Proceedings of the National Academy of Sciences, Volume 121, Issue 38, September 2024.

Klebsiella pneumoniae is an important pathogen causing difficult-to-treat urinary tract infections (UTIs). Over 1.5 million women per year suffer from recurrent UTI, reducing quality of life and causing substantial morbidity and mortality, especially in the hospital setting. Uropathogenic E. coli (UPEC) is the most prevalent cause of UTI. Like UPEC, K. pneumoniae relies on type 1 pili, tipped with

Connectomics research is making rapid advances, although models revealing general principles of connectional architecture are far from complete. Our analysis of 10 6 published connection reports indicates that the adult rat brain interregional connectome has about 76,940 of a possible 623,310 axonal connections between its 790 gray matter regions mapped in a reference atlas, equating to a network density

New data sources and AI methods for extracting information are increasingly abundant and relevant to decision-making across societal applications. A notable example is street view imagery, available in over 100 countries, and purported to inform built environment interventions (e.g., adding sidewalks) for community health outcomes. However, biases can arise when decision-making does not account for

Rising inequality has brought redistribution back on the political agenda. In theory, inequality aversion drives people’s support for redistribution. People can dislike both advantageous inequality (comparison relative to those worse off) and disadvantageous inequality (comparison relative to those better off). Existing experimental evidence reveals substantial variation across people in these preferences

Small-conductance Ca 2+ -activated K + channels (SK, K Ca 2) are gated solely by intracellular microdomain Ca 2+ . The channel has emerged as a therapeutic target for cardiac arrhythmias. Calmodulin (CaM) interacts with the CaM binding domain (CaMBD) of the SK channels, serving as the obligatory Ca 2+ sensor to gate the channels. In heterologous expression systems, phosphatidylinositol 4,5-bisphosphate

Mammalian Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) and Drosophila Yorkie (Yki) are transcription cofactors of the highly conserved Hippo signaling pathway. It has been long assumed that the YAP/TAZ/Yki signaling drives cell proliferation during organ growth. However, its instructive role in regulating developmentally programmed organ growth, if any,

Multispecies microbial communities drive most ecosystems on Earth. Chemical and biological interactions within these communities can affect the survival of individual members and the entire community. However, the prohibitively high number of possible interactions within a microbial community has made the characterization of factors that influence community development challenging. Here, we report

Myasthenia gravis (MG) is a chronic and severe disease of the skeletal neuromuscular junction (NMJ) in which the effects of neurotransmitters are attenuated, leading to muscle weakness. In the most common forms of autoimmune MG, antibodies attack components of the postsynaptic membrane, including the acetylcholine receptor (AChR) or muscle-specific kinase (MuSK). MuSK, a master regulator of NMJ development

The opportunistic pathogen Acinetobacter baumannii , carries variants of A. baumannii resistance islands (AbaR)-type genomic islands conferring multidrug resistance. Their pervasiveness in the species has remained enigmatic. The dissemination of AbaRs is intricately linked to their horizontal transfer via natural transformation, a process through which bacteria can import and recombine exogenous DNA

Cuprous copper [Cu(I)] is an essential cofactor for enzymes that support many fundamental cellular functions including mitochondrial respiration and suppression of oxidative stress. Neurons are particularly reliant on mitochondrial production of ATP, with many neurodegenerative diseases, including Parkinson’s disease, associated with diminished mitochondrial function. The gene MBLAC1 encodes a ribonuclease

We consider the refractive lensing effects of ionized cool ( T ∼ 10 4 K ) gas cloudlets in the circumgalactic medium (CGM) of galaxies. In particular, we discuss the combined effects of lensing from these cloudlets and scintillation from plasma screens in the Milky Way interstellar medium (ISM). We show that, if the CGM comprises a mist of subparsec cloudlets with column densities of order 10 17 cm

Family-based genome-wide association studies (GWASs) are often claimed to provide an unbiased estimate of the average causal effects (or average treatment effects; ATEs) of alleles, on the basis of an analogy between the random transmission of alleles from parents to children and a randomized controlled trial. We show that this claim does not hold in general. Because Mendelian segregation only randomizes

One of the longstanding aims of network neuroscience is to link a connectome’s topological properties—i.e., features defined from connectivity alone–with an organism’s neurobiology. One approach for doing so is to compare connectome properties with annotational maps. This type of analysis is popular at the meso-/macroscale, but is less common at the nano-scale, owing to a paucity of neuron-level connectome

