Table Of Contents Page, PNAS Volume 117, Number 27

PNAS July 7, 2020

This Week in PNAS

Opinion

Commentaries

Brief Reports

The chordless cycle sizes of spatially embedded networks are demonstrated to follow an exponential growth law similar to random graphs if the number of nodes N x is below a critical value N * . For covalent polymer networks, increasing the network size, as ...
Fish have somehow colonized isolated water bodies all over the world without human assistance. It has long been speculated that these colonization events are assisted by waterbirds, transporting fish eggs attached to their feet and feathers, yet empirical ...
The Casparian strip (CS) is a tight junction-like structure formed by lignin impregnation on the walls of endodermal cells in plant roots. The CS membrane domain (CSDM), demarked by the CASP proteins, is important for orienting lignification enzymes. Here,...

Physical Sciences

Applied Mathematics

We propose a latent variable model to discover faithful low-dimensional representations of high-dimensional data. The model computes a low-dimensional embedding that aims to preserve neighborhood relationships encoded by a sparse graph. The model both ...

Applied Physical Sciences

The resistance of a conventional insulator diverges as temperature approaches zero. The peculiar low-temperature resistivity saturation in the 4f Kondo insulator (KI) SmB6 has spurred proposals of a correlation-driven topological Kondo insulator (TKI) ...

Biophysics and Computational Biology

De novo emergence demands a transition from disordered polypeptides into structured proteins with well-defined functions. However, can polypeptides confer functions of evolutionary relevance, and how might such polypeptides evolve into modern proteins? ...

Chemistry

We report on a combined activation mechanism for a class B G-protein–coupled receptor (GPCR), the glucagon receptor. By computing the conformational free-energy landscape associated with the activation of the receptor–agonist complex and comparing it with ...
Infrared spectroscopic study of neutral water clusters is crucial to understanding of the hydrogen-bonding networks in liquid water and ice. Here we report infrared spectra of size-selected neutral water clusters, (H2O)n (n = 3−6), in the OH stretching ...
The preparation of stereochemistry- and sequence-defined polymers, in which different monomer units are arranged in an ordered fashion just like biopolymers, is of great interest and has been a long-standing goal for chemists due to the expectation of ...
Ice amorphization, low- to high-density amorphous (LDA-HDA) transition, as well as (re)crystallization in ice, under compression have been studied extensively due to their fundamental importance in materials science and polyamorphism. However, the nature ...

Earth, Atmospheric, and Planetary Sciences

Habitat heterogeneity and species diversity are often linked. On the deep seafloor, sediment variability and hard-substrate availability influence geographic patterns of species richness and turnover. The assumption of a generally homogeneous, sedimented ...
View related content:

The heterogeneous abyss

The Moon likely formed in a giant impact that left behind a fast-rotating Earth, but the details are still uncertain. Here, we examine the implications of a constraint that has not been fully exploited: The component of the Earth–Moon system’s angular ...

Engineering

Bioinspired architectural design for composites with much higher fracture resistance than that of individual constituent remains a major challenge for engineers and scientists. Inspired by the survival war between the mantis shrimps and abalones, we ...
The development of sustainable methods for the degradation of pollutants in water is an ongoing critical challenge. Anthropogenic organic micropollutants such as pharmaceuticals, present in our water supplies in trace quantities, are currently not ...
Bioelectronic scaffolds that support devices while promoting tissue integration could enable tissue hybrids with augmented electronic capabilities. Here, we demonstrate a photo–cross-linkable silk fibroin (PSF) derivative and investigate its structural, ...
Contactless manipulation of microparticles using acoustic waves holds promise for applications ranging from cell sorting to three-dimensional (3D) printing and tissue engineering. However, the unique potential of acoustic trapping to be applied in ...
Bioadhesives such as tissue adhesives, hemostatic agents, and tissue sealants have potential advantages over sutures and staples for wound closure, hemostasis, and integration of implantable devices onto wet tissues. However, existing bioadhesives display ...
Cell size is believed to influence cell growth and metabolism. Consistently, several studies have revealed that large cells have lower mass accumulation rates per unit mass (i.e., growth efficiency) than intermediate-sized cells in the same population. ...

