The heart pumps blood against the mechanical afterload from arterial resistance, and increased afterload may alter cardiac electrophysiology and contribute to life-threatening arrhythmias. However, the cellular and molecular mechanisms underlying mechanoelectric coupling in cardiomyocytes remain unclear. We developed an innovative patch-clamp-in-gel technology to embed cardiomyocytes in a three-dimensional

Conjugative plasmids are mobile elements that spread horizontally between bacterial hosts and often confer adaptive phenotypes, including antimicrobial resistance (AMR). Theory suggests that opportunities for horizontal transmission favor plasmids with higher transfer rates, whereas selection for plasmid carriage favors less-mobile plasmids. However, little is known about the mechanisms leading to

Gram-negative bacterial pathogens have an outer membrane that restricts entry of molecules into the cell. Water-filled protein channels in the outer membrane, so-called porins, facilitate nutrient uptake and are thought to enable antibiotic entry. Here, we determined the role of porins in a major pathogen, Pseudomonas aeruginosa, by constructing a strain lacking all 40 identifiable porins and 15 strains

Stress is often associated with pathophysiologic responses, like blood pressure (BP) reactivity, which when experienced repeatedly may be one pathway through which stress leads to poor physical health. Previous laboratory and field studies linking stress to physiological measures are limited by small samples, narrow demographics, and artificial stress manipulations, whereas large-scale studies often

Estimated millions of tons of plastic are dumped annually into oceans. Plastic has been produced only for 70 y, but the exponential rise of mass production leads to its widespread proliferation in all environments. As a consequence of their large abundance globally, microplastics are also found in many living organisms including humans. While the health impact of digested microplastics on living organisms

Bulk crystalline ices with ultralow densities have been demonstrated to be thermodynamically metastable at negative pressures. However, the direct formation of these bulk porous ices from liquid water at negative pressures is extremely challenging. Inspired by approaches toward porous media based on host–guest chemistry, such as metal–organic frameworks and covalent...

Molecular, polymeric, colloidal, and other classes of liquids can exhibit very large, spatially heterogeneous alterations of their dynamics and glass transition temperature when confined to nanoscale domains. Considerable progress has been made in understanding the related problem of near-interface relaxation and diffusion in thick films. However, the origin of “nanoconfinement effects” on the glassy

Streptomyces genomes harbor numerous, biosynthetic gene clusters (BGCs) encoding for drug-like compounds. While some of these BGCs readily yield expected products, many do not. Biosynthetic crypticity represents a significant hurdle to drug discovery, and the biological mechanisms that underpin it remain poorly understood. Polycyclic tetramate macrolactam (PTM) antibiotic production is widespread within

Loss-of-function mutations in acid beta-glucosidase 1 (GBA1) are among the strongest genetic risk factors for Lewy body disorders such as Parkinson’s disease (PD) and Lewy body dementia (DLB). Altered lipid metabolism in PD patient–derived neurons, carrying either GBA1 or PD αS mutations, can shift the physiological α-synuclein (αS) tetramer–monomer (T:M) equilibrium toward aggregation-prone monomers

Proinflammatory activation of macrophages in metabolic tissues is critically important in the induction of obesity-induced metaflammation. Here, we demonstrate that the soluble mannose receptor (sMR) plays a direct functional role in both macrophage activation and metaflammation. We show that sMR binds CD45 on macrophages and inhibits its phosphatase activity, leading to an Src/Akt/NF-κB–mediated cellular

Elastography is an imaging technique to reconstruct elasticity distributions of heterogeneous objects. Since cancerous tissues are stiffer than healthy ones, for decades, elastography has been applied to medical imaging for noninvasive cancer diagnosis. Although the conventional strain-based elastography has been deployed on ultrasound diagnostic-imaging devices, the results are prone to inaccuracies

The lymphatic system is involved in various biological processes, including fluid transport from the interstitium into the venous circulation, lipid absorption, and immune cell trafficking. Despite its critical role in homeostasis, lymphangiogenesis (lymphatic vessel formation) is less widely studied than its counterpart, angiogenesis (blood vessel formation). Although the incorporation of lymphatic

A delicate balance of noncovalent interactions directs the hierarchical self-assembly of molecular amphiphiles into spherical micelles that pack into three-dimensional periodic arrays, which mimic intermetallic crystals. Herein, we report the discovery that adding water to a mixture of an ionic surfactant and n-decane induces aperiodic ordering of oil-swollen spherical micelles into previously unrecognized

The motor protein dynein undergoes coordinated conformational changes of its domains during motility along microtubules. Previous single-molecule studies analyzed the motion of the AAA rings of the dynein homodimer, but not the distal microtubule-binding domains (MTBDs) that step along the track. Here, we simultaneously tracked with nanometer precision two MTBDs and one AAA ring of a single dynein

