Table Of Contents Page, PNAS Volume 121, Number 39
Lasker Awards 2024
The 2024 Albert Lasker Basic Medical Research Award was attributed to Zhijian (James)
Chen for “the discovery of the cGAS enzyme that senses foreign and self DNA, solving
the mystery of how DNA stimulates immune and inflammatory responses.” Bringing to
...
The discovery and development of GLP-1 based drugs that have revolutionized the treatment of obesity
The 2024 Lasker~DeBakey Clinical Medical Research Award has been given to Joel Habener
and Svetlana Mojsov for their discovery of a new hormone GLP-1(7-37) and to Lotte
Knudsen for her role in developing sustained acting versions of this hormone as a
...
This Week in PNAS
Opinion
Retrospective
Profile
Commentaries
Perspective
An N-degron is a degradation signal whose main determinant is a “destabilizing” N-terminal
residue of a protein. Specific N-degrons, discovered in 1986, were the first identified
degradation signals in short-lived intracellular proteins. These N-degrons ...
Letters
View the original article:
Voltage-induced calcium release in Caenorhabditis elegans body muscles
This article has a reply:Brief Reports
The “Returning Farmland to Lakes” (RFTL) project began in China following the catastrophic
1998 floods. It aims to recover flood storage capacity and mitigate flood risk to
agriculture and people. This flood adaptation strategy divides the floodplain into
...
New data sources and AI methods for extracting information are increasingly abundant
and relevant to decision-making across societal applications. A notable example is
street view imagery, available in over 100 countries, and purported to inform built
...
Physical Sciences
Applied Physical Sciences
Liquid–liquid phase separation, whereby two liquids spontaneously demix, is ubiquitous
in industrial, environmental, and biological processes. While isotropic fluids are
known to condense into spherical droplets in the binodal region, these dynamics are
...
Metamaterial has been captivated a popular notion, offering photonic functionalities
beyond the capabilities of natural materials. Its desirable functionality primarily
relies on well-controlled conditions such as structural resonance, dispersion, ...
We report a neutron spin echo (NSE) study of the nanoscale dynamics of the cell–cell
adhesion cadherin–catenin complex bound to vinculin. Our measurements and theoretical
physics analyses of the NSE data reveal that the dynamics of full-length α-catenin,
...
Astronomy
We consider the refractive lensing effects of ionized cool () gas cloudlets in the circumgalactic medium (CGM) of galaxies. In particular, we
discuss the combined effects of lensing from these cloudlets and scintillation from
plasma screens in the Milky ...
Biophysics and Computational Biology
Antibody-derived T-cell receptor (TCR) agonists are commonly used to activate T cells.
While antibodies can trigger TCRs regardless of clonotype, they bypass native T cell
signal integration mechanisms that rely on monovalent, membrane-associated, and ...
To respond and adapt, cells use surface receptors to sense environmental cues. While
biochemical signal processing inside the cell is studied in depth, less is known about
how physical processes during cell–cell contact impact signal acquisition. New ...
Chemistry
Despite its ubiquitous nature, the atomic structure of water in its liquid state is
still controversially debated. We use a combination of X-ray Raman scattering spectroscopy
in conjunction with ab initio and path integral molecular dynamics simulations ...
Knots containing metal atoms as part of their continuous strand backbone are termed
as metallaknots. While several metallaknots have been synthesized through one-pot
self-assembly, the designed synthesis of metallaknots by controlling the arrangement
of ...
Earth, Atmospheric, and Planetary Sciences
Future climate change may bring local benefits or penalties to surface air pollution,
resulting from changing temperature, precipitation, and transport patterns, as well
as changes in climate-sensitive natural precursor emissions. Here, we estimate the
...
Determining the mechanisms by which the earliest continental crust was generated and
reworked is important for constraining the evolution of Earth’s geodynamic, surface,
and atmospheric conditions. However, the details of early plate tectonic settings
...
Enhanced warming of the Arctic region relative to the rest of the globe, known as
Arctic amplification, is caused by a variety of diverse factors, many of which are
influenced by the Atlantic meridional overturning circulation (AMOC). Here, we quantify
...
While the dominant role of halogens in Arctic ozone loss during spring has been widely
studied in the last decades, the impact of sea-ice halogens on surface ozone abundance
over the northern hemisphere (NH) mid-latitudes remains unquantified. Here, we ...