Environmental Sciences

Earth system models (ESMs) project that global warming suppresses biological productivity in the Subarctic Atlantic Ocean as increasing ocean surface buoyancy suppresses two physical drivers of nutrient supply: vertical mixing and meridional circulation. ...
Despite very low concentrations of cobalt in marine waters, cyanobacteria in the genus Prochlorococcus retain the genetic machinery for the synthesis and use of cobalt-bearing cofactors (cobalamins) in their genomes. We explore cobalt metabolism in a ...

Physics

Oscillators are at the heart of optical lasers, providing stable, transform-limited pulses. Until now, laser oscillators have been available only in the infrared to visible and near-ultraviolet (UV) spectral region. In this paper, we present a study of an ...
Topological electrons in semimetals are usually vulnerable to chemical doping and environment change, which restricts their potential application in future electronic devices. In this paper, we report that the type-II Dirac semimetal V A l 3 hosts exceptional, ...
The interplay between spin–orbit coupling and structural inversion symmetry breaking in solids has generated much interest due to the nontrivial spin and magnetic textures which can result. Such studies are typically focused on systems where large atomic ...
In response to the coronavirus disease 2019 (COVID-19) pandemic, several national governments have applied lockdown restrictions to reduce the infection rate. Here we perform a massive analysis on near–real-time Italian mobility data provided by Facebook ...

Social Sciences

Economic Sciences

In response to the coronavirus disease 2019 (COVID-19) pandemic, several national governments have applied lockdown restrictions to reduce the infection rate. Here we perform a massive analysis on near–real-time Italian mobility data provided by Facebook ...

Environmental Sciences

Political Sciences

Widespread belief in misinformation circulating online is a critical challenge for modern societies. While research to date has focused on psychological and political antecedents to this phenomenon, few studies have explored the role of digital media ...

Psychological and Cognitive Sciences

Visual awareness is thought to result from integration of low- and high-level processing; instances of integration failure provide a crucial window into the cognitive and neural bases of awareness. We present neurophysiological evidence of complex ...
Human navigation relies on inputs to our paired eyes and ears. Although we also have two nasal passages, there has been little empirical indication that internostril differences yield directionality in human olfaction without involving the trigeminal ...

Social Sciences

How can governments and nonprofits design aid programs that afford dignity and facilitate beneficial outcomes for recipients? We conceptualize dignity as a state that manifests when the stigma associated with receiving aid is countered and recipients are ...

Biological Sciences

Biochemistry

The serum haptoglobin protein (Hp) scavenges toxic hemoglobin (Hb) leaked into the bloodstream from erythrocytes. In humans, there are two frequently occurring allelic forms of Hp, resulting in three genotypes: Homozygous Hp 1-1 and Hp 2-2, and ...
Many bacteria exist in a state of metabolic quiescence where energy consumption must be minimized so as to maximize available resources over a potentially extended period of time. As protein synthesis is the most energy intensive metabolic process in a ...
Cyanobacteriochromes (CBCRs) are small, bistable linear tetrapyrrole (bilin)-binding light sensors which are typically found as modular components in multidomain cyanobacterial signaling proteins. The CBCR family has been categorized into many lineages ...
Protein synthesis represents a major metabolic activity of the cell. However, how it is affected by aging and how this in turn impacts cell function remains largely unexplored. To address this question, herein we characterized age-related changes in both ...
Sphingolipids (SLs) are chemically diverse lipids that have important structural and signaling functions within mammalian cells. SLs are commonly defined by the presence of a long-chain base (LCB) that is normally formed by the conjugation of l-serine and ...
2(S)-dihydroxypropanesulfonate (DHPS) is a microbial degradation product of 6-deoxy-6-sulfo-d-glucopyranose (sulfoquinovose), a component of plant sulfolipid with an estimated annual production of 1010 tons. DHPS is also at millimolar levels in highly ...

