies for teaching science in art conservation and related cultural heritage fields. An overview will be given of how undergraduate chemistry curricula in the United States have used examples from cultural heritage. The field of art conservation will then be described with an emphasis on the science curricula taught in art conservation programs around the world. Challenges include relating theoretical learning to real-world applications and teaching scientific terminology and concepts to students who may have limited science backgrounds; as well, there is a lack of textbooks and resources with appropriate case studies. The newly launched CSEO online resource offers freely available, effective teaching methods in the form of modules developed by international educators in the field. The inaugural CSEO Conference 2022 served as an introduction to the online resource for a global audience and was the first dedicated conference to bring together heritage science educators to discuss challenges and teaching strategies with the goal of building such a resource. The conference facilitated discussions among participants about teaching strategies, with the intention that these topics would become modules for the online resource, available to all science educators.

The kinetically sluggish oxygen evolution reaction in proton exchange membrane water electrolyzers (PEMWEs) leads to high potentials of >1.5 V vs RHE at the anode electrode during operation. In contrast, an investigation with an in situ reference electrode indicates a much lower potential at the anode side of the bipolar plate which would allow the use of stainless steel and carbon as the bipolar plate materials. This decoupling is induced by the low conductivity of the circulating deionized water. In single cell electrolyzer tests, we show that carbon-coated 316L (C-316L) stainless steel is suitable as a bipolar plate material in contact with the anode and cathode sides of the PEMWE. The coating remains stable throughout the experiments, i.e., 720 h at the anode and 1000 h at the cathode side. Based on these results we regard carbon-coated stainless steel as a sustainable solution for the large-scale application of PEM water electrolysis since it might replace (Pt-coated) titanium in the bipolar plate.

Non-structural protein 2 (nsP2), which plays an essential role in replication of CHIKV, contains a protease, helicase, and methyltransferase-like domain. We executed a simple a screen using malachite green to detect compounds that decreased ATP hydrolysis and tested a library of diverse compounds to find inhibitors of CHIKV nsP2 helicase.

The cellular concentrations of splicing factors (SFs) are critical for controlling alternative splicing. Most serine and arginine-enriched (SR) protein SFs regulate their own concentration via a homeostatic feedback mechanism that involves regulation of inclusion of non-coding 'poison exons' (PEs) that target transcripts for nonsense-mediated decay. The importance of SR protein PE splicing during animal development is largely unknown despite PE ultra-conservation across animal genomes. To address this, we used mouse genetics to disrupt an ultra-conserved PE in the Tra2b gene encoding the SR protein Tra2β. Focussing on germ cell development, we found that Tra2b PE deletion causes azoospermia due to catastrophic cell death during meiotic prophase. Failure to proceed through meiosis was associated with increased Tra2b expression sufficient to drive aberrant Tra2β protein hyper-responsive splice patterns. Although critical for meiotic prophase, Tra2b PE deletion spared earlier mitotically active germ cells, even though these still required Tra2b gene function. Our data indicate that PE splicing control prevents the accumulation of toxic levels of Tra2β protein that are incompatible with meiotic prophase. This unexpected connection with male fertility helps explain Tra2b PE ultra-conservation and indicates the importance of evaluating PE function in animal models., Competing Interests: Disclosure and competing interests statement. The authors declare no competing interests and approve the current version of the manuscript., (© 2025. The Author(s).)

Competing Interests: Competing interests statement:The authors declare no competing interest.

Introduction: Leaf spot disease caused by the fungal pathogen Curvularia oryzae is one of the most common diseases found in oil palm ( Elaeis guineensis ) nurseries in South East Asia, and is most prevalent at the seedling stage. Severe infections result in localized necrotic regions of leaves that rapidly spread within nurseries leading to poor quality seedlings and high economic losses., Methods: To understand the molecular mechanisms of this plant-pathogen interaction, RNA-Seq was used to elucidate the transcriptomes of three oil palm genotypes with contrasting pathogen responses (G10 and G12, resistant and G14, susceptible) following infection with C. oryzae spores. Transcriptomes were obtained from Illumina NovaSeq 6000 sequencing of mRNA at four different time points (day 0, before treatment; day 1, 7, and 21 post treatment)., Results and Discussion: Analysis of differentially expressed gene (DEG) profiles in these three genotypes provided an overview of the genes involved in the plant defence. Genes involved in disease resistance, phytohormone biosynthesis, gene regulation (transcription factors), and those encoding proteins associated with cell wall hardening were identified and likely contribute to the resistance of oil palm to C. oryzae . Such genes represent good candidates for targets to enhance oil palm productivity and resilience through molecular breeding approaches., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wibowo, Susilo, Ernawan, Apriyanto, Alshaharni, Smith, Gatehouse and Edwards.)