The current model of replication-dependent (RD) histone biosynthesis posits that RD histone gene expression is coupled to DNA replication, occurring only in S phase of the cell cycle once DNA synthesis has begun. However, several key factors in the RD histone biosynthesis pathway are up-regulated by E2F or phosphorylated by CDK2, suggesting these processes may instead begin much earlier, at the point

The inheritance of predisposition to nonsyndromic familial nonmedullary thyroid cancer (FNMTC) remains unclear. Here, we report six individuals with papillary thyroid cancer (PTC) in two unrelated nonsyndromic FNMTC families. Whole-exome sequencing revealed two germ-line loss-of-function variants occurring within a 28-bp fragment of WDR77, which encodes a core member of a transmethylase complex formed

Genetic variance is not equal for all multivariate combinations of traits. This inequality, in which some combinations of traits have abundant genetic variation while others have very little, biases the rate and direction of multivariate phenotypic evolution. However, we still understand little about what causes genetic variance to differ among trait combinations. Here, we investigate the relative

The p53 pathway is a universal tumor suppressor mechanism that limits tumor progression by triggering apoptosis or permanent cell cycle arrest, called senescence. In recent years, efforts to reactivate p53 function in cancer have proven to be a successful therapeutic strategy in murine models and have gained traction with the development of a range of small molecules targeting mutant p53. However,

G protein–coupled receptors (GPCRs) are important pharmaceutical targets for the treatment of a broad spectrum of diseases. Although there are structures of GPCRs in their active conformation with bound ligands and G proteins, the detailed molecular interplay between the receptors and their signaling partners remains challenging to decipher. To address this, we developed a high-sensitivity, high-throughput

We extract the folding free energy landscape and the time-dependent friction function, the two ingredients of the generalized Langevin equation (GLE), from explicit-water molecular dynamics (MD) simulations of the α-helix forming polypeptide alanine9 for a one-dimensional reaction coordinate based on the sum of the native H-bond distances. Folding and unfolding times from numerical integration of the

The observational absence of giant convection cells near the Sun’s outer surface is a long-standing conundrum for solar modelers. We herein propose an explanation. Rotation strongly influences the internal dynamics, leading to suppressed convective velocities, enhanced thermal-transport efficiency, and (most significantly) relatively smaller dominant length scales. We specifically predict a characteristic

Creating invariant representations from an everchanging speech signal is a major challenge for the human brain. Such an ability is particularly crucial for preverbal infants who must discover the phonological, lexical, and syntactic regularities of an extremely inconsistent signal in order to acquire language. Within the visual domain, an efficient neural solution to overcome variability consists in

To mimic the mechanical response of passive biological cilia in complex fluids, we study the bending dynamics of an anchored elastic fiber submitted to a dilute granular suspension under shear. We show that the bending fluctuations of the fiber accurately encode minute variations of the granular suspension concentration. Indeed, besides the stationary bending induced by the continuous phase flow, the

Despite the remarkable variability music displays across cultures, certain recurrent musical features motivate the hypothesis that fundamental cognitive principles constrain the way music is produced. One such feature concerns the structure of musical scales. The vast majority of musical cultures use scales that are not uniformly symmetric—that is, scales that contain notes spread unevenly across the

Vaccine uptake is critical for mitigating the impact of COVID-19 in the United States, but structural inequities pose a serious threat to progress. Racial disparities in vaccination persist despite the increased availability of vaccines. We ask what factors are associated with such disparities. We combine data from state, federal, and other sources to estimate the relationship between social determinants

Constraints on CO2 emissions are confronting society with multiple massive challenges: creating new sources of clean energy beyond solar and wind; electrifying our transportation systems and using lighter weight materials; decarbonizing the industrial sector; and dealing with the economic fallout associated with shrinking the fossil hydrocarbon industry, which accounts for about 7% of the world economy

In early 2020, the trajectory of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic on the African continent was much discussed. Slow growth in mortality even prompted speculation that the continent might be “spared” as a result of an overall younger population, effective government responses (1), or perhaps even protection via cross-immunity from other coronaviruses. In 2021

Many bacteria, including the major human pathogen Pseudomonas aeruginosa, are naturally found in multicellular, antibiotic-tolerant biofilm communities, in which cells are embedded in an extracellular matrix of polymeric molecules. Cell–cell interactions within P. aeruginosa biofilms are mediated by CdrA, a large, membrane-associated adhesin present in the extracellular matrix of biofilms, regulated

