Table Of Contents Page, PNAS Volume 109, Number 2
This Week in PNAS
Letters (Online Only)
Commentaries
QnAs
Physical Sciences
Applied Physical Sciences
A critical early step in drug discovery is the screening of a chemical library. Typically,
promising compounds are identified in a primary screen and then more fully characterized
in a dose–response analysis with 7–10 data points per compound. Here, we ...
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Like charges stabilize emulsions, whereas opposite charges break emulsions. This is
the fundamental principle for many industrial and practical processes. Using micrometer-sized
pH-sensitive polymeric hydrogel particles as emulsion stabilizers, we prepare ...
Dynamic crack propagation drives catastrophic solid failures. In many amorphous brittle
materials, sufficiently fast crack growth involves small-scale, high-frequency microcracking
damage localized near the crack tip. The ultrafast dynamics of microcrack ...
In the cat or primate primary visual cortex (V1), normal vision corresponds to a state
where neural excitation patterns are driven by external visual stimuli. A spectacular
failure mode of V1 occurs when such patterns are overwhelmed by spontaneously ...
Astronomy
Life arose on Earth sometime in the first few hundred million years after the young
planet had cooled to the point that it could support water-based organisms on its
surface. The early emergence of life on Earth has been taken as evidence that the
...
Buckminsterfullerene (C60) was recently confirmed as the largest molecule identified in space. However, it
remains unclear how and where this molecule is formed. It is generally believed that
C60 is formed from the buildup of small carbonaceous compounds ...
Chemistry
Mass spectrometry (MS)-based proteome analysis relies heavily on the presence of complete
protein databases. Such a strategy is extremely powerful, albeit not adequate in the
analysis of unpredicted postgenome events, such as posttranslational ...
Synthesis of many proteins is tightly controlled at the level of translation, and
plays an essential role in fundamental processes such as cell growth and proliferation,
signaling, differentiation, or death. Methods that allow imaging and identification
...
Engineering
We describe a microchip designed to quantify the levels of a dozen cytoplasmic and
membrane proteins from single cells. We use the platform to assess protein–protein
interactions associated with the EGF-receptor-mediated PI3K signaling pathway. Single-...
Sustainability Science
Carbon capture and storage (CCS) is vital to reduce CO2 emissions to the atmosphere, potentially providing 20% of the needed reductions in
global emissions. Research and demonstration projects are important to increase scientific
understanding of CCS, and ...
Social Sciences
Social Sciences
Although some scholars maintain that education has little effect on intelligence quotient
(IQ) scores, others claim that IQ scores are indeed malleable, primarily through intervention
in early childhood. The causal effect of education on IQ at later ages ...
Biological Sciences
Applied Biological Sciences
A critical early step in drug discovery is the screening of a chemical library. Typically,
promising compounds are identified in a primary screen and then more fully characterized
in a dose–response analysis with 7–10 data points per compound. Here, we ...
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Biochemistry
The multifunctional, protein cross-linking transglutaminase 2 (TG2) is the main autoantigen
in celiac disease, an autoimmune disorder with defined etiology. Glutamine-rich gliadin
peptides from ingested cereals, after their deamidation by TG2, induce T-...
It is of pivotal importance for genome stability that repair DNA polymerases (Pols),
such as Pols λ and β, which all exhibit considerably reduced fidelity when replicating
undamaged DNA, are tightly regulated, because their misregulation could lead to ...
Biophysics and Computational Biology
Mass spectrometry (MS)-based proteome analysis relies heavily on the presence of complete
protein databases. Such a strategy is extremely powerful, albeit not adequate in the
analysis of unpredicted postgenome events, such as posttranslational ...
We describe a microchip designed to quantify the levels of a dozen cytoplasmic and
membrane proteins from single cells. We use the platform to assess protein–protein
interactions associated with the EGF-receptor-mediated PI3K signaling pathway. Single-...
The concept of DNA “repair centers” and the meaning of radiation-induced foci (RIF)
in human cells have remained controversial. RIFs are characterized by the local recruitment
of DNA damage sensing proteins such as p53 binding protein (53BP1). Here, we ...
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The planarity of peptide bonds is an assumption that underlies decades of theoretical
modeling of proteins. Peptide bonds strongly deviating from planarity are considered
very rare features of protein structure that occur for functional reasons. Here, ...
The scaffold protein for iron-sulfur cluster assembly, apo-IscU, populates two interconverting
conformational states, one disordered (D) and one structured (S) as revealed by extensive
NMR assignments. At pH 8 and 25 °C, approximately 70% of the protein ...
Regulation of protein function is often linked to a conformational switch triggered
by chemical or physical signals. To evaluate such conformational changes and to elucidate
the underlying molecular mechanisms of subsequent protein function, experimental ...
Cell Biology
Synthesis of many proteins is tightly controlled at the level of translation, and
plays an essential role in fundamental processes such as cell growth and proliferation,
signaling, differentiation, or death. Methods that allow imaging and identification
...
