Table Of Contents Page, PNAS Volume 113, Number 7
This Week in PNAS
Letters (Online Only)
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Rising morbidity and mortality in midlife among white non-Hispanic Americans in the 21st century
View related content:Age-aggregation bias in mortality trends
Urban and rural divergence in mortality trends: A comment on Case and Deaton
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Increased mortality for white middle-aged Americans not fully explained by causes suggested
Rising morbidity and mortality in midlife among white non-Hispanic Americans in the 21st century
View related content:Age-aggregation bias in mortality trends
This article has a reply:
View the original article:
Urban and rural divergence in mortality trends: A comment on Case and Deaton
Rising morbidity and mortality in midlife among white non-Hispanic Americans in the 21st century
Increased mortality for white middle-aged Americans not fully explained by causes suggested
This article has a reply:
This article replies to:
Rising morbidity and mortality in midlife among white non-Hispanic Americans in the 21st century
Age-aggregation bias in mortality trends
Increased mortality for white middle-aged Americans not fully explained by causes suggested
Urban and rural divergence in mortality trends: A comment on Case and Deaton
News Feature
QnAs
Retrospective
Commentaries
PNAS Plus Significance Statements
Physical Sciences
Applied Mathematics
Four decades ago, Leigh Van Valen presented the Red Queen’s hypothesis to account
for evolution of species within a multispecies ecological community [Van Valen L (1973)
Evol Theory 1(1):1–30]. The overall conclusion of Van Valen’s analysis was that ...
Applied Physical Sciences
Essential cellular functions as diverse as genome maintenance and tissue morphogenesis
rely on the dynamic organization of filamentous assemblies. For example, the precise
structural organization of DNA filaments has profound consequences on all DNA-...
Metallic glass (MG) is an important new category of materials, but very few rigorous
laws are currently known for defining its “disordered” structure. Recently we found
that under compression, the volume (V) of an MG changes precisely to the 2.5 power of ...
The procedure of curling a ribbon by running it over a sharp blade is commonly used
when wrapping presents. Despite its ubiquity, a quantitative explanation of this everyday
phenomenon is still lacking. We address this using experiment and theory, ...
Chemistry
Polycyclic aromatic hydrocarbons, in various charge and protonation states, are key
compounds relevant to combustion chemistry and astrochemistry. Here, we probe the
vibrational and electronic spectroscopy of gas-phase 9-, 1-, and 2-anthracenyl radicals
(...
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There is abundant, physiologically relevant knowledge about protein cores; they are
hydrophobic, exquisitely well packed, and nearly all hydrogen bonds are satisfied.
An equivalent understanding of protein surfaces has remained elusive because proteins
...
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A conventional metabolic pathway leads to a specific product. In stark contrast, there
are diversity-generating metabolic pathways that naturally produce different chemicals,
sometimes of great diversity. We demonstrate that for one such pathway, tru, ...
Earth, Atmospheric, and Planetary Sciences
The Mesoproterozoic Eon [1,600–1,000 million years ago (Ma)] is emerging as a key
interval in Earth history, with a unique geochemical history that might have influenced
the course of biological evolution on Earth. Indeed, although this time interval is
...
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Breathing room for early animals
View related content:No evidence for high atmospheric oxygen levels 1,400 million years ago
This article has a reply:Engineering
A major challenge of targeted molecular imaging and drug delivery in cancer is establishing
a functional combination of ligand-directed cargo with a triggered release system.
Here we develop a hydrogel-based nanotechnology platform that integrates tumor ...
Environmental Sciences
Elevational gradients of biodiversity have been widely investigated, and yet a clear
interpretation of the biotic and abiotic factors that determine how species richness
varies with elevation is still elusive. In mountainous landscapes, habitats at ...
Physics
Nonlinear charge transport in superconductor–insulator–superconductor (SIS) Josephson
junctions has a unique signature in the shuttled charge quantum between the two superconductors.
In the zero-bias limit Cooper pairs, each with twice the electron charge,...
Surfaces of ice are covered with thin liquid water layers, called quasi-liquid layers
(QLLs), even below their melting point (0 °C), which govern a wide variety of phenomena
in nature. We recently found that two types of QLL phases appear that exhibit ...