To advance the mission of in silico cell biology, modeling the interactions of large and complex biological systems becomes increasingly relevant. The combination of molecular dynamics (MD) simulations and Markov state models (MSMs) has enabled the construction of simplified models of molecular kinetics on long timescales. Despite its success, this approach is inherently limited by the size of the

Single-particle tracking (SPT) is a key tool for quantitative analysis of dynamic biological processes and has provided unprecedented insights into a wide range of systems such as receptor localization, enzyme propulsion, bacteria motility, and drug nanocarrier delivery. The inherently complex diffusion in such biological systems can vary drastically both in time and across systems, consequently imposing

Vertebrates have repeatedly modified skeletal structures to adapt to their environments. The threespine stickleback is an excellent system for studying skeletal modifications, as different wild populations have either increased or decreased the lengths of their prominent dorsal and pelvic spines in different freshwater environments. Here we identify a regulatory locus that has a major morphological

Optical cavities confine light on a small region in space, which can result in a strong coupling of light with materials inside the cavity. This gives rise to new states where quantum fluctuations of light and matter can alter the properties of the material altogether. Here we demonstrate, based on first-principles calculations, that such light-matter coupling induces a change of the collective phase

It is commonly assumed that cities are detrimental to mental health. However, the evidence remains inconsistent and at most, makes the case for differences between rural and urban environments as a whole. Here, we propose a model of depression driven by an individual's accumulated experience mediated by social networks. The connection between observed systematic variations in socioeconomic networks

In 1881 the first significant work on earthworm behavior and ecology was published (1). It was Charles Darwin´s last scientific book and is still a fascinating and rewarding read. In PNAS, Geier et al. (2) use an earthworm taken directly from nature to present a method that allows in situ...

In our everyday life, we are often exposed to addictive agents like pain killers, tobacco, alcohol, even food, sex, or video games. Although the majority of people will not develop an addiction upon contact with those agents, a part of the population will. What determines whether a person is going...

Optical cavities confine light on a small region in space, which can result in a strong coupling of light with materials inside the cavity. This gives rise to new states where quantum fluctuations of light and matter can alter the properties of the material altogether. Here we demonstrate, based on...

It is commonly assumed that cities are detrimental to mental health. However, the evidence remains inconsistent and at most, makes the case for differences between rural and urban environments as a whole. Here, we propose a model of depression driven by an individual’s accumulated experience mediated by social networks. The...

The rapid development of COVID-19 vaccines is a tremendous scientific response to the current global pandemic. However, vaccines per se do not save lives and restart economies. Their success depends on the number of people getting vaccinated. We used a survey experiment to examine the impact on vaccine intentions of...

ECOLOGY Upside-down jellyfish from the Florida Keys. How upside-down jellyfish engineer mangrove ecosystems Winds and tides roil the still waters of shallow coastal ecosystems, aiding nutrient transport, gas exchange, and predator–prey encounters. In contrast, sheltered habitats, such as mangroves, where such physical forces are rare, rely on biotic agents for...

MEDICAL SCIENCES Correction for “Embryonic stem cell-derived hematopoietic stem cells,” by Yuan Wang, Frank Yates, Olaia Naveiras, Patricia Ernst, and George Q. Daley, which was first published December 15, 2005; 10.1073/pnas.0506127102 (Proc. Natl. Acad. Sci. U.S.A. …

CHEMISTRY Correction for “Photochemistry of oxidized Hg(I) and Hg(II) species suggests missing mercury oxidation in the troposphere,” by Alfonso Saiz-Lopez, Oleg Travnikov, Jeroen E. Sonke, Colin P. Thackray, Daniel J. …

CELL BIOLOGY Correction for “Direction of flagellum beat propagation is controlled by proximal/distal outer dynein arm asymmetry,” by Beatrice Freya Lucy Edwards, Richard John Wheeler, Amy Rachel Barker, Flávia Fernandes Moreira-Leite, Keith Gull, and …

NEUROSCIENCE Correction for “Selective filtering defect at the axon initial segment in Alzheimer’s disease mouse models,” by Xiaqin Sun, Yu …

ECOLOGY Correction for “Predicting future invaders and future invasions,” by Alice Fournier, Caterina Penone, Maria Grazia Pennino, and Franck Courchamp, which was first published March 29, 2019; 10.1073/pnas.1803456116 (Proc. Natl. Acad. Sci. U.S.A. 116, 7905–7910).

