PNAS nexus最新文献

[This corrects the article DOI: 10.1093/pnasnexus/pgad186.].

Small subunit (SSU) ribosomal RNA (rRNA) gene amplicon sequencing is a foundational method in microbial ecology. Currently, short-read platforms are commonly employed for high-throughput applications of SSU rRNA amplicon sequencing, but at the cost of poor taxonomic classification due to limited fragment lengths. The Oxford Nanopore Technologies (ONT) platform can sequence full-length SSU rRNA genes, but its lower raw-read accuracy has so-far limited accurate taxonomic classification and de novo feature generation. Here, we present a sequencing workflow, termed ssUMI, that combines unique molecular identifier (UMI)-based error correction with newer (R10.4+) ONT chemistry and sample barcoding to enable high throughput near full-length SSU rRNA (e.g. 16S rRNA) amplicon sequencing. The ssUMI workflow generated near full-length 16S rRNA consensus sequences with 99.99% mean accuracy using a minimum subread coverage of 3×, surpassing the accuracy of Illumina short reads. The consensus sequences generated with ssUMI were used to produce error-free de novo sequence features with no false positives with two microbial community standards. In contrast, Nanopore raw reads produced erroneous de novo sequence features, indicating that UMI-based error correction is currently necessary for high-accuracy microbial profiling with R10.4+ ONT sequencing chemistries. We showcase the cost-competitive scalability of the ssUMI workflow by sequencing 87 time-series wastewater samples and 27 human gut samples, obtaining quantitative ecological insights that were missed by short-read amplicon sequencing. ssUMI, therefore, enables accurate and low-cost full-length 16S rRNA amplicon sequencing on Nanopore, improving accessibility to high-resolution microbiome science.

The cardiac KCNQ1 + KCNE1 (I_Ks) channel regulates heart rhythm under both normal and stress conditions. Under stress, the β-adrenergic stimulation elevates the intracellular cyclic adenosine monophosphate (cAMP) level, leading to KCNQ1 phosphorylation by protein kinase A and increased I_Ks, which shortens action potentials to adapt to accelerated heart rate. An impaired response to the β-adrenergic stimulation due to KCNQ1 mutations is associated with the occurrence of a lethal congenital long QT syndrome (type 1, also known as LQT1). However, the underlying mechanism of β-adrenergic stimulation of I_Ks remains unclear, impeding the development of new therapeutics. Here, we find that the unique properties of KCNQ1 channel gating with two distinct open states are key to this mechanism. KCNQ1's fully activated open (AO) state is more sensitive to cAMP than its intermediate open state. By enhancing the AO state occupancy, the small molecules ML277 and C28 are found to effectively enhance the cAMP sensitivity of the KCNQ1 channel, independent of KCNE1 association. This finding of enhancing AO state occupancy leads to a potential novel strategy to rescue the response of I_Ks to β-adrenergic stimulation in LQT1 mutants. The success of this approach is demonstrated in cardiac myocytes and also in a high-risk LQT1 mutation. In conclusion, the present study not only uncovers the key role of the AO state in I_Ks channel phosphorylation, but also provides a target for antiarrhythmic strategy.

The surge of pelagic Sargassum in the Intra-America Seas, particularly the Caribbean Sea, since the early 2010s has raised significant ecological concerns. This study emphasizes the need for a mechanistic understanding of Sargassum dynamics to elucidate the ecological impacts and uncertainties associated with blooms. By introducing a novel transport model, physical components such as ocean currents and winds are integrated with biological aspects affecting the Sargassum life cycle, including reproduction, grounded in an enhanced Maxey-Riley theory for floating particles. Nonlinear elastic forces among the particles are included to simulate interactions within and among Sargassum rafts. This promotes aggregation, consistent with observations, within oceanic eddies, which facilitate their transport. This cannot be achieved by the so-called leeway approach to transport, which forms the basis of current Sargassum modeling. Using satellite-derived data, the model is validated, outperforming the leeway model. Publicly accessible codes are provided to support further research and ecosystem management efforts. This comprehensive approach is expected to improve predictive capabilities and management strategies regarding Sargassum dynamics in affected regions, thus contributing to a deeper understanding of marine ecosystem dynamics and resilience.

Pollinator-plant interactions represent a core mutualism that underpins biodiversity in terrestrial ecosystems, and the loss of flowering plants is a major driver of pollinator declines. Bee attraction to flowers is mediated by both quantity of resources (the number of available flowers for exploration) and quality of resources (pollen nutritional value), but whether and how bees prioritize these factors is not well understood. Here, we leveraged a unique plant system to investigate the floral factors influencing bee foraging decisions. Recombinant inbred plant lines were generated by crossing the self-fertilizing Capsella rubella and the pollinator-dependent outcrosser C. grandiflora, to produce plants that varied across floral traits. Using enclosed arenas, we evaluated the foraging behavior of two solitary bee species, Osmia cornifrons and Megachile rotundata, to the isolated inflorescences from these lines. Visits from O. cornifrons were significantly positively correlated with the number of flowers, while M. rotundata visits were significantly positively associated with pollen nutrition, with a preference for plants with higher pollen protein-to-lipid content. Further experiments using artificial flowers confirmed that M. rotundata preferred flowers with higher protein:lipid ratios, while O. cornifrons visits were unaffected by nutrition. These studies demonstrate that, although both bee species collect pollen as their sole source of protein and lipids for themselves and/or their offspring, they differentially prioritize resource quantity (number of flowers) and quality (pollen nutritional content). These studies lay the groundwork for understanding how different foraging strategies evolved, and influence, plant-pollinator ecological networks.

