Tracking the spread of emerging pathogens is critical to the design of timely and effective public health responses. Policymakers face the challenge of allocating finite resources for testing and surveillance across locations, with the goal of maximizing the information obtained about the underlying trends in prevalence and incidence. We model this decision-making process as an iterative node classification

Phages, viruses of bacteria, play a pivotal role in Earth’s biosphere and hold great promise as therapeutic and diagnostic tools in combating infectious diseases. Attachment of phages to bacterial cells is a crucial initial step of the interaction. The classic assay to quantify the dynamics of phage attachment involves coculturing and enumeration of bacteria and phages, which is laborious, lengthy

Triple-negative breast cancer (TNBC) has profound unmet medical need globally for its devastating clinical outcome associated with rapid metastasis and lack of targeted therapies. Recently, lipid metabolic reprogramming especially fatty acid oxidation (FAO) has emerged as a major driver of breast cancer metastasis. Analyzing the expression of major FAO regulatory genes in breast cancer, we found selective

Macromolecular assembly depends on tightly regulated pairwise binding interactions that are selectively favored at assembly sites while being disfavored in the soluble phase. This selective control can arise due to molecular density-enhanced binding, as recently found for the kinetochore scaffold protein CENP-T. When clustered, CENP-T recruits markedly more Ndc80 complexes than its monomeric counterpart

Light is a major determinant of plant growth and survival. NONEXPRESSER OF PATHOGENESIS-RELATED GENES 1 (NPR1) acts as a receptor for salicylic acid (SA) and serves as the key regulator of SA-mediated immune responses. However, the mechanisms by which plants integrate light and SA signals in response to environmental changes, as well as the role of NPR1 in regulating plant photomorphogenesis, remain

Growth hormone (GH) has several metabolic effects, including a profound impact on glucose homeostasis. For example, GH oversecretion induces insulin resistance and increases the risk of developing diabetes mellitus. Here, we show that GH receptor (GHR) ablation in vesicular glutamate transporter 2 (VGLUT2)-expressing cells, which comprise a subgroup of glutamatergic neurons, led to a slight decrease

Quasiparticles are low-energy excitations with important roles in condensed matter physics. An intriguing example is provided by Majorana quasiparticles, which are equivalent to their antiparticles. Despite being implicated in neutrino oscillations and topological superconductivity, their experimental realizations remain very rare. Here, we propose a purely classical realization of Majorana fermions

Rare earth elements (REEs) are critical materials to modern technologies. They are obtained by selective separation from mining feedstocks consisting of mixtures of their trivalent cation. We are developing an all-aqueous, bioinspired, interfacial separation using peptides as amphiphilic molecular extractants. Lanthanide binding tags (LBTs) are amphiphilic peptide sequences based on the EF-hand metal

Ferroelectric nematic liquid crystals are polar fluids characterized by microscopic orientational ordering and macroscopic spontaneous polarizations. Within these fluids, domain walls that separate regions of different polarizations are ubiquitous. We demonstrate that the π walls in films of the polar fluids consist of twin half-integer surface disclinations spaced horizontally, enclosing a subdomain

Sandfly vectors transmit Leishmania through egestion of parasites into the host skin. The transmissible dose is shaped by Leishmania development in the sandfly gut, described as a sequential differentiation of promastigote morphotypes. Apart from isolated mammal-infective metacyclic promastigotes, little is known about the transcriptional programs and molecular markers for other stages coinhabiting

Photosystem II (PSII) catalyzes light-driven water oxidation that releases dioxygen into our atmosphere and provides the electrons needed for the synthesis of biomass. The catalysis occurs in the oxygen-evolving oxo-manganese-calcium (Mn 4 O 5 Ca) cluster that drives the oxidation and deprotonation of substrate water molecules leading to the O 2 formation. However, despite recent advances, the mechanism

