Table Of Contents Page, PNAS Volume 116, Number 28

PNAS July 9, 2019

This Week in PNAS

Inner Workings

Core Concepts

Retrospective

Commentaries

Perspective

Cell surface carbohydrates, termed “glycans,” are ubiquitous posttranslational effectors that can tune cancer progression. Often aberrantly displayed or found at atypical levels on cancer cells, glycans can impact essentially all progressive steps, from ...

Letters

Brief Report

Urban scaling research finds that agglomeration effects—the higher-than-expected outputs of larger cities—follow robust “superlinear” scaling relations in cross-sectional data. But the paradigm has predictive ambitions involving the dynamic scaling of ...

Physical Sciences

Applied Mathematics

Unsupervised learning makes manifest the underlying structure of data without curated training and specific problem definitions. However, the inference of relationships between data points is frustrated by the “curse of dimensionality” in high dimensions. ...
During metastasis, only a fraction of genetic diversity in a primary tumor is passed on to metastases. We calculate this fraction of transferred diversity as a function of the seeding rate between tumors. At one extreme, if a metastasis is seeded by a ...

Applied Physical Sciences

We present a mechanism for the anomalous behavior of the specific heat in low-temperature amorphous solids. The analytic solution of a mean-field model belonging to the same universality class as high-dimensional glasses, the spherical perceptron, ...
Adhesives are ubiquitous in daily life and industrial applications. They usually fall into one of two classes: strong but irreversible (e.g., superglues) or reversible/reusable but weak (e.g., pressure-sensitive adhesives and biological and biomimetic ...
The pinch-off of a bubble is an example of the formation of a singularity, exhibiting a characteristic separation of length and time scales. Because of this scale separation, one expects universal dynamics that collapse into self-similar behavior ...
Surface plasmon resonances of metallic nanostructures offer great opportunities to guide and manipulate light on the nanoscale. In the design of novel plasmonic devices, a central topic is to clarify the intricate relationship between the resonance ...
Plasmons, the collective oscillations of mobile electrons in metallic nanostructures, interact strongly with light and produce vivid colors, thus offering a new route to develop color printing technologies with improved durability and material simplicity ...
As biological signals are mainly based on ion transport, the differences in signal carriers have become a major issue for the intimate communication between electrical devices and biological areas. In this respect, an ionic device which can directly ...
Despite the enormous potential shown by recent biorefineries, the current bioeconomy still encounters multifaceted challenges. To develop a sustainable biorefinery in the future, multidisciplinary research will be essential to tackle technical ...
Mammals detect sound through mechanosensitive cells of the cochlear organ of Corti that rest on the basilar membrane (BM). Motions of the BM and organ of Corti have been studied at the cochlear base in various laboratory animals, and the assumption has ...

Astronomy

Matter evolved under the influence of gravity from minuscule density fluctuations. Nonperturbative structure formed hierarchically over all scales and developed non-Gaussian features in the Universe, known as the cosmic web. To fully understand the ...

Biophysics and Computational Biology

Walled cells of plants, fungi, and bacteria come with a large range of shapes and sizes, which are ultimately dictated by the mechanics of their cell wall. This stiff and thin polymeric layer encases the plasma membrane and protects the cells mechanically ...
The ability of animal cells to crawl, change their shape, and respond to applied force is due to their cytoskeleton: A dynamic, cross-linked network of actin protein filaments and myosin motors. How these building blocks assemble to give rise to cells’ ...
Biological organisms exhibit diverse strategies for adapting to varying environments. For example, a population of organisms may express the same phenotype in all environments (“unvarying strategy”) or follow environmental cues and express alternative ...
Despite being the subject of intense effort and scrutiny, kinases have proven to be consistently challenging targets in inhibitor drug design. A key obstacle has been promiscuity and consequent adverse effects of drugs targeting the ATP binding site. Here ...
The spatial variations of the intricate cytoarchitecture, fluid scalae, and mechano-electric transduction in the mammalian cochlea have long been postulated to provide the organ with the ability to perform a real-time, time-frequency processing of sound. ...
Ion channel proteins control ionic flux across biological membranes through conformational changes in their transmembrane pores. An exponentially increasing number of channel structures captured in different conformational states are now being determined; ...
Catalysis using iron–sulfur clusters and transition metals can be traced back to the last universal common ancestor. The damage to metalloproteins caused by reactive oxygen species (ROS) can prevent cell growth and survival when unmanaged, thus eliciting ...