Common tenrecs (Tenrec ecaudatus) are fossorial mammals that use burrows during both active and hibernating seasons in Madagascar and its neighboring islands. Prevailing thought was that tenrecs hibernate for 8-9 months individually, but 13 tenrecs were removed from the same sealed burrow 1 m deep from the surface. Such group hibernation in sealed burrows presumably creates a hypoxic and/or hypercapnic environment and suggests that this placental mammal may have an increased tolerance to hypoxia and hypercapnia. Higher tolerances to hypoxia and hypercapnia have been documented for other mammals capable of hibernation and to determine if this is the case for tenrecs, we exposed them to acute hypoxia (4 h of 16 or 7% O 2 ), progressive hypoxia (2 h of 16, 10 and 4% O 2 ), or progressive hypercapnia (2 h of 2, 5 and 10% CO 2 ) at cold (16 °C) or warm (28 °C) ambient temperatures (T a ). Oxygen equilibrium curves were also constructed on the whole blood of tenrecs at 10, 25, and 37 °C to determine if hemoglobin (Hb)-O 2 affinity contributes to hypoxia tolerance. In animals held at 16 °C, normoxic and normocapnic levels of oxygen consumption rate ( V ˙ O 2 ), body temperature (T b ), and heart rate (HR) were highly variable between individuals. This inter-individual variation was greatly reduced in animals held at 28 °C for oxygen consumption rate and body temperature. Both hypoxia (acute and progressive) and progressive hypercapnia led to decreases in V ˙ O 2 as well as the variation in V ˙ O 2 between animals held at 16 °C. The fall in oxygen consumption rate in 7% O 2 independent of changes in body temperature in tenrecs held at 16 °C is unique and not consistent with the typical hypoxic metabolic response seen in other hibernating species that depends on concomitant falls in T b . In animals held at 28 °C, exposure to O 2 levels as low as 4% and CO 2 levels as high as 10% had no significant effect on V ˙ O 2 , HR, or T b , indicative of high tolerance to both hypoxia and hypercapnia. High variation in heart rate remained between individuals in all gas compositions and at all temperatures. Tenrec Hb-O 2 affinity was similar to other homeothermic placental mammals and likely does not contribute to the increased hypoxia tolerance. Ultimately, our results suggest changes in T a dictate physiological responses to hypoxia or hypercapnia in tenrecs, responses more characteristic of reptiles than of most placental mammals. Given that numerous anatomical and physiological characteristics of tenrecs suggest that they may be representative of an ancestral placental mammal, our findings suggest the typical hypoxic metabolic response evolved later in mammalian evolution., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

