Table Of Contents Page, PNAS Volume 121, Number 22

PNAS May 28, 2024

This Week in PNAS

Editorial

Opinion

Retrospective

Commentaries

Perspective

The Amazon River Basin’s extraordinary social–ecological system is sustained by various water phases, fluxes, and stores that are interconnected across the tropical Andes mountains, Amazon lowlands, and Atlantic Ocean. This “Andes–Amazon–Atlantic” (AAA) ...

Letters

Brief Reports

The origin of the German cockroach, Blattella germanica, is enigmatic, in part because it is ubiquitous worldwide in human-built structures but absent from any natural habitats. The first historical records of this species are from ca. 250 years ago (ya) ...
The significance of biochemical cues in the tumor immune microenvironment in affecting cancer metastasis is well established, but the role of physical factors in the microenvironment remains largely unexplored. In this article, we investigated how the ...
Optimal decision-making balances exploration for new information against exploitation of known rewards, a process mediated by the locus coeruleus and its norepinephrine projections. We predicted that an exploitation-bias that emerges in older adulthood ...

Physical Sciences

Applied Physical Sciences

The complex sequential response of frustrated materials results from the interactions between material bits called hysterons. Hence, a central challenge is to understand and control these interactions, so that materials with targeted pathways and ...
The biophysical properties of lipid vesicles are important for their stability and integrity, key parameters that control the performance when these vesicles are used for drug delivery. The vesicle properties are determined by the composition of lipids ...
Understanding the dynamics of electric-double-layer (EDL) charging in porous media is essential for advancements in next-generation energy storage devices. Due to the high computational demands of direct numerical simulations and a lack of interfacial ...
The fangs, jaws, and mandibles of marine invertebrates such as Chiton and Glycera show excellent mechanical properties, which are mostly contributed to the interactions between metal (Fe, Cu, Zn, etc.) and oxygen-containing functional groups in proteins. ...

Biophysics and Computational Biology

The consistency of energy landscape theory predictions with available experimental data, as well as direct evidence from molecular simulations, have shown that protein folding mechanisms are largely determined by the contacts present in the native ...
For eukaryotic cells to heal wounds, respond to immune signals, or metastasize, they must migrate, often by adhering to extracellular matrix (ECM). Cells may also deposit ECM components, leaving behind a footprint that influences their crawling. Recent ...
Protein–protein and protein–water hydrogen bonding interactions play essential roles in the way a protein passes through the transition state during folding or unfolding, but the large number of these interactions in molecular dynamics (MD) simulations ...
Seasonal and pandemic-associated influenza strains cause highly contagious viral respiratory infections that can lead to severe illness and excess mortality. Here, we report on the optimization of our small-molecule inhibitor F0045(S) targeting the ...
The sodium (Na+) leak channel (NALCN) is a member of the four-domain voltage-gated cation channel family that includes the prototypical voltage-gated sodium and calcium channels (NaVs and CaVs, respectively). Unlike NaVs and CaVs, which have four lateral ...
The Hill functions, H h ( x ) = x h / ( 1 + x h ) , have been widely used in biology for over a century but, with the exception of H 1 , they have had no justification other than as a convenient fit to empirical data. Here, we show that they are the universal limit for the sharpness of ...

Chemistry

Current treatment options for diabetic wounds face challenges due to low efficacy, as well as potential side effects and the necessity for repetitive treatments. To address these issues, we report a formulation utilizing trisulfide-derived lipid ...
Elevated interstitial fluid pressure (IFP) within pathological tissues (e.g., tumors, obstructed kidneys, and cirrhotic livers) creates a significant hindrance to the transport of nanomedicine, ultimately impairing the therapeutic efficiency. Among these ...
Understanding the operando defect–tuning performance of catalysts is critical to establish an accurate structure–activity relationship of a catalyst. Here, with the tool of single-molecule super-resolution fluorescence microscopy, by imaging intermediate ...

Earth, Atmospheric, and Planetary Sciences

Warm water from the Southern Ocean has a dominant impact on the evolution of Antarctic glaciers and in turn on their contribution to sea level rise. Using a continuous time series of daily-repeat satellite synthetic-aperture radar interferometry data from ...

Engineering

Nanoparticles tethered with vasculature-binding epitopes have been used to deliver the drug into injured or diseased tissues via the bloodstream. However, the extent that blood flow dynamics affects nanoparticle retention at the target site after adhesion ...
Seamless integration of microstructures and circuits on three-dimensional (3D) complex surfaces is of significance and is catalyzing the emergence of many innovative 3D curvy electronic devices. However, patterning fine features on arbitrary 3D targets ...
Many soft materials yield under mechanical loading, but how this transition from solid-like behavior to liquid-like behavior occurs can vary significantly. Understanding the physics of yielding is of great interest for the behavior of biological, ...

Physics

Which phenomenon slows down the dynamics in supercooled liquids and turns them into glasses is a long-standing question of condensed matter. Most popular theories posit that as the temperature decreases, many events must occur in a coordinated fashion on ...

Social Sciences

Political Sciences

Private donors contributed more than $350 million to local election officials to support the administration of the 2020 election. Supporters argue these grants were neutral and necessary to maintain normal election operations during the pandemic, while ...