Chemistry

With the rapidly growing exploration of artificial molecular machines and their applications, there is a strong demand to develop molecular machines that can have their motional states and configuration/conformation changes detectable by more sensitive ...
Low coordinated sites on catalytic surfaces often enhance reactivity, but the underlying dynamical processes are poorly understood. Using two independent approaches, we investigate the reactivity of O2 impinging onto platinum and resolve how step edges on ...
Small variations in the primary amino acid sequence of extracellular matrix proteins can have profound effects on the biomineralization of hard tissues. For example, a change in one amino acid within the amelogenin protein can lead to drastic changes in ...
Hematophagous organisms produce a suite of salivary proteins which interact with the host’s coagulation machinery to facilitate the acquisition and digestion of a bloodmeal. Many of these biomolecules inhibit the central blood-clotting serine proteinase ...
Cisplatin [cis-diamminedichloroplatinum(II) (cis-DDP)] is one of the most successful anticancer agents effective against a wide range of solid tumors. However, its use is restricted by side effects and/or by intrinsic or acquired drug resistance. Here, we ...

Earth, Atmospheric, and Planetary Sciences

The fluxes of energy, water, and carbon from terrestrial ecosystems influence the atmosphere. Land–atmosphere feedbacks can intensify extreme climate events like severe droughts and heatwaves because low soil moisture decreases both evaporation and plant ...

Environmental Sciences

As an adaptation to the daily light–dark (diel) cycle, cyanobacteria exhibit diurnal rhythms of gene expression and cell cycle. The light–dark cycle also affects the life cycle of viruses (cyanophages) that infect the unicellular picocyanobacteria ...

Sustainability Science

A changing generation mix and growing demand for carbon-free electricity will almost certainly require dramatic changes in the infrastructure and topology of the electricity system. Rather than build new lines, one way to minimize social opposition and ...

Social Sciences

Economic Sciences

Scientists and inventors increasingly work in teams, raising fundamental questions about the nature of team production and making individual assessment increasingly difficult. Here we present a method for describing individual and team citation impact ...

Psychological and Cognitive Sciences

People often coordinate for mutual gain, such as keeping to opposite sides of a stairway, dubbing an object or place with a name, or assembling en masse to protest a regime. Because successful coordination requires complementary choices, these ...
Early abstract reasoning has typically been characterized by a “relational shift,” in which children initially focus on object features but increasingly come to interpret similarity in terms of structured relations. An alternative possibility is that this ...
Interoception, or the sense of the internal state of the body, is key to the adaptive regulation of our physiological needs. Recent theories contextualize interception within a predictive coding framework, according to which the brain both estimates and ...
Making good decisions requires people to appropriately explore their available options and generalize what they have learned. While computational models can explain exploratory behavior in constrained laboratory tasks, it is unclear to what extent these ...

Social Sciences

Recent research suggests that intergenerational income mobility has remained low and stable in America, but popular discourse routinely assumes that Americans are optimistic about mobility prospects in society. Examining these 2 seemingly contradictory ...

Biological Sciences

Anthropology

The human ilium is significantly shorter and broader than those of all other primates. In addition, it exhibits an anterior inferior iliac spine (AIIS) that emerges via a secondary center of ossification, which is unique to hominids (i.e., all taxa ...

Applied Biological Sciences

Amplification of signals by the hybridization chain reaction (HCR) is a powerful approach for increasing signal strength in single-molecule fluorescence in situ hybridization, but probes tagged with an HCR initiator sequence are prone to producing false ...
Genetic engineering of the mouse genome identified many genes that are essential for embryogenesis. Remarkably, the prevalence of concomitant placental defects in embryonic lethal mutants is highly underestimated and indicates the importance of detailed ...