When plants are exposed to drought stress, there is a trade-off between plant growth and stress responses. Here, we identified a signaling mechanism for the initial steps of the drought-growth trade-off. Phosphoproteomic profiling revealed that Raf13, a B1 subgroup Raf-like kinase, is dephosphorylated under drought conditions. Raf13 and the related B1-Raf Raf15 are required for growth rather than the

Oxidation of the sub-arc mantle driven by slab-derived fluids has been hypothesized to contribute to the formation of gold deposits in magmatic arc environments that host the majority of metal resources on Earth. However, the mechanism by which the infiltration of slab-derived fluids into the mantle wedge changes its oxidation state and affects Au enrichment remains poorly understood. Here, we present

The epidemiology and evolution of diseases unfold in populations that are rarely homogeneous. Instead, hosts infected by pathogens often form metapopulations, in which local populations connected by the movement of hosts experience different demographic and epidemiological conditions. Here, we develop a general theory of the evolution of pathogens in heterogeneous metapopulations. We reveal the following

The sharing of personal memories is a unique aspect of the human experience. Humans communicate to provide information, to influence, or even to amuse. How do we distinguish between credible and noncredible narratives? Forensic science has identified race, age, and detail quantity as influential. We do not know how the nature of narrated details impacts believability. We report two studies investigating

Formerly a common childhood pathogen, mumps virus (MuV) remains active worldwide, despite relatively high vaccine coverage. MuV is thought to infect the upper respiratory tract before disseminating to other organs; however, the early cellular targets of MuV in vivo are unknown. To address this, we generated a green fluorescent protein (GFP)-tagged vaccine strain (JL5) of MuV to infect leukocytic cell

Everything that the brain sees must first be encoded by the retina, which maintains a reliable representation of the visual world in many different, complex natural scenes while also adapting to stimulus changes. This study quantifies whether and how the brain selectively encodes stimulus features about scene identity in complex naturalistic environments. While a wealth of previous work has dug into

Diverse tissues in vivo present varying degrees of confinement, constriction, and compression to migrating cells in both homeostasis and disease. The nucleus in particular is subjected to external forces by the physical environment during confined migration. While many systems have been developed to induce nuclear deformation and analyze resultant functional changes, much remains unclear about dynamic

Resource availability dictates how fast and how much microbial populations grow. Quantifying the relationship between microbial growth and resource concentrations makes it possible to promote, inhibit, and predict microbial activity. Microbes require many resources, including macronutrients (e.g., carbon and nitrogen), micronutrients (e.g., metals), and complex nutrients like vitamins and amino acids

Inhibiting indoleamine 2,3 dioxygenase (IDO) for anticancer therapy has garnered significant attention in recent years. However, current IDO inhibitors face significant challenges which limit their clinical application. Here, we genetically engineered a high tryptophan-expressing Clostridium butyricum (L-Trp CB) strain that can colonize tumors strictly following systemic administration. We revealed

Drugs that eliminate senescent cells, senolytics, can be powerful when combined with prosenescence cancer therapies. Using a CRISPR/Cas9-based genetic screen, we identify here SLC25A23 as a vulnerability of senescent cancer cells. Suppressing SLC25A23 disrupts cellular calcium homeostasis, impairs oxidative phosphorylation, and interferes with redox signaling, leading to death of senescent cells. These

Detecting viral infection is a key role of the innate immune system. The genomes of some RNA viruses have a high CpG dinucleotide content relative to most vertebrate cell RNAs, making CpGs a molecular marker of infection. The human zinc-finger antiviral protein (ZAP) recognizes CpG, mediates clearance of the foreign CpG-rich RNA, and causes attenuation of CpG-rich RNA viruses. While ZAP binds RNA,

CRISPR-Cas9 genome editing systems have revolutionized plant gene functional studies by enabling the targeted introduction of insertion-deletions (INDELs) via the nonhomologous end-joining (NHEJ) pathway. Frameshift-inducing INDELs can introduce a premature termination codon and, in other instances, can lead to the appearance of new proteins. Here, we found that mutations in the rice jasmonate (JA)

