Geertsenjepsen6945

Predators can modulate disease transmission within prey populations by influencing prey demography and behavior. Predator-prey dynamics can involve multiple species in heterogeneous landscapes; however, studies of predation on disease transmission rarely consider the role of landscapes or the transmission among diverse prey species (i.e., spillover). We used high-resolution habitat and movement data to model spillover risk of the brainworm parasite (Parelaphostrongylus tenuis) between two prey species [white-tailed deer (Odocoileus virginianus) and moose (Alces alces)], accounting for predator [gray wolf (Canis lupus)] presence and landscape configuration. Results revealed that spring migratory movements of cervid hosts increased parasite spillover risk from deer to moose, an effect tempered by changes in elevation, land cover, and wolf presence. Wolves induced host-species segregation, a nonlethal mechanism that modulated disease emergence by reducing spatiotemporal overlap between infected and susceptible prey, showing that wildlife disease dynamics may change with landscape disturbance and the loss of large carnivores.Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, characterized by rapid progression, metastasis, and difficulty in diagnosis. However, there are no effective liquid-based testing methods available for PDAC detection. Here we introduce a minimally invasive approach that uses machine learning (ML) and lipidomics to detect PDAC. Through greedy algorithm and mass spectrum feature selection, we optimized 17 characteristic metabolites as detection features and developed a liquid chromatography-mass spectrometry-based targeted assay. In this study, 1033 patients with PDAC at various stages were examined. This approach has achieved 86.74% accuracy with an area under curve (AUC) of 0.9351 in the large external validation cohort and 85.00% accuracy with 0.9389 AUC in the prospective clinical cohort. Accordingly, single-cell sequencing, proteomics, and mass spectrometry imaging were applied and revealed notable alterations of selected lipids in PDAC tissues. We propose that the ML-aided lipidomics approach be used for early detection of PDAC.Aging of hematopoietic stem cells (HSCs) directly contributes to dysfunction of hematopoietic and immune systems due to aging-associated alterations in HSC features. How the function of adult HSCs is regulated during aging so that relevant pathologic abnormalities may occur, however, remains incompletely understood. Here, we report that ATF4 deficiency provokes severe HSC defects with multifaceted aging-like phenotype via cell-autonomous mechanisms. ATF4 deletion caused expansion of phenotypical HSCs with functional attrition, characterized by defective repopulating and self-renewal capacities and myeloid bias. Moreover, the ATF4−/− HSC defects were associated with elevated mitochondrial ROS production by targeting HIF1α. In addition, loss of ATF4 significantly delayed leukemogenesis in the MLL-AF9–induced leukemia model. Mechanistically, ATF4 deficiency impaired HSC function with aging-like phenotype and alleviated leukemogenesis by regulating HIF1α and p16Ink4a. Together, our findings suggest a possibility of developing new strategies for the prevention and management of HSC aging and related pathological conditions.We introduce a protocol addressing the conformance test problem, which consists in determining whether a process under test conforms to a reference one. We consider a process to be characterized by the set of end products it produces, which is generated according to a given probability distribution. We formulate the problem in the context of hypothesis testing and consider the specific case in which the objects can be modeled as pure loss channels. We demonstrate theoretically that a simple quantum strategy, using readily available resources and measurement schemes in the form of two-mode squeezed vacuum and photon counting, can outperform any classical strategy. We experimentally implement this protocol, exploiting optical twin beams, validating our theoretical results, and demonstrating that, in this task, there is a quantum advantage in a realistic setting.Despite being one of the most consequential processes in the utilization of structural materials, fatigue at the nano- and mesoscale has been marginally explored or understood even for the most promising nanocarbon forms—nanotubes and graphene. By combining atomistic models with kinetic Monte Carlo simulations, we show that a pristine carbon nanotube under ambient working conditions is essentially indefatigable—accumulating no structural memory of prior load; over time, it probabilistically breaks, abruptly. In contrast, by using coarse-grained modeling, we demonstrate that any practical assemblies of nanotubes, e.g., bundles and fibers, display a clear gradual strength degradation in cyclic tensile loading due to recurrence and ratchet-up of slip at the tube-tube interfaces, not occurring under static load even of equal amplitude.Two fundamentally different processes of rocky planet formation exist, but it is unclear which one built the terrestrial planets of the solar system. They formed either by collisions among planetary embryos from the inner solar system or by accreting sunward-drifting millimeter-sized “pebbles” from the outer solar system. We show that the isotopic compositions of Earth and Mars are governed by two-component mixing among inner solar system materials, including material from the innermost disk unsampled by meteorites, whereas the contribution of outer solar system material is limited to a few percent by mass. This refutes a pebble