For decades, it has been repeatedly claimed that the potent bacterial helicase-nuclease RecBCD (exonuclease V) destroys foreign (non-self) DNA, such as that of phages, but repairs and recombines cellular (self) DNA. While this would constitute a strong host-survival mechanism, no phage destroyed by RecBCD is ever specified in those claims. To determine which phages are destroyed by RecBCD, we searched for phage isolates that grow on Escherichia coli ΔrecBCD but not on recBCD+. In contrast to the prevailing claim, we found none among >80 new isolates from nature and >80 from previous collections. Based on these and previous observations, we conclude that RecBCD repairs broken DNA that can recombine but destroys DNA that cannot recombine and recycles the nucleotides., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Sonic hedgehog (Shh) is a morphogen with important roles in embryonic development and in the development of a number of cancers. Its activity is modulated by interactions with binding partners and co-receptors including heparin and heparin sulfate proteoglycans (HSPG). To identify antagonists of Shh/heparin binding, a diverse collection of 34,560 chemicals was screened in single point 384-well format. We identified and confirmed twenty six novel small molecule antagonists with diverse structures including four scaffolds that gave rise to multiple hits. Nineteen of the confirmed hits blocked binding of the N-terminal fragment of Shh (ShhN) to heparin with IC 50 values < 50 μM. In the Shh-responsive C3H10T1/2 cell model, four of the compounds demonstrated the ability to block ShhN-induced alkaline phosphatase activity. To demonstrate a direct and selective effect on ShhN ligand mediated activity, two of the compounds were able to block induction of Gli1 mRNA, a primary downstream marker for Shh signaling activity, in Shh-mediated but not Smoothened agonist (SAG)-mediated C3H10T1/2 cells. Direct binding of the two compounds to ShhN was confirmed by thermal shift assay and molecular docking simulations, with both compounds docking with the N-terminal heparin binding domain of Shh. Overall, our findings indicate that small molecule compounds that block ShhN binding to heparin and act to inhibit Shh mediated activity in vitro can be identified. We propose that the interaction between Shh and HSPGs provides a novel target for identifying small molecules that bind Shh, potentially leading to novel tool compounds to probe Shh ligand function., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aquatic ecosystems are often negatively affected by invasive species. However, biotic resistance by native species, either by competition or predation, can reduce the impacts of invasions by non-native species. The Western Mosquitofish ( Gambusia affinis ) is one of the most impactful invasive species of freshwater fish and cause declines in native fish populations. Using two mesocosm experiments conducted in different years, we examined the ecological interactions between juveniles of the native fish, Bluegill Sunfish ( Lepomis macrochirus ), and adults of the invasive fish, G. affinis . We found evidence for interactions between L. macrochirus and G. affinis . However, interactions did not appear symmetric, with L. macrochirus generally more affected by intraspecific interactions than interspecific interactions whereas G. affinis was more affected by interspecific interactions than intraspecific interactions. The presence of either species of fish led to a decrease in the number of large zooplankton and a tendency for a decrease in the total number of zooplankton. Based on these results, native L. macrochirus appear to be able to reduce the ability of non-native G. affinis to establish or maintain populations through both competition and predation (i.e., acting as an intraguild predator). The consistency of our results across both experiments, with their different designs and their occurring in different years, gives weight to these conclusions. The reduction of or prevention of establishment of populations of invasive G. affinis would likely benefit the aquatic communities of ponds with fish, especially small-bodied native fish., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Ecology and Evolution published by John Wiley & Sons Ltd.)

Previously, we showed that the germ cell-specific nuclear protein RBMXL2 represses cryptic splicing patterns during meiosis and is required for male fertility (Ehrmann et al., 2019). Here, we show that in somatic cells the similar yet ubiquitously expressed RBMX protein has similar functions. RBMX regulates a distinct class of exons that exceed the median human exon size. RBMX protein-RNA interactions are enriched within ultra-long exons, particularly within genes involved in genome stability, and repress the selection of cryptic splice sites that would compromise gene function. The RBMX gene is silenced during male meiosis due to sex chromosome inactivation. To test whether RBMXL2 might replace the function of RBMX during meiosis we induced expression of RBMXL2 and the more distantly related RBMY protein in somatic cells, finding each could rescue aberrant patterns of RNA processing caused by RBMX depletion. The C-terminal disordered domain of RBMXL2 is sufficient to rescue proper splicing control after RBMX depletion. Our data indicate that RBMX and RBMXL2 have parallel roles in somatic tissues and the germline that must have been conserved for at least 200 million years of mammalian evolution. We propose RBMX family proteins are particularly important for the splicing inclusion of some ultra-long exons with increased intrinsic susceptibility to cryptic splice site selection., Competing Interests: CS, SL, SA, GH, CD, KC, MG, IY, KJ, MK, IE, GS, SC, JM, SW, YB, DE No competing interests declared, (© 2023, Siachisumo, Luzzi, Aldalaqan et al.)