Psychological and Cognitive Sciences

Humans have the highly adaptive ability to learn from others’ memories. However, because memories are prone to errors, in order for others’ memories to be a valuable source of information, we need to assess their veracity. Previous studies have shown that ...
A representative democracy requires citizens to be politically engaged; however, a substantial portion of eligible United States voters do not vote. While structural (e.g., ease or difficulty of voting) and individual (e.g., political efficacy, civic ...
The transition to remote learning in the context of COVID-19 led to dramatic setbacks in education. Is the return to in-person classes sufficient to eliminate these losses eventually? We study this question using data from the universe of secondary ...

Social Sciences

Closing the achievement gap for minority students in higher education requires addressing the lack of belonging these students experience. This paper introduces a psychological intervention that strategically targets key elements within the learning ...

Sustainability Science

Electric school buses have been proposed as an alternative to reduce the health and climate impacts of the current U.S. school bus fleet, of which a substantial share are highly polluting old diesel vehicles. However, the climate and health benefits of ...

Biological Sciences

Anthropology

The aryl hydrocarbon receptor (AHR) is a transcription factor that has many functions in mammals. Its best known function is that it binds aromatic hydrocarbons and induces the expression of cytochrome P450 genes, which encode enzymes that metabolize ...

Applied Biological Sciences

Current treatment options for diabetic wounds face challenges due to low efficacy, as well as potential side effects and the necessity for repetitive treatments. To address these issues, we report a formulation utilizing trisulfide-derived lipid ...
NRF2 (nuclear factor erythroid-2-related factor 2) is a key regulator of genes involved in the cell’s protective response to oxidative stress. Upon activation by disturbed redox homeostasis, NRF2 promotes the expression of metabolic enzymes to eliminate ...

Biochemistry

Seasonal and pandemic-associated influenza strains cause highly contagious viral respiratory infections that can lead to severe illness and excess mortality. Here, we report on the optimization of our small-molecule inhibitor F0045(S) targeting the ...
Efforts to develop an HIV-1 vaccine include those focusing on conserved structural elements as the target of broadly neutralizing monoclonal antibodies. MAb D5 binds to a highly conserved hydrophobic pocket on the gp41 N-heptad repeat (NHR) coiled coil ...
C-terminal Domain Nuclear Envelope Phosphatase 1 (CTDNEP1) is a noncanonical protein serine/threonine phosphatase that has a conserved role in regulating ER membrane biogenesis. Inactivating mutations in CTDNEP1 correlate with the development of ...
The HapImmuneTM platform exploits covalent inhibitors as haptens for creating major histocompatibility complex (MHC)-presented tumor-specific neoantigens by design, combining targeted therapies with immunotherapy for the treatment of drug-resistant ...
Biomolecular condensates are cellular compartments that concentrate biomolecules without an encapsulating membrane. In recent years, significant advances have been made in the understanding of condensates through biochemical reconstitution and microscopic ...

Biophysics and Computational Biology

The consistency of energy landscape theory predictions with available experimental data, as well as direct evidence from molecular simulations, have shown that protein folding mechanisms are largely determined by the contacts present in the native ...
Elevated interstitial fluid pressure (IFP) within pathological tissues (e.g., tumors, obstructed kidneys, and cirrhotic livers) creates a significant hindrance to the transport of nanomedicine, ultimately impairing the therapeutic efficiency. Among these ...
Mitochondria play a central role in muscle metabolism and function. A unique family of iron–sulfur proteins, termed CDGSH Iron Sulfur Domain-containing (CISD/NEET) proteins, support mitochondrial function in skeletal muscles. The abundance of these ...

Cell Biology

For eukaryotic cells to heal wounds, respond to immune signals, or metastasize, they must migrate, often by adhering to extracellular matrix (ECM). Cells may also deposit ECM components, leaving behind a footprint that influences their crawling. Recent ...
The nonstructural protein 1 (Nsp1) of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) is a virulence factor that targets multiple cellular pathways to inhibit host gene expression and antiviral response. However, the underlying mechanisms of ...
Lysosomes are central players in cellular catabolism, signaling, and metabolic regulation. Cellular and environmental stresses that damage lysosomal membranes can compromise their function and release toxic content into the cytoplasm. Here, we examine how ...
The prion-like spread of protein aggregates is a leading hypothesis for the propagation of neurofibrillary lesions in the brain, including the spread of tau inclusions associated with Alzheimer’s disease. The mechanisms of cellular uptake of tau seeds and ...
O-GlcNAc transferase (OGT) is an essential mammalian enzyme that glycosylates myriad intracellular proteins and cleaves the transcriptional coregulator Host Cell Factor 1 to regulate cell cycle processes. Via these catalytic activities as well as ...

Ecology

The phagotrophic flagellates described as “typical excavates” have been hypothesized to be morphologically similar to the Last Eukaryotic Common Ancestor and understanding the functional ecology of excavates may therefore help shed light on the ecology of ...

