Table Of Contents Page, PNAS Volume 123, Number 1
This Week in PNAS
Commentaries
Letters
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Reply to Benito et al.: Problems in the Cretaceous evolution of the avian palatobasal joint
View the original article:Avian cranial kinesis is the result of increased encephalization during the origin of birds
Physical Sciences
Applied Mathematics
We propose a methodology that exploits large and diverse datasets to accurately estimate
the ambient medium’s Green’s functions in strongly scattering media. Given these estimates,
excellent imaging results are achieved, with a resolution that is better ...
Applied Physical Sciences
Intrinsically disordered proteins (IDPs) play a central role in shaping the dynamics
and material properties of biomolecular condensates. Understanding how sequence features
determine these properties is critical for elucidating physiological function and
...
Wetting of micropatterned surfaces is ubiquitous in nature and key to many technological
applications like spray cooling, inkjet printing, and semiconductor processing. Overcoming
the intrinsic, chemistry- and topography-governed wetting behaviors often ...
Traditional entropy-based methods—such as cross-entropy loss in classification problems—have
long been essential tools for representing the information uncertainty and physical
disorder in data and for developing artificial intelligence algorithms. ...
Understanding the mechanisms leading to complex coacervation is a fundamental challenge
in biomolecular sciences. Here, we explored the condensation transition and pretransitional
behavior of an archetypal system consisting of polyuridylic acid chains (...
Astronomy
Fluctuations and structure across a wide range of spatial and temporal scales are
frequently studied in the solar wind. The properties of the low-frequency fluctuations
are of relevance to turbulent energy injection into the plasma and the transport of
...
Chemistry
Concentrated hydrogen-bonded electrolytes (CoHBEs) are structured, electrochemically
stable, less-volatile alternatives to aqueous and dilute nonaqueous electrolytes,
however, with high viscosities that limit molecular diffusion. This work provides
an ...
Leveraging the continuous and rapid deposition and evaporation processes of water
microdroplets on photocatalyst surfaces, this study presents an innovative dual-state
stepwise methane conversion approach. This method significantly enhances the ...
The deployment of renewable energy necessitates reliable grid-scale storage technologies.
Aqueous metal battery systems are one of the promising candidates due to high safety,
low cost, and high theoretical capacity of metal anodes, yet their long-term ...
Detyrosination is a reversible posttranslational modification specific to α-tubulin,
which has been implicated in cancer progression and invasiveness by promoting epithelial-to-mesenchymal
transition. The members of the vasohibin family, VASH1 and VASH2, ...
A global exploration of the complex interplay between protein conformational changes
and phosphorylation events in cell–cell interactions is crucial for understanding
the dynamic nature of protein modifications. This understanding is essential for ...
Earth, Atmospheric, and Planetary Sciences
The stability of the West Antarctic Ice Sheet (WAIS), crucial for predicting future
sea-level rise, is threatened by ocean-forced melting in the Pacific sector of the
Southern Ocean. While some geological records and ice-sheet models suggest WAIS retreat
...
Climate records for the early Pleistocene in eastern Africa aid reconstruction of
the ecology and landscapes occupied by hominins. Environmental changes associated
with alternating wet/dry cycles during this critical interval in hominin evolution
are ...
Engineering
Metals usually fracture catastrophically at cryogenic temperatures and soften rapidly
at high temperatures. This dilemma arises from the incompatibility of strengthening
mechanisms across vast temperature regimes. Here, this work unveils a self-adaptive
...
Mathematics
We introduce computational methods for analytic combinatorics in several variables.
Our findings pertain to rational generating functions whose dominant singularity satisfies
either of two conditions, one of which frequently holds for recursions arising ...
Physics
In ice, it is well known that the orientation of H2O molecules is disordered by geometrical frustration. Ice-analogous materials having
a pyrochlore lattice display interesting phenomena such as the spin-ice state and
the magnetic monopole. In the spinel ...
Statistics
Big data approaches to discovering nongenetic risk factors have lagged behind genome-wide
association studies that routinely uncover novel genetic risk factors for diverse
diseases. Instead, epidemiology typically focuses on candidate risk factors. Since
...
Social Sciences
Anthropology
The decline of polygyny and the rise of monogamy among complex, stratified societies
characterized by high wealth inequality present a long-standing puzzle in anthropology.
Competing explanations suggest that monogamy either i) reduces reproductive ...
Demography
Social relationships are central to shaping international migration patterns, yet
the link between widescale network structure and mobility decisions remains poorly
understood. Here, we investigate two key mechanisms by which social networks influence
...
