Understanding how viral and host factors interact and how perturbations impact infection is the basis for designing antiviral interventions. Here we define the functional contribution of each viral and host factor involved in human cytomegalovirus infection in primary human fibroblasts through pooled CRISPR interference and nuclease screening. To determine how genetic perturbation of critical host

Replisome disassembly is the final step of eukaryotic DNA replication, and is triggered by ubiquitylation of the CMG (Cdc45-MCM-GINS) replicative helicase1–3. Despite being driven by evolutionarily diverse E3 ubiquitin ligases in different eukaryotes (SCFDia2 in budding yeast1, CUL2LRR1 in metazoa4–7), replisome disassembly is governed by a common regulatory principle, whereby CMG ubiquitylation is

Various approaches are approved for treating blood cancers and a few rare disorders—they may soon become standard care.

Letter to the Editor

Letter to the Editor

The value of studying wetlands, and the excavation of an ancient city in Sicily.

Letter to the Editor

Over the past few years the discipline has evolved in significant ways.

Tragic side effects plagued the field’s early years, but researchers are finding ways to minimize the risks.

Simple, regular checks could squelch some pernicious practices by unscrupulous publishers and preserve your digital presence.

To thwart publishing rackets that undermine scholars and scholarly publishing, legitimate journals should show their workings.

Cutting-edge microscopy techniques are allowing researchers to spy on the innards of cells in all their crowded glory.

The field is beginning to fulfill its potential. These therapies offer a glimpse of what’s to come.

Studies suggest that a reversal of the landmark Roe v. Wade decision would be detrimental for many.

Researchers, practitioners and patients must balance the discipline's promise with its reality.

Funding pledges from China and other countries need to be given in grants — which must include research grants — and not as a reward for taking out loans.

Considerable uncertainty surrounds the timeline of introductions and onsets of local transmission of SARS-CoV-2 globally1–7. Although a limited number of SARS-CoV-2 introductions were reported in January and February 20208,9, the narrowness of the initial testing criteria, combined with a slow growth in testing capacity and porous travel screening10, left many countries vulnerable to unmitigated, cryptic

The voltage-dependent motor protein Prestin (SLC26A5) is responsible for the electromotive behavior of outer hair cells and underlies the cochlear amplifier1. Knock out or impairment of Prestin causes severe hearing loss2–5. Despite Prestin’s key role in hearing, the mechanism by which mammalian Prestin senses voltage and transduces it into cellular-scale movements (electromotility) is poorly understood

The Delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has outcompeted previously prevalent variants and become a dominant strain worldwide. We report the structure, function, and antigenicity of its full-length spike (S) trimer and those of the Gamma and Kappa variants and compare their characteristics with the G614, Alpha, and Beta variants. Delta S can fuse membranes more

SARS-CoV-2 is a single-stranded RNA virus that causes coronavirus disease 2019 (COVID-19). Given its acute and often self-limiting course, components of the innate immune system are likely central in controlling virus replication thereby determining clinical outcome. Natural killer (NK) cells are innate lymphocytes with notable activity against a broad range of viruses, including RNA viruses1,2. NK

Dryness begets heat, and atmospheric moisture in the tropics is expected to be low on the hottest days in a warmer world.

EARTH, ATMOSPHERIC, AND PLANETARY SCIENCES A mesoscale convective system in South Dakota. Soil moisture and summer rainfall in central United States Interactions between soil moisture and precipitation play a major role in the central United States, where mesoscale convective systems (MCS) spanning over 100 kilometers account for 30–70% of warm-season...

Central questions for organ-specific autoimmune diseases such as type 1 diabetes (T1D) are, What are the relevant self-antigens of the destructive processes and Why does the immune system become interested in them? In PNAS, Anderson et al. (1) provide more evidence that insulin and its precursors constitute a key antigen in T1D. Nakayama, Eisenbarth, and coworkers had previously demonstrated that autoimmune

Accurate characterization of sexual dimorphism is crucial in evolutionary biology because of its significance in understanding present and past adaptations involving reproductive and resource use strategies of species. However, inferring dimorphism in fossil assemblages is difficult, particularly with relatively low dimorphism. Commonly used methods of estimating dimorphism levels in fossils include

Pest management practices in modern industrial agriculture have increasingly relied on insurance-based insecticides such as seed treatments that are poorly correlated with pest density or crop damage. This approach, combined with high invertebrate toxicity for newer products like neonicotinoids, makes it challenging to conserve beneficial insects and the services that they provide. We used a 4-y experiment

Snow is highly sensitive to atmospheric warming. However, because of the lack of sufficiently long snow avalanche time series and statistical techniques capable of accounting for the numerous biases inherent to sparse and incomplete avalanche records, the evolution of process activity in a warming climate remains little known. Filling this gap requires innovative approaches that put avalanche activity

