Table Of Contents Page, PNAS Volume 122, Number 5
Special Feature
Dialogues About the Practice of Science
Replication and the reported crises impacting many fields of research have become
a focal point for the sciences. This has led to reforms in publishing, methodological
design and reporting, and increased numbers of experimental replications coordinated
...
Measurement literacy is required for strong scientific reasoning, effective experimental
design, conceptual and empirical validation of measurement quantities, and the intelligible
interpretation of error in theory construction. This discourse examines ...
The preference for simple explanations, known as the parsimony principle, has long
guided the development of scientific theories, hypotheses, and models. Yet recent
years have seen a number of successes in employing highly complex models for scientific
...
Funding of curiosity-driven science is the lifeblood of scientific and technological
innovation. Various models of funding allocation became institutionalized in the 20th
century, shaping the present landscape of research funding. There are numerous ...
What is wrong with the peer review system? Is peer review sustainable? Useful? What
other models exist? These are central yet contentious questions in today’s academic
discourse. This perspective critically discusses alternative models and revisions
to ...
For most researchers, academic publishing serves two goals that are often misaligned—knowledge
dissemination and establishing scientific credentials. While both goals can encourage
research with significant depth and scope, the latter can also pressure ...
Large language models (LLMs) are being increasingly incorporated into scientific workflows.
However, we have yet to fully grasp the implications of this integration. How should
the advancement of large language models affect the practice of science? For ...
Automation transformed various aspects of our human civilization, revolutionizing
industries and streamlining processes. In the domain of scientific inquiry, automated
approaches emerged as powerful tools, holding promise for accelerating discovery,
...
This Week in PNAS
Science and Culture
Retrospective
Commentaries
Perspective
Traditional gendered arrangements—norms, roles, prejudices, and hierarchies—shape
every human life. Associated harms are primarily framed as women’s issues due to more
severe consequences women face. Yet, gendered arrangements also shape men’s ...
Letters
Brief Report
The rise and spread of ancient Indian Ocean Rim (IOR) trade networks profoundly impacted
southern Africa. Control over this trade played a critical role in the rise and maintenance
of complex societies of the second millennium CE such as Mapungubwe and ...
Physical Sciences
Chemistry
Enzyme–enzyme interactions are fundamental to the function of cells. Their atomistic
mechanisms remain elusive mainly due to limitations of in-cell measurements. We address
this challenge by atomistically modeling, for a total of ≈80 μs, a slice of the ...
The highest sheet symmetry form of graphyne, with one triple bond between each neighboring
hexagon in graphene, irreversibly transforms exothermically at ambient pressure and
low temperatures into a nongraphitic, planar-sheet, zero-bandgap phase ...
Computer Sciences
As knowledge accumulates in science and society in a distributed fashion, erroneous
derivations can be introduced into the corpus of knowledge. Such derivations can compromise
the validity of any units of knowledge that rely on them in the future. Can ...
Earth, Atmospheric, and Planetary Sciences
As an essential micronutrient, phosphorus plays a key role in oceanic biogeochemistry,
with its cycling intimately connected to the global carbon cycle and climate change.
Authigenic carbonate fluorapatite (CFA) has been suggested to represent a ...
CaSiO perovskite (CaPv) is the last major mineral in the Earth’s lower mantle whose elasticity
remains largely unresolved. Here, we investigate the elasticity of CaPv using ab initio
machine-learning force fields (MLFF). At room temperature, the ...
Engineering
Bubbles present in saline water typically exhibit a prolonged lifetime, making them
attractive for various engineering processes. Herein, we unveil a transition from
delayed bubble coalescence to rapid bursting within about one millisecond in salty
...
Carrier-free nanomedicines exhibited significant potential in elevating drug efficacy
and safety for tumor management, yet their self assembly typically relied on chemical
modifications of drugs or the incorporation of surfactants, thereby compromising ...
Preemptive identification of potential failure under loading of engineering structures
is a critical challenge. Our study presents an innovative approach to design built-in
prefailure indicators within multiscale structural designs with optimized load ...
Physics
In metals, electrons in a magnetic field undergo cyclotron motion, leading to oscillations
in physical properties called quantum oscillations. This phenomenon has never been
seen in a robust insulator because there are no mobile electrons. We report an ...
Social Sciences
Psychological and Cognitive Sciences
In mixed-gender couples, men are older than women on average. Scholars and laypeople
presume that this arrangement reflects mirrored preferences such that men desire younger
partners and women desire older partners. Nevertheless, relevant published data ...
Experiencing negative content through art has a unique power to transform our perceptions
and foster engagement. While this idea has been widely discussed, empirical evidence
is scarce, since experimental testing of art experiences poses significant ...
Social Sciences
The urgent calls for action on climate change underscore the importance of increasing
sustainable behavior among individuals who have traditionally veered away from it,
such as those on the political right. Utilizing data from four geopolitical regions
...