Plant roots represent about a quarter of global plant biomass and constitute a primary source of soil organic carbon (C). Yet, considerable uncertainty persists regarding root litter decomposition and their responses to global change factors (GCFs). Much of this uncertainty stems from a limited understanding of the multifactorial effects of GCFs and it remains unclear how these effects are mediated by litter quality, soil conditions and microbial functionality. Using complementary field decomposition and laboratory incubation approaches, we assessed the relative controls of GCF-mediated changes in root litter traits and soil and microbial properties on fine-root decomposition under warming, nitrogen (N) enrichment, and precipitation alteration. We found that warming and N enrichment accelerated fine-root decomposition by over 10%, and their combination showed an additive effect, while precipitation reduction suppressed decomposition overall by 12%, with the suppressive effect being most significant under warming-alone and N enrichment-alone conditions. Significantly, changes in litter quality played a dominant role and accelerated fine-root decomposition by 15% ~ 18% under warming and N enrichment, while changes in soil and microbial properties were predominant and reduced decomposition by 7% ~ 10% under precipitation reduction and the combined warming and N enrichment. Examining only the decomposition environment or litter properties in isolation can distort global change effects on root decomposition, underestimating precipitation reduction impacts by 38% and overstating warming and N effects by up to 73%. These findings highlight that the net impact of GCFs on root litter decomposition hinges on the interplay between GCF-modulated root decomposability and decomposition environment, as well as on the synergistic or antagonistic relationships among GCFs themselves. Our study emphasizes that integrating the legacy effects of multiple GCFs on root traits, soil conditions and microbial functionality would improve our prediction of C and nutrient cycling under interactive global change scenarios., (© 2024 John Wiley & Sons Ltd.)

How fetal and maternal cell types have co-evolved to enable mammalian placentation poses a unique evolutionary puzzle. Here, we present a multi-species atlas integrating single-cell transcriptomes from six species bracketing therian mammal diversity. We find that invasive trophoblasts share a gene-expression signature across eutherians, and evidence that endocrine decidual cells evolved stepwise from an immunomodulatory cell type retained in Tenrec with affinity to human decidua of menstruation. We recover evolutionary patterns in ligand-receptor signaling: fetal and maternal cells show a pronounced tendency towards disambiguation, but a predicted arms race dynamic between them is limited. We reconstruct cell communication networks of extinct mammalian ancestors, finding strong integration of fetal trophoblast into maternal networks. Together, our results reveal a dynamic history of cell type and signaling evolution., Synopsis: The fetal-maternal interface is one of the most intense loci of cell-cell signaling in the human body. Invasion of cells from the fetal placenta into the uterus, and the corresponding transformation of maternal tissues called decidualization, first evolved in the stem lineage of eutherian mammals( 1 , 2 ). Single-cell studies of the human fetal-maternal interface have provided new insight into the cell type diversity and cell-cell interactions governing this chimeric organ( 3-5 ). However, the fetal-maternal interface is also one of the most rapidly evolving, and hence most diverse, characters among mammals( 6 ), and an evolutionary analysis is missing. Here, we present and compare single-cell data from the fetal-maternal interface of species bracketing key events in mammal phylogeny: a marsupial (opossum, Monodelphis domestica ), the afrotherian Tenrec ecaudatus, and four Euarchontoglires - guinea pig and mouse (Rodentia) together with recent macaque and human data (primates) ( 4 , 5 , 7 ). We infer cell type homologies, identify a gene-expression signature of eutherian invasive trophoblast conserved over 99 million years, and discover a predecidual cell in the tenrec which suggests stepwise evolution of the decidual stromal cell. We reconstruct ancestral cell signaling networks, revealing the integration of fetal cell types into the interface. Finally, we test two long-standing theoretical predictions, the disambiguation hypothesis( 8 ) and escalation hypothesis( 9 ), at transcriptome-wide scale, finding divergence between fetal and maternal signaling repertoires but arms race dynamics restricted to a small subset of ligand-receptor pairs. In so doing, we trace the co-evolutionary history of cell types and their signaling across mammalian viviparity.

