Table Of Contents Page, PNAS Volume 121, Number 49
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Perspective
Why microbes harm their hosts is a fundamental question in evolutionary biology with
broad relevance to our understanding of infectious diseases. Several hypotheses have
been proposed to explain this "evolution of virulence." In this perspective, we ...
Letters
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Brief Reports
The attempted assassination of Donald Trump led to widespread concern that the event
would escalate political violence between U.S. partisans. While some politicians pleaded
for Americans to unite against political violence and “turn down the temperature”
...
Cyanobacteria are highly abundant in the marine photic zone and primary drivers of
the conversion of inorganic carbon into biomass. To date, all studied cyanobacterial
lineages encode carbon fixation machinery relying upon form I Rubiscos within a CO2-...
Physical Sciences
Applied Mathematics
Stylized experiments, the public goods game and its variants thereof, have taught
us the peculiar reproducible fact that humans tend to cooperate (or contribute to
shared resources) more than expected from economically rational assumptions. There
have ...
Applied Physical Sciences
The physics of membranes, a classic subject, acquires new momentum from two-dimensional
(2D) materials multilayers. This work reports the surprising results emerged during
a theoretical study of equilibrium geometry of bilayers as freestanding membranes.
...
Biophysics and Computational Biology
Dynamin 1 (Dyn1) GTPase, a principal driver of membrane fission during synaptic endocytosis,
self-assembles into short mechanoactive helices cleaving the necks of endocytic vesicles.
While structural information about Dyn1 helix is abundant, little is ...
Machine learning (ML) is transforming the investigation of complex biological processes.
In enzymatic catalysis, one significant challenge is identifying the reactive conformations
(RC) of the enzyme:substrate complex where the substrate assumes a precise ...
Type II topoisomerase DNA gyrase transduces the energy of ATP hydrolysis into the
negative supercoiling of DNA. The postulated catalytic mechanism involves stabilization
of a chiral DNA loop followed by the passage of the T-segment through the temporarily
...
The internal organization of cells is largely determined by the architecture and orientation
of the microtubule network. Microtubules serve as polar tracks for the selective transport
of specific molecular motors toward either their plus or minus ends. ...
Chemistry
While hydroxyl radical is commonly named as the Fenton product responsible for DNA
and RNA damage in cells, here we demonstrate that the cellular reaction generates
carbonate radical anion due to physiological bicarbonate levels. In human and Escherichia ...
The key first step in the oligomerization of monomers is to find an initiator, which
is usually done by thermolysis or photolysis. We present a markedly different approach
that initiates acid-catalyzed polymerization at the surface of water films or water
...
Computer Sciences
AI assistants, such as ChatGPT, are being increasingly used by students in higher
education institutions. While these tools provide opportunities for improved teaching
and education, they also pose significant challenges for assessment and learning ...
Earth, Atmospheric, and Planetary Sciences
The Voyager spacecraft discovered that the ice giants Uranus and Neptune have nondipolar
magnetic fields, defying expectations that a thick interior layer of planetary ices
would generate strong dipolar fields. Stanley and Bloxham showed that nondipolar ...
In the late spring to summer season of 2023, Canada witnessed unprecedented wildfires,
with an extensive burning area and smoke spreading as far as the East Coast of the
United States and Europe. Here, using multisource data analysis and climate model
...
Multiple recent record-shattering weather events raise questions about the adequacy
of climate models to effectively predict and prepare for unprecedented climate impacts
on human life, infrastructure, and ecosystems. Here, we show that extreme heat in
...
Engineering
Gustation is one of the five innate sensations for humans, distinguishing from vision,
auditory, tactile, and olfaction, as which is a close and chemically induced sense.
Despite the fact that a handful of gustation display technologies have been ...
Continuous monitoring and closed-loop therapy of soft wound tissues is of particular
interest in biomedical research and clinical practices. An important focus is on the
development of implantable bioelectronics that can measure time-dependent temperature
...
Ordered polar structures in oxide nanofilms play a pivotal role in the development
of nanoelectronic applications. Hitherto, ordered polar structures have been restricted
to a limited number of ferroelectric materials, and there is no effective scheme to
...