Biochemistry

Despite being the subject of intense effort and scrutiny, kinases have proven to be consistently challenging targets in inhibitor drug design. A key obstacle has been promiscuity and consequent adverse effects of drugs targeting the ATP binding site. Here ...
Cisplatin [cis-diamminedichloroplatinum(II) (cis-DDP)] is one of the most successful anticancer agents effective against a wide range of solid tumors. However, its use is restricted by side effects and/or by intrinsic or acquired drug resistance. Here, we ...
R-SNAREs (soluble N-ethylmaleimide–sensitive factor receptor), Q-SNAREs, and Sec1/Munc18 (SM)-family proteins are essential for membrane fusion in exocytic and endocytic trafficking. The yeast vacuolar tethering/SM complex HOPS (homotypic fusion and ...
In the disease familial amyloidosis, Finnish type (FAF), also known as AGel amyloidosis (AGel), the mechanism by which point mutations in the calcium-regulated actin-severing protein gelsolin lead to furin cleavage is not understood in the intact protein. ...
Carboxylases are biocatalysts that capture and convert carbon dioxide (CO2) under mild conditions and atmospheric concentrations at a scale of more than 400 Gt annually. However, how these enzymes bind and control the gaseous CO2 molecule during catalysis ...
Microbial conversion of aromatic compounds is an emerging and promising strategy for valorization of the plant biopolymer lignin. A critical and often rate-limiting reaction in aromatic catabolism is O-aryl-demethylation of the abundant aromatic methoxy ...

Biophysics and Computational Biology

Walled cells of plants, fungi, and bacteria come with a large range of shapes and sizes, which are ultimately dictated by the mechanics of their cell wall. This stiff and thin polymeric layer encases the plasma membrane and protects the cells mechanically ...
Mammals detect sound through mechanosensitive cells of the cochlear organ of Corti that rest on the basilar membrane (BM). Motions of the BM and organ of Corti have been studied at the cochlear base in various laboratory animals, and the assumption has ...
The spatial variations of the intricate cytoarchitecture, fluid scalae, and mechano-electric transduction in the mammalian cochlea have long been postulated to provide the organ with the ability to perform a real-time, time-frequency processing of sound. ...
Ion channel proteins control ionic flux across biological membranes through conformational changes in their transmembrane pores. An exponentially increasing number of channel structures captured in different conformational states are now being determined; ...
High-quality and high-throughput prediction of enzyme commission (EC) numbers is essential for accurate understanding of enzyme functions, which have many implications in pathologies and industrial biotechnology. Several EC number prediction tools are ...
The T cell receptor (TCR) initiates the elimination of pathogens and tumors by T cells. To avoid damage to the host, the receptor must be capable of discriminating between wild-type and mutated self and nonself peptide ligands presented by host cells. ...
Three-dimensional genome structure plays a pivotal role in gene regulation and cellular function. Single-cell analysis of genome architecture has been achieved using imaging and chromatin conformation capture methods such as Hi-C. To study variation in ...

Cell Biology

It is well recognized that metastasis can occur early in the course of lung adenocarcinoma (LAD) development, and yet the molecular mechanisms driving this capability of rapid metastasis remain incompletely understood. Here we reported that a long ...
Endoplasmic reticulum (ER) membrane junctions are formed by the dynamin-like GTPase atlastin (ATL). Deletion of ATL results in long unbranched ER tubules in cells, and mutation of human ATL1 is linked to hereditary spastic paraplegia. Here, we demonstrate ...
Most normal and tumor cells are protected from tumor necrosis factor α (TNFα)-induced apoptosis. Here, we identify the MAP3 kinase tumor progression locus-2 (TPL2) as a player contributing to the protection of a subset of tumor cell lines. The combination ...

Developmental Biology

Genomic analyses of patients with congenital heart disease (CHD) have identified significant contribution from mutations affecting cilia genes and chromatin remodeling genes; however, the mechanism(s) connecting chromatin remodeling to CHD is unknown. ...
Wnt/Wingless (Wg) signaling controls many aspects of animal development and is deregulated in different human cancers. The transcription factor dTcf/Pangolin (Pan) is the final effector of the Wg pathway in Drosophila and has a dual role in regulating the ...