Microorganisms, including bacteria, archaea, viruses, fungi, and protists, are essential to life on Earth and the functioning of the biosphere. Here, we discuss the key roles of microorganisms in achieving the United Nations Sustainable Development Goals (SDGs), highlighting recent and emerging advances in microbial research and technology that can facilitate our transition toward a sustainable future. Given the central role of microorganisms in the biochemical processing of elements, synthesizing new materials, supporting human health, and facilitating life in managed and natural landscapes, microbial research and technologies are directly or indirectly relevant for achieving each of the SDGs. More importantly, the ubiquitous and global role of microbes means that they present new opportunities for synergistically accelerating progress toward multiple sustainability goals. By effectively managing microbial health, we can achieve solutions that address multiple sustainability targets ranging from climate and human health to food and energy production. Emerging international policy frameworks should reflect the vital importance of microorganisms in achieving a sustainable future., Competing Interests: Declaration of interests M.Z.A. is on the board of the Native BioData Consortium (NBDC; https://nativebio.org/); D.R. is co-chair of Just Transition Commission (https://www.justtransition.scot/); J.K.J. is chair of the Scientific Advisory Board for Oath Inc. (https://www.oathinc.com/); J.A.N. has a patent holding: North JA, Tabita FR, Young SJ, and Murali S. 2021. Nitrogenase-like enzyme system that catalyzes methionine, ethylene, and methane biogenesis. P2021-099-6249; WIPO 20240060037., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Austropuccinia psidii is the causal pathogen of myrtle rust disease of Myrtaceae. To gain understanding of the initial infection process, gene expression in germinating A. psidii urediniospores and in Leptospermum scoparium -inoculated leaves were investigated via analyses of RNA sequencing samples taken 24 and 48 h postinoculation (hpi). Principal component analyses of transformed transcript count data revealed differential gene expression between the uninoculated L. scoparium control plants that correlated with the three plant leaf resistance phenotypes (immunity, hypersensitive response, and susceptibility). Gene expression in the immune resistant plants did not significantly change in response to fungal inoculation, whereas susceptible plants showed differential expression of genes in response to fungal challenge. A putative disease resistance gene, jg24539.t1, was identified in the L. scoparium hypersensitive response phenotype family. Expression of this gene may be associated with the phenotype and could be important for further understanding the plant hypersensitive response to A. psidii challenge. Differential expression of pathogen genes was found between samples taken 24 and 48 hpi, but there were no significant differences in pathogen gene expression that were associated with the three different plant leaf resistance phenotypes. There was a significant decrease in the abundance of fungal transcripts encoding three putative effectors and a putative carbohydrate-active enzyme between 24 and 48 hpi, suggesting that the encoded proteins are important during the initial phase of infection. These transcripts, or their translated proteins, may be potential targets to impede the early phases of fungal infection by this wide-host-range obligate biotrophic basidiomycete., Competing Interests: The author(s) declare no conflict of interest.

The effect of population bottlenecks and genome reduction on enzyme function is poorly understood. Candidatus Liberibacter solanacearum is a bacterium with a reduced genome that is transmitted vertically to the egg of an infected psyllid-a population bottleneck that imposes genetic drift and is predicted to affect protein structure and function. Here, we define the function of Ca. L. solanacearum dihydrodipicolinate synthase (CLsoDHDPS), which catalyzes the committed branchpoint reaction in diaminopimelate and lysine biosynthesis. We demonstrate that CLsoDHDPS is expressed in Ca. L. solanacearum and expression is increased ~2-fold in the insect host compared to in planta. CLsoDHDPS has decreased thermal stability and increased aggregation propensity, implying mutations have destabilized the enzyme but are compensated for through elevated chaperone expression and a stabilized oligomeric state. CLsoDHDPS uses a ternary-complex kinetic mechanism, which is to date unique among DHDPS enzymes, has unusually low catalytic ability, but an unusually high substrate affinity. Structural studies demonstrate that the active site is more open, and the structure of CLsoDHDPS with both pyruvate and the substrate analogue succinic-semialdehyde reveals that the product is both structurally and energetically different and therefore evolution has in this case fashioned a new enzyme. Our study suggests the effects of genome reduction and genetic drift on the function of essential enzymes and provides insights on bacteria-host co-evolutionary associations. We propose that bacteria with endosymbiotic lifestyles present a rich vein of interesting enzymes useful for understanding enzyme function and/or informing protein engineering efforts., (© 2024 The Author(s). Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society.)

