Table Of Contents Page, PNAS Volume 112, Number 47
This Week in PNAS
Letters (Online Only)
View the original article:
Temporal and spatial variation of the human microbiota during pregnancy
This article has a reply:Reply to Keelan and Payne: Microbiota-related pathways for preterm birth
News Feature
Commentaries
PNAS Plus Significance Statements
The Engineering of Biology and Medicine PNAS 100th Anniversary Special Feature (Free Online)
Introduction
Perspectives
Imaging reveals complex structures and dynamic interactive processes, located deep
inside the body, that are otherwise difficult to decipher. Numerous imaging modalities
harness every last inch of the energy spectrum. Clinical modalities include magnetic
...
There is a growing need to enhance our capabilities in medical and environmental diagnostics.
Synthetic biologists have begun to focus their biomolecular engineering approaches
toward this goal, offering promising results that could lead to the ...
In 2000 the United States launched the National Nanotechnology Initiative and, along
with it, a well-defined set of goals for nanomedicine. This Perspective looks back
at the progress made toward those goals, within the context of the changing landscape
...
Biomaterials that interface with biological systems are used to deliver drugs safely
and efficiently; to prevent, detect, and treat disease; to assist the body as it heals;
and to engineer functional tissues outside of the body for organ replacement. The
...
Organ and tissue loss through disease and injury motivate the development of therapies
that can regenerate tissues and decrease reliance on transplantations. Regenerative
medicine, an interdisciplinary field that applies engineering and life science ...
Nanoparticle technologies intended for human administration must be designed to interact
with, and ideally leverage, a living host environment. Here, we describe smart nanosystems
classified in two categories: (i) those that sense the host environment and ...
Immunotherapy has great potential to treat cancer and prevent future relapse by activating
the immune system to recognize and kill cancer cells. A variety of strategies are
continuing to evolve in the laboratory and in the clinic, including therapeutic ...
Physical Sciences
Applied Mathematics
We recently used in situ Hi-C to create kilobase-resolution 3D maps of mammalian genomes.
Here, we combine these maps with new Hi-C, microscopy, and genome-editing experiments
to study the physical structure of chromatin fibers, domains, ...
View related content:
Predictive model of 3D domain formation via CTCF-mediated extrusion
Accurate real-time tracking of influenza outbreaks helps public health officials make
timely and meaningful decisions that could save lives. We propose an influenza tracking
model, ARGO (AutoRegression with GOogle search data), that uses publicly ...
A scientist’s choice of research problem affects his or her personal career trajectory.
Scientists’ combined choices affect the direction and efficiency of scientific discovery
as a whole. In this paper, we infer preferences that shape problem selection ...
Pathological changes in excitability of cortical tissue commonly underlie the initiation
and spread of seizure activity in patients suffering from epilepsy. Accordingly, monitoring
excitability and controlling its degree using antiepileptic drugs (AEDs) ...
Applied Physical Sciences
Microtubules (MTs) are hollow cytoskeletal filaments assembled from αβ-tubulin heterodimers.
Tau, an unstructured protein found in neuronal axons, binds to MTs and regulates their
dynamics. Aberrant Tau behavior is associated with neurodegenerative ...
Transient electric fields, which are an important but hardly explored parameter of
laser plasmas, can now be diagnosed experimentally with combined ultrafast temporal
resolution and field sensitivity, using femtosecond to picosecond electron or proton
...
The assembly of tiny magnetic particles in external magnetic fields is important for
many applications ranging from data storage to medical technologies. The development
of ever smaller magnetic structures is restricted by a size limit, where the ...
In the classic theory of solid adhesion, surface energy drives deformation to increase
contact area whereas bulk elasticity opposes it. Recently, solid surface stress has
been shown also to play an important role in opposing deformation of soft materials.
...
Topological mechanical metamaterials are artificial structures whose unusual properties
are protected very much like their electronic and optical counterparts. Here, we present
an experimental and theoretical study of an active metamaterial—composed of ...
