Unicellular eukaryotic phytoplankton, such as diatoms, rely on microbial communities for survival despite lacking specialized compartments to house microbiomes (e.g., animal gut). Microbial communities have been widely shown to benefit from diatom excretions that accumulate within the microenvironment surrounding phytoplankton cells, known as the phycosphere. However, mechanisms that enable diatoms

Identifying computational mechanisms for memorization and retrieval of data is a long-standing problem at the intersection of machine learning and neuroscience. Our main finding is that standard overparameterized deep neural networks trained using standard optimization methods implement such a mechanism for real-valued data. Empirically, we show that 1) overparameterized autoencoders store training

A high percentage of pediatric gliomas and bone tumors reportedly harbor missense mutations at glycine 34 in genes encoding histone variant H3.3. We find that these H3.3 G34 mutations directly alter the enhancer chromatin landscape of mesenchymal stem cells by impeding methylation at lysine 36 on histone H3 (H3K36) by SETD2, but not by the NSD1/2 enzymes. The reduction of H3K36 methylation by G34 mutations

Strong local institutions are important for the successful governance of common-pool resources (CPRs), but why do such institutions emerge in the first place and why do they sometimes not emerge at all? We argue that voluntary local leaders play an important role in the initiation of self-governance institutions because such leaders can directly affect local users’ perceived costs and benefits associated

Priming of CD8+ T cells by dendritic cells (DCs) is crucial for the generation of effective antitumor immune responses. Here, we describe a liposomal vaccine carrier that delivers tumor antigens to human CD169/Siglec-1+ antigen-presenting cells using gangliosides as targeting ligands. Ganglioside-liposomes specifically bound to CD169 and were internalized by in vitro-generated monocyte-derived DCs

Recent measurements of the elastic constants in lyotropic chromonic liquid crystals (LCLCs) have revealed an anomalously small twist elastic constant compared to the splay and bend constants. Interestingly, measurements of the elastic constants in the micellar lyotropic liquid crystals (LLCs) that are formed by surfactants, by far the most ubiquitous and studied class of LLCs, are extremely rare and

Desmosomes are cell–cell junctions that link tissue cells experiencing intense mechanical stress. Although the structure of the desmosomal cadherins is known, the desmosome architecture—which is essential for mediating numerous functions—remains elusive. Here, we recorded cryo-electron tomograms (cryo-ET) in which individual cadherins can be discerned; they appear variable in shape, spacing, and tilt

The recent recognition that many symbioses exhibit daily rhythms has encouraged research into the partner dialogue that drives these biological oscillations. Here we characterized the pivotal role of the versatile cytokine macrophage migration inhibitory factor (MIF) in regulating a metabolic rhythm in the model light-organ symbiosis between Euprymna scolopes and Vibrio fischeri. As the juvenile host

Galectin-3 is a glycan-binding protein (GBP) that binds β-galactoside glycan structures to orchestrate a variety of important biological events, including the activation of hepatic stellate cells and regulation of immune responses. While the requisite glycan epitopes needed to bind galectin-3 have long been elucidated, the cellular glycoproteins that bear these glycan signatures remain unknown. Given

We report a systematic combinatorial exploration of affinity enhancement of antibodies by insertions and deletions (InDels). Transposon-based introduction of InDels via the method TRIAD (transposition-based random insertion and deletion mutagenesis) was used to generate large libraries with random in-frame InDels across the entire single-chain variable fragment gene that were further recombined and

Most proteins have evolved to spontaneously fold into native structure and specifically bind with their partners for the purpose of fulfilling biological functions. According to Darwin, protein sequences evolve through random mutations, and only the fittest survives. The understanding of how the evolutionary selection sculpts the interaction patterns for both biomolecular folding and binding is still

We develop an early warning system and subsequent optimal intervention policy to avoid the formation of disproportional dominance (“winner takes all,” WTA) in growing complex networks. This is modeled as a system of interacting agents, whereby the rate at which an agent establishes connections to others is proportional to its already existing number of connections and its intrinsic fitness. We derive