Social Sciences
Psychological and Cognitive Sciences
Winning a competition engenders subsequent unrelated unethical behavior. Five studies
reveal that after a competition has taken place winners behave more dishonestly than
competition losers. Studies 1 and 2 demonstrate that winning a competition increases
...
How universal is human conceptual structure? The way concepts are organized in the
human brain may reflect distinct features of cultural, historical, and environmental
background in addition to properties universal to human cognition. Semantics, or ...
Decades of animal and human neuroimaging research have identified distinct, but overlapping,
striatal zones, which are interconnected with separable corticostriatal circuits,
and are crucial for the organization of functional systems. Despite continuous ...
Sustainability Science
Research about ecosystem services (ES) often aims to generate knowledge that influences
policies and institutions for conservation and human development. However, we have
limited understanding of how decision-makers use ES knowledge or what factors ...
Biological Sciences
Anthropology
How universal is human conceptual structure? The way concepts are organized in the
human brain may reflect distinct features of cultural, historical, and environmental
background in addition to properties universal to human cognition. Semantics, or ...
Biochemistry
Although the importance of the nonuniform progression of elongation in translation
is well recognized, there have been few attempts to explore this process by directly
profiling nascent polypeptides, the relevant intermediates of translation. Such ...
Mycobacterium tuberculosis is a significant source of global morbidity and mortality. Moxifloxacin and other
fluoroquinolones are important therapeutic agents for the treatment of tuberculosis,
particularly multidrug-resistant infections. To guide the ...
Mycobacterium tuberculosis (Mtb) infects one-third of the world’s population and in 2013 accounted for 1.5 million
deaths. Fluoroquinolone antibacterials, which target DNA gyrase, are critical agents
used to halt the progression from multidrug-resistant ...
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A conventional metabolic pathway leads to a specific product. In stark contrast, there
are diversity-generating metabolic pathways that naturally produce different chemicals,
sometimes of great diversity. We demonstrate that for one such pathway, tru, ...
Cancer cells reprogram their metabolism to promote growth and proliferation. The genetic
evidence pointing to the importance of the amino acid serine in tumorigenesis is striking.
The gene encoding the enzyme 3-phosphoglycerate dehydrogenase (PHGDH), ...
Posttranslational modifications (PTMs) are key contributors to chromatin function.
The ability to comprehensively link specific histone PTMs with specific chromatin
factors would be an important advance in understanding the functions and genomic targeting
...
Over 30 years ago, GGDEF domain-containing enzymes were shown to be diguanylate cyclases
that produce cyclic di-GMP (cdiG), a second messenger that modulates the key bacterial
lifestyle transition from a motile to sessile biofilm-forming state. Since then,...
Isomerization reactions are fundamental in biology, and isomers usually differ in
their biological role and pharmacological effects. In this study, we have cataloged
the isomerization reactions known to occur in biology using a combination of manual
and ...
Acyltransferases (ATs) are key determinants of building block specificity in polyketide
biosynthesis. Despite the importance of protein–protein interactions between AT and
acyl carrier protein (ACP) during the acyltransfer reaction, the mechanism of ACP
...
Biophysics and Computational Biology
Essential cellular functions as diverse as genome maintenance and tissue morphogenesis
rely on the dynamic organization of filamentous assemblies. For example, the precise
structural organization of DNA filaments has profound consequences on all DNA-...
It is well known that polyelectrolyte complexes and coacervates can form on mixing
oppositely charged polyelectrolytes in aqueous solutions, due to mainly electrostatic
attraction between the oppositely charged polymers. Here, we report the first (to
the ...
The degree of informatic independence between the physical properties of amino acids
as encoded in actual protein sequences is calculated. It is shown that no physical
property can be identified that carries significantly less information than others
and ...
Cell polarity refers to a functional spatial organization of proteins that is crucial
for the control of essential cellular processes such as growth and division. To establish
polarity, cells rely on elaborate regulation networks that control the ...
Cell Biology
Recent genomic studies challenge the conventional model that each metastasis must
arise from a single tumor cell and instead reveal that metastases can be composed
of multiple genetically distinct clones. These intriguing observations raise the question:
...
Intratumoral heterogeneity is an inherent feature of most human cancers and has profound
implications for cancer therapy. As a result, there is an emergent need to explore
previously unmapped mechanisms regulating distinct subpopulations of tumor cells ...
