Table Of Contents Page, PNAS Volume 108, Number 40
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Commentaries
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PNAS Plus (Author Summaries and Research Articles)
Physical Sciences – Engineering – Biological Sciences – Biochemistry
The realization of artificial biochemical reaction networks with unique functionality
is one of the main challenges for the development of synthetic biology. Due to the
reduced number of components, biochemical circuits constructed in vitro promise to
be ...
QnAs
Physical Sciences
Applied Physical Sciences
A multiplexed, ratiometric method is described that can confidently distinguish between
cancerous and noncancerous epithelial prostate cells in vitro. The technique is based
on bright surface-enhanced resonance Raman scattering (SERRS) biotags (SBTs) ...
In recent years the study of resting state brain networks (RSNs) has become an important
area of neuroimaging. The majority of studies have used functional magnetic resonance
imaging (fMRI) to measure temporal correlation between blood-oxygenation-level–...
Chemistry
This paper presents a proof-of-principle method, called InfoBiology, to write and
encode data using arrays of genetically engineered strains of Escherichia coli with fluorescent proteins (FPs) as phenotypic markers. In InfoBiology, we encode,
send, and ...
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The nucleoprotein (NP) of the influenza virus exists as trimers, and its tail-loop
binding pocket has been suggested as a potential target for antiinfluenza therapeutics.
The possibility of NP as a drug target was validated by the recent reports that ...
By applying a phase-modulation fluorescence approach to 2D electronic spectroscopy,
we studied the conformation-dependent exciton coupling of a porphyrin dimer embedded
in a phospholipid bilayer membrane. Our measurements specify the relative angle and
...
Hydrophobicity underpins self-assembly in many natural and synthetic molecular and
nanoscale systems. A signature of hydrophobicity is its temperature dependence. The
first experimental evaluation of the temperature and size dependence of hydration
free ...
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We report the observation of liquid-liquid phase separation in a solution of human
monoclonal antibody, IgG2, and the effects of human serum albumin, a major blood protein,
on this phase separation. We find a significant reduction of phase separation ...
Understanding how electric fields and their fluctuations in the active site of enzymes
affect efficient catalysis represents a critical objective of biochemical research.
We have directly measured the dynamics of the electric field in the active site of
a ...
Earth, Atmospheric, and Planetary Sciences
The Regional Earthquake Likelihood Models (RELM) test of earthquake forecasts in California
was the first competitive evaluation of forecasts of future earthquake occurrence.
Participants submitted expected probabilities of occurrence of M≥4.95 ...
Engineering
The realization of artificial biochemical reaction networks with unique functionality
is one of the main challenges for the development of synthetic biology. Due to the
reduced number of components, biochemical circuits constructed in vitro promise to
be ...
Focused ultrasound activation of systemically administered microbubbles is a noninvasive
and localized drug delivery method that can increase vascular permeability to large
molecular agents. Yet the range of acoustic parameters responsible for drug ...
Environmental Sciences
Nectar drinkers must feed quickly and efficiently due to the threat of predation.
While the sweetest nectar offers the greatest energetic rewards, the sharp increase
of viscosity with sugar concentration makes it the most difficult to transport. We
here ...
Geology
Industrialized societies which continue to use fossil fuel energy sources are considering
adoption of Carbon Capture and Storage (CCS) technology to meet carbon emission reduction
targets. Deep geological storage of CO2 onshore faces opposition regarding ...
Physics
The behavior of matter near zero temperature continuous phase transitions, or “quantum
critical points” is a central topic of study in condensed matter physics. In fermionic
systems, fundamental questions remain unanswered: the nature of the quantum ...
Sustainability Science
We assess the economic value of life-cycle air emissions and oil consumption from
conventional vehicles, hybrid-electric vehicles (HEVs), plug-in hybrid-electric vehicles
(PHEVs), and battery electric vehicles in the US. We find that plug-in vehicles may
...
Social Sciences
Environmental Sciences
Industrialized societies which continue to use fossil fuel energy sources are considering
adoption of Carbon Capture and Storage (CCS) technology to meet carbon emission reduction
targets. Deep geological storage of CO2 onshore faces opposition regarding ...
Biological Sciences
Applied Biological Sciences
This paper presents a proof-of-principle method, called InfoBiology, to write and
encode data using arrays of genetically engineered strains of Escherichia coli with fluorescent proteins (FPs) as phenotypic markers. In InfoBiology, we encode,
send, and ...