The small intestine epithelium undergoes rapid and continuous regeneration supported
by crypt intestinal stem cells (ISCs). Bmi1 and Lgr5 have been independently identified
to mark long-lived multipotent ISCs by lineage tracing in mice; however, the ...
Zuo1 functions as a J-protein cochaperone of its partner Hsp70. In addition, the C
terminus of Zuo1 and the N terminus of Ssz1, with which Zuo1 forms a heterodimer,
can independently activate the Saccharomyces cerevisiae transcription factor pleiotropic ...
Bacterial microcompartments are proteinaceous complexes that catalyze metabolic pathways
in a manner reminiscent of organelles. Although microcompartment structure is well
understood, much less is known about their assembly and function in vivo. We show
...
Developmental Biology
Lipid-modified Wnt/Wingless (Wg) proteins can signal to their target cells in a short-
or long-range manner. How these hydrophobic proteins travel through the extracellular
environment remains an outstanding question. Here, we report on a Wg binding ...
Homeostatic mechanisms can eliminate abnormal cells to prevent diseases such as cancer.
However, the underlying mechanisms of this surveillance are poorly understood. Here
we investigated how clones of cells mutant for the neoplastic tumor suppressor gene
...
In mammals, the sperm deliver mRNA of unknown function into the oocytes during fertilization.
The role of sperm microRNAs (miRNAs) in preimplantation development is unknown. miRNA
profiling identified six miRNAs expressed in the sperm and the zygotes but ...
Ecology
Population growth rate is a fundamental ecological and evolutionary characteristic
of living organisms, but individuals must balance the metabolism devoted to biosynthesis
and reproduction against the maintenance of existing structure and other ...
In many social animals, group-mates cooperate to defend their range against intrusion
by neighboring groups. Because group size tends to be highly variable, such conflicts
are often asymmetric. Although numerical superiority is assumed to provide a ...
Environmental Sciences
In November 2007, the container ship Cosco Busan released 54,000 gallons of bunker fuel oil into San Francisco Bay. The accident oiled
shoreline near spawning habitats for the largest population of Pacific herring on
the west coast of the continental ...
Eutrophication and global climate change lead to expansion of hypoxia in the ocean,
often accompanied by the production of hydrogen sulfide, which is toxic to higher
organisms. Chemoautotrophic bacteria are thought to buffer against increased sulfide
...
Evolution
The origin of Plasmodium falciparum in South America is controversial. Some studies suggest a recent introduction during
the European colonizations and the transatlantic slave trade. Other evidence—archeological
and genetic—suggests a much older origin. ...
An important question in biology is why some animals are able to regenerate, whereas
others are not. The basal chordate amphioxus is uniquely positioned to address the
evolution of regeneration. We report here the high regeneration potential of the ...
Genetics
In Escherichia coli crosstalk between DNA supercoiling, nucleoid-associated proteins and major RNA polymerase
σ initiation factors regulates growth phase-dependent gene transcription. We show
that the highly conserved spatial ordering of relevant genes ...
The generation of mature functional RNAs from nascent transcripts requires the precise
and coordinated action of numerous RNAs and proteins. One such protein family, the
ribonuclease III (RNase III) endonucleases, includes Rnt1, which functions in fungal
...
Copy number variants (CNVs) represent a substantial source of genomic variation in
vertebrates and have been associated with numerous human diseases. Despite this, the
extent of CNVs in the zebrafish, an important model for human disease, remains unknown.
...
Immunology
Systemic lupus erythematosus (SLE), the prototypic systemic autoimmune disease, is
a debilitating multisystem autoimmune disorder characterized by chronic inflammation
and extensive immune dysregulation in multiple organ systems, resulting in significant
...
Aire is a transcriptional regulator that induces expression of peripheral tissue antigens
(PTA) in thymic medullary epithelial cells (MECs), driving immunological self-tolerance
in differentiating T cells. To elucidate its mechanistic pathways, we ...
The inverse correlation between DNA methylation and lineage-specific gene expression
during T helper cell development is well documented. However, the specific functions
of the de novo methyltransferases Dnmt3a and Dnmt3b in cytokine gene regulation have
...
Neutrophil migration to inflamed sites is crucial for both the initiation of inflammation
and resolution of infection, yet these cells are involved in perpetuation of different
chronic inflammatory diseases. Gastrin-releasing peptide (GRP) is a ...
Medical Sciences
The inactivation of the p53 tumor suppressor pathway in many cancers often increases
their resistance to anticancer therapy. Here we show that a previously proposed strategy
directed to Wip1 inhibition could be ineffective in tumors lacking p53. On the ...
Protein-trafficking pathways are targeted here in human melanoma cells using methods
independent of oncogene mutational status, and the ability to up-regulate and down-regulate
tumor treatment sensitivity is demonstrated. Sensitivity of melanoma cells to ...