The pathological deposition of proteins is a hallmark of several devastating neurodegenerative diseases. These pathological deposits comprise aggregates of proteins that adopt distinct structures named strains. However, the molecular factors responsible for the formation of distinct aggregate strains are unknown. Here, we show that the serine/threonine kinase GSK3β catalyzes the aggregation of the

Decades after being replaced with digital platforms, analogue computing has experienced a surging interest following developments in metamaterials and intricate fabrication techniques. Specifically, wave-based analogue computers which impart spatial transformations on an incident wavefront, commensurate with a desired mathematical operation, have gained traction owing to their ability to directly encode

Microorganisms in marine oxygen minimum zones (OMZs) drive globally impactful biogeochemical processes. One such process is multistep denitrification (NO 3 – →NO 2 – →NO→N 2 O→N 2 ), which dominates OMZ bioavailable nitrogen (N) loss and nitrous oxide (N 2 O) production. Denitrification-derived N loss is typically measured and modeled as a single step, but observations reveal that most denitrifiers

The discovery that sponges (Porifera) can fully regenerate from aggregates of dissociated cells launched them as one of the earliest experimental models to study the evolution of cell adhesion and allorecognition in animals. This process depends on an extracellular glycoprotein complex called the Aggregation Factor (AF), which is composed of proteins thought to be unique to sponges. We used quantitative

Immunotherapies have emerged as an effective treatment option for immune-related diseases, such as cancer and inflammatory diseases. However, variations in patient responsiveness limit the broad applicability and success of these immunotherapies. Noninvasive whole-body imaging of the immune status of individual patients during immunotherapy could enable the prediction and monitoring of the patient’s

Tissue inflammation is often broadly associated with cellular damage, yet sterile inflammation also plays critical roles in beneficial tissue remodeling. In the central nervous system, this is observed through a predominantly innate immune response in retinal vascular diseases such as age-related macular degeneration, diabetic retinopathy, and retinopathy of prematurity. Here, we set out to elucidate

Combinatorial networks of cell adhesion molecules and cell surface receptors drive fundamental aspects of neural circuit establishment and function. However, the intracellular signals orchestrated by these cell surface complexes remain less understood. Here, we report that the Gα12/13 pathway lies downstream of several GPCRs with critical synaptic functions. Impairment of the Gα12/13 pathway in postnatal

The integrity of the blood–retina barrier (BRB) is crucial for phototransduction and vision, by tightly restricting transport of molecules between the blood and surrounding neuronal cells. Breakdown of the BRB leads to the development of retinal diseases. Here, we show that Netrin-1/Unc5b and Norrin/Lrp5 signaling establish a zonated endothelial cell gene expression program that controls BRB integrity

Immune surveillance depends in part on the recognition of peptide variants by T cell antigen receptors. Given that both normal B cells and malignant B cells accumulate mutations we chose a murine model of multiple myeloma to test conditions to induce cell-mediated immunity targeting malignant plasma cell (PC) clones but sparing of normal PCs. Revealing a previously unknown function for intracellular

Eukaryotic nuclear genomes often encode distinct sets of translation machinery for function in the cytosol vs. organelles (mitochondria and plastids). This raises questions about why multiple translation systems are maintained even though they are capable of comparable functions and whether they evolve differently depending on the compartment where they operate. These questions are particularly interesting

The issue of antibiotic resistance is a critical concern for public health, prompting numerous investigations into the impact of treatment strategies on preventing or slowing down the emergence of resistance. While existing studies have predominantly focused on chromosomal resistance mutations, the consequences of often clinically more relevant plasmid-conferred resistance remain insufficiently explored

Proteins become asymmetrically distributed in the one-cell Caenorhabditis elegans embryo thanks to reaction–diffusion mechanisms that are often entangled in complex feedback loops. Cortical polarity drives the enrichment of the RNA-binding proteins MEX-5 and MEX-6 in the anterior cytoplasm through concentration gradients. MEX-5 and MEX-6 promote the patterning of other cytoplasmic factors, including