The acquisition of new RNA functions through evolutionary processes was essential for the diversification of RNA-based primordial biology and its subsequent transition to modern biology. However, the mechanisms by which RNAs access new functions remain unclear. Do RNA enzymes need completely new folds to support new but related functions, or is reoptimization of the active site sufficient? What are

Liquid–liquid phase separation, whereby two liquids spontaneously demix, is ubiquitous in industrial, environmental, and biological processes. While isotropic fluids are known to condense into spherical droplets in the binodal region, these dynamics are poorly understood for structured fluids. Here, we report the unique observation of condensate networks, which spontaneously assemble during the demixing

Synechococcus elongatus is an important cyanobacterium that serves as a versatile and robust model for studying circadian biology and photosynthetic metabolism. Its transcriptional regulatory network (TRN) is of fundamental interest, as it orchestrates the cell’s adaptation to the environment, including its response to sunlight. Despite the previous characterization of constituent parts of the S. elongatus

In rivers, the addition of finer sediment to a coarser riverbed is known to increase the mobility of the coarser fraction. Two mechanisms have been suggested for this: a geometric mechanism whereby smaller sizes smooth the bed, increasing near-bed velocity and thus mobility of the larger sizes, and a viscous mechanism whereby a transitionally smooth turbulent boundary layer forms, rendering the coarser

Modern molecular microbiology elucidates the organizational principles of bacterial biofilms via detailed examination of the interplay between signaling and gene regulation. A complementary biophysical approach studies the mesoscopic dependencies at the cellular and multicellular levels with a distinct focus on intercellular forces and mechanical properties of whole biofilms. Here, motivated by recent

Enterotoxigenic Escherichia coli (ETEC) cause hundreds of millions of diarrheal illnesses annually ranging from mildly symptomatic cases to severe, life-threatening cholera-like diarrhea. Although ETEC are associated with long-term sequelae including malnutrition, the acute diarrheal illness is largely self-limited. Recent studies indicate that in addition to causing diarrhea, the ETEC heat-labile

Animals are born with extensive innate behavioral capabilities, which arise from neural circuits encoded in the genome. However, the information capacity of the genome is orders of magnitude smaller than that needed to specify the connectivity of an arbitrary brain circuit, indicating that the rules encoding circuit formation must fit through a “genomic bottleneck” as they pass from one generation

An N-degron is a degradation signal whose main determinant is a “destabilizing” N-terminal residue of a protein. Specific N-degrons, discovered in 1986, were the first identified degradation signals in short-lived intracellular proteins. These N-degrons are recognized by a ubiquitin-dependent proteolytic system called the Arg/N-degron pathway. Although bacteria lack the ubiquitin system, they also

Capillarity-driven transport in nanoporous solids is widespread in nature and crucial for modern liquid-infused engineering materials. During imbibition, curved menisci driven by high negative Laplace pressures exert an enormous contractile load on the porous matrix. Due to the challenge of simultaneously monitoring imbibition and deformation with high spatial resolution, the resulting coupling of

The transport of biopolymers across nanopores is an important biological process currently under investigation for the rapid analysis of DNA and proteins. While the transport of DNA is generally understood, methods to induce unfolded protein translocation have only recently been discovered (Yu et al., 2023, Sauciuc et al., 2023). Here, we found that during electroosmotically driven translocation of

Proceedings of the National Academy of Sciences, Volume 121, Issue 37, September 2024.

Proceedings of the National Academy of Sciences, Volume 121, Issue 37, September 2024.

Proceedings of the National Academy of Sciences, Volume 121, Issue 37, September 2024.