Neurons are dependent on proper trafficking of lipids to neighboring glia for lipid exchange and disposal of potentially lipotoxic metabolites, producing distinct lipid distribution profiles among various cell types of the central nervous system. Little is known of the cellular distribution of neutral lipids in the substantia nigra (SN) of Parkinson’s disease (PD) patients and its relationship to inflammatory

The path toward Li-ion batteries with higher energy densities will likely involve use of thin lithium (Li)-metal anode (<50 µm thickness), whose cyclability today remains limited by dendrite formation and low coulombic efficiency (CE). Previous studies have shown that the solid–electrolyte interface (SEI) of the Li metal plays a crucial role in Li-electrodeposition and -stripping behavior. However

Accurately estimating human mobility and gauging its relationship with virus transmission is critical for the control of COVID-19 spreading. Using mobile device location data of over 100 million monthly active samples, we compute origin–destination travel demand and aggregate mobility inflow at each US county from March 1 to June 9, 2020. Then, we quantify the change of mobility inflow across the nation

The field of deep learning has positioned itself in the past decade as a prominent and extremely fruitful engineering discipline. This comeback of neural networks in the early 2000s swept the machine learning community, and soon after found itself immersed in practically every scientific, social, and technological front. A growing series of contributions established this field as leading to state-of-the-art

The initial public health response to the breakout of COVID-19 required fundamental changes in individual behavior, such as isolation at home or wearing masks. The effectiveness of these policies hinges on generalized public obedience. Yet, people’s level of compliance may depend on their beliefs regarding the pandemic. We use original data from two waves of a survey conducted in March and April 2020

Human rhinoviruses (RVs) are positive-strand RNA viruses that cause respiratory tract disease in children and adults. Here we show that the innate immune signaling protein STING is required for efficient replication of members of two distinct RV species, RV-A and RV-C. The host factor activity of STING was identified in a genome-wide RNA interference (RNAi) screen and confirmed in primary human small

The origin of water’s anomalies has been a matter of long-standing debate. A two-state model, dating back to Röntgen, relies on the dynamical coexistence of two types of local structures—locally favored tetrahedral structure (LFTS) and disordered normal-liquid structure (DNLS)—in liquid water. Phenomenologically, this model not only explains water’s thermodynamic anomalies but also can rationalize

Probing the binding between a microbe and surface is critical for understanding biofilm formation processes, developing biosensors, and designing biomaterials, but it remains a challenge. Here, we demonstrate a method to measure the interfacial forces of bacteria attached to the surface. We tracked the intrinsic fluctuations of individual bacterial cells using an interferometric plasmonic imaging technique

Modular organization of the spinal motor system is thought to reduce the cognitive complexity of simultaneously controlling the large number of muscles and joints in the human body. Although modular organization has been confirmed in the hindlimb control system of several animal species, it has yet to be established in the forelimb motor system or in primates. Expanding upon experiments originally

Localization of RNAs at protrusive regions of cells is important for single-cell migration on two-dimensional surfaces. Protrusion-enriched RNAs encode factors linked to cancer progression, such as the RAB13 GTPase and the NET1 guanine nucleotide exchange factor, and are regulated by the tumor-suppressor protein APC. However, tumor cells in vivo often do not move as single cells but rather utilize

Humans create metacognitive beliefs about their performance across many levels of abstraction—from local confidence in individual decisions to global estimates of our skills and abilities. Despite a rich literature on the neural basis of local confidence judgements, how global self-performance estimates (SPEs) are constructed remains unknown. Using functional magnetic resonance imaging, we scanned

The sea anemone Nematostella vectensis (Anthozoa, Cnidaria) is a powerful model for characterizing the evolution of genes functioning in venom and nervous systems. Although venom has evolved independently numerous times in animals, the evolutionary origin of many toxins remains unknown. In this work, we pinpoint an ancestral gene giving rise to a new toxin and functionally characterize both genes in