Decades of research have established that mammalian transcription factors (TFs) bind to each gene’s regulatory regions and cooperatively control tissue specificity, timing, and intensity of gene transcription. Mapping the combination of TF binding sites genome wide is critically important for understanding functional genomics. Here, we report a technique to measure TFs’ binding sites on the human genome

Predator–prey interactions are a major driver of microbiome dynamics, but remain difficult to predict. While several prey traits potentially impact resistance to predation, their effects in a multispecies context remain unclear. Here, we leverage synthetic bacterial communities of varying complexity to identify traits driving palatability for nematodes, a main consumer of bacteria in soil. We assessed

The H3K9me3-specific histone methyltransferase SETDB1 is critical for proper regulation of developmental processes, but the underlying mechanisms are only partially understood. Here, we show that deletion of Setdb1 in mouse fetal liver hematopoietic stem and progenitor cells (HSPCs) results in compromised stem cell function, enhanced myeloerythroid differentiation, and impaired lymphoid development

Cytokines constitute a family of proteins that modulate the immune system and are secreted by many cells. CXCL12, along with its receptor CXCR4, are essential players in numerous processes. Dysregulation of their function underlie the mechanism(s) of several pathologies, including malignancies. Here, we demonstrate an unexpected effect of the cytokine and its receptor: In both cells and animal models

Estimating the cost to society from a ton of CO 2 —termed the social cost of carbon (SCC)—requires connecting a model of the climate system with a representation of the economic and social effects of changes in climate, and the aggregation of diverse, uncertain impacts across both time and space. A growing literature has examined the effect of fundamental structural elements of the models supporting

Decisions about solar geoengineering (SG) entail risk–risk tradeoffs between the direct risks of SG and SG’s ability to reduce climate risks. Quantitative comparisons between these risks are needed to inform public policy. We evaluate idealized SG’s effectiveness in reducing deaths from warming using two climate models and an econometric analysis of temperature-attributable mortality. We find SG’s

Infectious disease can reduce labor productivity and incomes, trapping subpopulations in a vicious cycle of ill health and poverty. Efforts to boost African farmers’ agricultural production through fertilizer use can inadvertently promote the growth of aquatic vegetation that hosts disease vectors. Recent trials established that removing aquatic vegetation habitat for snail intermediate hosts reduces

The tropical archipelago of Wallacea was first settled by anatomically modern humans (AMH) by 50 thousand years ago (kya), with descendent populations thought to have remained genetically isolated prior to the arrival of Austronesian seafarers around 3.5 kya. Modern Wallaceans exhibit a longitudinal countergradient of Papuan- and Asian-related ancestries widely considered as evidence for mixing between

Seaweed farming comprises over half of global coastal and marine aquaculture production by mass; however, the future of the industry is increasingly threatened by disease outbreaks. Nature-based solutions provided by enhancing functions of coinciding species or ecosystems offer an opportunity to increase yields by reducing disease outbreaks while conserving biodiversity. Seagrass ecosystems can reduce

In muscle, titin proteins connect myofilaments together and are thought to be critical for contraction, especially during residual force enhancement (RFE) when steady-state force is elevated after an active stretch. We investigated titin’s function during contraction using small-angle X-ray diffraction to track structural changes before and after 50% titin cleavage and in the RFE-deficient, mdm titin

Numerous missions to the Moon have identified and documented volatile deposits associated with permanently shadowed regions. A series of science goals for the Artemis Program is to explore these volatile deposits and return samples to Earth. Volatiles in these reservoirs may consist of a variety of species whose stable isotope characteristics could elucidate both their sources and the processes instrumental

Semiaquatic taxa, including humans, often swim at the air–water interface where they waste energy generating surface waves. For fully marine animals however, theory predicts the most cost-efficient depth-use pattern for migrating, air-breathing species that do not feed in transit is to travel at around 2 to 3 times the depth of their body diameter, to minimize the vertical distance traveled while avoiding