BRCA1 (breast cancer type 1 susceptibility protein) is a multifunctional tumor suppressor
involved in DNA damage response, DNA repair, chromatin regulation, and mitotic chromosome
segregation. Although the nuclear functions of BRCA1 have been investigated ...
The regulation of the axonal proteome is key to generate and maintain neural function.
Fast and slow axoplasmic waves have been known for decades, but alternative mechanisms
to control the abundance of axonal proteins based on local synthesis have also ...
Developmental Biology
Spermatogonial stem cells (SSCs) are a subpopulation of undifferentiated spermatogonia
located in a niche at the base of the seminiferous epithelium delimited by Sertoli
cells and peritubular myoid (PM) cells. SSCs self-renew or differentiate into ...
Tissue nonautonomous effects of fat body methionine metabolism on imaginal disc repair in Drosophila
Regulatory mechanisms for tissue repair and regeneration within damaged tissue have
been extensively studied. However, the systemic regulation of tissue repair remains
poorly understood. To elucidate tissue nonautonomous control of repair process, it
is ...
Ecology
Understanding how climate influences ecosystems is complicated by the many correlated
and interrelated impacting factors. Here we quantify climate effects on Calanus finmarchicus in the northeastern Norwegian Sea and southwestern Barents Sea. By combining ...
Evolution
Four decades ago, Leigh Van Valen presented the Red Queen’s hypothesis to account
for evolution of species within a multispecies ecological community [Van Valen L (1973)
Evol Theory 1(1):1–30]. The overall conclusion of Van Valen’s analysis was that ...
Immunology and Inflammation
Activation of an anticancer innate immune response is highly desirable because of
its inherent ability to generate an adaptive antitumor T-cell response. However, insufficient
safety of innate immune modulators limits clinical use to topical applications. ...
Structurally disparate molecules reportedly engage and activate Toll-like receptor
(TLR) 4 and other TLRs, yet the interactions that mediate binding and activation by
dissimilar ligands remain unknown. We describe Neoseptins, chemically synthesized
...
The dynamics and molecular mechanisms underlying vaccine immunity in early childhood
remain poorly understood. Here we applied systems approaches to investigate the innate
and adaptive responses to trivalent inactivated influenza vaccine (TIV) and MF59-...
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Systems vaccinology informs influenza vaccine immunogenicity
Patients with pemphigus vulgaris (PV) harbor antibodies reactive against self-antigens
expressed at the surface of keratinocytes, primarily desmoglein (Dsg) 3 and, to a
lesser extent, Dsg1. Conventionally, only antibodies targeting these molecules have
...
Tristetraprolin (TTP) is an inducible, tandem zinc-finger mRNA binding protein that
binds to adenylate-uridylate–rich elements (AREs) in the 3′-untranslated regions (3′UTRs)
of specific mRNAs, such as that encoding TNF, and increases their rates of ...
Tle1 (transducin-like enhancer of split 1) is a corepressor that interacts with a
variety of DNA-binding transcription factors and has been implicated in many cellular
functions; however, physiological studies are limited. Tle1-deficient (Tle1Δ/Δ) mice, ...
Medical Sciences
A major challenge of targeted molecular imaging and drug delivery in cancer is establishing
a functional combination of ligand-directed cargo with a triggered release system.
Here we develop a hydrogel-based nanotechnology platform that integrates tumor ...
Reservoirs of infectious HIV-1 persist despite years of combination antiretroviral
therapy and make curing HIV-1 infections a major challenge. Most of the proviral DNA
resides in CD4+T cells. Some of these CD4+T cells are clonally expanded; most of the ...
Induced pluripotent stem cells (iPS cells) represent a unique tool for the study of
the pathophysiology of human disease, because these cells can be differentiated into
multiple cell types in vitro and used to generate patient- and tissue-specific disease
...
Dyslipidemia associated with triglyceride-rich lipoproteins (TRLs) represents an important
residual risk factor for cardiovascular and chronic kidney disease in patients with
type 1 diabetes (T1D). Levels of growth hormone (GH) are elevated in T1D, which ...
