Table Of Contents Page, PNAS Volume 121, Number 42
This Week in PNAS
Opinion
Retrospective
Commentaries
Brief Reports
The glymphatic pathway was defined in rodents as a network of perivascular spaces
(PVSs) that facilitates organized distribution of cerebrospinal fluid (CSF) into the
brain parenchyma. To date, perivascular CSF and cerebral interstitial fluid exchange
has ...
Antibodies are an essential component of the antiviral response in many species, but
to date, there is no compelling evidence that bats are capable of eliciting a robust
humoral immunity, including neutralizing antibodies. Here, we report that infection
...
Phtheirospermum japonicum is a hemiparasitic plant of the Orobanchaceae, the largest family of parasitic plants.
It extracts water and nutrients from other plants through haustoria along its roots.
Haustoriogenesis, the formation of haustoria, is ...
Understanding the historical perception and value of teacher personalities reveals
key educational priorities and societal expectations. This study analyzes the evolution
of teachers’ ascribed Big Five personality traits from 1800 to 2019, drawing on ...
Tissue-resident natural killer (trNK) cells are present in the human lung, yet their
metabolic function is unknown. NK cell effector and metabolic function are intrinsically
linked therefore targeting metabolism presents therapeutic potential in ...
Physical Sciences
Applied Mathematics
The global steady state of a system in thermal equilibrium exponentially favors configurations
with lesser energy. This principle is a powerful explanation of self-organization
because energy is a local property of configurations. For nonequilibrium ...
Applied Physical Sciences
Strong steels are primarily fabricated by introducing spatial obstacles (e.g., stacking
faults and precipitates) that inhibit dislocation slips under stress to achieve high
strength. However, for most low-carbon steels, such obstacles are difficult to ...
Droplets of one fluid in a second, immiscible fluid are typically spherical in shape
due to the interfacial tension between the two fluids. Shear forces can lead to droplet
deformation when they are subjected to flow, and these effects can be further ...
Astronomy
The detection of numerous and relatively bright galaxies at redshifts z > 9 has prompted new investigations into the star-forming properties of high-redshift
galaxies. Using local forms of the initial mass function (IMF) to estimate stellar
masses of ...
Biophysics and Computational Biology
The peripheral endoplasmic reticulum (ER) forms a dense, interconnected, and constantly
evolving network of membrane-bound tubules in eukaryotic cells. While individual structural
elements and the morphogens that stabilize them have been described, a ...
A key challenge in molecular biology is to decipher the mapping of protein sequence
to function. To perform this mapping requires the identification of sequence features
most informative about function. Here, we quantify the amount of information (in bits)...
Cytoskeleton remodeling which generates force and orchestrates signaling and trafficking
to govern cell migration remains poorly understood, partly due to a lack of an investigation
tool with high system flexibility, spatiotemporal resolution, and ...
Surface-attached cells can sense and respond to shear flow, but planktonic (free-swimming)
cells are typically assumed to be oblivious to any flow that carries them. Here, we
find that planktonic bacteria can transcriptionally respond to flow, inducing ...
Chemistry
Copper homeostasis mechanisms are critical for bacterial resistance to copper-induced
stress. The Escherichia coli multicopper oxidase copper efflux oxidase (CueO) is part of the copper detoxification
system in aerobic conditions. CueO contains a ...
Zeaxanthin (Zea) is a key component in the energy-dependent, rapidly reversible, nonphotochemical
quenching process (qE) that regulates photosynthetic light harvesting. Previous transient
absorption (TA) studies suggested that Zea can participate in ...
Earth, Atmospheric, and Planetary Sciences
Carbonate minerals are of particular interest in paleoenvironmental research as they
are an integral part of the carbon and water cycles, both of which are relevant to
habitability. Given that these cycles are less constrained on Mars than they are on
...
Summer temperature extremes can have large impacts on humans and the biosphere, and
an increase in heat extremes is one of the most visible symptoms of climate change.