Economic Sciences
Computer-assisted learning (CAL) offers an affordable way to implement a mastery learning
approach in the classroom. However, while experimental research suggests CAL can enhance
student outcomes, such findings often rely on experimental conditions not ...
Social Sciences
Stemming from physics and later applied to other fields such as ecology, the theory
of critical transitions suggests that some regime shifts are preceded by statistical
early warning signals. Reddit’s r/place experiment, a large-scale social game, ...
Sustainability Science
Desertification threatens 24% of the world’s land area across 126 countries and affects
35% of the global population. However, mainstream global efforts to combat desertification
prioritize short-term vegetation greening over addressing resource ...
Biological Sciences
Biochemistry
The aggregation of transthyretin (TTR) results in life-threatening transthyretin amyloidosis.
Familial forms of the disease arise from point mutations that destabilize the TTR
tetramer, leading to its dissociation and/or monomer unfolding and subsequent ...
Nuclear factor erythroid 2-like 1 (NFE2L1/Nrf1), an endoplasmic reticulum (ER)-associated
transcription factor, is responsible for the coordinated expression of proteasome
subunit genes upon proteasomal dysfunction. N-glycosylated proteins undergo protein ...
The chemical modification N6-methyladenosine (m6A) is catalyzed by the m6A methyltransferase complex (MTC) comprising METTL3 and METTL14 in the nucleus. Structural
evidence reveals that METTL3 primarily functions as the catalytic core, while METTL14
...
Folate-mediated one-carbon metabolism is implicated in several pathologies including
neural tube defects (NTDs), cancer, and neurodegenerative disorders, whereas diabetes
is associated with NTDs and peripheral neuropathy (PN). The development of ...
The precise recognition of specific peptide–major histocompatibility complex (pMHC)
complexes by T cell receptors (TCRs) plays a key role in infectious disease, cancer,
and autoimmunity. A critical step in many immunobiological studies is the ...
E3 ligases partner with E2 enzymes to regulate vast eukaryotic biology. The hierarchical
nature of these pairings, with >600 E3s and ~40 E2s in humans, necessitates that E2s
cofunction with numerous different E3s. Here, focusing on E3s in the RING-between-...
Deep mutational scanning couples a protein’s activity to DNA sequencing for high-throughput
assessment of the effects of all single amino acid substitutions, but it largely uses
indirect assays, like cell proliferation, as proxy for protein activity. Here,...
Biophysics and Computational Biology
Nucleic acid base pair open states that are actively driven to expose normally hidden
sequences and host reactions with processing proteins have been highly studied. However,
the spontaneous natural base pair opening behavior of native duplexes is still ...
Cholesterol homeostasis in mammalian cells relies on the interaction between two endoplasmic
reticulum (ER) sterol-sensing membrane proteins, Scap and Insig. Their interaction
regulates activation of transcription factors called sterol regulatory element–...
Recent cryoelectron microscopy data have revealed significant conformational rearrangements
of the megadalton spliceosome structure during splicing, an essential catalytic process
for maturing most human transcripts. However, the molecular trigger of ...
Cell Biology
Detyrosination is a reversible posttranslational modification specific to α-tubulin,
which has been implicated in cancer progression and invasiveness by promoting epithelial-to-mesenchymal
transition. The members of the vasohibin family, VASH1 and VASH2, ...
Androgen receptor (AR) signaling is essential for prostate cancer (PCa) cell growth
and remains a key therapeutic target in castration-resistant PCa (CRPC). While circular
RNAs (circRNAs) are increasingly recognized as important regulatory molecules, ...
A subset of the four-pass transmembrane proteins called C8 tetraspanins (TspanC8)
can bind and promote the cell surface localization of ADAM10 (A Disintegrin and Metalloproteinase
10). ADAM10 is a conserved transmembrane metalloprotease essential for ...
Diabetes and insulin resistance (IR) remain major global health challenges, underscoring
the need for novel therapeutic strategies. Here, we identify an autophagy-independent
role of circulating autophagy-related gene 7 (ATG7) in metabolic regulation. ...
Microtubules have been extensively studied for their interactions at the outer surface
and ends, yet the regulatory mechanisms within the microtubule lumen, particularly
in singlet microtubules, remain poorly understood. Here, we developed a proximity-...
Aging is closely associated with cardiovascular diseases, the leading cause of mortality
worldwide. Mitochondrial dysfunction is a hallmark of cardiovascular aging. Most of
the heart’s ATP is produced at the cristae, specialized subcompartments where ...
Replication stress (RS) is a major driver of genomic instability and a hallmark of
cancer cells. Although dynamic heterochromatin remodeling has been implicated in RS
response, the precise mechanisms remain unclear. The CHAMP1 complex, composed of CHAMP1,
...
