561975 research outputs found
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Charting WIMP territories at the neutrino floor
No full textWe establish comprehensive theoretical benchmarks for weakly interacting massive particles (WIMPs) accessible to ultimate direct detection experiments, focusing on the challenging parameter space between current experimental limits and the irreducible neutrino background. We systematically examine both thermal freeze-out and freeze-in production mechanisms across a range of simplified dark matter models, including s-channel scalar and vector portals, t-channel mediator scenarios, and electroweakly interacting multiplets. For thermal relics, we identify parameter regions where suppressed direct detection cross sections naturally arise through momentum-dependent interactions and blind-spot configurations, while maintaining the correct relic abundance. We extensively investigate freeze-in scenarios, demonstrating how feebly interacting massive particles in portal models can populate experimentally accessible parameter space despite their ultraweak couplings. Additionally, we explore how nonstandard cosmological histories —including early matter domination and fast-expanding Universe scenarios—can dramatically alter the relationship between relic density and detection prospects, opening new avenues for discovery. Our analysis provides a roadmap for next-generation experiments approaching the neutrino floor, highlighting complementary detection strategies and identifying the most promising theoretical targets for ultimate sensitivity dark matter searches. These benchmarks establish the theoretical foundation for the final push toward comprehensive coverage of well-motivated WIMP parameter space
Who Uses AI in Research, and for What? Large-Scale Survey Evidence from Germany
No full textThe integration of AI into scientific work holds significant potential to accelerate innovation. We surveyed researchers in two leading German research organizations to examine AI adoption, barriers, and perceived impact on research. Researchers are widely using AI tools – often for primary and creative tasks – and many expect the technology to be transformative for research. Effective use appears linked to both hands-on experience and engagement with learning resources. A persistent gender gap in AI use is closely associated with differences in familiarity, suggesting a potential focus for organizational efforts. Legal uncertainty and privacy concerns also emerge as major barriers, with researchers calling for clear, high-level regulatory guidance. Overall, our findings suggest directions where institutional actions might be explored to promote more equitable and effective AI adoption
Extending the chemical space of glutarimide-based cereblon ligands through an efficient Rh(II)-catalyzed X-H insertion reaction
No full textIn this work we present an easy, one-step synthetic protocol to explore a large chemical space of glutarimide-based cereblon (CRBN) ligands for targeted protein degradation. It is built upon our recently suggested approach to generating structurally diverse series of alpha-substituted glutarimide derivatives through an efficient Rh(II)-catalyzed X-H insertion reaction of 3-diazopiperidine-2,6-dione, with moderate to high yields. In total, 25 glutarimide derivatives incorporating variable side chains were synthesized and evaluated in vitro. All ligands showed a favorable lipophilicity, and several were able to outperform the binding affinity of thalidomide as a reference. In addition, most compounds showed low intrinsic cytotoxicity in myeloma cell lines and human peripheral blood mononuclear cells, and did not recruit canonical neosubstrates. A cellular thermal shift assay further demonstrated that the most potent analogs stabilize CRBN in live cells, confirming their on-target engagement. The development of the series was accompanied by a crystallographic study, which rationalizes the observed improvements in binding affinity and neosubstrate selectivity, and can support further development towards molecular glue activity and PROTACs design
Evolution of sensory systems underlies the emergence of predatory feeding behaviors in nematodes