Engineering
Developmental biology-inspired strategies for tissue-building have extraordinary promise
for regenerative medicine, spurring interest in the relationship between cell biophysical
properties and morphological transitions. However, mapping gene or protein ...
Hydrogen, the lightest and most abundant element in the universe, plays essential
roles in a variety of clean energy technologies and industrial processes. For over
a century, it has been known that hydrogen can significantly degrade the mechanical
...
The progression of many solid tumors is accompanied by temporal and spatial changes
in the stiffness of the extracellular matrix (ECM). Cancer cells adapt to soft and
stiff ECM through mechanisms that are not fully understood. It is well known that
there ...
Multispecies microbial communities drive most ecosystems on Earth. Chemical and biological
interactions within these communities can affect the survival of individual members
and the entire community. However, the prohibitively high number of possible ...
Mathematics
We show that integer partitions, the fundamental building blocks in additive number
theory, detect prime numbers in an unexpected way. Answering a question of Schneider,
we show that the primes are the solutions to special equations in partition ...
Physics
Despite its ubiquitous nature, the atomic structure of water in its liquid state is
still controversially debated. We use a combination of X-ray Raman scattering spectroscopy
in conjunction with ab initio and path integral molecular dynamics simulations ...
The discovery of the quantum Hall effect has established the foundation of the field
of topological condensed matter physics. An amazingly accurate quantization of the
Hall conductance, now enshrined in quantum metrology, is stable against any reasonable
...
The heavy fermion (HF) state of -electron systems is of great current interest since it exhibits various exotic phases
and phenomena that are reminiscent of the Kondo effect in -electron HF systems. Here, we present a combined infrared spectroscopy and ...
Statistics
A standard practice in statistical hypothesis testing is to mention the P-value alongside the accept/reject decision. We show the advantages of mentioning
an e-value instead. With P-values, it is not clear how to use an extreme observation (e.g. ) for ...
Social Sciences
Demography
The racial gap in infant mortality is a pressing public-health concern, and [B. N.
Greenwood et al., Proc. Natl. Acad. Sci. U.S.A. 117, 21194–21200 (2020), 10.1073/pnas.1913405117] suggest that Black newborns are more likely to survive if cared for by ...
View related content:
Economic Sciences
Can we use data on the biographies of historical figures to estimate the GDP per capita
of countries and regions? Here, we introduce a machine learning method to estimate
the GDP per capita of dozens of countries and hundreds of regions in Europe and ...
Rising inequality has brought redistribution back on the political agenda. In theory,
inequality aversion drives people’s support for redistribution. People can dislike
both advantageous inequality (comparison relative to those worse off) and ...
Political Sciences
Whether and when to censor hate speech are long-standing points of contention in the
US. The latest iteration of these debates entails grappling with content regulation
on social media in an age of intense partisan polarization. But do partisans disagree
...
Psychological and Cognitive Sciences
The prevalence of depression is a major societal health concern, and there is an ongoing
need to develop tools that predict who will become depressed. Past research suggests
that depression changes the language we use, but it is unclear whether language ...
Sustainability Science
Future climate change may bring local benefits or penalties to surface air pollution,
resulting from changing temperature, precipitation, and transport patterns, as well
as changes in climate-sensitive natural precursor emissions. Here, we estimate the
...
Biological Sciences
Agricultural Sciences
Realizing the full potential of genome editing for crop improvement has been slow
due to inefficient methods for reagent delivery and the reliance on tissue culture
for creating gene-edited plants. RNA viral vectors offer an alternative approach for
...
Biochemistry
Huntington’s disease (HD) and spinocerebellar ataxia type 3 (SCA3) are the two most
prevalent polyglutamine (polyQ) neurodegenerative diseases, caused by CAG (encoding
glutamine) repeat expansion in the coding region of the huntingtin (HTT) and ataxin-3
(...
Biophysics and Computational Biology
Small-conductance Ca2+-activated K+ channels (SK, KCa2) are gated solely by intracellular microdomain Ca2+. The channel has emerged as a therapeutic target for cardiac arrhythmias. Calmodulin
(CaM) interacts with the CaM binding domain (CaMBD) of the SK ...
The adenosine di-phosphate (ADP) ribosylation factor (Arf) small guanosine tri-phosphate
(GTP)ases function as molecular switches to activate signaling cascades that control
membrane organization in eukaryotic cells. In Arf1, the GDP/GTP switch does not ...