Erectile dysfunction (ED) is a major threat to male fertility and quality of life,
and mesenchymal stromal cells (MSCs) are a promising therapeutic option. However,
therapeutic outcomes are compromised by low MSC retention and survival rates in corpus
...
Environmental Sciences
Continental freshwater discharge influences sea surface salinity variability near world’s megadeltas
Sea surface salinity () is a key parameter in the thermohaline circulation of global oceans. Near the megadeltas,
inland streamflow through large catchments plays a crucial role in mediating salinity.
While some regional studies have investigated how is ...
Physics
A wide range of disordered materials, from biological to geological assemblies, feature
discrete elements undergoing large shape changes. How significant geometrical variations
at the microscopic scale affect the response of the assembly, in particular ...
Social Sciences
Anthropology
Since their domestication, horses have accompanied mankind, and humans have constantly
shaped horses according to their needs through stallion-centered breeding. Consequently,
the male-specific portion of the Y chromosome (MSY) is extremely uniform in ...
Demography
The identification of causal relationships between specific genes and social, behavioral,
and health outcomes is challenging due to environmental confounding from population
stratification and dynastic genetic effects. Existing methods to eliminate ...
Economic Sciences
Land use change is crucial to addressing the existential threats of climate change
and biodiversity loss while enhancing food security [M. Zurek et al., Science 376, 1416–1421 (2022)]. The interconnected and spatially varying nature of the impacts
of land ...
Stylized experiments, the public goods game and its variants thereof, have taught
us the peculiar reproducible fact that humans tend to cooperate (or contribute to
shared resources) more than expected from economically rational assumptions. There
have ...
Political Sciences
In Europe, the tendency among immigrants and descendants to seek out and interact
with other coethnics has raised concern for their integration as it can reduce contact
with the ethnic majority. Though policymakers implement large-scale integration ...
Psychological and Cognitive Sciences
Visual working memory (VWM) retains representations of past visual information for
future action. Yet to date, most studies have approached VWM as just serving perception
beyond the immediate. Whether and how prospective actions shape information in VWM
...
We report the findings of an adversarial collaboration examining whether the cognitive
reflection test (CRT) measures anything beyond mathematical aptitude and, if so, whether
its incremental predictive validity can be attributed to reflection, per se. We ...
With climate change intensifying, building resilience against climate-related shocks
is now a global imperative. Historically, many societies have faced natural hazards,
with some adapting through specific social and cultural practices. Understanding ...
Social rejection hurts, but it can also be informative: Through experiences of acceptance
and rejection, people identify partners interested in connecting with them and choose
which ties to cement or to sever. What is it that people actually learn from ...
Social Sciences
Traditional models of social learning by imitation are based on simple contagion—where
an individual may imitate a more successful neighbor following a single interaction.
But real-world contagion processes are often complex, meaning that multiple ...
Sustainability Science
Land use change is crucial to addressing the existential threats of climate change
and biodiversity loss while enhancing food security [M. Zurek et al., Science 376, 1416–1421 (2022)]. The interconnected and spatially varying nature of the impacts
of land ...
Biological Sciences
Agricultural Sciences
Broad complex (Br-C) and eip93F (E93) transcription factors promote insect metamorphosis
from larva to pupa and from pupa to adult, respectively. Recently, chronologically
inappropriate morphogenesis (Chinmo) has been proposed as a larval specifier in ...
Applied Biological Sciences
Erectile dysfunction (ED) is a major threat to male fertility and quality of life,
and mesenchymal stromal cells (MSCs) are a promising therapeutic option. However,
therapeutic outcomes are compromised by low MSC retention and survival rates in corpus
...
Clinical trials in cancer are ideally built on a foundation of sound mechanistic rationale
and well-validated drug activity in relevant disease models. The screening of approved
and investigational drugs in cell-based phenotypic assays can provide ...
Biochemistry
While hydroxyl radical is commonly named as the Fenton product responsible for DNA
and RNA damage in cells, here we demonstrate that the cellular reaction generates
carbonate radical anion due to physiological bicarbonate levels. In human and Escherichia ...
Type II topoisomerase DNA gyrase transduces the energy of ATP hydrolysis into the
negative supercoiling of DNA. The postulated catalytic mechanism involves stabilization
of a chiral DNA loop followed by the passage of the T-segment through the temporarily
...