Combinatorial treatment of glioblastoma with temozolomide (TMZ) plus 5-ethynyl-2′-deoxyuridine (EdU)
Glioblastoma (GBM) is the most aggressive malignant primary brain tumor in adults,
with incidence peaking in later life. It is commonly treated with surgery followed
by administration of ionizing radiation and the DNA-alkylating agent temozolomide
(TMZ). ...
Ecology
Stemming from physics and later applied to other fields such as ecology, the theory
of critical transitions suggests that some regime shifts are preceded by statistical
early warning signals. Reddit’s r/place experiment, a large-scale social game, ...
After consumption by herbivores, plant antimicrobial defense compounds may enhance
herbivore immunity to pathogenic microbes. In conifer-bark beetle interactions, beetles
ingest large quantities of phloem tissue containing high concentrations of ...
Wildfires significantly alter soil carbon (C) and nitrogen (N), reducing microbial
richness and biomass, while selecting for “fire-loving” pyrophilous microbes that
drive postfire nutrient cycling. However, the genomic strategies and functional trade-offs
...
Ecological traps occur when animals erroneously choose habitats that lower their fitness,
drawn by cues that are adaptive in most instances, but not all. Most ecological traps
result from anthropogenic changes that make habitats less beneficial, yet still ...
A major challenge for community ecology is using spatiotemporal data to infer parameters
of dynamical models without conducting laborious experiments. We present a framework
from statistical physics—Maximum Caliber—to characterize the temporal dynamics of
...
Evolution
Identifying the factors that drive individuals in a population to conform to the same
behavior or to exhibit behavioral diversity is crucial for understanding collective
decision-making, information transmission, and culture, yet remains challenging. Here,...
Immunology and Inflammation
Many animals have multiple organs or tissues that are colonized by diverse microbiota.
The female Hawaiian bobtail squid, Euprymna scolopes, has two organs with distinct symbiotic communities: the accessory nidamental gland
(ANG) and the light organ (LO). ...
Chronic infections induce CD8 T cell exhaustion, marked by impaired effector function.
While intrinsic drivers are well studied, the role of the surrounding metabolic environment
in shaping exhausted CD8 T cells (Tex) is less understood. Using untargeted ...
Lysine lactylation is a crucial posttranslational modification (PTM) that regulates
protein function. Here, this study revealed that L-lactic acid promotes host immune
response and inhibits viral infection by inducing Interferon Regulatory Factor 9 (IRF9)
...
Nanoparticle immunogens excel at rapidly inducing high levels of circulating antibodies
and are being deployed as part of several novel vaccines. However, their ability to
elicit memory B cell responses is less well understood. Here, we compared serologic
...
Medical Sciences
Big data approaches to discovering nongenetic risk factors have lagged behind genome-wide
association studies that routinely uncover novel genetic risk factors for diverse
diseases. Instead, epidemiology typically focuses on candidate risk factors. Since
...
Messenger RNA (mRNA) vaccines rely on lipid nanoparticles (LNPs) for in vivo delivery,
yet conventional formulations exhibit inefficient tissue targeting, undesired hepatic
accumulation, and limited understanding of the delivery–response relationship, ...
Hepatitis C virus (HCV) infection frequently progresses to chronicity rather than
spontaneous clearance, resulting in severe liver diseases including cirrhosis and
hepatocellular carcinoma. The molecular mechanisms governing infection outcomes remain
...
Apolipoprotein AV (APOA5) regulates intravascular triglyceride metabolism by binding
to the angiopoietin-like protein 3/8 complex (ANGPTL3/8) and suppressing its ability
to unfold the native conformation of lipoprotein lipase (LPL). LPL unfolding results
...
Microbiology
The cell surface of gram-negative Escherichia coli is rich in glycoconjugates, including O-antigen (O-Ag) and enterobacterial common
antigen polysaccharides, which mediate interactions with the environment. Enzymes
called nucleotidyltransferases produce ...
High-risk human papillomaviruses (HPVs) activate the Ataxia Telangiectasia Mutated
and Ataxia Telangiectasia and Rad3-Related pathways by inducing DNA breaks through
the action of viral oncoproteins E6 and E7, which target factors such as topoisomerases.
...
Uncontrolled systemic inflammatory responses are a critical pathological feature of
fatal Ebola virus (EBOV) infection. While some inflammatory responses may originate
from mononuclear phagocytes (MNPs), nonimmune cells vastly outnumber MNPs and may
be an ...
