Table Of Contents Page, PNAS Volume 113, Number 46
This Week in PNAS
Letters (Online Only)
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Metabolic features of chronic fatigue syndrome
This article has a reply:Reply to Vogt et al.: Metabolomics and chronic fatigue syndrome
Inner Workings
Retrospective
Commentaries
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PNAS Plus Significance Statements
Perspective
This Perspective offers a summary of the recommendations in the Institute of Medicine
report Dying in America. How we die is a deeply personal issue that each of us will face. However, the approach
to end-of-life (EOL) care in the United States needs ...
Physical Sciences
Applied Physical Sciences
We introduce an energy functional for ground-state electronic structure calculations.
Its variables are the natural spin-orbitals of singlet many-body wave functions and
their joint occupation probabilities deriving from controlled approximations to the
...
Collections of interacting, self-propelled particles have been extensively studied
as minimal models of many living and synthetic systems from bird flocks to active
colloids. However, the influence of active rotations in the absence of self-propulsion
(...
A cholesteric liquid crystal (CLC) formed by chiral molecules represents a self-assembled
one-dimensionally periodic helical structure with pitch in the submicrometer and micrometer range. Because of the spatial periodicity of
the dielectric permittivity,...
A degenerate p-type conduction of cuprous iodide (CuI) thin films is achieved at the
iodine-rich growth condition, allowing for the record high room-temperature conductivity
of ∼156 S/cm for as-deposited CuI and ∼283 S/cm for I-doped CuI. At the same time,...
Noninvasive functional imaging of molecular and cellular processes of vision may have
immense impact on research and clinical diagnostics. Although suitable intrinsic optical
signals (IOSs) have been observed ex vivo and in immobilized animals in vivo, ...
View related content:
Noninvasive imaging of the photoreceptor mosaic response to light stimulation
Biophysics and Computational Biology
The HIV-1 envelope (Env) glycoprotein, a trimer of gp120–gp41 heterodimers, relies
on conformational flexibility to function in fusing the viral and host membranes.
Fusion is achieved after gp120 binds to CD4, the HIV-1 receptor, and a coreceptor,
...
Chemistry
Plankton, corals, and other organisms produce calcium carbonate skeletons that are
integral to their survival, form a key component of the global carbon cycle, and record
an archive of past oceanographic conditions in their geochemistry. A key aspect of
...
The bacteria harbored by fungus-growing ants produce a variety of small molecules
that help maintain a complex multilateral symbiosis. In a survey of antifungal compounds
from these bacteria, we discovered selvamicin, an unusual antifungal polyene ...
Hydrophobicity of macroscopic planar surface is conventionally characterized by the
contact angle of water droplets. However, this engineering measurement cannot be directly
extended to surfaces of proteins, due to the nanometer scale of amino acids and ...
Earth, Atmospheric, and Planetary Sciences
The isotopic diversity of oceanic island basalts (OIB) is usually attributed to the
influence, in their sources, of ancient material recycled into the mantle, although
the nature, age, and quantities of this material remain controversial. The unradiogenic
...
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Environmental Sciences
Examples of wetland deposits can be found across the globe and are known for preserving
organic archaeological and environmental remains that are vitally important to our
understanding of past human–environment interactions. The Mesolithic site of Star
...
Given the threats that tropical cyclones (TC) pose to people and infrastructure, there
is significant interest in how the climatology of these storms may change with climate.
The global historical record has been extensively examined, but it is short and ...
Physics
High-entropy alloys are made from random mixtures of principal elements on simple
lattices, stabilized by a high mixing entropy. The recently discovered body-centered
cubic (BCC) Ta-Nb-Hf-Zr-Ti high-entropy alloy superconductor appears to display ...
Interface-induced superconductivity at ∼25 K at ambient pressure in undoped CaFe2As2 single crystals
Superconductivity has been reversibly induced/suppressed in undoped CaFe2As2 (Ca122) single crystals through proper thermal treatments, with Tc at ∼25 K at ambient pressure and up to 30 K at 1.7 GPa. We found that Ca122 can be
stabilized in two distinct ...
Social Sciences
Environmental Sciences
Individuals, communities, and societies ascribe a diverse array of values to landscapes.
These values are shaped by the aesthetic, cultural, and recreational benefits and
services provided by those landscapes. However, across the globe, processes such as
...
Psychological and Cognitive Sciences
Visual sensitivity is markedly reduced during an eye movement. Peri-saccadic vision
is also characterized by a mislocalization of the briefly presented stimulus closer
to the saccadic target. These features are commonly viewed as obligatory elements
of ...