No full textUnderstanding how animal behavior evolves remains a major challenge, with few studies linking genetic changes to differences in neural function and behavior across species. Here, we identify specific sensory adaptations associated with the emergence of predatory feeding behaviors in the nematode Pristionchus pacificus. While Caenorhabditis elegans uses contact-dependent sensing primarily to avoid threats, P. pacificus has co-opted this modality to support both avoidance and prey detection, enabling context-dependent predatory behavior. To uncover a potential mechanism underlying the evolution of P. pacificus prey perception, we mutated 27 canonical mechanosensory genes and assessed their function using behavioral assays, automated behavioral tracking, and a machine learning analysis of behavioral states. While several mutants showed mechanosensory defects, Ppa-mec-6 mutants specifically also impaired prey detection, indicating the emergence of a mechanosensory module linked to predatory behavior. Furthermore, disrupting both mechanosensation alongside chemosensation revealed a synergistic influence for these modalities. Crucially, Ppa-mec-6 is expressed in the environmentally exposed IL2 neurons that represent the first point of predator–prey contact. Moreover, silencing Ppa-mec-6 expressing cells induced severe predation defects validating their importance for prey sensing. Thus, predation evolved through the co-option of mechanosensory and chemosensory systems that act together to shape the evolution of complex behavioral traits
Language nonselective lexical access in bilinguals: Input modality matters
No full textIt has been argued that lexical access in bilinguals is language nonselective. However, little is known about how the input modality (spoken or written) affects cross-language activation during listening and reading. The current study characterizes the nature of within- and cross-language competition for spoken and written words in adults who are bilingual and biliterate in Spanish and English. Using a recently developed cross-modality version of the Visual World Paradigm, we found that competition differs for spoken and written words. For spoken words, the auditory stimulus unfolds overtime giving an additional boost to within- and cross-language competition. Conversely, written words can be seen at once, and thus, incremental processing is less of a factor, resulting in less competition within a language and no competition across languages. The findings show that word recognition is fundamentally language nonselective but can behave in selective ways depending on the modality of the input and language experience
The transition from monocyte to tissue-resident macrophage requires DHPS
No full textTissue-resident macrophages (RTMs) form during embryogenesis, self-renew locally, and regulate tissue homeostasis by clearing dead cells and debris1-6. During tissue damage, however, bone-marrow-derived monocytes enter tissues and differentiate into RTMs, repairing the tissue and replenishing macrophages in the niche1. The universal cell-intrinsic mechanisms that control the monocyte-to-RTM transition and the maintenance of mature RTMs across tissues remain elusive3. Here we show that deoxyhypusine synthase (DHPS), an enzyme that mediates spermidine-dependent hypusine modification of translation factor eIF5A5,7, is required for RTM differentiation and maintenance. Mice with myeloid cell lack of DHPS (Dhps-ΔM mice) had a global defect in RTMs across tissues, resulting in persistent but ultimately futile monocyte influx. Transcriptional analyses of DHPS-deficient macrophages indicated a block in their ability to differentiate into mature RTMs, whereas proteomics revealed defects in cell adhesion and signalling pathways. Sequencing of ribosome-engaged transcripts identified a subset of mRNAs involved in cell adhesion and signalling that rely on DHPS for efficient translation. Imaging of DHPS-deficient macrophages in tissues showed differences in morphology and tissue interactions, which were correlated with their failed RTM differentiation. DHPS-deficient macrophages were also defective in critical homeostatic RTM functions including efferocytosis and tissue maintenance. Together, our results demonstrate a cell-intrinsic, tissue-agnostic pathway that drives differentiation of monocyte-derived macrophages into RTMs
Mechanical forces regulate the composition and fate of stalled nascent chains
No full textThe ribosome-associated quality control (RQC) pathway resolves stalled ribosomes. As part of RQC, stalled nascent polypeptide chains (NCs) are appended with CArboxy-Terminal amino acid tails (CAT tails) in an mRNA-free, non-canonical elongation process. The relationship between CAT tail composition (alanine [Ala] and threonine [Thr] in yeast) and function has remained unknown. Using biochemical approaches in yeast, we discovered that mechanical forces on the NC regulate CAT tailing. We propose that CAT tailing initially operates in "extrusion mode," which increases NC lysine accessibility for on-ribosome ubiquitylation. Thr in CAT tails prevents the formation of polyalanine, which forms alpha-helices that lower extrusion efficiency and disrupt termination of CAT tailing. After NC ubiquitylation, pulling forces on the NC switch CAT tailing to an Ala-only "release mode," which facilitates NC release and degradation. Failure to switch from extrusion to release mode leads to the accumulation of NCs on large ribosomal subunits and proteotoxic aggregation of Thr-rich CAT tails