Despite the importance of transparent communication of uncertainty surrounding scientific findings, there are concerns that communicating uncertainty might damage the public perception and dissemination of science. Yet, a lack of empirical research on the potential impact of uncertainty communication on the diffusion of scientific findings poses challenges in assessing such claims. We studied the effect of uncertainty in a field study and a controlled experiment. In Study 1, a natural language processing analysis of over 2 million social media (Twitter/X) messages about scientific findings revealed that more uncertain messages were shared less often. Study 2 replicated this pattern using an experimental design where participants were presented with large-language-model (LLM)-generated high- and low-uncertainty messages. These results underscore the role of uncertainty in the dissemination of scientific findings and inform the ongoing debates regarding the benefits and the risks of uncertainty in science communication.

Cessation of flow in yield stress fluids results in a stress relaxation process that eventually leads to a finite residual stress. Both the rate of stress relaxation and the magnitude of the residual stresses systematically depend on the preceding flow conditions. To assess the microscopic origin of this memory effect, we combine experiments with large-scale computer simulations, exploring the behavior of jammed suspensions of soft repulsive particles. A spatiotemporal analysis of particle motion reveals that memory formation during flow is primarily governed by the emergence of domains of spatially correlated nonaffine displacements. These domains imprint the configuration of stress imbalances that drive dynamics upon flow cessation, as evidenced by a striking equivalence of the spatial correlation patterns in particle displacements observed during flow and upon flow cessation. Additional contributions to stress relaxation result from the particle packing that reorganizes to minimize the resistance to flow by decreasing the number of locally stiffer configurations. Regaining rigidity upon flow cessation drives further relaxation and effectively sets the magnitude of the residual stress. Our findings highlight that flow in yield stress fluids can be seen as a training process during which the material stores information of the flowing state through the development of domains of correlated particle displacements and the reorganization of particle packings optimized to sustain the flow. This encoded memory can then be retrieved in flow cessation experiments.

Uterine contraction patterns vary during the ovulatory cycle and throughout pregnancy, but prior measurements have produced limited and conflicting information on these patterns. We combined a virally delivered genetically encoded calcium reporter (GCaMP8m) and ultra-widefield imaging in live nonpregnant mice to characterize uterine calcium dynamics at organ scale throughout the estrous cycle. Prior to ovulation (proestrus and estrus), uterine excitations primarily initiated in a region near the oviduct, but after ovulation (metestrus and diestrus), excitations initiated at loci homogeneously distributed throughout the organ. The frequency of excitation events was lowest in proestrus and estrus, higher in metestrus, and highest in diestrus. These results establish a platform for mapping uterine activity and demonstrate that an anatomically localized trigger for uterine excitations depends on the estrous cycle phase.

Cochlear hair cells can be killed by loud noises, ototoxic drugs, and natural aging. Once lost, mammalian hair cells do not naturally regenerate, leading to permanent hearing loss. Since the mammalian cochlea lacks any intrinsic ability to regenerate, genetic reprogramming of cochlear supporting cells that lie adjacent to hair cells is a potential option for hearing restoration therapies. We targeted cochlear supporting cells with three hair cell transcription factors: Atoh1, or Atoh1 + Gfi1, or Atoh1 + Gfi1 + Pou4f3 and found that 1- and 2-factor reprogramming is not sufficient to reprogram adult supporting cells into hair cells. However, activation of all three hair cell transcription factors reprogrammed some adult supporting cells into hair cell-like cells. We found that killing endogenous hair cells significantly improved the ability of supporting cells to be reprogrammed and regenerated numerous hair cell-like cells throughout the length of the cochlea. These regenerated hair cell-like cells expressed myosin VIIa and parvalbumin, as well as the mature outer hair cell protein prestin, were innervated, expressed proteins associated with ribbon synapses, and formed rudimentary stereociliary bundles. Finally, we demonstrate that supporting cells remained responsive to transcription factor reprogramming for at least 6 weeks after hair cell damage, suggesting that hair cell reprogramming may be effective in the chronically deafened cochlea.

Terrorists and other transnational extremist groups are responsible for thousands of civilian deaths. In confronting extremists, governments have relied heavily on threats, demands, denunciations, and other forms of verbal conflict. Do these efforts at verbal coercion have any effect on terrorist behavior? This analysis focuses on the Islamic State in Iraq and Syria (ISIS), which continues to be the world's deadliest terrorist group and was responsible for recent high-profile attacks in Baghdad, Vienna, Kabul, and Russia. We use Bayesian structural vector autoregression models to analyze daily event data on interactions between ISIS and foreign governments for the 2014-2020 period. We find that verbal conflict initiated by governments not only failed to deter ISIS but in fact increased the frequency of ISIS's attacks on civilians. Additional empirical analyses, combined with evidence from ISIS's publications and public statements, suggest that this effect resulted from a perceived credibility deficit. Extremists use terror attacks to signal that they have the capabilities and willingness to inflict pain and suffering on civilian targets. Government attempts to coerce extremist groups verbally, rather than militarily, reflect an underestimation of the group's capabilities and resolve. In an effort to solidify their reputations, extremists engage in further violence toward civilians, thus leading to worse humanitarian consequences. We extend the analysis to Al-Qaeda in Iraq and Boko Haram and find similar results.