Aberrant activation of hedgehog (Hh) signaling has been implicated in various cancers. Current FDA-approved inhibitors target the seven-transmembrane receptor Smoothened, but resistance to these drugs has been observed. It has been proposed that a more promising strategy to target this pathway is at the GLI1 transcription factor level. GANT61 was the first small molecule identified to directly suppress GLI-mediated activity; however, its development as a potential anti-cancer agent has been hindered by its modest activity and aqueous chemical instability. Our study aimed to identify novel GLI1 inhibitors. JChem searches identified fifty-two compounds similar to GANT61 and its active metabolite, GANT61-D. We combined high-throughput cell-based assays and molecular docking to evaluate these analogs. Five of the fifty-two GANT61 analogs inhibited activity in Hh-responsive C3H10T1/2 and Gli-reporter NIH3T3 cellular assays without cytotoxicity. Two of the GANT61 analogs, BAS 07019774 and Z27610715, reduced Gli1 mRNA expression in C3H10T1/2 cells. Treatment with BAS 07019774 significantly reduced cell viability in Hh-dependent glioblastoma and lung cancer cell lines. Molecular docking indicated that BAS 07019774 is predicted to bind to the ZF4 region of GLI1, potentially interfering with its ability to bind DNA. Our findings show promise in developing more effective and potent GLI inhibitors.

Regular exercise has many physical and brain health benefits, yet the molecular mechanisms mediating exercise effects across tissues remain poorly understood. Here we analyzed 400 high-quality DNA methylation, ATAC-seq, and RNA-seq datasets from eight tissues from control and endurance exercise-trained (EET) rats. Integration of baseline datasets mapped the gene location dependence of epigenetic control features and identified differing regulatory landscapes in each tissue. The transcriptional responses to 8 weeks of EET showed little overlap across tissues and predominantly comprised tissue-type enriched genes. We identified sex differences in the transcriptomic and epigenomic changes induced by EET. However, the sex-biased gene responses were linked to shared signaling pathways. We found that many G protein-coupled receptor-encoding genes are regulated by EET, suggesting a role for these receptors in mediating the molecular adaptations to training across tissues. Our findings provide new insights into the mechanisms underlying EET-induced health benefits across organs., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Antimicrobial resistance (AMR) is a growing threat to health globally, with the potential to render numerous medical procedures so dangerous as to be impractical. There is therefore an urgent need for new molecules that function through novel mechanisms of action to combat AMR. The bacterial DNA-repair and SOS-response pathways promote survival of pathogens in infection settings and also activate hypermutation and resistance mechanisms, making these pathways attractive targets for new therapeutics. Small molecules, such as IMP-1700, potentiate DNA damage and inhibit the SOS response in methicillin-resistant S. aureus ; however, understanding of the structure-activity relationship (SAR) of this series is lacking. We report here the first comprehensive SAR study of the IMP-1700 scaffold, identifying key pharmacophoric groups and delivering the most potent analogue reported to date, OXF-077. Furthermore, we demonstrate that as a potent inhibitor of the mutagenic SOS response, OXF-077 suppresses the rate of ciprofloxacin resistance emergence in S. aureus . This work supports SOS-response inhibitors as a novel means to combat AMR, and delivers OXF-077 as a tool molecule for future development., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Poor communication within healthcare teams occurs commonly, contributing to inefficiency, medical errors, conflict, and other adverse outcomes. Interprofessional bedside rounds (IBR) are a promising model that brings two or more health professions together with patients and families as part of a consistent, team-based routine to share information and collaboratively arrive at a daily plan of care. The purpose of this systematic scoping review was to investigate the breadth and quality of IBR literature to identify and describe gaps and opportunities for future research. We followed an adapted Arksey and O'Malley Framework and PRISMA scoping review guidelines. PubMed, CINAHL, PsycINFO, and Embase were systematically searched for key IBR words and concepts through June 2020. Seventy-nine articles met inclusion criteria and underwent data abstraction. Study quality was assessed using the Mixed Methods Assessment Tool. Publications in this field have increased since 2014, and the majority of studies reported positive impacts of IBR implementation across an array of team, patient, and care quality/delivery outcomes. Despite the preponderance of positive findings, great heterogeneity, and a reliance on quantitative non-randomized study designs remain in the extant research. A growing number of interventions to improve safety, quality, and care experiences in hospital settings focus on redesigning daily inpatient rounds. Limited information on IBR characteristics and implementation strategies coupled with widespread variation in terminology, study quality, and design create challenges in assessing the effectiveness of models of rounds and optimal implementation strategies. This scoping review highlights the need for additional studies of rounding models, implementation strategies, and outcomes that facilitate comparative research.