Biophysics and Computational Biology

We report on a combined activation mechanism for a class B G-protein–coupled receptor (GPCR), the glucagon receptor. By computing the conformational free-energy landscape associated with the activation of the receptor–agonist complex and comparing it with ...
Bioinspired architectural design for composites with much higher fracture resistance than that of individual constituent remains a major challenge for engineers and scientists. Inspired by the survival war between the mantis shrimps and abalones, we ...
Ribosome biogenesis is a complex process, and dozens of factors are required to facilitate and regulate the subunit assembly in bacteria. The 2′-O-methylation of U2552 in 23S rRNA by methyltransferase RrmJ is a crucial step in late-stage assembly of the ...
Repulsive guidance molecules (RGMs) are cell surface proteins that regulate the development and homeostasis of many tissues and organs, including the nervous, skeletal, and immune systems. They control fundamental biological processes, such as migration ...
KIF3AC is a mammalian neuron-specific kinesin-2 implicated in intracellular cargo transport. It is a heterodimer of KIF3A and KIF3C motor polypeptides which have distinct biochemical and motile properties as engineered homodimers. Single-molecule motility ...
The RNA polymerase (RNAP) trigger loop (TL) is a mobile structural element of the RNAP active center that, based on crystal structures, has been proposed to cycle between an “unfolded”/“open” state that allows an NTP substrate to enter the active center ...
Liquid−liquid phase separation of multivalent intrinsically disordered protein−RNA complexes is ubiquitous in both natural and biomimetic systems. So far, isotropic liquid droplets are the most commonly observed topology of RNA−protein condensates in ...

Cell Biology

Cell size is believed to influence cell growth and metabolism. Consistently, several studies have revealed that large cells have lower mass accumulation rates per unit mass (i.e., growth efficiency) than intermediate-sized cells in the same population. ...
Muscle contraction depends on the cyclical interaction of myosin and actin filaments. Therefore, it is important to understand the mechanisms of polymerization and depolymerization of muscle myosins. Muscle myosin 2 monomers exist in two states: one with ...
Stemness encompasses the capability of a cell for self-renewal and differentiation. The stem cell maintains a balance between proliferation, quiescence, and regeneration via interactions with the microenvironment. Previously, we showed that ectopic ...
Mitochondria are known to play an essential role in photoreceptor function and survival that enables normal vision. Within photoreceptors, mitochondria are elongated and extend most of the inner-segment length, where they supply energy for protein ...
The p53 family member p73 has a complex gene structure, including alternative promoters and alternative splicing of the 3′ UTR. This results in a complex range of isoforms whose biological relevance largely remains to be determined. By deleting exon 13 (...

Developmental Biology

Mammalian cells contain two isoforms of RNA polymerase III (Pol III) that differ in only a single subunit, with POLR3G in one form (Pol IIIα) and the related POLR3GL in the other form (Pol IIIβ). Previous research indicates that POLR3G and POLR3GL are ...
The mechanisms used by embryos to pattern tissues across their axes has fascinated developmental biologists since the founding of embryology. Here, using single-cell technology, we interrogate complex patterning defects and define a Hedgehog (Hh)–...

Ecology

Habitat heterogeneity and species diversity are often linked. On the deep seafloor, sediment variability and hard-substrate availability influence geographic patterns of species richness and turnover. The assumption of a generally homogeneous, sedimented ...
View related content:

The heterogeneous abyss

Inbreeding is often avoided in natural populations by passive processes such as sex-biased dispersal. But, in many social animals, opposite-sexed adult relatives are spatially clustered, generating a risk of incest and hence selection for active ...

Evolution

De novo emergence demands a transition from disordered polypeptides into structured proteins with well-defined functions. However, can polypeptides confer functions of evolutionary relevance, and how might such polypeptides evolve into modern proteins? ...
Despite very low concentrations of cobalt in marine waters, cyanobacteria in the genus Prochlorococcus retain the genetic machinery for the synthesis and use of cobalt-bearing cofactors (cobalamins) in their genomes. We explore cobalt metabolism in a ...
Trade-offs between growth, reproduction, and lifespan constrain animal life histories, leading to evolutionary diversification of life history cycles in different environments. In female mammals, gestation and lactation are expected to impose the major ...
Mobile genetic elements (MGEs), such as plasmids, promote bacterial evolution through horizontal gene transfer (HGT). However, the rules governing the repertoire of traits encoded on MGEs remain unclear. In this study, we uncovered the central role of ...