Grain refinement can make conventional metals several times stronger, but this comes
at dramatic loss of ductility. Here we report a heterogeneous lamella structure in
Ti produced by asymmetric rolling and partial recrystallization that can produce an
...
Chemistry
A long-standing contradiction in the field of mononuclear Mo enzyme research is that
small-molecule chemistry on active-site mimic compounds predicts ligand participation
in the electron transfer reactions, but biochemical measurements only suggest metal-...
Earth, Atmospheric, and Planetary Sciences
Oceanic uptake of anthropogenic carbon dioxide (CO2) has acidified open-ocean surface waters by 0.1 pH units since preindustrial times.
Despite unequivocal evidence of ocean acidification (OA) via open-ocean measurements
for the past several decades, it ...
Evidence of life on Earth is manifestly preserved in the rock record. However, the
microfossil record only extends to ∼3.5 billion years (Ga), the chemofossil record
arguably to ∼3.8 Ga, and the rock record to 4.0 Ga. Detrital zircons from Jack Hills,
...
View related content:
Desert wetlands are keystone ecosystems in arid environments and are preserved in
the geologic record as groundwater discharge (GWD) deposits. GWD deposits are inherently
discontinuous and stratigraphically complex, which has limited our understanding of
...
Engineering
Heteroatom doping is an efficient way to modify the chemical and electronic properties
of graphene. In particular, boron doping is expected to induce a p-type (boron)-conducting behavior to pristine (nondoped) graphene, which could lead
to diverse ...
This article has a correction:
Correction for Lv et al., Ultrasensitive gas detection of large-area boron-doped graphene
We report a fabrication method for flexible and printable thermal sensors based on
composites of semicrystalline acrylate polymers and graphite with a high sensitivity
of 20 mK and a high-speed response time of less than 100 ms. These devices exhibit
...
The ability of humans to distinguish the delicate differences in food flavors depends
mostly on retronasal smell, in which food volatiles entrained into the airway at the
back of the oral cavity are transported by exhaled air through the nasal cavity to
...
Physics
We report an analytical study of the vibrational spectrum of the simplest model of
jamming, the soft perceptron. We identify two distinct classes of soft modes. The
first kind of modes are related to isostaticity and appear only in the close vicinity
of ...
Designing and controlling particle self-assembly into robust and reliable high-performance
smart materials often involves crystalline ordering in curved spaces. Examples include
carbon allotropes like graphene, synthetic materials such as colloidosomes, ...
We determine conditions on the filling of electrons in a crystalline lattice to obtain
the equivalent of a band insulator—a gapped insulator with neither symmetry breaking
nor fractionalized excitations. We allow for strong interactions, which precludes
a ...
Social Sciences
Economic Sciences
Prior studies have shown that traders quickly converge to the price–quantity equilibrium
in markets for goods that are immediately consumed, but they produce speculative price
bubbles in resalable asset markets. We present a stock-flow model of durable ...
Psychological and Cognitive Sciences
Emotional responses to biologically significant events are essential for human survival.
Do human emotions lawfully track changes in the acoustic environment? Here we report
that changes in acoustic attributes that are well known to interact with human ...
Social Sciences
A scientist’s choice of research problem affects his or her personal career trajectory.
Scientists’ combined choices affect the direction and efficiency of scientific discovery
as a whole. In this paper, we infer preferences that shape problem selection ...
Biological Sciences
Applied Biological Sciences
Mapping landscape friction to locate isolated tsetse populations that are candidates for elimination
Tsetse flies are the cyclical vectors of deadly human and animal trypanosomes in sub-Saharan
Africa. Tsetse control is a key component for the integrated management of both plagues,
but local eradication successes have been limited to less than 2% of the ...
Biochemistry
The organization of membranes, the cytosol, and the nucleus of eukaryotic cells can
be controlled through phase separation of lipids, proteins, and nucleic acids. Collective
interactions of multivalent molecules mediated by modular binding domains can ...
View related content:
Allosteric N-WASP activation by an inter-SH3 domain linker in Nck
Actin filament networks assemble on cellular membranes in response to signals that
locally activate neural Wiskott–Aldrich-syndrome protein (N-WASP) and the Arp2/3 complex.