The virus causing COVID-19 has spread rapidly worldwide and threatens millions of lives. It remains unknown, as of April 2020, whether summer weather will reduce its spread, thereby alleviating strains on hospitals and providing time for vaccine development. Early insights from laboratory studies and research on related viruses predicted that COVID-19 would decline with higher temperatures, humidity

Until recently, the field of plant breeding looked a lot like it did in centuries past. A breeder might examine, for example, which tomato plants were most resistant to drought and then cross the most promising plants to produce the most drought-resistant offspring. This process would be repeated, plant generation after generation, until, over the course of roughly seven years, the breeder arrived

Does the human mind resemble the machines that can behave like it? Biologically inspired machine-learning systems approach “human-level” accuracy in an astounding variety of domains, and even predict human brain activity—raising the exciting possibility that such systems represent the world like we do. However, even seemingly intelligent machines fail in strange and “unhumanlike” ways, threatening

Cyclin-dependent kinase 7 (CDK7), Cyclin H, and the RING-finger protein MAT1 form the heterotrimeric CDK-activating kinase (CAK) complex which is vital for transcription and cell-cycle control. When associated with the general transcription factor II H (TFIIH) it activates RNA polymerase II by hyperphosphorylation of its C-terminal domain (CTD). In the absence of TFIIH the trimeric complex phosphorylates

Plants utilize a two-tiered immune system consisting of pattern recognition receptor (PRR)-triggered immunity (PTI) and effector-triggered immunity (ETI) to defend themselves against pathogenic microbes. The receptor protein kinase BAK1 plays a central role in multiple PTI signaling pathways in Arabidopsis. However, double mutants made by BAK1 and its closest paralog BKK1 exhibit autoimmune phenotypes

To obtain insights into striatal neural processes underlying reward-based learning and movement control, we examined spatial organizations of striatal neurons related to movement and reward-based learning. For this, we recorded the activity of direct- and indirect-pathway neurons (D1 and A2a receptor-expressing neurons, respectively) in mice engaged in probabilistic classical conditioning and open-field

The obligate intracellular bacteria Chlamydia trachomatis, the causative agent of trachoma and sexually transmitted diseases, multiply in a vacuolar compartment, the inclusion. From this niche, they secrete “effector” proteins, that modify cellular activities to enable bacterial survival and proliferation. Here, we show that the host autophagy-related protein 16-1 (ATG16L1) restricts inclusion growth

To unravel the functional properties of the brain, we need to untangle how neurons interact with each other and coordinate in large-scale recurrent networks. One way to address this question is to measure the functional influence of individual neurons on each other by perturbing them in vivo. Application of such single-neuron perturbations in mouse visual cortex has recently revealed feature-specific

Sensing of pathogens by Toll-like receptor 4 (TLR4) induces an inflammatory response; controlled responses confer immunity but uncontrolled responses cause harm. Here we define how a multimodular scaffold, GIV (a.k.a. Girdin), titrates such inflammatory response in macrophages. Upon challenge with either live microbes or microbe-derived lipopolysaccharides (a ligand for TLR4), macrophages with GIV

Methyl-7-guanosine (m7G) “capping” of coding and some noncoding RNAs is critical for their maturation and subsequent activity. Here, we discovered that eukaryotic translation initiation factor 4E (eIF4E), itself a cap-binding protein, drives the expression of the capping machinery and increased capping efficiency of ∼100 coding and noncoding RNAs. To quantify this, we developed enzymatic (cap quantification;

Moral behavior requires learning how our actions help or harm others. Theoretical accounts of learning propose a key division between “model-free” algorithms that cache outcome values in actions and “model-based” algorithms that map actions to outcomes. Here, we tested the engagement of these mechanisms and their neural basis as participants learned to avoid painful electric shocks for themselves and

We probe complex optical spectra at high resolution over a broad span in almost complete darkness. Using a single photon-counting detector at light power levels that are a billion times weaker than commonly employed, we observe interferences in the counting statistics with two separate mode-locked femtosecond lasers of slightly different repetition frequencies, each emitting a comb of evenly spaced