Ribosomally synthesized and posttranslationally modified peptides (RiPPs) are a structurally
diverse group of natural products that bacteria employ in their survival strategies.
Herein, we characterized the structure, the biosynthetic pathway, and the ...
Phosphoglycosyl transferases (PGTs) are membrane proteins that initiate glycoconjugate
biosynthesis by transferring a phospho-sugar moiety from a soluble nucleoside diphosphate
sugar to a membrane-embedded polyprenol phosphate acceptor. The centrality of ...
Biophysics and Computational Biology
Dynamin 1 (Dyn1) GTPase, a principal driver of membrane fission during synaptic endocytosis,
self-assembles into short mechanoactive helices cleaving the necks of endocytic vesicles.
While structural information about Dyn1 helix is abundant, little is ...
The internal organization of cells is largely determined by the architecture and orientation
of the microtubule network. Microtubules serve as polar tracks for the selective transport
of specific molecular motors toward either their plus or minus ends. ...
Intrinsically disordered protein regions (IDRs) are well established as contributors
to intermolecular interactions and the formation of biomolecular condensates. In particular,
RNA-binding proteins (RBPs) often harbor IDRs in addition to folded RNA-...
Pathogenic variants in KCNQ2 encoding Kv7.2 voltage-gated potassium channel subunits cause developmental encephalopathies
(KCNQ2-encephalopathies), both with and without epilepsy. We herein describe the clinical,
in vitro, and in silico features of two ...
Neurofilaments (NFs) are multisubunit, bottlebrush-shaped intermediate filaments abundant
in the axonal cytoskeleton. Each NF subunit contains a long intrinsically disordered
tail domain, which protrudes from the NF core to form a “brush” surrounding each ...
Synaptic vesicles (SVs) store and transport neurotransmitters to the presynaptic active
zone for release by exocytosis. After release, SV proteins and excess membrane are
recycled via endocytosis, and new SVs can be formed in a clathrin-dependent manner.
...
Hinge sites of proteins play a key role in mediating conformational mechanics. Among
them, those involved in the most collective modes of motion, also called global hinges,
are of particular interest, as they support cooperative rearrangements that are ...
Cell Biology
The Mitochondrial Unfolded Protein Response (UPRmt), a mitochondria-originated stress response to altered mitochondrial proteostasis,
plays important roles in various pathophysiological processes. In this study, we revealed
that the endoplasmic reticulum (...
Telomeric DNA sequences are difficult to replicate. Replication forks frequently pause
or stall at telomeres, which can lead to telomere truncation and dysfunction. In addition
to being at chromosome ends, telomere repeats are also present at internal ...
Using genetically engineered mice and cell lines derived from genetically engineered
mice we show that depletion of ER delimited Ca2+ stores activates heteromeric Ca2+ entry (SOCE) channels formed obligatorily, but not exclusively by Orai1 molecules.
...
Adenocarcinomas from multiple tissues can converge to treatment-resistant small cell
neuroendocrine (SCN) cancers composed of ASCL1, POU2F3, NEUROD1, and YAP1 subtypes.
We investigated how mitochondrial metabolism influences SCN cancer (SCNC) progression.
...
Ecology
The temporal stability of forest productivity is a key ecosystem function and an essential
service to humanity. Plot-scale tree diversity experiments with observations over
10 to 11 y indicate that tree diversity increases stability under various ...
Habitats with intermittent flooding, such as paddy soils, are crucial reservoirs in
the global carbon pool; however, the effect of phage–host interactions on the biogeochemical
cycling of carbon in paddy soils remains unclear. Hence, this study applied ...
Environmental Sciences
Antibiotic resistance is a global public health threat. Many factors contribute to
this issue, with human antibiotic consumption being significant among them. Analyzing
trends and patterns in consumption can aid in developing policies to mitigate the
...
Evolution
The key first step in the oligomerization of monomers is to find an initiator, which
is usually done by thermolysis or photolysis. We present a markedly different approach
that initiates acid-catalyzed polymerization at the surface of water films or water
...
Traditional models of social learning by imitation are based on simple contagion—where
an individual may imitate a more successful neighbor following a single interaction.
But real-world contagion processes are often complex, meaning that multiple ...