APPLIED BIOLOGICAL SCIENCES Correction for “Mutational fitness landscapes reveal genetic and structural improvement pathways for a vaccine-elicited HIV-1 broadly neutralizing antibody,” by Bharat Madan, Baoshan Zhang, Kai Xu, Cara W. Chao, Sijy O’Dell, Jacy R. Wolfe, Gwo-Yu Chuang, Ahmed S. Fahad, Hui Geng, Rui Kong, Mark K. Louder, Thuy Duong Nguyen, Reda Rawi, Arne …

Concerns over overexploitation have fueled an ongoing debate on the current state and future prospects of global capture fisheries, associated threats to marine biodiversity, and declining yields available for human consumption. Management reforms have aimed to reduce fishing pressure and recover depleted stocks to biomass and exploitation rates that allow for maximum sustainable yield. Recent analyses

Abdominal aortic aneurysm (AAA) is characterized by aorta dilation due to wall degeneration, which mostly occurs in elderly males. Vascular aging is implicated in degenerative vascular pathologies, including AAA. Cyclic nucleotide phosphodiesterases, by hydrolyzing cyclic nucleotides, play critical roles in regulating vascular structure remodeling and function. Cyclic nucleotide phosphodiesterase 1C

Dragline silk of golden orb-weaver spiders (Nephilinae) is noted for its unsurpassed toughness, combining extraordinary extensibility and tensile strength, suggesting industrial application as a sustainable biopolymer material. To pinpoint the molecular composition of dragline silk and the roles of its constituents in achieving its mechanical properties, we report a multiomics approach, combining high-quality

This article draws on official criminal histories for multiple birth cohorts spanning a 17-y difference in birth year to study how social change can alter our understanding of influential theories and policies about criminal offender groups. Arrest histories are linked to comprehensive longitudinal measurement on over 1,000 individuals originally from Chicago. Using group-based trajectory modeling

Biotic interactions between Africa and Eurasia across the Levant have invoked particular attention among scientists aiming to unravel early human dispersals. However, it remains unclear whether behavioral capacities enabled early modern humans to surpass the Saharo–Arabian deserts or if climatic changes triggered punctuated dispersals out of Africa. Here, we report an unusual subfossil assemblage discovered

Polyhydroxyalkanoates (PHAs) are biodegradable polyesters that are intracellularly accumulated as distinct insoluble granules by various microorganisms. PHAs have attracted much attention as sustainable substitutes for petroleum-based plastics. However, the formation of PHA granules and their characteristics, such as localization, volume, weight, and density of granules, in an individual live bacterial

Despite overall improvements in health and living standards in the Western world, health and social disadvantages persist across generations. Using nationwide administrative databases linked for 2.1 million Danish citizens, we leveraged a three-generation approach to test whether multiple, different health and social disadvantages—poor physical health, poor mental health, social welfare dependency

Honeybees are renowned for their perfectly hexagonal honeycomb, hailed as the pinnacle of biological architecture for its ability to maximize storage area while minimizing building material. However, in natural nests, workers must regularly transition between different cell sizes, merge inconsistent combs, and optimize construction in constrained geometries. These spatial obstacles pose challenges

There are sex differences in somatosensory sensitivity. Circulating estrogens appear to have a pronociceptive effect that explains why females are reported to be more sensitive to pain than males. Although itch symptoms develop during pregnancy in many women, the underlying mechanism of female-specific pruritus is unknown. Here, we demonstrate that estradiol, but not progesterone, enhances histamine-evoked

There are multiple sources of data giving information about the number of SARS-CoV-2 infections in the population, but all have major drawbacks, including biases and delayed reporting. For example, the number of confirmed cases largely underestimates the number of infections, and deaths lag infections substantially, while test positivity rates tend to greatly overestimate prevalence. Representative

Mechanisms controlling myelination during central nervous system (CNS) maturation play a pivotal role in the development and refinement of CNS circuits. The transcription factor THAP1 is essential for timing the inception of myelination during CNS maturation through a cell-autonomous role in the oligodendrocyte lineage. Here, we demonstrate that THAP1 modulates the extracellular matrix (ECM) composition

Localized carbon reduction strategies are especially critical in states and regions that lack top-down climate leadership. This paper illustrates the use of coupled systems in assessments of subnational climate solutions with a case study of Georgia, a state located in the southeastern United States that does not have statewide climate goals or plans. The paper illustrates how robust place-specific

Regulatory T cells (Tregs) play fundamental roles in maintaining peripheral tolerance to prevent autoimmunity and limit legitimate immune responses, a feature hijacked in tumor microenvironments in which the recruitment of Tregs often extinguishes immune surveillance through suppression of T-effector cell signaling and tumor cell killing. The pharmacological tuning of Treg activity without impacting

Overcoming the COVID-19 pandemic requires motivating the vast majority of Americans to get vaccinated. However, vaccination rates have become politically polarized, and a substantial proportion of Republicans have remained vaccine hesitant for months. Here, we explore how endorsements by party elites affect Republicans’ COVID-19 vaccination intentions and attitudes. In a preregistered survey experiment