Species expanding into new habitats as a result of climate change or human introductions will frequently encounter resident competitors. Theoretical models suggest that such interspecific competition can alter the speed of expansion and the shape of expanding range boundaries. However, competitive interactions are rarely considered when forecasting the success or speed of expansion, in part because

The p53 tumor suppressor protein is a transcription factor and master stress response mediator, and it is subject to reduction-oxidation (redox)-dependent regulation. The P47S variant of TP53, which exists primarily in African-descent populations, associates with an elevated abundance of low molecular weight (LMW) thiols, including glutathione (GSH) and coenzyme A (CoA). Here we show that S47 and P47

Molecular recognition binding sites that specifically identify a target molecule are essential for life science research, clinical diagnoses, and therapeutic development. Corona phase molecular recognition is a technique introduced to generate synthetic recognition at the surface of a nanoparticle corona, but it remains an important question whether such entities can achieve the specificity of natural

Horizontal gene transfer (HGT) confers the rapid acquisition of novel traits and is pervasive throughout microbial evolution. Despite the central role of HGT, the evolutionary forces that drive the dynamics of HGT alleles in evolving populations are poorly understood. Here, we show that HGT alters the evolutionary dynamics of genetic variation, so that deleterious genetic variants, including antibiotic

Imagine seeing the world from the perspective of an infant: surrounded by novel sights, sounds, and smells but not knowing the significance of any of it. How does an infant begin to make sense of such stimuli without instructions? Richard N. Aslin, a developmental psychologist at Haskins Laboratories in Connecticut, has made landmark contributions to our understanding of how infants learn about their

Ling et al. (1) suggest that the exquisite subnanometer voltage-dependent motility observed in cultured neurons results in part from voltage-dependent tension changes at the membrane and are pseudolinear with the transmembrane potential, Ψ. Unfortunately, they (1) modeled the tension change with an expression by Zhang et al. (2) that was derived with ill-posed boundary conditions (3) and has been subsequently

In PNAS (1), we report the full-field interferometric imaging of the dynamics of neuronal deformations during the action potential. The imaging methodology we describe provides a noninvasive approach to observation of the neural signaling and also allows scientists to verify their models with more degrees of freedom provided by the spatial distribution of the deformations, compared to previous single-point

MEDICAL SCIENCES Correction for “Long-term neurocognitive benefits of FLASH radiotherapy driven by reduced reactive oxygen species,” by Pierre Montay-Gruel, Munjal M. Acharya, Kristoffer Petersson, Leila Alikhani, Chakradhar Yakkala, Barrett D. Allen, Jonathan Ollivier, Benoit Petit, Patrik Gonçalves Jorge, Amber R. Syage, Thuan A. Nguyen, Al Anoud D. Baddour, Celine Lu, Paramvir Singh, Raphael Moeckli

ENVIRONMENTAL SCIENCES Correction for “A global-level assessment of the effectiveness of protected areas at resisting …

BIOPHYSICS AND COMPUTATIONAL BIOLOGY Correction for “Direct label-free imaging of nanodomains in biomimetic and biological membranes by cryogenic electron microscopy,” by Frederick A. Heberle, Milka Doktorova, Haden L. Scott, Allison D. Skinkle, …

ENVIRONMENTAL SCIENCES, EARTH, ATMOSPHERIC, AND PLANETARY SCIENCES Correction for “Identifying airborne transmission as the dominant route for the spread of COVID-19,” by Renyi Zhang, Yixin Li, Annie L. Zhang, Yuan Wang, and Mario J. Molina, which was first published June 11, 2020; 10.1073/pnas.2009637117 (Proc. Natl. Acad. Sci. U.S.A. 117, 14857–14863).