Legionella pneumophila, the causative agent of Legionnaires’ disease, utilizes a type IV secretion system
(T4SS) to translocate effectors into host cells, modulating diverse cellular processes
to create a replication-permissive niche. Here, we ...
Effective control of viral infection requires rapid induction of the innate immune
response, especially the type I and type III interferon (IFN) systems. Despite the
critical role of IFN induction in host defense, numerous studies have established
that ...
Getah virus (GETV) is a mosquito-borne alphavirus. It has posed a threat to various
livestock and humans during decades of evolution and spread. However, the viral determinants
and mechanisms underlying enhanced virulence remain largely unknown. In this ...
Acinetobacter baumannii is an Enterococcus, Staphylococcus, Klebsiella, Acinetobacter, Pseudomonas, and Enterobacter species (ESKAPE) pathogen linked to healthcare-associated diseases. Due to evolved
resistance, last-resort antibiotics such as the ...
Neuroscience
Polyserine domains mediate the association of some nuclear RNA-binding proteins with
cytoplasmic tau aggregates occurring in tauopathy models and patient samples. In cell
lines, polyserine domains mediate colocalization with tau aggregates and promote ...
Mass effect, characterized by the compression and deformation of neural tissue from
space-occupying lesions, can lead to debilitating neurological symptoms and poses
a significant clinical challenge. In the primary brain tumor glioblastoma (GBM), we
have ...
For reasons not fully understood, proresolving immune processes sometimes fail to
engage after peripheral nerve injury (PNI), leading to enhanced neuropathic pain and
inflammation. Here, we implicate reduced efferocytosis due to proteolytic cleavage
of ...
Striatal output is dynamically modulated by cholinergic interneurons (CINs), the primary
source of acetylcholine in the striatum. CINs have been classically viewed as a random
and homogeneous population, but recent evidence suggests heterogeneity in their ...
A key aspect of healthy social functioning in both humans and nonhuman primates is
the ability to extract status-related information from observing the social signals
exchanged between individuals. Knowing the social status of others determines how
long ...
Physiology
The timing of metamorphosis in insects determines adult body size and influences aspects
of fitness including flight performance and fecundity. The regulation of metamorphosis
has been well studied in model insects but determining the cue that initiates ...
Pregnancy and lactation are reproductive periods that require major energy and nutrient
investment by the mother. Dietary perturbations over reproduction can impair offspring
development and increase the risk of metabolic disease for the mother. However, ...
Hibernation is a seasonal survival strategy employed by certain mammals that, through
torpor use, reduces overall energy expenditure and permits long-term fasting. Although
fasting solves the challenge of winter food scarcity, it also removes dietary ...
Plant Biology
During the development of the rice female gametophyte (FG, embryo sac), there exists
a free-nuclear stage wherein eight nuclei, originating from the same mother cell nucleus,
respectively migrate to specific positions to acquire distinct cell identities ...
Plants face the constant challenge of reconciling antagonistic environmental signals,
such as nutrient-driven growth and water deficit–induced stress responses. However,
the molecular mechanisms that integrate these conflicting pathways remain poorly ...
Chlamydomonas acclimates to repeated low (LL) or high light (HL) days by changing
the abundance of photosynthetic complexes and the ultrastructure of its thylakoid
membranes. These phenotypes persist through the night phases, suggesting a readiness
for ...
Population Biology
Restoring genetic diversity through assisted migration is increasingly recognized
as a crucial strategy to counteract inbreeding depression and boost genetic variation
in small and fragmented populations yet concerns about outbreeding depression often
...
Interventions to slow the spread of SARS-CoV-2 significantly disrupted the transmission
of other pathogens. As interventions lifted, whether and when human pathogens would
eventually return to their prepandemic dynamics remains to be answered. Here, we ...
Systems Biology
A global exploration of the complex interplay between protein conformational changes
and phosphorylation events in cell–cell interactions is crucial for understanding
the dynamic nature of protein modifications. This understanding is essential for ...
Corrections
Cover image: Pictured is a 13-lined ground squirrel (Ictidomys tridecemlineatus) during hibernation. Matthew Regan et al. explored the ability of I. tridecemlineatus to salvage carbon from waste urea with the help of gut microbes, while fasting during the roughly six-month hibernation season. The authors found that symbiotic bacteria recycled urea carbon into acetate, which serves as an energy source for both gut microbes and host, while maintaining an environment conducive to fermentation of intestinal mucins, another host-derived nutrient source. The results suggest that host–microbe mutualisms may be widespread in fasting mammals. See the article by Regan et al. e2518978123. Image credit: Robert Streiffer (University of Wisconsin-Madison, Madison, WI).
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