Concepts organize the relationship among individual stimuli or events by highlighting
shared features. Often, new goals require updating conceptual knowledge to reflect
relationships based on different goal-relevant features. Here, our aim is to determine
...
Social Sciences
Social interactions increasingly take place online. Friendships and other offline
social ties have been repeatedly associated with human longevity, but online interactions
might have different properties. Here, we reference 12 million social media ...
Binary decisions of agents coupled in networks can often be classified into two types:
“coordination,” where an agent takes an action if enough neighbors are using that
action, as in the spread of social norms, innovations, and viral epidemics, and “...
Sustainability Science
Individuals, communities, and societies ascribe a diverse array of values to landscapes.
These values are shaped by the aesthetic, cultural, and recreational benefits and
services provided by those landscapes. However, across the globe, processes such as
...
Biological Sciences
Anthropology
Examples of wetland deposits can be found across the globe and are known for preserving
organic archaeological and environmental remains that are vitally important to our
understanding of past human–environment interactions. The Mesolithic site of Star
...
Biochemistry
The HIV-1 envelope (Env) glycoprotein, a trimer of gp120–gp41 heterodimers, relies
on conformational flexibility to function in fusing the viral and host membranes.
Fusion is achieved after gp120 binds to CD4, the HIV-1 receptor, and a coreceptor,
...
The proteasome is the major engine of protein degradation in all eukaryotic cells.
At the heart of this machine is a heterohexameric ring of AAA (ATPases associated
with diverse cellular activities) proteins that unfolds ubiquitylated target proteins
that ...
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The 3C-like protease (3CLpro) of severe acute respiratory syndrome coronavirus (SARS-CoV) cleaves 11 sites in
the polyproteins, including its own N- and C-terminal autoprocessing sites, by recognizing
P4–P1 and P1′. In this study, we determined the ...
In Drosophila, P-element transposition causes mutagenesis and genome instability during hybrid
dysgenesis. The P-element 31-bp terminal inverted repeats (TIRs) contain sequences
essential for transposase cleavage and have been implicated in DNA repair via ...
We identify a target for treating obesity and type 2 diabetes, the consumption of
calories by an increase in the metabolic rate of resting skeletal muscle. The metabolic
rate of skeletal muscle can be increased by shifting myosin heads from the super-...
STAT6 participates in classical IL-4/IL-13 signaling and stimulator of interferon
genes-mediated antiviral innate immune responses. Aberrations in STAT6-mediated signaling
are linked to development of asthma and diseases of the immune system. In addition,
...
Telomerase replicates chromosome ends to facilitate continued cell division. Mutations
that compromise telomerase function result in stem cell failure diseases, such as
dyskeratosis congenita (DC). One such mutation (K170Δ), residing in the telomerase-...
Methanotrophic bacteria use methane, a potent greenhouse gas, as their primary source
of carbon and energy. The first step in methane metabolism is its oxidation to methanol.
In almost all methanotrophs, this chemically challenging reaction is catalyzed ...
Biophysics and Computational Biology
The mechanical properties of cells impact on their architecture, their migration,
intracellular trafficking, and many other cellular functions and have been shown to
be modified during cancer progression. We have developed an approach to map the ...
This article has a correction:
Correction for Mandal et al., Mapping intracellular mechanics on micropatterned substrates
An essential early step in the assembly of human spliceosomes onto pre-mRNA involves
the recognition of regulatory RNA cis elements in the 3′ splice site by the U2 auxiliary factor (U2AF). The large (U2AF65)
and small (U2AF35) subunits of the U2AF ...
Microtubules are structural polymers inside of cells that are subject to posttranslational
modifications. These posttranslational modifications create functionally distinct
subsets of microtubule networks in the cell, and acetylation is the only ...
In eukaryotic cells, membranous vesicles and organelles are transported by ensembles
of motor proteins. These motors, such as kinesin-1, have been well characterized in
vitro as single molecules or as ensembles rigidly attached to nonbiological ...
Spatially and temporally coordinated variations of the cytosolic free calcium concentration
([Ca2+]c) play a crucial role in a variety of tissues. In the developing sensory epithelium
of the mammalian cochlea, elevation of extracellular adenosine ...
HIV type-1 (HIV-1) contains a pseudodiploid RNA genome that is selected for packaging
and maintained in virions as a noncovalently linked dimer. Genome dimerization is
mediated by conserved elements within the 5′-leader of the RNA, including a palindromic
...
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The 3D structure determination of biological macromolecules by X-ray crystallography
suffers from a phase problem: to perform Fourier transformation to calculate real
space density maps, both intensities and phases of structure factors are necessary;
...