An inactive conformation of N-WASP is stabilized by intramolecular contacts ...
The dicistrovirus intergenic region internal ribosome entry site (IRES) adopts a triple-pseudoknotted
RNA structure and occupies the core ribosomal E, P, and A sites to directly recruit
the ribosome and initiate translation at a non-AUG codon. A subset of ...
A long-standing contradiction in the field of mononuclear Mo enzyme research is that
small-molecule chemistry on active-site mimic compounds predicts ligand participation
in the electron transfer reactions, but biochemical measurements only suggest metal-...
G-quadruplex structures formed by guanine-rich nucleic acids are implicated in essential
physiological and pathological processes and nanodevices. G-quadruplexes are normally
composed of four Gn (n ≥ 3) tracts assembled into a core of multiple stacked G-...
Small RNA pathways are important players in posttranscriptional regulation of gene
expression. These pathways play important roles in all aspects of cellular physiology
from development to fertility to innate immunity. However, almost nothing is known
...
Myosins use a conserved structural mechanism to convert the energy from ATP hydrolysis
into a large swing of the force-generating lever arm. The precise timing of the lever
arm movement with respect to the steps in the actomyosin ATPase cycle has not been
...
Enzymes in heteromeric, allosterically regulated complexes catalyze a rich array of
chemical reactions. Separating the subunits of such complexes, however, often severely
attenuates their catalytic activities, because they can no longer be activated by
...
Biophysics and Computational Biology
Microtubules (MTs) are hollow cytoskeletal filaments assembled from αβ-tubulin heterodimers.
Tau, an unstructured protein found in neuronal axons, binds to MTs and regulates their
dynamics. Aberrant Tau behavior is associated with neurodegenerative ...
We recently used in situ Hi-C to create kilobase-resolution 3D maps of mammalian genomes.
Here, we combine these maps with new Hi-C, microscopy, and genome-editing experiments
to study the physical structure of chromatin fibers, domains, ...
View related content:
Predictive model of 3D domain formation via CTCF-mediated extrusion
The design of stable, functional proteins is difficult. Improved design requires a
deeper knowledge of the molecular basis for design outcomes and properties. We previously
used a bioinformatics and energy function method to design a symmetric superfold ...
Microtubules and their associated proteins perform a broad array of essential physiological
functions, including mitosis, polarization and differentiation, cell migration, and
vesicle and organelle transport. As such, they have been extensively studied at ...
Host factor protein Cyclophilin A (CypA) regulates HIV-1 viral infectivity through
direct interactions with the viral capsid, by an unknown mechanism. CypA can either
promote or inhibit viral infection, depending on host cell type and HIV-1 capsid (CA)
...
Cell Biology
The major underpinning of massive cell death associated with myocardial infarction
involves opening of the mitochondrial permeability transition pore (mPTP), resulting
in disruption of mitochondria membrane integrity and programmed necrosis. Studies
in ...
Lung adenocarcinoma, a major form of non-small cell lung cancer, is the leading cause
of cancer deaths. The Cancer Genome Atlas analysis of lung adenocarcinoma has identified
a large number of previously unknown copy number alterations and mutations, ...
Defects in the innate immune system in the lung with attendant bacterial infections
contribute to lung tissue damage, respiratory insufficiency, and ultimately death
in the pathogenesis of cystic fibrosis (CF). Professional phagocytes, including alveolar
...
Regulated shedding of the ectodomain of cell membrane proteins by proteases is a common
process that releases the extracellular domain from the cell and activates cell signaling.
Ectodomain shedding occurs in the immediate extracellular juxtamembrane ...
Developmental Biology
During the human in vitro fertilization procedure in the assisted reproductive technology,
intracytoplasmic sperm injection is routinely used to inject a spermatozoon or a less
mature elongating spermatid into the oocyte. In some infertile men, round ...