Both cardiac myocytes and cardiac stem cells (CSCs) express the receptor of growth
hormone releasing hormone (GHRH), activation of which improves injury responses after
myocardial infarction (MI). Here we show that a GHRH-agonist (GHRH-A; JI-38) reverses
...
Acute graft-versus-host disease (GvHD) is a major complication that prevents successful
outcomes after allogeneic bone marrow transplantation (BMT), an effective therapy
for hematological malignancies. Several studies demonstrate that donor T cells and
...
Because oncogene MET and EGF receptor (EGFR) inhibitors are in clinical development
against several types of cancer, including glioblastoma, it is important to identify
predictive markers that indicate patient subgroups suitable for such therapies. We
...
Diverse mutations in the genes encoding hemoglobin (Hb) have been characterized in
human disease. We describe here a mutation in the mouse Hbb-b2 gene, denoted Plt12, that precisely mimics the human hemoglobin Hotel Dieu variant. The mutation results
in ...
Diurnal variation in inflammatory and immune function is evident in the physiology
and pathology of humans and animals, but molecular mechanisms and mediating cell types
that provide this gating remain unknown. By screening cytokine responses in mice to
...
Microbiology
The ability of human CMV (HCMV) to enter and establish a latent infection in myeloid
cells is crucial for survival and transmission in the human population. Initial pathogen
binding and entry triggers a number of antiviral responses, including the ...
The human microbiome plays a key role in a wide range of host-related processes and
has a profound effect on human health. Comparative analyses of the human microbiome
have revealed substantial variation in species and gene composition associated with
a ...
Varicella-zoster virus (VZV) is a human α-herpesvirus that causes varicella (chickenpox)
during primary infection and zoster (shingles) upon reactivation. Like other viruses,
VZV must subvert the intrinsic antiviral defenses of differentiated human cells ...
Neuroscience
Release of substance P (SP) from nociceptive nerve fibers and activation of its receptor
neurokinin 1 (NK1) are important effectors in the transmission of pain signals. Nonetheless,
the role of SP in muscle pain remains unknown. Here we show that a single ...
When animals move, respiration increases to adapt for increased energy demands; the
underlying mechanisms are still not understood. We investigated the neural substrates
underlying the respiratory changes in relation to movement in lampreys. We showed
...
This article has a correction:
Correction for Gariépy et al., Specific neural substrate linking respiration to locomotion
Voltage-dependent gating of ion channels is essential for electrical signaling in
excitable cells, but the structural basis for voltage sensor function is unknown.
We constructed high-resolution structural models of resting, intermediate, and activated
...
In the cat or primate primary visual cortex (V1), normal vision corresponds to a state
where neural excitation patterns are driven by external visual stimuli. A spectacular
failure mode of V1 occurs when such patterns are overwhelmed by spontaneously ...
The type 1 ryanodine receptor (RyR1) is expressed widely in the brain, with high levels
in the cerebellum, hippocampus, and hypothalamus. We have shown that L-type Ca2+ channels in terminals of hypothalamic magnocellular neurons are coupled to RyRs,
as ...
The AMP-activated kinase (AMPK) senses the energy status of cells and regulates fuel
availability, whereas hypothalamic AMPK regulates food intake. We report that inositol
polyphosphate multikinase (IPMK) regulates glucose signaling to AMPK in a pathway
...
Calorie restriction delays brain senescence and prevents neurodegeneration, but critical
regulators of these beneficial responses other than the NAD+-dependent histone deacetylase Sirtuin-1 (Sirt-1) are unknown. We report that effects
of calorie ...
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder involving
an extensive loss of motoneurons. Aberrant excitability of motoneurons has been implicated
in the pathogenesis of selective motoneuronal death in ALS. d-Serine, an ...
Plant Biology
To allow rhizobial infection of legume roots, plant cell walls must be locally degraded
for plant-made infection threads (ITs) to be formed. Here we identify a Lotus japonicus nodulation pectate lyase gene (LjNPL), which is induced in roots and root hairs ...
Flower production and crop yields are highly influenced by the architectures of inflorescences.
In the compound inflorescences of tomato and related nightshades (Solanaceae), new
lateral inflorescence branches develop on the flanks of older branches that ...
Corrections
Cover image: Zebrafish (pictured) are a model organism for studying human disease, although the extent of genetic variation between commonly used laboratory strains is not well understood. Kim H. Brown et al. found a high level of copy number variants (CNVs)—gains and losses of large sequences of DNA—among fish representing three commonly used laboratory strains. About 70% of all identified CNVs appeared to be strain-specific. The authors suggest that the extensive genetic variation within and among strains may have functional effects that could potentially confound studies intended for translation to human diseases. See the article by Brown et al. on pages 529–534. Image courtesy of William T. Lester (Massachusetts General Hospital, Boston) and Charles Lee.
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