Proper folding of proteins is critical to producing the biological machinery essential
for cellular function. The rates and energetics of a protein’s folding process, which
is described by its energy landscape, are encoded in the amino acid sequence. Over
...
Fusion of lipid bilayers is usually prevented by large energy barriers arising from
removal of the hydration shell, formation of highly curved structures, and, eventually,
fusion pore widening. Here, we measured the force-dependent lifetime of fusion ...
Cell Biology
Fibrodysplasia ossificans progressiva (FOP) patients carry a missense mutation in
ACVR1 [617G > A (R206H)] that leads to hyperactivation of BMP-SMAD signaling. Contrary
to a previous study, here we show that FOP fibroblasts showed an increased efficiency
...
Neurons depend on oxidative phosphorylation for energy generation, whereas astrocytes
do not, a distinctive feature that is essential for neurotransmission and neuronal
survival. However, any link between these metabolic differences and the structural
...
Protein kinase A (PKA) phosphorylates Gli proteins, acting as a negative regulator
of the Hedgehog pathway. PKA was recently detected within the cilium, and PKA activity
specifically in cilia regulates Gli processing. Using a cilia-targeted genetically
...
Developmental Biology
Developmental gene regulatory networks (GRNs) are assemblages of gene regulatory interactions
that direct ontogeny of animal body plans. Studies of GRNs operating in the early
development of euechinoid sea urchins have revealed that little appreciable ...
The hemochorial placenta develops from the coordinated multilineage differentiation
of trophoblast stem (TS) cells. An invasive trophoblast cell lineage remodels uterine
spiral arteries, facilitating nutrient flow, failure of which is associated with ...
Ecology
For over 40 y the dominant theory of stomatal behavior has been that plants should
open stomates until the carbon gained by an infinitesimal additional opening balances
the additional water lost times a water price that is constant at least over short
...
Climate change is altering the frequency and severity of forest disturbances such
as wildfires and bark beetle outbreaks, thereby increasing the potential for sequential
disturbances to interact. Interactions can amplify or dampen disturbances, yet the
...
In temperate countries, influenza outbreaks are well correlated to seasonal changes
in temperature and absolute humidity. However, tropical countries have much weaker
annual climate cycles, and outbreaks show less seasonality and are more difficult
to ...
View related content:
Timing and periodicity of influenza epidemics
View related content:Does influenza drive absolute humidity?
This article has a reply:Reply to Baskerville and Cobey: Misconceptions about causation with synchrony and seasonal drivers
In evergreen conifers, where the foliage amount changes little with season, accurate
detection of the underlying “photosynthetic phenology” from satellite remote sensing
has been difficult, presenting challenges for global models of ecosystem carbon ...
Countershading, the widespread tendency of animals to be darker on the side that receives
strongest illumination, has classically been explained as an adaptation for camouflage:
obliterating cues to 3D shape and enhancing background matching. However, ...
Climate change is expected to exacerbate drought for many plants, making drought tolerance
a key driver of species and ecosystem responses. Plant drought tolerance is determined
by multiple traits, but the relationships among traits, either within ...
Environmental Sciences
Plankton, corals, and other organisms produce calcium carbonate skeletons that are
integral to their survival, form a key component of the global carbon cycle, and record
an archive of past oceanographic conditions in their geochemistry. A key aspect of
...
Conventional calculations of the global carbon budget infer the land sink as a residual
between emissions, atmospheric accumulation, and the ocean sink. Thus, the land sink
accumulates the errors from the other flux terms and bears the largest ...
Evolution
Serine is the only amino acid that is encoded by two disjoint codon sets so that a
tandem substitution of two nucleotides is required to switch between the two sets.
Previously published evidence suggests that, for the most evolutionarily conserved
...
Symbiotic relationships promote biological diversification by unlocking new ecological
niches. Over evolutionary time, hosts and symbionts often enter intimate and permanent
relationships, which must be maintained and regulated for both lineages to ...
Genetics
Duchenne muscular dystrophy (DMD) is an incurable X-linked genetic disease that is
caused by a mutation in the dystrophin gene and affects one in every 3,600 boys. We previously showed that long telomeres
protect mice from the lethal cardiac disease seen ...
Gene fusions and fusion products were thought to be unique features of neoplasia.
However, more and more studies have identified fusion RNAs in normal physiology. Through
RNA sequencing of 27 human noncancer tissues, a large number of fusion RNAs were ...