accretion origin of the terrestrial planets but is consistent with collisional growth from inner solar system embryos. The low fraction of outer solar system material in Earth and Mars indicates the presence of a persistent dust-drift barrier in the disk, highlighting the specific pathway of rocky planet formation in the solar system.Marked epigenetic reprogramming is essential to convert terminally differentiated gametes to totipotent embryos. It remains puzzling why postfertilization global DNA reprogramming occurs in mammals but not in nonmammalian vertebrates. In zebrafish, global methylome inheritance is however accompanied by extensive enhancer “dememorization” as they become fully methylated. By depleting maternal dnmt1 using oocyte microinjection, we eliminated DNA methylation in early embryos, which died around gastrulation with severe differentiation defects. Notably, methylation deficiency leads to derepression of adult tissue–specific genes and CG-rich enhancers, which acquire ectopic transcription factor binding and, unexpectedly, histone H3 lysine 4 trimethylation (H3K4me3). By contrast, embryonic enhancers are generally CG-poor and evade DNA methylation repression. Hence, global DNA hypermethylation inheritance coupled with enhancer dememorization installs an epigenetic gate that safeguards embryonic programs and ensures temporally ordered gene expression. We propose that “enhancer dememorization” underlies and unifies distinct epigenetic reprogramming modes in early development between mammals and nonmammals.The mitochondrial inner membrane ABC transporter Atm1 exports an unknown substrate to the cytosol for iron-sulfur protein biogenesis, cellular iron regulation, and tRNA thio-modification. Mutations in the human relative ABCB7 cause the iron storage disease XLSA/A. We determined 3D structures of two complementary states of Atm1 in lipid nanodiscs by electron cryo-microscopy at 2.9- to 3.4-Å resolution. The inward-open structure resembled the known crystal structure of nucleotide-free apo-Atm1 closely. The occluded conformation with bound AMP-PNP-Mg2+ showed a tight association of the two nucleotide-binding domains, a rearrangement of the C-terminal helices, and closure of the putative substrate-binding cavity in the homodimeric transporter. We identified a hydrophobic patch on the C-terminal helices of yeast Atm1, which is unique among type IV ABC transporters of known structure. Truncation mutants of yeast Atm1 suggest that the C-terminal helices stabilize the dimer, yet are not necessary for closure of the nucleotide-binding domains.Efficient external radiation is essential for solar cells to achieve high power conversion efficiency (PCE). The classical limit of 1/2n2 (n, refractive index) for electroluminescence quantum efficiency (ELQE) has recently been approached by perovskite solar cells (PSCs). Photon recycling (PR) and light scattering can provide an opportunity to surpass this limit. We investigate the role of PR and scattering in practical device operation using a radiative PSC with an ELQE (13.7% at 1 sun) that significantly surpasses the classical limit (7.4%). selleck products We experimentally analyze the contributions of PR and scattering to this strong radiation. A novel optical model reveals an increase of 39 mV in the voltage of our PSC. This analysis can provide design principles for future PSCs to approach the Shockley-Queisser efficiency limit.Heparan sulfate (HS) polysaccharides are master regulators of diverse biological processes via sulfated motifs that can recruit specific proteins. 3-O-sulfation of HS/heparin is crucial for anticoagulant activity, but despite emerging evidence for roles in many other functions, a lack of tools for deciphering structure-function relationships has hampered advances. Here, we describe an approach integrating synthesis of 3-O-sulfated standards, comprehensive HS disaccharide profiling, and cell engineering to address this deficiency. Its application revealed previously unseen differences in 3-O-sulfated profiles of clinical heparins and 3-O-sulfotransferase (HS3ST)–specific variations in cell surface HS profiles. The latter correlated with functional differences in anticoagulant activity and binding to platelet factor 4 (PF4), which underlies heparin-induced thrombocytopenia, a known side effect of heparin. Unexpectedly, cells expressing the HS3ST4 isoenzyme generated HS with potent anticoagulant activity but weak PF4 binding. The data provide new insights into 3-O-sulfate structure-function and demonstrate proof of concept for tailored cell-based synthesis of next-generation heparins.Photosynthesis fuels life on Earth using sunlight as energy source. However, light has a simultaneous detrimental effect on the enzyme triggering photosynthesis and producing oxygen, photosystem II (PSII). Photoinhibition, the light-dependent decrease of PSII activity, results in a major limitation to aquatic and land photosynthesis and occurs upon all environmental stress conditions. In this work, we investigated the molecular origins of photoinhibition focusing on the paradoxical energy dissipation process of unknown nature coinciding with PSII damage. Integrating spectroscopic, biochemical, and computational approaches, we demonstrate that the site of this quenching process is the PSII reaction center. We propose that the formation of quenching and the closure of PSII stem from the same event. We lastly reveal the heterogeneity of PSII upon photoinhibition using structure-function modeling of excitation energy transfer. This work unravels the functional details of the damage-induced energy dissipation at the heart of photosynthesis.