Across many cities, estimates of methane emissions from natural gas (NG) distribution and end use based on atmospheric measurements have generally been more than double bottom-up estimates. We present a top-down study of NG methane emissions from the Boston urban region spanning 8 y (2012 to 2020) to assess total emissions, their seasonality, and trends. We used methane and ethane observations from

There is an ongoing unprecedented loss in insects, both in terms of richness and biomass. The usage of pesticides, especially neonicotinoid insecticides, has been widely suggested to be a contributor to this decline. However, the risks of neonicotinoids to natural insect populations have remained largely unknown due to a lack of field-realistic experiments. Here, we used an outdoor experiment to determine

The competition between turbulent convection and global rotation in planetary and stellar interiors governs the transport of heat and tracers, as well as magnetic field generation. These objects operate in dynamical regimes ranging from weakly rotating convection to the “geostrophic turbulence” regime of rapidly rotating convection. However, the latter regime has remained elusive in the laboratory

Agricultural expansion into subtropical and tropical forests causes major environmental damage, but its wider social impacts often remain hidden. Forest-dependent smallholders are particularly strongly impacted, as they crucially rely on forest resources, are typically poor, and often lack institutional support. Our goal was to assess forest-smallholder dynamics in relation to expanding commodity agriculture

Methyl farnesoate (MF) plays hormonal regulatory roles in crustaceans. An epoxidated form of MF, known as juvenile hormone (JH), controls metamorphosis and stimulates reproduction in insects. To address the evolutionary significance of MF epoxidation, we generated mosquitoes completely lacking either of the two enzymes that catalyze the last steps of MF/JH biosynthesis and epoxidation, respectively:

Strawberry (Fragaria spp.) has emerged as a model system for various fundamental and applied research in recent years. In total, the genomes of five different species have been sequenced over the past 10 y. Here, we report chromosome-scale reference genomes for five strawberry species, including three newly sequenced species’ genomes, and genome resequencing data for 128 additional accessions to estimate

Intensifying wildfire activity and climate change can drive rapid forest compositional shifts. In boreal North America, black spruce shapes forest flammability and depends on fire for regeneration. This relationship has helped black spruce maintain its dominance through much of the Holocene. However, with climate change and more frequent and severe fires, shifts away from black spruce dominance to

Letter to the Editor

Insight is more important than vision in theoretical physics, says Sofia Qvafort.

Developmental geneticist Maria Leptin hopes to keep the European Research Council true to its founding mission.

Four junior researchers with disabilities describe their career experiences to date, and how colleagues can act as allies.

How a win in the Supreme Court challenged a linchpin of the genetic-testing industry.

Researchers have dated a Norse settlement in Canada to ad 1021. Plus: why elephants are evolving to lose their tusks, and how mix-and-match COVID vaccines have aced the effectiveness test.

An animated tale of giant solar storms, ancient sagas and the latest radiocarbon dating technology.

“Sometimes when you ask a functional question, you get an evolutionary answer,” says Jennifer Marshall Graves, a leader in the field of epigenetics and comparative genomics. Her team’s vast body of research on Australian fauna has helped the distinguished professor at Melbourne’s La Trobe University (LTU) uncover fundamental insights into mammalian sex chromosomes and sex-determining genes. Elected

The Epstein–Barr virus (EBV) transforms resting B cells and is involved in the development of B cell lymphomas. We report here that the viral noncoding RNA EBER2 accelerates B cell growth by potentiating expression of the UCHL1 deubiquitinase that itself increased expression of the Aurora kinases and of cyclin B1. Importantly, this effect was also visible in Burkitt’s lymphoma cells that express none

The hydroxyl radical (OH) sets the oxidative capacity of the atmosphere and, thus, profoundly affects the removal rate of pollutants and reactive greenhouse gases. While observationally derived constraints exist for global annual mean present-day OH abundances and interannual variability, OH estimates for past and future periods rely primarily on global atmospheric chemistry models. These models disagree

Very little is known about how domestication was constrained by the quantitative genetic architecture of crop progenitors and how quantitative genetic architecture was altered by domestication. Yang et al. [C. J. Yang et al., Proc. Natl. Acad. Sci. U.S.A. 116, 5643–5652 (2019)] drew multiple conclusions about how genetic architecture influenced and was altered by maize domestication based on one sympatric

Mesenchymal stem cells (MSCs), which exert regulatory effects on various immune cells, have been a promising therapy for inflammatory bowel disease treatment. However, their therapeutic effects are limited by lack of nutritional supply, immune system attack, and low accumulation on the target site. Here, inspired by the natural incubation mechanism of roe, we present immune-isolating, wet-adhesive