Environmental Sciences

Dynamic ecosystems, such as the Amazon forest, are expected to show critical slowing down behavior, or slower recovery from recurrent small perturbations, as they approach an ecological threshold to a different ecosystem state. Drought occurrences are ...

Evolution

Speciation is often driven by selective processes like those associated with viability, mate choice, or local adaptation, and “speciation genes” have been identified in many eukaryotic lineages. In contrast, neutral processes are rarely considered as the ...
Males and females often have different roles in reproduction, although the origin of these differences has remained controversial. Explaining the enigmatic reversed sex roles where males sacrifice their mating potential and provide full parental care is a ...
Over the course of multiple divisions, cells accumulate diverse nongenetic, somatic damage including misfolded and aggregated proteins and cell wall defects. If the rate of damage accumulation exceeds the rate of dilution through cell growth, a dedicated ...

Immunology and Inflammation

Long noncoding RNAs (lncRNAs) account for the largest portion of RNA from the transcriptome, yet most of their functions remain unknown. Here, we performed two independent high-throughput CRISPRi screens to understand the role of lncRNAs in monocyte ...
Staphylococcus aureus (S. aureus) can evade antibiotics and host immune defenses by persisting within infected cells. Here, we demonstrate that in infected host cells, S. aureus type VII secretion system (T7SS) extracellular protein B (EsxB) interacts ...
Antigen presentation via major histocompatibility complex class I (MHC-I) molecules is essential for surveillance by the adaptive immune system. Central to this process is the peptide-loading complex (PLC), which translocates peptides from the cytosol to ...
Humoral immunity depends on the germinal center (GC) reaction where B cells are tightly controlled for class-switch recombination and somatic hypermutation and finally generated into plasma and memory B cells. However, how protein SUMOylation regulates ...

Medical Sciences

Megalin (low-density lipoprotein receptor-related protein 2) is a giant glycoprotein of about 600 kDa, mediating the endocytosis of more than 60 ligands, including those of proteins, peptides, and drug compounds [S. Goto, M. Hosojima, H. Kabasawa, A. ...

Microbiology

Leaf yellowing is a well-known phenotype that attracts phloem-feeding insects. However, it remains unclear how insect-vectored plant pathogens induce host leaf yellowing to facilitate their own transmission by insect vectors. Here, we report that an ...

Neuroscience

Speech impediments are a prominent yet understudied symptom of Parkinson’s disease (PD). While the subthalamic nucleus (STN) is an established clinical target for treating motor symptoms, these interventions can lead to further worsening of speech. The ...
The striato-nigral (Str-SN) circuit is composed of medium spiny neuronal projections that are mainly sent from the striatum to the midbrain substantial nigra (SN), which is essential for regulating motor behaviors. Dysfunction of the Str-SN circuitry may ...
We report the reliable detection of reproducible patterns of blood-oxygenation-level-dependent (BOLD) MRI signals within the white matter (WM) of the spinal cord during a task and in a resting state. Previous functional MRI studies have shown that BOLD ...
After central nervous system injury, a rapid cellular and molecular response is induced. This response can be both beneficial and detrimental to neuronal survival in the first few days and increases the risk for neurodegeneration if persistent. ...
Ketamine is an N-methyl-D-aspartate (NMDA)-receptor antagonist that produces sedation, analgesia, and dissociation at low doses and profound unconsciousness with antinociception at high doses. At high and low doses, ketamine can generate gamma ...

Pharmacology

The sodium (Na+) leak channel (NALCN) is a member of the four-domain voltage-gated cation channel family that includes the prototypical voltage-gated sodium and calcium channels (NaVs and CaVs, respectively). Unlike NaVs and CaVs, which have four lateral ...

Physiology

Adult male animals typically court and attempt to mate with females, while attacking other males. Emerging evidence from mice indicates that neurons expressing the estrogen receptor ESR1 in behaviorally relevant brain regions play a central role in ...
Maintaining the structure of cardiac membranes and membrane organelles is essential for heart function. A critical cardiac membrane organelle is the transverse tubule system (called the t-tubule system) which is an invagination of the surface membrane. A ...

Plant Biology

Plant root systems play a pivotal role in plant physiology and exhibit diverse phenotypic traits. Understanding the genetic mechanisms governing root growth and development in model plants like maize is crucial for enhancing crop resilience to drought and ...
Spontaneous gain or loss of DNA methylation occurs in plant and animal genomes, and DNA methylation changes can lead to meiotically stable epialleles that generate heritable phenotypic diversity. However, it is unclear whether transgenerational epigenetic ...

Psychological and Cognitive Sciences

Humans have the highly adaptive ability to learn from others’ memories. However, because memories are prone to errors, in order for others’ memories to be a valuable source of information, we need to assess their veracity. Previous studies have shown that ...
In mammals, offspring vocalizations typically encode information about identity and body condition, allowing parents to limit alloparenting and adjust care. But how do these vocalizations mediate parental behavior in species faced with the problem of ...

Systems Biology

The Hill functions, H h ( x ) = x h / ( 1 + x h ) , have been widely used in biology for over a century but, with the exception of H 1 , they have had no justification other than as a convenient fit to empirical data. Here, we show that they are the universal limit for the sharpness of ...

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