The fact that rapid brain size increase was clearly a key aspect of human evolution
has prompted many studies focusing on this phenomenon, and many suggestions as to
the underlying evolutionary patterns and processes. No study to date has however ...
Genetics
The identification of causal relationships between specific genes and social, behavioral,
and health outcomes is challenging due to environmental confounding from population
stratification and dynastic genetic effects. Existing methods to eliminate ...
Mesoamerican nephropathy (MeN) is a progressive kidney disease found on the Pacific
coast of Central America primarily in young male agricultural workers without typical
kidney disease risk factors. While it is generally accepted that environmental ...
Variants in the gene NDP cause Norrie disease, a severe dual-sensory disorder characterized by congenital
blindness due to disrupted retinal vascular development and progressive hearing loss
accompanied by sensory hair cell death. NDP encodes the secreted ...
Over 50 hereditary degenerative disorders are caused by expansions of short tandem
DNA repeats (STRs). (GAA)n repeat expansions are responsible for Friedreich’s ataxia as well as late-onset cerebellar
ataxias (LOCAs). Thus, the mechanisms of (GAA)n repeat ...
The fork protection complex (FPC), composed of Mrc1, Tof1, and Csm3, supports rapid
and stable DNA replication. Here, we show that FPC activity also introduces DNA damage
by increasing DNA topological stress during replication. Mrc1 action increases DNA
...
RNA interference (RNAi) is an evolutionarily conserved pathway that defends against
viral infections in diverse organisms. Caenorhabditis elegans mutations that enhance RNAi have revealed pathways that may regulate antiviral defense.
A genetic screen for ...
Immunology and Inflammation
The major histocompatibility complex class I related protein (MR1) presents microbially
derived vitamin B2 precursors to mucosal-associated invariant T (MAIT) cells. MR1
can also present other metabolites to activate MR1-restricted T cells expressing more
...
Phenazine biosynthesis-like domain-containing protein (PBLD) has been reported to
be involved in the development of many cancers. However, whether PBLD regulates innate
immune responses and viral replication is unclear. In this study, although it was
...
Lethal COVID-19 outcomes are attributed to classic cytokine storm. We revisit this
using RNA sequencing of nasopharyngeal and 40 autopsy samples from patients dying
of SARS-CoV-2. Subsets of the 100 top-upregulated genes in nasal swabs are upregulated
in ...
Combining a T cell-targeting mRNA vaccine encoding the conserved SARS-CoV-2 RNA-dependent
RNA polymerase, RdRp, with a Spike-encoding mRNA vaccine may offer an additional pathway
toward COVID-19 protection. Here, we show that a nucleoside-modified RdRp ...
Autophagy is a key innate immune defense mechanism in intestinal epithelial cells.
Bacterial invasion of epithelial cells activates antibacterial autophagy through a
process that requires the innate immune adaptor protein MYD88, yet how MYD88 signaling
...
Medical Sciences
Gustation is one of the five innate sensations for humans, distinguishing from vision,
auditory, tactile, and olfaction, as which is a close and chemically induced sense.
Despite the fact that a handful of gustation display technologies have been ...
Estrogen deficiency, which is linked to various pathological conditions such as primary
ovarian insufficiency and postmenopausal osteoporosis, disrupts the delicate balance
between bone formation and resorption. This imbalance leads to bone loss and an ...
Microbiology
Neutralizing antibodies (nAbs) play a crucial role in virology, antibody drug development,
and vaccine research. In this study, we investigated the synergistic effect of two
hepatitis E virus (HEV) nAbs, 8H3, and 8C11, which have exhibited enhanced ...
In Mycobacterium tuberculosis (Mtb), proteins that are posttranslationally modified with a prokaryotic ubiquitin-like
protein (Pup) can be degraded by bacterial proteasomes. A single Pup-ligase and depupylase
shape the pupylome, but the mechanisms ...
In contrast to the large body of work on bioactive natural products from individually
cultivated bacteria, the chemistry of environmental microbial communities remains
largely elusive. Here, we present a comprehensive bioinformatic and functional study
on ...
Bacterial microcompartments (BMCs) are prokaryotic organelles that consist of a protein
shell which sequesters metabolic reactions in its interior. While most of the substrates
and products are relatively small and can permeate the shell, many of the ...