This article has a correction:
During meiosis, homologous chromosomes associate to form the synaptonemal complex
(SC), a structure essential for fertility. Information about the epigenetic features
of chromatin within this structure at the level of superresolution microscopy is largely
...
Substantial proportions of mammalian genomes comprise repetitive elements including
endogenous retrotransposons. Although these play diverse roles during development,
their appropriate silencing is critically important in maintaining genomic integrity
in ...
Environmental Sciences
Oceanic uptake of anthropogenic carbon dioxide (CO2) has acidified open-ocean surface waters by 0.1 pH units since preindustrial times.
Despite unequivocal evidence of ocean acidification (OA) via open-ocean measurements
for the past several decades, it ...
The desiccation of upper soil horizons is a common phenomenon, leading to a decrease
in soil microbial activity and mineralization. Recent studies have shown that fungal
communities and fungal-based food webs are less sensitive and better adapted to soil
...
In large regions of the open ocean, iron is a limiting resource for phytoplankton.
The reduction of iron quota and the recycling of internal iron pools are among the
diverse strategies that phytoplankton have evolved to allow them to grow under ...
Evolution
The prevailing view that the evolution of cells in a tumor is driven by Darwinian
selection has never been rigorously tested. Because selection greatly affects the
level of intratumor genetic diversity, it is important to assess whether intratumor
...
Genetics
The long noncoding X-inactivation–specific transcript (Xist gene) is responsible for mammalian X-chromosome dosage compensation between the sexes,
the process by which one of the two X chromosomes is inactivated in the female soma.
Xist is essential for ...
View related content:
Imprinted X chromosome inactivation offers up a double dose of epigenetics
View related content:Previous genome-wide association studies (GWAS) of HIV-1–infected populations have
been underpowered to detect common variants with moderate impact on disease outcome
and have not assessed the phenotypic variance explained by genome-wide additive effects.
...
Immunology and Inflammation
Signaling through the immune checkpoint programmed cell death protein-1 (PD-1) enables
tumor progression by dampening antitumor immune responses. Therapeutic blockade of
the signaling axis between PD-1 and its ligand programmed cell death ligand-1 (PD-L1)
...
The receptor-like tyrosine phosphatase CD45 regulates antigen receptor signaling by
dephosphorylating the C-terminal inhibitory tyrosine of the src family kinases. However,
despite its abundance, the function of the large, alternatively spliced ...
Dendritic cells (DCs) link innate and adaptive immunity and use a host of innate immune
and inflammatory receptors to respond to pathogens and inflammatory stimuli. Although
DC maturation via canonical NF-κB signaling is critical for many of these ...
Medical Sciences
Targeting CD146 with a 64Cu-labeled antibody enables in vivo immunoPET imaging of high-grade gliomas
Given the highly heterogeneous character of brain malignancies and the associated
implication for its proper diagnosis and treatment, finding biomarkers that better
characterize this disease from a molecular standpoint is imperative. In this study,
we ...
Copy number variations (CNVs) have been implicated in human diseases. However, it
remains unclear how they affect immune dysfunction and autoimmune diseases, including
rheumatoid arthritis (RA). Here, we identified a novel leukocyte-specific protein
1 (...
Evidence from numerous cancers suggests that increased aggressiveness is accompanied
by up-regulation of signaling pathways and acquisition of properties common to stem
cells. It is unclear if different subtypes of late-stage cancer vary in stemness ...
View related content:
Noninvasive prenatal testing (NIPT) using sequencing of fetal cell-free DNA from maternal
plasma has enabled accurate prenatal diagnosis of aneuploidy and become increasingly
accepted in clinical practice. We investigated whether NIPT using semiconductor ...
Hearing loss is the main limitation of radiation therapy for vestibular schwannoma
(VS), and identifying treatment options that minimize hearing loss are urgently needed.
Treatment with bevacizumab is associated with tumor control and hearing improvement
...
Microbiology
Phosphatidylserine (PS) receptors contribute to two crucial biological processes:
apoptotic clearance and entry of many enveloped viruses. In both cases, they recognize
PS exposed on the plasma membrane. Here we demonstrate that phosphatidylethanolamine
(...