Multiple mechanisms have been proposed that would predict faster warming of heat ...
Compound drought–heatwaves (CDHWs) accelerate the warming and drying of soils, triggering
soil compound drought–heatwaves (SCDHWs) that jeopardize the health of soil ecosystems.
Nevertheless, the behavior of these events worldwide and their responses to ...
Estimates of sedimentary organic carbon burial fluxes based on inventory and isotope
mass balance methods have been divergent. A new calculation of the isotope mass balance
using a revised assessment of the inputs to the ocean-atmosphere system resolves ...
Anthropogenic activities emit ~2,000 Mg y−1 of the toxic pollutant mercury (Hg) into the atmosphere, leading to long-range transport
and deposition to remote ecosystems. Global anthropogenic emission inventories report
increases in Northern Hemispheric (...
Constitutive models of fault friction form the basis of physics-based simulations
of seismic activity. A generally accepted framework for the slip-rate and state dependence
of friction involves a thermally activated process, whereby the probability of ...
Engineering
Catalytic oxidation through the transfer of lattice oxygen from metal oxides to reactants,
namely the Mars–van Krevelen mechanism, has been widely reported. In this study, we
evidence the overlooked oxidation route that features the in situ formation of ...
The concurrent preservation of morphological, structural, and genomic attributes within
biological samples is paramount for comprehensive insights into biological phenomena
and disease mechanisms. However, current preservation methodologies (e.g., ...
Incomplete understanding of metastatic disease mechanisms continues to hinder effective
treatment of cancer. Despite remarkable advancements toward the identification of
druggable targets, treatment options for patients in remission following primary ...
Environmental Sciences
Methylmercury (MeHg) is a bioaccumulating neurotoxin mainly produced by anaerobic
microorganisms, with methanogen being one of the important methylators. A critical
aspect for understanding the mechanism for microbial mercury (Hg) methylation is the
...
Allometric scaling relations are widely used to link biological processes to body
size in nature. Several studies have shown that such scaling laws hold also for natural
ecosystems, including individual trees and forests, riverine metabolism, and river
...
Physics
Amorphous solids relax via slow molecular rearrangement induced by thermal fluctuations
or applied stress. Microscopic structural signatures predicting these structural relaxations
have been long searched for but have so far only been found in dynamic ...
Confined motions in complex environments are ubiquitous in microbiology. These situations
invariably involve the intricate coupling between fluid flow, soft boundaries, surface
forces, and fluctuations. In the present study, such a coupling is ...
The extraction of gold (Au) from electronic waste (e-waste) has both environmental
impact and inherent value. Improper e-waste disposal poses environmental and health
risks, entailing substantial remediation and healthcare costs. Large efforts are applied
...
Social Sciences
Environmental Sciences
Crop switching, in which farmers grow a crop that is novel to a given field, can help
agricultural systems adapt to changing environmental, cultural, and market forces.
Yet while regional crop production trends receive significant attention, relatively
...
Psychological and Cognitive Sciences
In recent decades, many jurisdictions have moved toward legalizing euthanasia and
assisted suicide, alongside a near-universal increase in public acceptance of medical
aid in dying. Here, we draw on a comprehensive quantitative review of current laws
on ...
Maximizing the welfare of society requires distributing goods between groups of people
with different preferences. Such decisions are difficult because different moral principles
impose irreconcilable solutions. For example, utilitarian efficiency (...
Sustainability Science
The amount of ocean protected from fishing and other human impacts has often been
used as a metric of conservation progress. However, protection efforts have highly
variable outcomes that depend on local conditions, which makes it difficult to quantify
...
Biological Sciences
Agricultural Sciences
Crop switching, in which farmers grow a crop that is novel to a given field, can help
agricultural systems adapt to changing environmental, cultural, and market forces.
Yet while regional crop production trends receive significant attention, relatively
...
Most measurements and models of forest carbon cycling neglect the carbon flux associated
with the turnover of branch biomass, a physiological process quantified for other
organs (fine roots, leaves, and stems). Synthesizing data from boreal, temperate,
...