Ecology

Birds inhabiting hot, arid regions are among the terrestrial organisms most vulnerable to climate change. The potential for increasingly frequent and intense heat waves to cause lethal dehydration and hyperthermia is well documented, but the consequences ...

Environmental Sciences

The fluxes of energy, water, and carbon from terrestrial ecosystems influence the atmosphere. Land–atmosphere feedbacks can intensify extreme climate events like severe droughts and heatwaves because low soil moisture decreases both evaporation and plant ...
As an adaptation to the daily light–dark (diel) cycle, cyanobacteria exhibit diurnal rhythms of gene expression and cell cycle. The light–dark cycle also affects the life cycle of viruses (cyanophages) that infect the unicellular picocyanobacteria ...

Evolution

The sunflower family, Asteraceae, comprises 10% of all flowering plant species and displays an incredible diversity of form. Asteraceae are clearly monophyletic, yet resolving phylogenetic relationships within the family has proven difficult, hindering ...
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Origin of sunflower family

Conflict between groups of individuals is a prevalent feature in human societies. A common theoretical explanation for intergroup conflict is that it provides benefits to individuals within groups in the form of reproduction-enhancing resources, such as ...
The major histocompatibility complex (MHC) is a central component of the vertebrate immune system and hence evolves in the regime of a host–pathogen evolutionary race. The MHC is associated with quantitative traits which directly affect fitness and are ...

Genetics

Preimplantation genetic testing for aneuploidy (PGT-A) with trophectoderm (TE) biopsy is widely applied in in vitro fertilization (IVF) to identify aneuploid embryos. However, potential safety concerns regarding biopsy and restrictions to only those ...

Immunology and Inflammation

We have recently defined a novel population of PD-1 (programmed cell death 1)+ TCF1 (T cell factor 1)+ virus-specific CD8 T cells that function as resource cells during chronic LCMV infection and provide the proliferative burst seen after PD-1 blockade. ...
Mosquito immunity is composed of both cellular and humoral factors that provide protection from invading pathogens. Immune cells known as hemocytes, have been intricately associated with phagocytosis and innate immune signaling. However, the lack of ...

Medical Sciences

During metastasis, only a fraction of genetic diversity in a primary tumor is passed on to metastases. We calculate this fraction of transferred diversity as a function of the seeding rate between tumors. At one extreme, if a metastasis is seeded by a ...
Loss-of-function mutations in the Wnt inhibitor secreted frizzled receptor protein 4 (SFRP4) cause Pyle’s disease (OMIM 265900), a rare skeletal disorder characterized by wide metaphyses, significant thinning of cortical bone, and fragility fractures. In ...
Epstein−Barr virus (EBV) induces histone modifications to regulate signaling pathways involved in EBV-driven tumorigenesis. To date, the regulatory mechanisms involved are poorly understood. In this study, we show that EBV infection of epithelial cells is ...
Emerging evidence has established primary nephrotic syndrome (NS), including focal segmental glomerulosclerosis (FSGS), as a primary podocytopathy. Despite the underlying importance of podocyte endoplasmic reticulum (ER) stress in the pathogenesis of NS, ...
The cyclic guanosine-3′,5′-monophosphate (cGMP)-dependent protein kinase (PKG) was identified >25 y ago; however, efforts to obtain a structure of the entire PKG enzyme or catalytic domain from any species have failed. In malaria parasites, cooperative ...
Vascular endothelial growth factor (VEGF) signaling in tumor cells mediated by neuropilins (NRPs) contributes to the aggressive nature of several cancers, including triple-negative breast cancer (TNBC), independently of its role in angiogenesis. ...
We previously reported that the nonsteroidal compound CpdX, which was initially characterized 20 y ago as a possible gestagen and, shortly afterward, as a possible drug for treatments of inflammatory diseases, selectively triggers the NFκB/AP1-mediated ...
Seventy years after the discovery of their anti-inflammatory properties, glucocorticoids (GCs) remain the mainstay treatment for major allergic and inflammatory disorders, such as atopic dermatitis, asthma, rheumatoid arthritis, colitis, and ...