Three-quarters of the estimated 390 million dengue virus (DENV) infections each year
are clinically inapparent. People with inapparent dengue virus infections are generally
considered dead-end hosts for transmission because they do not reach sufficiently
...
Neuroscience
Fragile X syndrome is a common cause of intellectual disability and autism spectrum
disorder. The gene underlying the disorder, fragile X mental retardation 1 (FMR1), is silenced in most cases by a CGG-repeat expansion mutation in the 5′ untranslated
...
Pathological changes in excitability of cortical tissue commonly underlie the initiation
and spread of seizure activity in patients suffering from epilepsy. Accordingly, monitoring
excitability and controlling its degree using antiepileptic drugs (AEDs) ...
The ability of humans to distinguish the delicate differences in food flavors depends
mostly on retronasal smell, in which food volatiles entrained into the airway at the
back of the oral cavity are transported by exhaled air through the nasal cavity to
...
The NMDA receptor (R) plays important roles in brain physiology and pathology as an
ion channel. Here we examine the ion flow-independent coupling of agonist to the NMDAR
cytoplasmic domain (cd). We measure FRET between fluorescently tagged cytoplasmic
...
View related content:
Conformational signaling required for synaptic plasticity by the NMDA receptor complex
The NMDA receptor (NMDAR) is known to transmit important information by conducting
calcium ions. However, some recent studies suggest that activation of NMDARs can trigger
synaptic plasticity in the absence of ion flow. Does ligand binding transmit ...
The primate brain contains a set of face-selective areas, which are thought to extract
the rich social information that faces provide, such as emotional state and personal
identity. The nature of this information raises a fundamental question about these
...
View related content:
In the mammalian cochlea, acoustic information is carried to the brain by the predominant
(95%) large-diameter, myelinated type I afferents, each of which is postsynaptic to
a single inner hair cell. The remaining thin, unmyelinated type II afferents ...
Pharmacology
The sigma-1 receptor (Sig-1R) chaperone at the endoplasmic reticulum (ER) plays important
roles in cellular regulation. Here we found a new function of Sig-1R, in that it translocates
from the ER to the nuclear envelope (NE) to recruit chromatin-...
Plant Biology
Inorganic phosphate (Pi) is stored in the vacuole, allowing plants to adapt to variable
Pi availability in the soil. The transporters that mediate Pi sequestration into vacuole
remain unknown, however. Here we report the functional characterization of ...
The maize genome is relatively large (∼2.3 Gb) and has a complex organization of interspersed
genes and transposable elements, which necessitates frequent boundaries between different
types of chromatin. The examination of maize genes and conserved ...
The allocation of carbon and nitrogen resources to the synthesis of plant proteins,
carbohydrates, and lipids is complex and under the control of many genes; much remains
to be understood about this process. QQS (Qua-Quine Starch; At3g30720), an orphan ...
Psychological and Cognitive Sciences
Emotional responses to biologically significant events are essential for human survival.
Do human emotions lawfully track changes in the acoustic environment? Here we report
that changes in acoustic attributes that are well known to interact with human ...
Systems Biology
Diurnal oscillations of gene expression are a hallmark of rhythmic physiology across
most living organisms. Such oscillations are controlled by the interplay between the
circadian clock and feeding rhythms. Although rhythmic mRNA accumulation has been
...
Corrections (Online Only)
Cover image: Pictured are adult mesenchymal stem cells grown in a methylacrylate polymer spot, one of thousands on a microarray used in combinatorial development of biomaterials. The Engineering of Biology and Medicine PNAS 100th Anniversary Special Feature, appearing in this issue, reviews the progress made in the past century in biological and medical engineering, along with challenges in the effort to improve quality of life through nanotechnology, biomaterials, immunotherapy, and other fields. See the Introduction to the Special Feature by Mark E. Davis and Robert Langer on page 14423. Image courtesy of Benjamin Larson (Harvard–MIT Health Sciences and Technology, Cambridge, MA).
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