Immunology and Inflammation
The protein encoded by the autoimmune-associated protein tyrosine phosphatase nonreceptor
type 22 gene, PTPN22, has wide-ranging effects in immune cells including suppression of T-cell receptor
signaling and promoting efficient production of type I ...
Despite the impressive rates of clinical response to programmed death 1 (PD-1) blockade
in multiple cancers, the majority of patients still fail to respond to this therapy.
The CT26 tumor in mice showed similar heterogeneity, with most tumors unaffected ...
Gasdermin B (GSDMB) on chromosome 17q21 demonstrates a strong genetic linkage to asthma,
but its function in asthma is unknown. Here we identified that GSDMB is highly expressed
in lung bronchial epithelium in human asthma. Overexpression of GSDMB in ...
Medical Sciences
Hutchinson–Gilford progeria syndrome (HGPS) is a rare genetic disease caused by defective
prelamin A processing, leading to nuclear lamina alterations, severe cardiovascular
pathology, and premature death. Prelamin A alterations also occur in ...
Janus kinases (JAKs) classically signal by activating STAT transcription factors but
can also regulate gene expression by epigenetically phosphorylating histone H3 on
tyrosine 41 (H3Y41-P). In diffuse large B-cell lymphomas (DLBCLs), JAK signaling is
a ...
Social interactions increasingly take place online. Friendships and other offline
social ties have been repeatedly associated with human longevity, but online interactions
might have different properties. Here, we reference 12 million social media ...
Noninvasive functional imaging of molecular and cellular processes of vision may have
immense impact on research and clinical diagnostics. Although suitable intrinsic optical
signals (IOSs) have been observed ex vivo and in immobilized animals in vivo, ...
View related content:
Noninvasive imaging of the photoreceptor mosaic response to light stimulation
Congestive heart failure is one of the leading causes of disability in long-term survivors
of cancer. The anthracycline antibiotic doxorubicin (DOX) is used to treat a variety
of cancers, but its utility is limited by its cumulative cardiotoxicity. As ...
Prodigiosin, a natural red pigment produced by numerous bacterial species, has exhibited
promising anticancer activity; however, the molecular mechanisms of action of prodigiosin
on malignant cells remain unclear. Aberrant activation of the Wnt/β-catenin ...
Deficiency in PTEN (phosphatase and tensin homolog deleted on chromosome 10) is the
underlying cause of PTEN hamartoma tumor syndrome and a wide variety of human cancers.
In skin epidermis, we have previously identified an autocrine FGF signaling induced
...
Multiple myeloma (MM) has proven clinically susceptible to modulation of pathways
of protein homeostasis. Blockade of proteasomal degradation of polyubiquitinated misfolded
proteins by the proteasome inhibitor bortezomib (BTZ) achieves responses and ...
Microbiology
Spatial ordering of macromolecular components inside cells is important for cellular
physiology and replication. In bacteria, ParA/B systems are known to generate various
intracellular patterns that underlie the transport and partitioning of low-copy-...
The bacteria harbored by fungus-growing ants produce a variety of small molecules
that help maintain a complex multilateral symbiosis. In a survey of antifungal compounds
from these bacteria, we discovered selvamicin, an unusual antifungal polyene ...
Expression of HIV-1 matrix protein p17 and association with B-cell lymphoma in HIV-1 transgenic mice
HIV-1 infection is associated with increased risk for B-cell lymphomas. How HIV infection
promotes the development of lymphoma is unclear, but it may involve chronic B-cell
activation, inflammation, and/or impaired immunity, possibly leading to a loss of
...
Cyclic diguanosine monophosphate (c-di-GMP) is a second messenger that controls diverse
functions in bacteria, including transitions from planktonic to biofilm lifestyles,
virulence, motility, and cell cycle. Here we describe TolR, a hybrid two-component
...
Clostridium thermocellum can ferment cellulosic biomass to formate and other end products, including CO2. This organism lacks formate dehydrogenase (Fdh), which catalyzes the reduction of
CO2 to formate. However, feeding the bacterium 13C-bicarbonate and ...
Signal peptides of membrane proteins are cleaved by signal peptidase once the nascent
proteins reach the endoplasmic reticulum. Previously, we reported that, contrary to
the paradigm, the signal peptide of ruminant CD18, the β subunit of β2 integrins, is ...
The oceanic N2-fixing cyanobacterium Trichodesmium spp. form extensive surface blooms and contribute significantly to marine carbon
and nitrogen cycles in the oligotrophic subtropical and tropical oceans. Trichodesmium grows in salinities from 27 to 43 ...