Small bubbles in fluids rise to the surface due to Archimede’s force. Remarkably, in turbulent flows this process is severely hindered by the presence of vortex filaments, which act as moving potential wells, dynamically trapping light particles and bubbles. Quantifying the statistical weights and roles of vortex filaments in turbulence is, however, still an outstanding experimental and computational

During homeostasis, the endoplasmic reticulum (ER) maintains productive transmembrane and secretory protein folding that is vital for proper cellular function. The ER-resident HSP70 chaperone, binding immunoglobulin protein (BiP), plays a pivotal role in sensing ER stress to activate the unfolded protein response (UPR). BiP function is regulated by the bifunctional enzyme filamentation induced by cyclic-AMP

Cryptococcus neoformans has emerged as a frontrunner among deadly fungal pathogens and is particularly life-threatening for many HIV-infected individuals with compromised immunity. Multiple virulence factors contribute to the growth and survival of C. neoformans within the human host, the two most prominent of which are the polysaccharide capsule and melanin. As both of these features are associated

Understanding the structure in the nanoscopic region of water that is in direct contact with solid surfaces, so-called contact layer, is key to quantifying macroscopic properties that are of interest to e.g. catalysis, ice nucleation, nanofluidics, gas adsorption, and sensing. We explore the structure of the water contact layer on various technologically relevant solid surfaces, namely graphene, MoS

Human voltage-gated proton (hHv1) channels are crucial for regulating essential biological processes such as immune cell respiratory burst, sperm capacitation, and cancer cell migration. Despite the significant concentration difference between protons and other ions in physiological conditions, hHv1 demonstrates remarkable proton selectivity. Our calculations of single-proton, cation, and anion permeation

Here we announce the construction and properties of a big commutative subalgebra of the Kirillov algebra attached to a finite dimensional irreducible representation of a complex semisimple Lie group. They are commutative finite flat algebras over the cohomology of the classifying space of the group. They are isomorphic with the equivariant intersection cohomology of affine Schubert varieties, endowing

Chaperone-mediated autophagy (CMA) is a selective form of autophagy that contributes to the maintenance of cellular homeostasis. CMA activity declines with age in most tissues and systems, including the immune system, due to a reduction in levels of lysosome-associated membrane protein type 2A (LAMP2A), an essential CMA component. In this study, we show that overexpressing a copy of hLAMP2A within

Dynein is the primary molecular motor responsible for retrograde intracellular transport of a variety of cargoes, performing successive nanometer-sized steps within milliseconds. Due to the limited spatiotemporal precision of established methods for molecular tracking, current knowledge of dynein stepping is essentially limited to slowed-down measurements in vitro. Here, we use MINFLUX fluorophore

Endometriosis negatively impacts the health-related quality of life of 190 million women worldwide. Novel advances in nonhormonal treatments for this debilitating condition are desperately needed. Macrophages play a vital role in the pathophysiology of endometriosis and represent a promising therapeutic target. In the current study, we revealed the full transcriptomic complexity of endometriosis-associated

Hamilton’s rule provides the cornerstone for our understanding of the evolution of all forms of social behavior, from altruism to spite, across all organisms, from viruses to humans. In contrast to the standard prediction from Hamilton’s rule, recent studies have suggested that altruistic helping can be favored even if it does not benefit relatives, as long as it decreases the environmentally induced

The in vivo three-dimensional genomic architecture of adult mature neurons at homeostasis and after medically relevant perturbations such as axonal injury remains elusive. Here, we address this knowledge gap by mapping the three-dimensional chromatin architecture and gene expression program at homeostasis and after sciatic nerve injury in wild-type and cohesin-deficient mouse sensory dorsal root ganglia

Proceedings of the National Academy of Sciences, Volume 121, Issue 38, September 2024.

Detection of cytosolic DNA by the cyclic GMP-AMP (cGAMP) synthase (cGAS)–stimulator of interferon genes (STING) pathway provides immune defense against pathogens and cancer but can also cause autoimmunity when overactivated. The exonuclease three prime repair exonuclease 1 (TREX1) degrades DNA in the cytosol and prevents cGAS activation by self-DNA. Loss-of-function mutations of the TREX1 gene are

Higher-order topological phases in non-Hermitian photonics revolutionize the understanding of wave propagation and modulation, which lead to hierarchical states in open systems. However, intrinsic insulating properties endorsed by the lattice symmetry of photonic crystals fundamentally confine the robust transport only at explicit system boundaries, letting alone the flexible reconfiguration in hierarchical

In interval reproduction tasks, animals must remember the event starting the interval and anticipate the time of the planned response to terminate the interval. The interval reproduction task thus allows for studying both memory for the past and anticipation of the future. We analyzed previously published recordings from the rodent medial prefrontal cortex [J. Henke et al. , eLife 10 , e71612 (2021)]