Biological Sciences
Agricultural Sciences
Seed color is a critical quality trait in numerous plant species. In oilseed Brassica crops, including rapeseed and mustard, yellow seeds are distinguished by their significantly
higher oil content and faster germination rates compared to black or brown ...
The stinkbug Riptortus pedestris, notorious for inducing soybean staygreen-like syndrome, employs a range of salivary
proteins to manipulate the host plant for its benefit. Here, we show that RpSP1, a
salivary protein specific to Pentatomomorpha, triggers ...
Biochemistry
Mutations in Leucine-rich repeat kinase 2 (LRRK2) and PTEN-induced kinase 1 (PINK1)
are associated with familial Parkinson’s disease (PD). LRRK2 phosphorylates Rab guanosine
triphosphatase (GTPases) within the Switch II domain while PINK1 directly ...
Cellular actin networks exhibit distinct assembly and disassembly dynamics, primarily
driven by multicomponent reactions occurring at the two ends of actin filaments. While
barbed ends are recognized as the hotspot for polymerization, depolymerization is
...
The formation of superoxide dismutase 1 (SOD1) filaments has been implicated in amyotrophic
lateral sclerosis (ALS). Although the disulfide bond formed between Cys57 and Cys146
in the active state has been well studied, the role of the reduced cysteine ...
Ten-eleven translocation (TET) enzymes oxidize 5-methylcytosine (mC) in DNA, contributing
to the regulation of gene transcription. Diverse mutations of TET2 are frequently
found in various blood cancers, yet the full scope of their functional consequences
...
ClpXP is a two-component mitochondrial matrix protease. The caseinolytic mitochondrial
matrix peptidase chaperone subunit X (ClpX) recognizes and translocates protein substrates
into the degradation chamber of the caseinolytic protease P (ClpP) for ...
The design of organic–peptide hybrids has the potential to combine our vast knowledge
of protein design with small molecule engineering to create hybrid structures with
complex functions. Here, we describe the computational design of a photoswitchable
Ca2+...
Hsp70, Hsp90, and ClpB/Hsp100 are molecular chaperones that help regulate proteostasis.
Bacterial and yeast Hsp70s and their cochaperones function synergistically with Hsp90s
to reactivate inactive and aggregated proteins by a mechanism that requires a ...
Biophysics and Computational Biology
Enzyme–enzyme interactions are fundamental to the function of cells. Their atomistic
mechanisms remain elusive mainly due to limitations of in-cell measurements. We address
this challenge by atomistically modeling, for a total of ≈80 μs, a slice of the ...
In mammals, the four subunit isoforms HCN1–4 assemble to form functional homotetrameric
and heterotetrameric hyperpolarization-activated cyclic nucleotide-modulated (HCN)
ion channels. Despite the outstanding relevance of HCN channels for organisms, ...
Accurate chromosome segregation in mitosis depends on proper connections of sister
chromatids, through microtubules, to the opposite poles of the early mitotic spindle.
Transiently, many inaccurate connections are formed and rapidly corrected throughout
...
The functional architecture of the long-lived neuronal microtubule (MT) cytoskeleton
is maintained by various MT-associated proteins (MAPs), most of which are known to
bind to the MT outer surface. However, electron microscopy (EM) has long ago revealed
...
Cell Biology
The ε4 variant of human apolipoprotein E (APOE4) is a key genetic risk factor for neurodegeneration in Alzheimer’s disease and elevated
all-cause mortality in humans. Understanding the factors and mechanisms that can mitigate
the harmful effects of APOE4 ...
Chromobox 2 (CBX2), a crucial component of the polycomb repressive complex (PRC),
has been implicated in the development of various human cancers. However, its role
in the regulation of tumor immunogenicity and immune evasion remains inadequately
...
Developmental Biology
Classical tissue recombination experiments demonstrate that cell-fate determination
along the anterior–posterior axis of the Müllerian duct occurs prior to postnatal
day 7 in mice. However, little is known about how these cell types are maintained
in ...
Anti-Müllerian hormone (AMH) protects the ovarian reserve from chemotherapy, and this
effect is most pronounced with Doxorubicin (DOX). However, DOX toxicity and AMH rescue
mechanisms in the ovary have remained unclear. Herein, we characterize the ...
Aging is a complex process that affects multiple organs, and the discovery of a pharmacological
approach to ameliorate aging is considered the Holy Grail of medicine. Here, we performed
an N-ethyl-N-nitrosourea forward genetic screening in zebrafish and ...
Understanding how epithelial cells in the female reproductive tract (FRT) differentiate
is crucial for reproductive health, yet the underlying mechanisms remain poorly defined.
At birth, FRT epithelium is highly malleable, allowing differentiation into ...
Ecology
Wildlife populations are not static. Intrinsic and extrinsic factors affect individuals,
which lead to spatiotemporal variation in population density and range. Yet, dynamics
in density and their drivers are rarely documented, due in part to the inherent ...