Microbiology

To establish infection, enteric pathogens integrate environmental cues to navigate the gastrointestinal tract (GIT) and precisely control expression of virulence determinants. During passage through the GIT, pathogens encounter relatively high levels of ...
Collective behavior in spatially structured groups, or biofilms, is the norm among microbes in their natural environments. Though biofilm formation has been studied for decades, tracing the mechanistic and ecological links between individual cell ...
Bacterial conjugation systems are members of the large type IV secretion system (T4SS) superfamily. Conjugative transfer of F plasmids residing in the Enterobacteriaceae was first reported in the 1940s, yet the architecture of F plasmid-encoded transfer ...
Bacterial spores can remain dormant for years but possess the remarkable ability to germinate, within minutes, once nutrients become available. However, it still remains elusive how such instant awakening of cellular machineries is achieved. Utilizing ...
Vibrio species cause infectious diseases in humans and animals, but they can also live as commensals within their host tissues. How Vibrio subverts the host defenses to mount a successful infection remains poorly understood, and this knowledge is critical ...

Neuroscience

South African ball-rolling dung beetles exhibit a unique orientation behavior to avoid competition for food: after forming a piece of dung into a ball, they efficiently escape with it from the dung pile along a straight-line path. To keep track of their ...
Characterized by a dismal survival rate and limited response to therapy, glioblastoma (GBM) remains one of the most aggressive human malignancies. Recent studies of the role of tumor-associated macrophages (TAMs) in the progression of GBMs have ...
Piezo channels are mechanically activated ion channels that confer mechanosensitivity to a variety of different cell types. Piezos oligomerize as propeller-shaped homotrimers that are thought to locally curve the membrane into spherical domes that project ...
Stroke is a major cause of serious disability due to the brain’s limited capacity to regenerate damaged tissue and neuronal circuits. After ischemic injury, a multiphasic degenerative and inflammatory response is coupled with severely restricted vascular ...
While mutations in the SNCA gene (α-synuclein [α-syn]) are causal in rare familial forms of Parkinson’s disease (PD), the prevalence of α-syn aggregates in the cortices of sporadic disease cases emphasizes the need to understand the link between α-syn ...
Animal models of central nervous system (CNS) demyelination, including toxin-induced focal demyelination and immune-mediated demyelination through experimental autoimmune encephalomyelitis (EAE), have provided valuable insights into the mechanisms of ...
Tsetse flies transmit trypanosomiasis to humans and livestock across much of sub-Saharan Africa. Tsetse are attracted by olfactory cues emanating from their hosts. However, remarkably little is known about the cellular basis of olfaction in tsetse. We ...

Plant Biology

Strigolactones (SLs), a group of terpenoid lactones derived from carotenoids, are plant hormones that control numerous aspects of plant development. Although the framework of SL signaling that the repressor DWARF 53 (D53) could be SL-dependently degraded ...
Lateral root organogenesis plays an essential role in elaborating plant root system architecture. In Arabidopsis, the AP2 family transcription factor PUCHI controls cell proliferation in lateral root primordia. To identify potential targets of PUCHI, we ...
Insects have evolved effectors to conquer plant defense. Most known insect effectors are isolated from sucking insects, and examples from chewing insects are limited. Moreover, the targets of insect effectors in host plants remain unknown. Here, we ...
Endocytosis is essential to all eukaryotes, but how cargoes are selected for internalization remains poorly characterized. Extracellular cargoes are thought to be selected by transmembrane receptors that bind intracellular adaptors proteins to initiate ...

Psychological and Cognitive Sciences

Two types of working memory (WM) have recently been proposed: (i) active WM, relying on sustained neural firing, and (ii) activity-silent WM, for which firing returns to baseline, yet memories may be retained by short-term synaptic changes. Activity-...

Systems Biology

Catalysis using iron–sulfur clusters and transition metals can be traced back to the last universal common ancestor. The damage to metalloproteins caused by reactive oxygen species (ROS) can prevent cell growth and survival when unmanaged, thus eliciting ...
Transplanted stromal cells have demonstrated considerable promise as therapeutic agents in diverse disease settings. Paracrine signaling can be an important mediator of these therapeutic effects at the sites of acute or persistent injury and inflammation. ...

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