Anthropology
Human fetuses at term are large relative to the dimensions of the maternal birth canal,
implying that their birth can be associated with difficulties. The tight passage through
the human birth canal can lead to devastating outcomes if birth becomes ...
Applied Biological Sciences
Incomplete understanding of metastatic disease mechanisms continues to hinder effective
treatment of cancer. Despite remarkable advancements toward the identification of
druggable targets, treatment options for patients in remission following primary ...
Lepidopterans commonly feed on plant material, being the most significant insect herbivores
in nature. Despite plant resistance to herbivory, such as producing toxic secondary
metabolites, herbivores have developed mechanisms encoded in their genomes to ...
Biochemistry
I had my eyes set on DNA replication research when I took my first molecular biology
course in graduate school. My election to the National Academy of Sciences came just
when I was retiring from active research. It gives me an opportunity to reflect on
my ...
Copper homeostasis mechanisms are critical for bacterial resistance to copper-induced
stress. The Escherichia coli multicopper oxidase copper efflux oxidase (CueO) is part of the copper detoxification
system in aerobic conditions. CueO contains a ...
Replication stress describes endogenous and exogenous challenges to DNA replication
in the S-phase. Stress during this critical process causes helicase–polymerase decoupling
at replication forks, triggering the S-phase checkpoint, which orchestrates ...
The assembly of β-barrel proteins into membranes is mediated by the evolutionarily
conserved β-barrel assembly machine (BAM) complex. In Escherichia coli, BAM folds numerous substrates which vary considerably in size and shape. How BAM
is able to ...
The cotranslational misfolding of the cystic fibrosis transmembrane conductance regulator
chloride channel (CFTR) plays a central role in the molecular basis of CF. The misfolding
of the most common CF variant (ΔF508) remodels both the translational ...
ATP-grasp superfamily enzymes contain a hand-like ATP-binding fold and catalyze a
variety of reactions using a similar catalytic mechanism. More than 30 protein families
are categorized in this superfamily, and they are involved in a plethora of cellular
...
Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that has been responsible
for numerous large-scale outbreaks in the last twenty years. Currently, there are
no FDA-approved therapeutics for any alphavirus infection. CHIKV nonstructural protein
2 (...
Biophysics and Computational Biology
Intrinsically disordered regions (IDRs) are structurally flexible protein segments
with regulatory functions in multiple contexts, such as in the assembly of biomolecular
condensates. Since IDRs undergo more rapid evolution than ordered regions, ...
In the past decade, topological data analysis has emerged as a powerful algebraic
topology approach in data science. Although knot theory and related subjects are a
focus of study in mathematics, their success in practical applications is quite limited
...
Structural biology is experiencing a paradigm shift from targeted structural determination
to structure-guided discovery of previously uncharacterized bioentities. We employed
cryoelectron microscopy (cryo-EM) to analyze filtered water samples collected ...
Cell Biology
The peripheral endoplasmic reticulum (ER) forms a dense, interconnected, and constantly
evolving network of membrane-bound tubules in eukaryotic cells. While individual structural
elements and the morphogens that stabilize them have been described, a ...
Tumor-targeted therapies have often been inefficient due to the lack of concomitant
control over the tumor microenvironment. Using an immunocompetent autologous breast
cancer model, we investigated a MAtrix REgulating MOtif (MAREMO)-mimicking peptide,
...
Profound functional switch of key regulatory factors may play a major role in homeostasis
and disease. Dysregulation of circadian rhythm (CR) is strongly implicated in cancer
with mechanisms poorly understood. We report here that the function of REV-ERBα, ...
Elevated lipid synthesis is one of the best-characterized metabolic alterations in
cancer and crucial for membrane expansion. As a key rate-limiting enzyme in de novo
fatty acid synthesis, ATP-citrate lyase (ACLY) is frequently up-regulated in tumors
and ...