Introduction: Based on a large body of previous research suggesting that smell loss was a predictor of COVID-19, we investigated the ability of SCENTinel®, a newly validated rapid olfactory test that assesses odor detection, intensity, and identification, to predict SARS-CoV-2 infection in a community sample., Methods: Between April 5, 2021, and July 5, 2022, 1,979 individuals took one SCENTinel® test, completed at least one physician-ordered SARS-CoV-2 PCR test, and endorsed a list of self-reported symptoms., Results: Among the of SCENTinel® subtests, the self-rated odor intensity score, especially when dichotomized using a previously established threshold, was the strongest predictor of SARS-CoV-2 infection. SCENTinel® had high specificity and negative predictive value, indicating that those who passed SCENTinel® likely did not have a SARS-CoV-2 infection. Predictability of the SCENTinel® performance was stronger when the SARS-CoV-2 Delta variant was dominant rather than when the SARS-CoV-2 Omicron variant was dominant. Additionally, SCENTinel® predicted SARS-CoV-2 positivity better than using a self-reported symptom checklist alone., Discussion: These results indicate that SCENTinel® is a rapid assessment tool that can be used for population-level screening to monitor abrupt changes in olfactory function, and to evaluate spread of viral infections like SARS-CoV-2 that often have smell loss as a symptom., Competing Interests: On behalf of DR, VP, and PD, the Monell Chemical Senses Center and Temple University have been awarded patent protection (US patent no 11,337,640) and this patent has been licensed to Ahersla Health, Inc. DR, VP, and PD may benefit financially through their institution’s patent policy. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hunter, Zola, Ho, Kallen, Adjei-Danquah, Achenbach, Smith, Gershon, Reed, Schalet, Parma and Dalton.)

Repair of broken DNA is essential for life; the reactions involved can also promote genetic recombination to aid evolution. In Escherichia coli, RecBCD enzyme is required for the major pathway of these events. RecBCD is a complex ATP-dependent DNA helicase with nuclease activity controlled by Chi recombination hotspots (5'-GCTGGTGG-3'). During rapid DNA unwinding, when Chi is in a RecC tunnel, RecB nuclease nicks DNA at Chi. Here, we test our signal transduction model - upon binding Chi (step 1), RecC signals RecD helicase to stop unwinding (step 2); RecD then signals RecB (step 3) to nick at Chi (step 4) and to begin loading RecA DNA strand-exchange protein (step 5). We discovered that ATP-γ-S, like the small molecule RecBCD inhibitor NSAC1003, causes RecBCD to nick DNA, independent of Chi, at novel positions determined by the DNA substrate length. Two RecB ATPase-site mutants nick at novel positions determined by their RecB:RecD helicase rate ratios. In each case, we find that nicking at the novel position requires steps 3 and 4 but not step 1 or 2, as shown by mutants altered at the intersubunit contacts specific for each step; nicking also requires RecD helicase and RecB nuclease activities. Thus, altering the RecB ATPase site, by small molecules or mutation, sensitizes RecD to signal RecB to nick DNA (steps 4 and 3, respecitvely) without the signal from RecC or Chi (steps 1 and 2). These new, enzymatic results strongly support the signal transduction model and provide a paradigm for studying other complex enzymes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Competing Interests: MM is the founder and CEO of an LLM startup.

SUMMARYRecBCD enzyme is a multi-functional protein that initiates the major pathway of homologous genetic recombination and DNA double-strand break repair in Escherichia coli . It is also required for high cell viability and aids proper DNA replication. This 330-kDa, three-subunit enzyme is one of the fastest, most processive helicases known and contains a potent nuclease controlled by Chi sites, hotspots of recombination, in DNA. RecBCD undergoes major changes in activity and conformation when, during DNA unwinding, it encounters Chi (5'-GCTGGTGG-3') and nicks DNA nearby. Here, we discuss the multitude of mutations in each subunit that affect one or another activity of RecBCD and its control by Chi. These mutants have given deep insights into how the multiple activities of this complex enzyme are coordinated and how it acts in living cells. Similar studies could help reveal how other complex enzymes are controlled by inter-subunit interactions and conformational changes., Competing Interests: The authors declare no conflict of interest.