The lentivirus equine infectious anemia virus (EIAV) encodes the small protein S2,
a pathogenic determinant that is important for virus replication and disease progression
in horses. No molecular function had been linked to this accessory protein. We ...
Neuroscience
Brain areas within the lateral parietal cortex (LPC) and ventral temporal cortex (VTC)
have been shown to code for abstract quantity representations and for symbolic numerical
representations, respectively. To explore the fast dynamics of activity within ...
Rett syndrome (RTT) arises from loss-of-function mutations in methyl-CpG binding protein
2 gene (Mecp2), but fundamental aspects of its physiological mechanisms are unresolved. Here, by
whole-cell recording of synaptic responses in MeCP2 mutant mice in ...
Optogenetic methods have been highly effective for suppressing neural activity and
modulating behavior in rodents, but effects have been much smaller in primates, which
have much larger brains. Here, we present a suite of technologies to use optogenetics
...
Concepts organize the relationship among individual stimuli or events by highlighting
shared features. Often, new goals require updating conceptual knowledge to reflect
relationships based on different goal-relevant features. Here, our aim is to determine
...
Many forms of short-term synaptic plasticity rely on regulation of presynaptic voltage-gated
Ca2+ type 2.1 (CaV2.1) channels. However, the contribution of regulation of CaV2.1 channels to other forms of neuroplasticity and to learning and memory are not
...
In the vertebrate retina, three types of photoreceptors—visual photoreceptor cones
and rods and the intrinsically photosensitive retinal ganglion cells (ipRGCs)—converged
through evolution to detect light and regulate image- and nonimage-forming ...
Calcium threshold shift enables frequency-independent control of plasticity by an instructive signal
At glutamatergic synapses, both long-term potentiation (LTP) and long-term depression
(LTD) can be induced at the same synaptic activation frequency. Instructive signals
determine whether LTP or LTD is induced, by modulating local calcium transients. ...
Innate immune cells play a key role in the pathogenesis of multiple sclerosis and
experimental autoimmune encephalomyelitis (EAE). Current clinical imaging is restricted
to visualizing secondary effects of inflammation, such as gliosis and blood–brain
...
There are profound sex differences in the incidence of many psychiatric disorders.
Although these disorders are frequently linked to social stress and to deficits in
social engagement, little is known about sex differences in the neural mechanisms
that ...
Population Biology
Respiratory syncytial virus (RSV) is the most common cause of US infant hospitalization.
Additionally, RSV is responsible for 10,000 deaths annually among the elderly across
the United States, and accounts for nearly as many hospitalizations as influenza.
...
Natal philopatry, the return of individuals to their natal area for reproduction,
has advantages and disadvantages for animal populations. Natal philopatry may generate
local genetic adaptation, but it may also increase the probability of inbreeding that
...
Plant Biology
Peroxisomes are ubiquitous eukaryotic organelles that play pivotal roles in a suite
of metabolic processes and often act coordinately with other organelles, such as chloroplasts
and mitochondria. Peroxisomes import proteins to the peroxisome matrix by ...
The ubiquity of nonparental hybrid phenotypes, such as hybrid vigor and hybrid inferiority,
has interested biologists for over a century and is of considerable agricultural importance.
Although examples of both phenomena have been subject to intense ...
Psychological and Cognitive Sciences
Visual sensitivity is markedly reduced during an eye movement. Peri-saccadic vision
is also characterized by a mislocalization of the briefly presented stimulus closer
to the saccadic target. These features are commonly viewed as obligatory elements
of ...
Although music is ubiquitous in human societies, there are some people for whom music
holds no reward value despite normal perceptual ability and preserved reward-related
responses in other domains. The study of these individuals with specific musical ...
Previous evidence indicates that the brain stores memory in two complementary systems,
allowing both rapid plasticity and stable representations at different sites. For
memory to be established in a long-lasting neocortical store, many learning ...
Corrections (Online Only)
Cover image: Pictured is a cross section of black peppercorns with yellowish cores containing several biologically active molecules, including an abundance of the piperine alkaloid. Leonardo Nogara et al. screened more than 2,000 molecules to identify candidates with the ability to raise the metabolic rate of resting skeletal muscle, a potential approach to mitigate obesity and diabetes. The authors found that piperine destabilized myosin filaments and shifted resting muscle fibers from a state of low to high metabolic activity, suggesting that piperine might aid the development of therapies for obesity and type 2 diabetes. See the article by Nogara et al. on pages 13009–13014. Image courtesy of Leonardo Nogara and Manuela Marabita (Università degli Studi di Padova, Padova, Italy).
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