Microbiology
We report on the properties and function of two herpes simplex virus-1 (HSV-1) microRNAs
(miRNAs) designated “miR-H28” and “miR-H29.” Both miRNAs accumulate late in productive
infection at a time when, for the most part, viral DNA and proteins have been ...
Autophagy is an essential component of innate immunity, enabling the detection and
elimination of intracellular pathogens. Legionella pneumophila, an intracellular pathogen that can cause a severe pneumonia in humans, is able to
modulate autophagy through ...
Neuroscience
In Drosophila, olfactory sensory neurons (OSNs) rely primarily on two types of chemoreceptors,
odorant receptors (Ors) and ionotropic receptors (Irs), to convert odor stimuli into
neural activity. The cellular signaling of these receptors in their native ...
Lewy bodies (LBs) are intraneuronal inclusions consisting primarily of fibrillized
human α-synuclein (hα-Syn) protein, which represent the major pathological hallmark
of Parkinson's disease (PD). Although doubling hα-Syn expression provokes LB pathology
...
In mature neurons AMPA receptors cluster at excitatory synapses primarily on dendritic
spines, whereas GABAA receptors cluster at inhibitory synapses mainly on the soma and dendritic shafts.
The molecular mechanisms underlying the precise sorting of these ...
Decades of animal and human neuroimaging research have identified distinct, but overlapping,
striatal zones, which are interconnected with separable corticostriatal circuits,
and are crucial for the organization of functional systems. Despite continuous ...
Visual processing depends critically on the receptive field (RF) properties of visual
neurons. However, comprehensive characterization of RFs beyond the primary visual
cortex (V1) remains a challenge. Here we report fine RF structures in secondary visual
...
There is evidence from the visual, verbal, and tactile memory domains that the midventrolateral
prefrontal cortex plays a critical role in the top–down modulation of activity within
posterior cortical areas for the selective retrieval of specific aspects ...
It is well established that ongoing cognitive functions affect the trajectories of
limb movements mediated by corticospinal circuits, suggesting an interaction between
cognition and motor action. Although there are also many demonstrations that decision
...
Parkinson’s disease (PD) is an age-related neurodegenerative disorder characterized
by the accumulation of protein aggregates comprised of α-synuclein (α-syn). A major
barrier in treatment discovery for PD is the lack of identifiable therapeutic pathways
...
Cell-type–specific G protein-coupled receptor (GPCR) signaling regulates distinct
neuronal responses to various stimuli and is essential for axon guidance and targeting
during development. However, its function in axonal regeneration in the mature CNS
...
Phasic dopamine signaling participates in associative learning by reinforcing associations
between outcomes (unconditioned stimulus; US) and their predictors (conditioned stimulus;
CS). However, prior work has always engendered these associations with ...
Physiology
Dysfunction of pacemaker activity in the sinoatrial node (SAN) underlies “sick sinus”
syndrome (SSS), a common clinical condition characterized by abnormally low heart
rate (bradycardia). If untreated, SSS carries potentially life-threatening symptoms,
...
Plant Biology
Drought stress is an important environmental factor limiting plant productivity. In
this study, we screened drought-resistant transgenic plants from 65 promoter-pyrabactin resistance 1-like (PYL) abscisic acid (ABA) receptor gene combinations and ...
Sustainability Science
Research about ecosystem services (ES) often aims to generate knowledge that influences
policies and institutions for conservation and human development. However, we have
limited understanding of how decision-makers use ES knowledge or what factors ...
SI Correction (Online Only)
Cover image: Pictured is a heart-shaped pancreatic neuroendocrine tumor from a 12-week-old mouse, with tumor β-cells stained red and the surrounding exocrine tissue stained blue. Eliane Cortez et al. found that deleting the gene for platelet-derived growth factor DD (PDGF-DD) delayed tumor growth in a mouse model of pancreatic cancer, and that PDGF-DD stimulated proliferation of pancreatic β-tumor cells by binding to a subset of tumor cells expressing PDGF receptor β (PDGFRβ) and inducing secretion of additional growth factors. The results suggest that drugs targeting PDGFRβ may be useful in treating pancreatic neuroendocrine tumors. See the article by Cortez et al. on pages E864–E873. Image courtesy of Eliane Cortez, Michael Bartoschek, and Kristian Pietras (Lund University, Lund, Sweden).
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