Immunology and Inflammation

HIV-1 latency is a major barrier to cure. Identification of small molecules that destabilize latency and allow immune clearance of infected cells could lead to treatment-free remission. In vitro models of HIV-1 latency involving cell lines or primary ...
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Turning up the heat on HIV-1

During pregnancy, invading HLA-G+ extravillous trophoblasts (EVT) play a key role in placental development, uterine spiral artery remodeling, and prevention of detrimental maternal immune responses to placental and fetal antigens. Failures of these ...
RIG-I, MDA5, and LGP2 comprise the RIG-I–like receptors (RLRs). RIG-I and MDA5 are essential pathogen recognition receptors sensing viral infections while LGP2 has been described as both RLR cofactor and negative regulator. After sensing and binding to ...
Patients infected with influenza are at high risk of secondary bacterial infection, which is a major proximate cause of morbidity and mortality. We have shown that in mice, prior infection with influenza results in increased inflammation and mortality ...
The transcriptome of eukaryotic cells is constantly monitored for errors to avoid the production of undesired protein variants. The evolutionarily conserved nonsense-mediated mRNA decay (NMD) pathway degrades aberrant mRNAs, but also functions in the ...
Src family kinase Lck plays critical roles during T cell development and activation, as it phosphorylates the TCR/CD3 complex to initiate TCR signaling. Lck is present either in coreceptor-bound or coreceptor-unbound (free) forms, and we here present ...

Medical Sciences

Bromine and peroxidasin (an extracellular peroxidase) are essential for generating sulfilimine cross-links between a methionine and a hydroxylysine within collagen IV, a basement membrane protein. The sulfilimine cross-links increase the structural ...
Despite broad appreciation of their clinical utility, it has been unclear how vitamin B12 and folic acid (FA) function at the molecular level to directly prevent their hallmark symptoms of deficiency like anemia or birth defects. To this point, B12 and FA ...
Combination use of BRAF V600E inhibitor dabrafenib and MEK inhibitor trametinib has become a standard treatment for human cancers harboring BRAF V600E. Its anticancer efficacies vary, however, with dramatic efficacy in some patients and drug resistance/...
In humans, a subset of placental cytotrophoblasts (CTBs) invades the uterus and its vasculature, anchoring the pregnancy and ensuring adequate blood flow to the fetus. Appropriate depth is critical. Shallow invasion increases the risk of pregnancy ...
Albuminuria is an independent risk factor for the progression to end-stage kidney failure, cardiovascular morbidity, and premature death. As such, discovering signaling pathways that modulate albuminuria is desirable. Here, we studied the transcriptomes ...
After acute kidney injury (AKI), patients either recover or alternatively develop fibrosis and chronic kidney disease. Interactions between injured epithelia, stroma, and inflammatory cells determine whether kidneys repair or undergo fibrosis, but the ...

Microbiology

The skin of humans and animals is colonized by commensal and pathogenic fungi and bacteria that share this ecological niche and have established microbial interactions. Malassezia are the most abundant fungal skin inhabitant of warm-blooded animals and ...
In eukaryotic cells, the N-terminal amino moiety of many proteins is modified by N-acetyltransferases (NATs). This protein modification can alter the folding of the target protein; can affect binding interactions of the target protein with substrates, ...
Neurotropic strains of mouse hepatitis virus (MHV), a coronavirus, cause acute and chronic demyelinating encephalomyelitis with similarities to the human disease multiple sclerosis. Here, using a lineage-tracking system, we show that some cells, primarily ...
Through a process called “bioturbation,” burrowing macrofauna have altered the seafloor habitat and modified global carbon cycling since the Cambrian. However, the impact of macrofauna on the community structure of microorganisms is poorly understood. ...
Burkholderia pseudomallei is the causative agent of melioidosis, an infectious disease in the tropics and subtropics with high morbidity and mortality. The facultative intracellular bacterium induces host cell fusion through its type VI secretion system 5 ...
The cytosolic DNA sensor cGMP-AMP synthase (cGAS) synthesizes the noncanonical cyclic dinucleotide 2′3′-cGAMP to activate the adaptor protein stimulator of IFN genes (STING), thus awakening host immunity in response to DNA pathogen infection. However, ...