Liquid-like protein condensates have recently attracted much attention due to their
critical roles in biological phenomena. They typically show high fluidity and reversibility
for exhibiting biological functions, while occasionally serving as sites for ...
Cell Biology
Neutrophils utilize a variety of metabolic sources to support their crucial functions
as the first responders in innate immunity. Here, through in vivo and ex vivo isotopic
tracing, we examined the contributions of different nutrients to neutrophil ...
It is well established that DNA Damage Regulated Autophagy Modulator 1 (DRAM1), a
lysosomal protein and a target of p53, participates in autophagy. The cellular functions
of DRAM1 beyond autophagy remain elusive. Here, we show p53-dependent upregulation
...
Mammalian Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding
motif (TAZ) and Drosophila Yorkie (Yki) are transcription cofactors of the highly conserved Hippo signaling
pathway. It has been long assumed that the YAP/TAZ/Yki ...
Ovulation is critical for sexual reproduction and consists of the process of liberating
fertilizable oocytes from their somatic follicle capsules, also known as follicle
rupture. The mechanical force for oocyte expulsion is largely unknown in many ...
Developmental Biology
Developmental biology-inspired strategies for tissue-building have extraordinary promise
for regenerative medicine, spurring interest in the relationship between cell biophysical
properties and morphological transitions. However, mapping gene or protein ...
Pathogenic variants in SF3B4, a component of the U2 snRNP complex important for branchpoint
sequence recognition and splicing, are responsible for the acrofacial disorders Nager
and Rodriguez Syndrome, also known as SF3B4-related syndromes. Patients ...
A number of studies have demonstrated that it is possible to directly convert one
cell type to another by factor-mediated transdifferentiation, but in the vast majority
of cases, the resulting reprogrammed cells are unable to maintain their new cell ...
Ecology
The increasing duration of drought induced by global climate change has reduced forest
productivity. Biodiversity is believed to mitigate the effects of drought, thereby
enhancing the stability of tree growth. However, the effects of species richness on
...
Evolution
Sex-differential selection (SDS), which occurs when the fitness effects of alleles
differ between males and females, can have profound impacts on the maintenance of
genetic variation, disease risk, and other key aspects of natural populations. Because
the ...
Mammals as a rule have seven cervical vertebrae, a number which remains remarkably
conserved. Occasional deviations of this number are usually due to the presence of
cervical ribs on the seventh vertebra, indicating a homeotic transformation from a
...
Fluctuating environments that consist of regular cycles of co-occurring stress are
a common challenge faced by cellular populations. For a population to thrive in constantly
changing conditions, an ability to coordinate a rapid cellular response is ...
Insects represent the most diverse animal group, yet previous phylogenetic analyses
based on morphological and molecular data have failed to agree on the evolutionary
relationships of early insects and their six-legged relatives (together constituting
the ...
Algae mostly occur either as unicellular (microalgae) or multicellular (macroalgae)
species, both being uninucleate. There are important exceptions, however, as some
unicellular algae are multinucleate and macroscopic, some of which inhabit tropical
seas ...
Genetics
Most eukaryotes have one nucleus and nuclear genome per cell. Ciliates have instead
evolved distinct nuclei that coexist in each cell: a silent germline vs. transcriptionally
active somatic nuclei. In the best-studied model species, both nuclei can divide ...
Immunology and Inflammation
Antibody-derived T-cell receptor (TCR) agonists are commonly used to activate T cells.
While antibodies can trigger TCRs regardless of clonotype, they bypass native T cell
signal integration mechanisms that rely on monovalent, membrane-associated, and ...
Systemic inflammation elicits sickness behaviors and fever by engaging a complex neuronal
circuitry that begins in the preoptic area of the hypothalamus. Ectotherms such as
teleost fish display sickness behaviors in response to infection or inflammation,
...
Uveitis is a vision-threatening disease primarily driven by a dysregulated immune
response, with retinal microglia playing a pivotal role in its progression. Although
the transcription factor EGR2 is known to be closely associated with uveitis, including
...
Long COVID occurs in a small but important minority of patients following COVID-19,
reducing quality of life and contributing to healthcare burden. Although research
into underlying mechanisms is evolving, immunity is understudied. SARS-CoV-2-specific
T ...