Background: Multiple challenges impede interprofessional teamwork and the provision of high-quality care to hospitalized patients., Objective: To evaluate the effect of interventions to redesign hospital care delivery on teamwork and patient outcomes., Design: Pragmatic controlled trial. Hospitals selected 1 unit for implementation of interventions and a second to serve as a control. (ClinicalTrials.gov: NCT03745677)., Setting: Medical units at 4 U.S. hospitals., Participants: Health care professionals and hospitalized medical patients., Intervention: Mentored implementation of unit-based physician teams, unit nurse-physician coleadership, enhanced interprofessional rounds, unit-level performance reports, and patient engagement activities., Measurements: Primary outcomes were teamwork climate among health care professionals and adverse events experienced by patients. Secondary outcomes were length of stay (LOS), 30-day readmissions, and patient experience. Difference-in-differences (DID) analyses of patient outcomes compared intervention versus control units before and after implementation of interventions., Results: Among 155 professionals who completed pre- and postintervention surveys, the median teamwork climate score was higher after than before the intervention only for nurses ( n  = 77) (median score, 88.0 [IQR, 77.0 to 91.0] vs. 80.0 [IQR, 70.0 to 89.0]; P  = 0.022). Among 3773 patients, a greater percentage had at least 1 adverse event after compared with before the intervention on control units (change, 1.61 percentage points [95% CI, 0.01 to 3.22 percentage points]). A similar percentage of patients had at least 1 adverse event after compared with before the intervention on intervention units (change, 0.43 percentage point [CI, -1.25 to 2.12 percentage points]). A DID analysis of adverse events did not show a significant difference in change (adjusted DID, -0.92 percentage point [CI, -2.49 to 0.64 percentage point]; P  = 0.25). Similarly, there were no differences in LOS, readmissions, or patient experience., Limitation: Adverse events occurred less frequently than anticipated, limiting statistical power., Conclusion: Despite improved teamwork climate among nurses, interventions to redesign care for hospitalized patients were not associated with improved patient outcomes., Primary Funding Source: Agency for Healthcare Research and Quality., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-0953.

Transcription factors (TFs) play a key role in regulating gene expression and responses to stimuli. We conducted an integrated analysis of chromatin accessibility, DNA methylation, and RNA expression across eight rat tissues following endurance exercise training (EET) to map epigenomic changes to transcriptional changes and determine key TFs involved. We uncovered tissue-specific changes and TF motif enrichment across all omic layers, differentially accessible regions (DARs), differentially methylated regions (DMRs), and differentially expressed genes (DEGs). We discovered distinct routes of EET-induced regulation through either epigenomic alterations providing better access for TFs to affect target genes, or via changes in TF expression or activity enabling target gene response. We identified TF motifs enriched among correlated epigenomic and transcriptomic alterations, DEGs correlated with exercise-related phenotypic changes, and EET-induced activity changes of TFs enriched for DEGs among their gene targets. This analysis elucidates the unique transcriptional regulatory mechanisms mediating diverse organ effects of EET., Competing Interests: S.C.B. has equity in Emmyon, Inc and receives grant funding from Calico Life Sciences. M.P.S. is a cofounder and scientific advisor of Personalis, Qbio, January AI, Filtricine, SensOmics, Protos, Fodsel, Rthm, Marble and scientific advisor of Genapsys, Swaz, Jupiter. S.B.M. is a consultant for BioMarin, MyOme and Tenaya Therapeutics.

Endurance exercise is an important health modifier. We studied cell-type specific adaptations of human skeletal muscle to acute endurance exercise using single-nucleus (sn) multiome sequencing in human vastus lateralis samples collected before and 3.5 hours after 40 min exercise at 70% VO 2 max in four subjects, as well as in matched time of day samples from two supine resting circadian controls. High quality same-cell RNA-seq and ATAC-seq data were obtained from 37,154 nuclei comprising 14 cell types. Among muscle fiber types, both shared and fiber-type specific regulatory programs were identified. Single-cell circuit analysis identified distinct adaptations in fast, slow and intermediate fibers as well as LUM -expressing FAP cells, involving a total of 328 transcription factors (TFs) acting at altered accessibility sites regulating 2,025 genes. These data and circuit mapping provide single-cell insight into the processes underlying tissue and metabolic remodeling responses to exercise., Competing Interests: Declaration of Interests: SCS is interim Chief Scientific Officer, consultant, and equity owner of GNOMX Corp. The authors declare no other competing interests.