Self-amplifying RNA replicons are promising platforms for vaccine generation. Their defects in one or more essential functions for viral replication, particle assembly, or dissemination make them highly safe as vaccines. We previously showed that the deletion of the envelope (E) gene from the Middle East respiratory syndrome coronavirus (MERS-CoV) produces a replication-competent propagation-defective

Contact tracing is a pillar of COVID-19 response, but language access and equity have posed major obstacles. COVID-19 has disproportionately affected minority communities with many non–English-speaking members. Language discordance can increase processing times and hamper the trust building necessary for effective contact tracing. We demonstrate how matching predicted patient language with contact

Monocytes are rapidly recruited to inflamed tissues where they differentiate into monocyte-derived macrophages (mo-mac) or dendritic cells (mo-DC). At infection sites, monocytes encounter a broad range of microbial motifs. How pathogen recognition impacts monocyte fate decision is unclear. Here, we show, using an in vitro model allowing the simultaneous differentiation of human mo-mac and mo-DC, that

Although we agree with Dutta et al. (1) that our conclusion could be more comprehensive, we disagree that our study design and interpretations are biased (2). Neutrophils in asthma are linked to worsening symptoms, but their role as key determinant cells remains obscure in the pathogenesis (3). Reducing neutrophilic inflammation in asthma does not yield any meaningful outcome in clinical trials and

Tungsten (W) is a metal that is generally thought to be seldom used in biology. We show here that a W-containing oxidoreductase (WOR) family is diverse and widespread in the microbial world. Surprisingly, WORs, along with the tungstate-specific transporter Tup, are abundant in the human gut microbiome, which contains 24 phylogenetically distinct WOR types. Two model gut microbes containing six types

Drosophila is a powerful model in which to perform genetic screens, but screening assays that are both rapid and can be used to examine a wide variety of cellular and molecular pathways are limited. Drosophila offer an extensive toolbox of GFP-based transcriptional reporters, GFP-tagged proteins, and driver lines, which can be used to express GFP in numerous subpopulations of cells. Thus, a tool that

How signaling units spontaneously arise from a noisy cellular background is not well understood. Here, we show that stochastic membrane deformations can nucleate exploratory dendritic filopodia, dynamic actin-rich structures used by neurons to sample its surroundings for compatible transcellular contacts. A theoretical analysis demonstrates that corecruitment of positive and negative curvature-sensitive

Phase transitions are emergent phenomena where microscopic interactions drive a disordered system into a collectively ordered phase. Near the boundary between two phases, the system can exhibit critical, scale-invariant behavior. Here, we report on a second-order phase transition accompanied by critical behavior in a system of warm cesium spins driven by linearly polarized light. The ordered phase

Complex body movements require complex dynamics and coordination among neurons in motor cortex. Conversely, a long-standing theoretical notion supposes that if many neurons in motor cortex become excessively synchronized, they may lack the necessary complexity for healthy motor coding. However, direct experimental support for this idea is rare and underlying mechanisms are unclear. Here we recorded

Decisions are based on the subjective values of choice options. However, subjective value is a theoretical construct and not directly observable. Strikingly, distinct theoretical models competing to explain how subjective values are assigned to choice options often make very similar behavioral predictions, which poses a major difficulty for establishing a mechanistic, biologically plausible explanation

People frequently search the internet for information. Eight experiments (n = 1,917) provide evidence that when people “Google” for online information, they fail to accurately distinguish between knowledge stored internally—in their own memories—and knowledge stored externally—on the internet. Relative to those using only their own knowledge, people who use Google to answer general knowledge questions

Motor control requires a coordinated ensemble of spatiotemporally precise neural oscillations across a distributed motor network, particularly in the beta range (15 to 30 Hz) to successfully plan and execute volitional actions. While substantial evidence implicates beta activity as critical to motor control, the molecular processes supporting these microcircuits and their inherent oscillatory dynamics

Many viruses directly engage and require the dynein–dynactin motor–adaptor complex in order to transport along microtubules (MTs) to the nucleus and initiate infection. HIV type 1 (HIV-1) exploits dynein, the dynein adaptor BICD2, and core dynactin subunits but unlike several other viruses, does not require dynactin-1 (DCTN1). The underlying reason for HIV-1’s variant dynein engagement strategy and

We believe there are a few shortcomings in the study design and data interpretation in the research article by Wang et al. (1). These include 1) cell selection bias, 2) cytokine selection bias from single-cell transcriptomics (SCT) data, and 3) lack of a lipopolysaccharide+dexamethasone (LPS+DEX) control group in the mouse model of steroid-resistant asthma (SRA) exacerbation.