We know little about the mechanisms through which leader–follower dynamics during dyadic play shape infants’ language acquisition. We hypothesized that infants’ decisions to visually explore a specific object signal focal increases in endogenous attention, and that when caregivers respond to these proactive behaviors by naming the object it boosts infants’ word learning. To examine this, we invited

Over the past decade, there has been a shift in the way charities deliver humanitarian aid. Historically, the most prevalent way to help the global poor was by providing in-kind asset transfers. Recently, alternatives to in-kind aid, such as cash aid, have been increasing in prevalence. Although there has been widespread endorsement from the academic community and the public on the popularizing model

Proceedings of the National Academy of Sciences, Volume 121, Issue 38, September 2024.

Proceedings of the National Academy of Sciences, Volume 121, Issue 38, September 2024.

Proceedings of the National Academy of Sciences, Volume 121, Issue 38, September 2024.

Proceedings of the National Academy of Sciences, Volume 121, Issue 38, September 2024.

Urbanization has accelerated dramatically across the world over the past decades. Urban influence on surface temperatures is now being considered as a correction term in climatological datasets. Although prior research has investigated urban influences on precipitation for specific cities or selected thunderstorm cases, a comprehensive examination of urban precipitation anomalies on a global scale

A major next step in hematopoietic stem cell (HSC) biology is to enhance our quantitative understanding of cellular and evolutionary dynamics involved in undisturbed hematopoiesis. Mathematical models have been and continue to be key in this respect, and are most powerful when parameterized experimentally and containing sufficient biological complexity. In this paper, we use data from label propagation

The existence of viable human pathogens in bioaerosols which can cause infection or affect human health has been the subject of little research. In this study, data provided by 10 tropospheric aircraft surveys over Japan in 2014 confirm the existence of a vast diversity of microbial species up to 3,000 m height, which can be dispersed above the planetary boundary layer over distances of up to 2,000

Modern life requires many different metal ions, which enable diverse biochemical functions. It is commonly assumed that metal ions’ environmental availabilities controlled the evolution of early life. We argue that evolution can only explore the chemistry that life encounters, and fortuitous chemical interactions between metal ions and biological compounds can only be selected for if they first occur

Adolescence is a period of substantial social–emotional development, accompanied by dramatic changes to brain structure and function. Social isolation due to lockdowns that were imposed because of the COVID-19 pandemic had a detrimental impact on adolescent mental health, with the mental health of females more affected than males. We assessed the impact of the COVID-19 pandemic lockdowns on adolescent

The presence of livestock inside protected areas, or “livestock encroachment,” is a global conservation concern because livestock is broadly thought to negatively affect wildlife. The Maasai Mara National Reserve (MMNR), Kenya, exemplifies this tension as livestock is believed to have resulted in the declining wildlife populations, contributing to the strict and sometimes violent exclusion measures

Despite growing scientific alarm about anthropogenic climate change, the world is not on track to solve the crisis. Inaction may be partially explained by skepticism about climate change and resistance to proenvironmental policies from people who are motivated to maintain the status quo (i.e., conservative-rightists). Therefore, practical interventions are needed. In the present research program, we

Despite longstanding excitement and progress toward understanding liquid–liquid phase separation in natural and artificial membranes, fundamental questions have persisted about which molecules are required for this phenomenon. Except in extraordinary circumstances, the smallest number of components that has produced large-scale, liquid–liquid phase separation in bilayers has stubbornly remained at

More than 50% of all animal species are insects that undergo complete metamorphosis. The key innovation of these holometabolous insects is a pupal stage between the larva and adult when most structures are completely rebuilt. Why this extreme lifestyle evolved is unclear. Here, we test the hypothesis that a trade-off between growth and differentiation explains the evolution of this novelty. Using a

Are members of marginalized communities silenced on social media when they share personal experiences of racism? Here, we investigate the role of algorithms, humans, and platform guidelines in suppressing disclosures of racial discrimination. In a field study of actual posts from a neighborhood-based social media platform, we find that when users talk about their experiences as targets of racism, their

Although it is well documented that exposure to fine particulate matter (PM 2.5 ) increases the risk of several adverse health outcomes, less is known about its relationship with economic opportunity. Previous studies have relied on regression modeling, which implied strict assumptions regarding confounding adjustments and did not explore geographical heterogeneity. We obtained data for 63,165 US census