Kirsten rat sarcoma virus (KRAS) mutation is associated with malignant tumor transformation
and drug resistance. However, the development of clinically effective targeted therapies
for KRAS-mutant cancer has proven to be a formidable challenge. Here, we ...
Developmental Biology
Tumors can induce systemic disturbances in distant organs, leading to physiological
changes that enhance host morbidity. In Drosophila cancer models, tumors have been
known for decades to cause hypervolemic “bloating” of the abdominal cavity. Here we
use ...
Posttranscriptional regulation of gene expression by RNA-binding proteins can enhance
the speed and robustness of cell state transitions by controlling RNA stability, localization,
or if, when, or where mRNAs are translated. The RNA helicase YTHDC2 is ...
Ecology
One of the most dramatic changes occurring on our planet is the ever-increasing extensive
use of artificial light at night, which drastically altered the environment to which
nocturnal animals are adapted. Such light pollution has been identified as a ...
View related content:
Harmonic radar suggests greater impact of light pollution for nocturnal insects
Environmental Sciences
Methylmercury (MeHg) is a bioaccumulating neurotoxin mainly produced by anaerobic
microorganisms, with methanogen being one of the important methylators. A critical
aspect for understanding the mechanism for microbial mercury (Hg) methylation is the
...
Evolution
Many human pathogens, including malaria, dengue, influenza, Streptococcuspneumoniae, and cytomegalovirus, coexist as multiple genetically distinct strains. Understanding
how these multistrain pathogens evolve is of critical importance for forecasting ...
Mitochondrial function relies on the coordinated expression of mitochondrial and nuclear
genes, exhibiting remarkable resilience despite high mitochondrial mutation rates.
The nuclear compensation mechanism suggests deleterious mitochondrial alleles drive
...
In the first live-bearing mammals, pregnancy was likely short and ended with a brief
period of inflammatory maternal–fetal interaction. This mode of reproduction has been
retained in many marsupials. While inflammation is key to successful implantation
in ...
Immunology and Inflammation
A key challenge in molecular biology is to decipher the mapping of protein sequence
to function. To perform this mapping requires the identification of sequence features
most informative about function. Here, we quantify the amount of information (in bits)...
Kaposi’s sarcoma-associated herpesvirus (KSHV) encodes a viral G protein-coupled receptor,
KSHV-GPCR, that contributes to KSHV immune evasion and pathogenesis of Kaposi’s sarcoma.
KSHV-GPCR shares a high similarity with CXC chemokine receptors CXCR2 and ...
Cardiac myosin-specific (MyHC) T cells drive the disease pathogenesis of immune checkpoint
inhibitor–associated myocarditis (ICI-myocarditis). To determine whether MyHC T cells
are tissue-resident memory T (TRM) cells, we characterized cardiac TRM cells ...
Medical Sciences
Histone Deacetylase 3 (HDAC3) function in vivo is nuanced and directed in a tissue-specific
fashion. The importance of HDAC3 in Kras mutant lung tumors has recently been identified, but HDAC3 function in this context
remains to be fully elucidated. Here, ...
The analysis of tissues of origin of cell-free DNA (cfDNA) is of research and diagnostic
interest. Many studies focused on bisulfite treatment or immunoprecipitation protocols
to assess the tissues of origin of cfDNA. DNA loss often occurs during such ...
Microbiology
Surface-attached cells can sense and respond to shear flow, but planktonic (free-swimming)
cells are typically assumed to be oblivious to any flow that carries them. Here, we
find that planktonic bacteria can transcriptionally respond to flow, inducing ...
The rise of antimicrobial failure is a global emergency, and causes beyond typical
genetic resistance must be determined. One probable factor is the existence of subpopulations
of transiently growth-arrested bacteria, persisters, that endure antibiotic ...
Neuroscience
Maximizing the welfare of society requires distributing goods between groups of people
with different preferences. Such decisions are difficult because different moral principles
impose irreconcilable solutions. For example, utilitarian efficiency (...
