Table Of Contents Page, PNAS Volume 121, Number 22
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
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Reply to Carrapa et al.: Central Puna uplift: Addressing criticisms, affirming conclusions
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Reply to Gahlot and Singh: A pivotal role of neuronal MML-1 in Caenorhabditis elegans
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, , have been widely used in biology for over a century but, with the exception of , 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, ...
Sensations of heat and touch produced by receptors in the skin are of essential importance
for perceptions of the physical environment, with a particularly powerful role in
interpersonal interactions. Advances in technologies for replicating these ...
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
Foraging mechanisms in excavate flagellates shed light on the functional ecology of early eukaryotes
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
IL-22 plays a critical role in defending against mucosal infections, but how IL-22
production is regulated is incompletely understood. Here, we show that mice lacking
IL-33 or its receptor ST2 (IL-1RL1) were more resistant to Streptococcus pneumoniae lung ...
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, , have been widely used in biology for over a century but, with the exception of , 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 ...
Corrections
Retraction
Cover image: Pictured is a field-grown crown root system of the maize mutant pils6. Craig L. Cowling et al. uncovered a role for the ZmPILS6 protein in regulating root growth in maize. Plants with modified ZmPILS6 displayed reduced root area and reduced lateral root formation, both of which are desirable traits in agriculture. The ZmPILS6 protein localizes to the endoplasmic reticulum in cells and helps control the distribution of the plant hormone auxin in primary roots. According to the authors, despite resembling PILS proteins that curb root growth in other land plants, ZmPILS6 promotes root growth in maize. See the article by Cowling et al. e2313216121. Image credit: Visual illustration designed by China Rose (artist), using a microscopic photograph provided by Craig L. Cowling.
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