Medical Sciences
The assessment of social determinants of health (SDoH) within healthcare systems is
crucial for comprehensive patient care and addressing health disparities. Current
challenges arise from the limited inclusion of structured SDoH information within
...
Myasthenia gravis (MG) is a chronic and severe disease of the skeletal neuromuscular
junction (NMJ) in which the effects of neurotransmitters are attenuated, leading to
muscle weakness. In the most common forms of autoimmune MG, antibodies attack ...
Androgens exert their effects primarily by binding to the androgen receptor (AR),
a ligand-dependent nuclear receptor. While androgens have anabolic effects on skeletal
muscle, previous studies reported that AR functions in myofibers to regulate skeletal
...
Immune evasion is not only critical for tumor initiation and progression, but also
determines the efficacy of immunotherapies. Through iterative in vivo CRISPR screens
with seven syngeneic tumor models, we identified core and context-dependent immune
...
Microbiology
Multispecies microbial communities drive most ecosystems on Earth. Chemical and biological
interactions within these communities can affect the survival of individual members
and the entire community. However, the prohibitively high number of possible ...
Bacterial biofilms have been implicated in several chronic infections. After initial
attachment, a critical first step in biofilm formation is a cell inducing a surface-sensing
response. In the Gram-negative opportunistic pathogen Pseudomonas aeruginosa, ...
Klebsiella pneumoniae is an important pathogen causing difficult-to-treat urinary tract infections (UTIs).
Over 1.5 million women per year suffer from recurrent UTI, reducing quality of life
and causing substantial morbidity and mortality, especially in ...
The opportunistic pathogen Acinetobacter baumannii, carries variants of A. baumannii resistance islands (AbaR)-type genomic islands conferring multidrug resistance. Their
pervasiveness in the species has remained enigmatic. The dissemination of AbaRs is
...
The Pentamer complex of Human Cytomegalovirus (HCMV) consists of the viral glycoproteins
gH, gL, UL128, UL130, and UL131 and is incorporated into infectious virions. HCMV
strains propagated extensively in vitro in fibroblasts carry UL128, UL130, or UL131
...
Neuroscience
Cuprous copper [Cu(I)] is an essential cofactor for enzymes that support many fundamental
cellular functions including mitochondrial respiration and suppression of oxidative
stress. Neurons are particularly reliant on mitochondrial production of ATP, with
...
Adult central nervous system (CNS) neurons down-regulate growth programs after injury,
leading to persistent regeneration failure. Coordinated lipids metabolism is required
to synthesize membrane components during axon regeneration. However, lipids also ...
Parkinson’s disease (PD) is typically a sporadic late-onset disorder, which has made
it difficult to model in mice. Several transgenic mouse models bearing mutations in
SNCA, which encodes alpha-Synuclein (α-Syn), have been made, but these lines do not ...
Connectomics research is making rapid advances, although models revealing general
principles of connectional architecture are far from complete. Our analysis of 106 published connection reports indicates that the adult rat brain interregional connectome
...
Plant Biology
A fundamental assumption in plant science posits that leaf air spaces remain vapor
saturated, leading to the predominant view that stomata alone control leaf water loss.
This concept has been pivotal in photosynthesis and water-use efficiency research.
...
Population Biology
Genomic studies of endangered species have primarily focused on describing diversity
patterns and resolving phylogenetic relationships, with the overarching goal of informing
conservation efforts. However, few studies have investigated genomic diversity ...
Psychological and Cognitive Sciences
There has been much progress in understanding human social learning, including recent
studies integrating social information into the reinforcement learning framework.
Yet previous studies often assume identical payoffs between observer and demonstrator,
...
Correction
SI Correction
Cover image: Pictured are rescue tigers (Panthera tigris) at In-Sync Exotics Wildlife Rescue and Educational Center in Wylie, Texas. Ellie Armstrong, Jazlyn Mooney et al. explored the genomic diversity of the privately owned captive tiger population in the United States based on genomic sequencing of 138 individuals. The study population had ancestry from all six extant wild tiger subspecies and measures of genetic diversity and inbreeding that were comparable to wild tiger populations. The results could help inform tiger conservation efforts and illegal trafficking investigations. See the article by Armstrong, Mooney et al. e2402924121. Image credit: Keri Ostermann (In-Sync Exotics Wildlife Rescue and Educational Center, Wylie, TX).
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