Herpes simplex virus 1 (HSV-1) latently infected neurons display diverse patterns
in the distribution of the viral genomes within the nucleus. A key pattern involves
quiescent HSV-1 genomes sequestered in promyelocytic leukemia nuclear bodies (PML
NBs) ...
Neuroscience
Social rejection hurts, but it can also be informative: Through experiences of acceptance
and rejection, people identify partners interested in connecting with them and choose
which ties to cement or to sever. What is it that people actually learn from ...
The brain is thought to execute cognitive control by actively maintaining and flexibly
updating patterns of neural activity that represent goals and rules. However, while
actively maintaining patterns of activity requires robustness against noise and ...
The ability to follow the evolutionary trajectories of specific neuronal cell types
has led to major insights into the evolution of the vertebrate brain. Here, we study
how cave life in the Mexican tetra (Astyanax mexicanus) has affected an identified ...
During postnatal life, leptin specifies neuronal inputs to the paraventricular nucleus
of the hypothalamus (PVH) and activates agouti-related peptide (AgRP) neurons in the
arcuate nucleus of the hypothalamus. Activity-dependent developmental mechanisms ...
Synaptic loss and dendritic degeneration are common pathologies in several neurodegenerative
diseases characterized by progressive cognitive and/or motor decline, such as Alzheimer’s
disease (AD) and frontotemporal dementia/amyotrophic lateral sclerosis (...
Protein post-translational modifications (PTM) play a crucial role in the modulation
of synaptic function and their alterations are involved in the onset and progression
of neurodegenerative disorders. S-palmitoylation is a PTM catalyzed by zinc finger
...
Orientation is one of the most salient features in visual scenes. Neurons at multiple
levels of the visual system detect orientation, but in many cases, the underlying
biophysical mechanisms remain unresolved. Here, we studied mechanisms for orientation
...
Flexible control of pectoral appendages enables motor behaviors of vastly different
strength, speed, and amplitude, as in a human playing the piano or throwing a ball.
Such control necessitates a fine-tuned, coordinated activation of motoneurons, which
is ...
GNAO1 encodes the alpha subunit of the heterotrimeric Go protein. Despite being the most
abundant G protein at synapses, the role of Go in the brain remains unclear, primarily
because of the high mortality associated with developmental and epileptic ...
Spinal motor neuron (MN) dysfunction is the cause of a number of clinically significant
movement disorders. Despite the recent approval of gene therapeutics targeting these
MN-related disorders, there are no viral delivery mechanisms that achieve MN-...
Plant Biology
Actin cytoskeleton drives the targeted transport of cell wall components to sustain
the tip growth of pollen tubes for double fertilization; however, the underlying mechanism
remains largely unknown. Arabidopsis formin 5 (AtFH5), an actin-nucleating ...
Plants have evolved photoreceptors to optimize their development during primary growth,
including germination, hypocotyl elongation, cotyledon opening, and root growth, allowing
them to adapt to challenging light conditions. The light signaling ...
Efforts to improve photosynthetic performance are increasingly employing natural genetic
variation. However, genetic variation in the organellar genomes (plasmotypes) is often
disregarded due to the difficulty of studying the plasmotypes and the lack of ...
Population Biology
Since their domestication, horses have accompanied mankind, and humans have constantly
shaped horses according to their needs through stallion-centered breeding. Consequently,
the male-specific portion of the Y chromosome (MSY) is extremely uniform in ...
Psychological and Cognitive Sciences
Low cerebrospinal (CSF) arginine vasopressin (AVP) concentration is a biomarker of
social impairment in low-social monkeys and children with autism, suggesting that
AVP administration may improve primate social functioning. However, AVP administration
...
Corrections
Cover image: Pictured are blood vessels in a spiral-shaped cochlea. Aara Patel et al. explored an approach to prevent progressive hearing loss associated with Norrie disease, which is caused by a variant in the gene encoding the protein norrin. Activation of a stabilized form of the protein β-catenin, which is thought to participate in the norrin signaling pathway in blood vessels, prevented outer hair cell death in the cochlea and hearing loss in mouse models of Norrie disease. According to the authors, rescuing the norrin signaling pathway may prevent some forms of hearing loss. See the article by Patel et al. e2322124121. Image credit: Aara Patel and Jane Sowden.
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