With rapid economic growth and urbanization, self-sufficiency in crop production has become central to China’s agriculture policy. Accurate crop production statistics are essential for research, monitoring, and planning. Although researchers agree that China’s statistical authority has considerably modernized over time, China’s economic statistics have still been viewed as unreliable and often overstated

China started to implement comprehensive measures to mitigate traffic pollution at the end of 1990s, but the comprehensive effects, especially on ambient air quality and public health, have not yet been systematically evaluated. In this study, we analyze the effects of vehicle emission control measures on ambient air pollution and associated deaths attributable to long-term exposures of fine particulate

Diagnostic radiologists are experts in discriminating and classifying medical images for clinically significant anomalies. Does their perceptual expertise confer an advantage in unfamiliar visual tasks? Here, this issue was investigated by comparing the performance of 10 radiologists and 2 groups of novices on the ability to detect novel visual signals: band-limited textures in noise. Observers performed

The ability of developing complex internal representations of the environment is considered a crucial antecedent to the emergence of humans’ higher cognitive functions. Yet it is an open question whether there is any fundamental difference in how humans and other good visual learner species naturally encode aspects of novel visual scenes. Using the same modified visual statistical learning paradigm

A characteristic of adaptive behavior is its goal-directed nature. An ability to act in a goal-directed manner is progressively refined during development, but this refinement can be impacted by the emergence of psychiatric disorders. Disorders of compulsivity have been framed computationally as a deficit in model-based control, and have been linked also to abnormal frontostriatal connectivity. However

As the COVID-19 pandemic continues, formulating targeted policy interventions that are informed by differential severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission dynamics will be of vital importance to national and regional governments. We develop an individual-level model for SARS-CoV-2 transmission that accounts for location-dependent distributions of age, household structure

The rapid growth rate of COVID-19 continues to threaten to overwhelm healthcare systems in multiple countries. In response, severely affected countries have had to impose a range of public health strategies achieved via nonpharmaceutical interventions. Broadly, these strategies have fallen into two categories: 1) “mitigation,” which aims to achieve herd immunity by allowing the severe acute respiratory

COVID-19 has emerged as one of the deadliest and most disruptive events in recent human history. Drawing from political science and psychological theories, we examine the effects of daily confirmed cases in a country on citizens’ support for the political leader through the first 120 d of 2020. Using three unique datasets which comprise daily approval ratings of head of government (n = 1,411,200) across

Plant photosynthesis and growth are often limited by the activity of the CO2-fixing enzyme Rubisco. The broad kinetic diversity of Rubisco in nature is accompanied by differences in the composition and compatibility of the ancillary proteins needed for its folding, assembly, and metabolic regulation. Variations in the protein folding needs of catalytically efficient red algae Rubisco prevent their

The plant trans-Golgi network (TGN) is a central trafficking hub where secretory, vacuolar, recycling, and endocytic pathways merge. Among currently known molecular players involved in TGN transport, three different adaptor protein (AP) complexes promote vesicle generation at the TGN with different cargo specificity and destination. Yet, it remains unresolved how sorting into diverging vesicular routes

The nuclear receptor REVERBα is a core component of the circadian clock and proposed to be a dominant regulator of hepatic lipid metabolism. Using antibody-independent ChIP-sequencing of REVERBα in mouse liver, we reveal a high-confidence cistrome and define direct target genes. REVERBα-binding sites are highly enriched for consensus RORE or RevDR2 motifs and overlap with corepressor complex binding

Endometriosis is a highly prevalent gynecological disease with severe negative impacts on life quality and financial burden. Unfortunately, there is no cure for this disease, which highlights the need for further investigation about the pathophysiology of this disease to provide clues for developing novel therapeutic regimens. Herein, we identified that vascular endothelial growth factor (VEGF)-C,

After more than two decades of study, many fundamental questions remain unanswered about the dynamics of glass-forming materials confined to thin films. Experiments and simulations indicate that free interfaces enhance dynamics over length scales larger than molecular sizes, and this effect strengthens at lower temperatures. The nature of the influence of interfaces, however, remains a point of significant