Neuroscience

Axon regeneration is regulated by a neuron-intrinsic transcriptional program that is suppressed during development but that can be reactivated following peripheral nerve injury. Here we identify Prom1, which encodes the stem cell marker prominin-1, as a ...
The insular cortex (INS) is extensively connected to the central nucleus of the amygdala (CEA), and both regions send convergent projections into the caudal lateral hypothalamus (LHA) encompassing the parasubthalamic nucleus (PSTN). However, the ...
Huntington disease (HD) is caused by an expansion mutation of the N-terminal polyglutamine of huntingtin (mHTT). mHTT is ubiquitously present, but it induces noticeable damage to the brain’s striatum, thereby affecting motor, psychiatric, and cognitive ...

Pharmacology

Carbonic anhydrases (CAs; EC 4.2.1.1) are metalloenzymes present in mammals with 16 isoforms that differ in terms of catalytic activity as well as cellular and tissue distribution. CAs catalyze the conversion of CO2 to bicarbonate and protons and are ...
Food and drug products contain diverse and abundant small-molecule additives (excipients) with unclear impacts on human physiology, drug safety, and response. Here, we evaluate their potential impact on intestinal drug absorption. By screening 136 unique ...

Plant Biology

The intracellular redox state is one of the key factors regulating various physiological phenomena in the cell. Monitoring this state is therefore important for understanding physiological homeostasis in cells. Various fluorescent sensor proteins have ...
Puzzle-shaped pavement cells provide a powerful model system to investigate the cellular and subcellular processes underlying complex cell-shape determination in plants. To better understand pavement cell-shape acquisition and the role of auxin in this ...
The mechanical principles for fast snapping in the iconic Venus flytrap are not yet fully understood. In this study, we obtained time-resolved strain distributions via three-dimensional digital image correlation (DIC) for the outer and inner trap-lobe ...
In the indeterminate nodules of a model legume Medicago truncatula, ∼700 nodule-specific cysteine-rich (NCR) peptides with conserved cysteine signature are expressed. NCR peptides are highly diverse in sequence, and some of these cationic peptides exhibit ...

Psychological and Cognitive Sciences

Visual awareness is thought to result from integration of low- and high-level processing; instances of integration failure provide a crucial window into the cognitive and neural bases of awareness. We present neurophysiological evidence of complex ...
Human navigation relies on inputs to our paired eyes and ears. Although we also have two nasal passages, there has been little empirical indication that internostril differences yield directionality in human olfaction without involving the trigeminal ...

Systems Biology

The extent to which immune cell phenotypes in the peripheral blood reflect within-tumor immune activity prior to and early in cancer therapy is unclear. To address this question, we studied the population dynamics of tumor and immune cells, and immune ...

Corrections

View the cover image for PNAS Vol.117; No.27
View the cover image for PNAS Vol.117; No.27

Cover image: Pictured are embryonic dorsal root ganglion neurons from an in vitro model system for axon regeneration and degeneration. Through a murine study, Jinyoung Lee et al. identified the stem cell marker gene Prom1 as an intrinsic factor of axon regeneration. The encoded protein prominin-1, which binds cholesterol, down-regulates the expression of genes involved in cholesterol metabolism, reducing cellular cholesterol levels and enabling neuronal regrowth. The findings suggest that cholesterol metabolism is a potential therapeutic target for regenerating injured neurons. See the article by Lee et al. on pages 15955–15966. Image credit: Yongcheol Cho.

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