A central question for neuroscience is how to characterize brain representations of
perceptual and cognitive content. An ideal characterization should distinguish different
functional regions with robustness to noise and idiosyncrasies of individual ...
Alcohol consumption during adolescence has been associated with neuroanatomical abnormalities
and the appearance of future disorders. However, the latest advances in this field
point to the existence of risk profiles which may lead to some individuals ...
Developmental and epileptic encephalopathies (DEE) are rare but devastating and largely
intractable childhood epilepsies. Genetic variants in ARHGEF9, encoding a scaffolding protein important for the organization of the postsynaptic
density of inhibitory ...
The cerebellum is critical for sensorimotor learning. The specific contribution that
it makes, however, remains unclear. Inspired by the classic finding that for declarative
memories, medial temporal lobe (MTL) structures provide a gateway to the ...
The Ca2+ sensor synaptotagmin-1 (Syt1) triggers neurotransmitter release together with the
neuronal sensitive factor attachment protein receptor (SNARE) complex formed by syntaxin-1,
SNAP25, and synaptobrevin. Moreover, Syt1 increases synaptic vesicle (SV)...
Hyperpolarization-activated, cyclic nucleotide–gated (HCN) channels generate the cationic
Ih current in neurons and regulate the excitability of neuronal networks. The function
of HCN channels depends, in part, on their subcellular localization. Of the ...
Predictive coding is a fundamental function of the cortex. The predictive routing
model proposes a neurophysiological implementation for predictive coding. Predictions
are fed back from the deep-layer cortex via alpha/beta (8 to 30 Hz) oscillations.
They ...
Aging is the biggest risk factor for Parkinson’s disease (PD), suggesting that age-related
changes in the brain promote dopamine neuron vulnerability. It is unclear, however,
whether aging alone is sufficient to cause significant dopamine neuron loss, and ...
Pharmacology
Glucocerebrosidase (GCase) is implicated in both a rare, monogenic disorder (Gaucher
disease, GD) and a common, multifactorial condition (Parkinson’s disease, PD); hence,
it is an urgent therapeutic target. To identify correctors of severe protein ...
Physiology
The disposable soma theory (DST) posits that organisms age and die because of a direct
trade-off in resource allocation between reproduction and somatic maintenance. DST
predicts that investments in reproduction accentuate somatic damage which increase
...
Plant Biology
Zeaxanthin (Zea) is a key component in the energy-dependent, rapidly reversible, nonphotochemical
quenching process (qE) that regulates photosynthetic light harvesting. Previous transient
absorption (TA) studies suggested that Zea can participate in ...
Canopy shade enhances the activity of PHYTOCHROME INTERACTING FACTORs (PIFs) to boost
auxin synthesis in the cotyledons. Auxin, together with local PIFs and their positive
regulator CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1), promotes hypocotyl growth to ...
In this study, we show that the potato (Solanum tuberosum) pattern recognition receptor (PRR) NEMATODE-INDUCED LEUCINE-RICH REPEAT (LRR)-RLK1
(StNILR1) functions as a dual receptor, recognizing both nematode-associated molecular
pattern ascaroside #18 (...
Sustainability Science
The amount of ocean protected from fishing and other human impacts has often been
used as a metric of conservation progress. However, protection efforts have highly
variable outcomes that depend on local conditions, which makes it difficult to quantify
...
Correction
Editorial Expression of Concern
Cover image: Pictured is an infant Japanese macaque (Macaca fuscata). Katharina E. Pink, Barbara Fischer et al. examined 27 years of data on Japanese macaques in Austria and found no evidence of birth-associated mortality, despite the fact that fetal heads are large relative to the maternal birth canal. In humans, a similarly tight passage can lead to maternal and fetal death if birth is obstructed. According to the authors, the lack of birth-associated mortality in macaques suggests flexibility in the macaque skull, pelvis, or both, resulting in fewer birth complications than in humans. See the article by Pink et al. e2316189121. Image credit: Angela Stojan (University of Vienna, Vienna, Austria).
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