Climate change is impacting forests in complex ways, with indirect effects arising
from interactions between tree growth and reproduction often overlooked. Our 43-y
study of European beech (Fagus sylvatica) showed that rising summer temperatures since ...
Evolution
In the pregenomic era, scientists were puzzled by the observation that haploid genome
size (the C-value) did not correlate well with organismal complexity. This phenomenon,
called the “C-value paradox,” is mostly explained by the fact that protein-coding
...
Phenotypic plasticity may pave the way for rapid adaptation to newly encountered environments.
Although it is often contested, there is growing evidence that initial plastic responses
of ancestral populations to new environmental cues may promote ...
Immunology and Inflammation
HIV-1 envelope broadly neutralizing antibodies represent a promising component of
HIV-1 cure strategies. To evaluate the therapeutic efficacy of combination monoclonal
antibodies (mAbs) in a rigorous nonhuman primate model, we tested different ...
Medical Sciences
Recent studies have demonstrated that chronic stress can enhance the development of
multiple human diseases, including cancer. However, the role of chronic stress in
esophageal carcinogenesis and its underlying molecular mechanisms remain unclear.
This ...
Tumor cells reshape iron and lipid metabolism for their rapid proliferation. However,
how tumor cells coordinate the interplay between tumor cell–specific iron homeostasis
and lipid metabolism reprogramming to counteract energy shortages remains unclear.
...
The ionizable lipid component of lipid nanoparticle (LNP) formulations is essential
for mRNA delivery by facilitating endosomal escape. Conventionally, these lipids are
synthesized through complex, multistep chemical processes that are both time-consuming
...
Microbiology
Heterocytes, specialized cells for nitrogen fixation in cyanobacteria, are surrounded
by heterocyte glycolipids (HGs), which contribute to protection of the nitrogenase
enzyme from oxygen. Diverse HGs preserve in the sediment and have been widely used
as ...
Microbial mats are stratified communities often dominated by unicellular and filamentous
phototrophs within an exopolymer matrix. It is challenging to quantify the dynamic
responses of community members in situ as they experience steep gradients and rapid
...
The cytoplasmic membrane of bacteria is composed of a phospholipid bilayer made up
of a diverse set of lipids. Phosphatidylglycerol (PG) is one of the principal constituents
and its production is essential for growth in many bacteria. All the enzymes ...
Despite growing awareness of their importance in soil ecology, the genetic and physiological
traits of bacterial predators are still relatively poorly understood. In the course
of a Myxococcus xanthus predator evolution experiment, we identified a class ...
Bacterial receptors feed into multiple signal transduction pathways that regulate
a variety of cellular processes including gene expression, second messenger levels,
and motility. Receptors are typically activated by signal binding to ligand-binding
...
The mammalian Hippo kinases, MST1 and MST2, regulate organ development and suppress
tumor formation by balancing cell proliferation and death. In macrophages, inflammasomes
detect molecular patterns from invading pathogens or damaged host cells and ...
Toxoplasma bradyzoites reside in tissue cysts that undergo cycles of expansion, rupture, and
release to foster chronic infection. The glycosylated cyst wall acts as a protective
barrier, although the processes responsible for formation, remodeling, and ...
Neuroscience
The hippocampal dentate gyrus (DG) is thought to orthogonalize inputs from the entorhinal
cortex (pattern separation) and relay this information to the CA3 region. In turn,
attractor dynamics in CA3 perform a pattern completion or error correction ...
Physiology
The L-type Ca2+ channel (CaV1.2) is essential for cardiac excitation–contraction coupling. To contribute to the
inward Ca2+ flux that drives Ca2+-induced-Ca2+-release, CaV1.2 channels must be expressed on the sarcolemma; thus the regulatory mechanisms ...
Plant Biology
The chloroplast genome encodes key components of the photosynthetic light reaction
machinery as well as the large subunit of the enzyme central for carbon fixation,
Ribulose-1,5-bisphosphat-carboxylase/-oxygenase (RuBisCo). Its expression is predominantly
...
Systems Biology
Electric fields in terrestrial environments are used by caterpillars to detect their
predators, as foraging cues by pollinators, and facilitate ballooning by spiders.
This study shows that electric fields facilitate transportation and detection of ...
Corrections
Cover image: Pictured is an artistic representation of conversations about scientific practices, including observation, experimentation, theory, and analysis. A collection of articles in the Dialogues About the Practice of Science Special Feature explores the implications, pros and cons, and relevance to specific goals of emerging and traditional scientific practices and methods. Together, the articles highlight issues related to the replication and reproducibility crisis, the importance of measurement, the roles of complexity and simplicity in modeling, how science is funded and published, and the potential impact of AI. See the Introduction to the Special Feature, e2423782122. Image credit: Holly Westfall (artist) and Joachim Vandekerckhove (University of California Irvine, Irvine, CA).
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