View related content:
A multiplexed, ratiometric method is described that can confidently distinguish between
cancerous and noncancerous epithelial prostate cells in vitro. The technique is based
on bright surface-enhanced resonance Raman scattering (SERRS) biotags (SBTs) ...
It is increasingly recognized that material surface topography is able to evoke specific
cellular responses, endowing materials with instructive properties that were formerly
reserved for growth factors. This opens the window to improve upon, in a cost-...
Biochemistry
The realization of artificial biochemical reaction networks with unique functionality
is one of the main challenges for the development of synthetic biology. Due to the
reduced number of components, biochemical circuits constructed in vitro promise to
be ...
Several classes of small noncoding RNAs are key players in cellular metabolism including
mRNA decoding, RNA processing, and mRNA stability. Here we show that a tRNAAsp isodecoder, corresponding to a human tRNA-derived sequence, binds to an embedded
Alu ...
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tRNA: Vast reservoir of RNA molecules with unexpected regulatory function
The nucleoprotein (NP) of the influenza virus exists as trimers, and its tail-loop
binding pocket has been suggested as a potential target for antiinfluenza therapeutics.
The possibility of NP as a drug target was validated by the recent reports that ...
So far, only a few of the interactions between the ≈30 nucleoporins comprising the
modular structure of the nuclear pore complex have been defined at atomic resolution.
Here we report the crystal structure, at 2.6 Å resolution, of a heterotrimeric complex,...
Many bacterial toxins form proteinaceous pores that facilitate the translocation of
soluble effector proteins across cellular membranes. With anthrax toxin this process
may be monitored in real time by electrophysiology, where fluctuations in ionic ...
Basic peptides covalently linked to nucleic acids, or chemically modified nucleic
acids, enable the insertion of such a conjugate into bacteria grown in liquid medium
and mammalian cells in tissue culture. A unique peptide, derived from human T cells,
has ...
Centromere protein A (CENP-A) is a histone H3 variant that marks centromere location
on the chromosome. To study the subunit structure and folding of human CENP-A-containing
chromatin, we generated a set of nucleosomal arrays with canonical core histones ...
Regiospecific desaturation of long-chain saturated fatty acids has been described
as approaching the limits of the discriminatory power of enzymes because the substrate
entirely lacks distinguishing features close to the site of dehydrogenation. To ...
Mutations in rumi result in a temperature-sensitive loss of Notch signaling in Drosophila. Drosophila Rumi is a soluble, endoplasmic reticulum-retained protein with a CAP10 domain that
functions as a protein O-glucosyltransferase. In human and mouse ...
Biophysics and Computational Biology
By applying a phase-modulation fluorescence approach to 2D electronic spectroscopy,
we studied the conformation-dependent exciton coupling of a porphyrin dimer embedded
in a phospholipid bilayer membrane. Our measurements specify the relative angle and
...
We report the observation of liquid-liquid phase separation in a solution of human
monoclonal antibody, IgG2, and the effects of human serum albumin, a major blood protein,
on this phase separation. We find a significant reduction of phase separation ...
Understanding how electric fields and their fluctuations in the active site of enzymes
affect efficient catalysis represents a critical objective of biochemical research.
We have directly measured the dynamics of the electric field in the active site of
a ...
Nectar drinkers must feed quickly and efficiently due to the threat of predation.
While the sweetest nectar offers the greatest energetic rewards, the sharp increase
of viscosity with sugar concentration makes it the most difficult to transport. We
here ...
As the simplest and most prevalent motif of protein folding, α-helix initiation is
the starting point of macromolecular complexity. In this work, helix initiation was
directly measured via ultrafast temperature-jump spectroscopy on the smallest possible
...
Theoretical studies predict hydrophobic matching between transmembrane domains of
proteins and bilayer lipids to be a physical mechanism by which membranes laterally
self-organize. We now experimentally study the direct consequences of mismatching
of ...
The structural and functional conversion of the nonselective NaK channel to a K+ selective channel (NaK2K) allows us to identify two key residues, Tyr and Asp in
the filter sequence of TVGYGD, that participate in interactions central to stabilizing the K+ ...
Despite advances in resolution accompanying the development of high-field superconducting
magnets, biomolecular applications of NMR require multiple dimensions in order to
resolve individual resonances, and the achievable resolution is typically limited
...
Cell Biology
Inhibitor of apoptosis-stimulating protein of p53 (iASPP) is the most ancient member
of the ASPP family of proteins and an evolutionarily conserved inhibitor of p53. iASPP
is also a binding partner and negative regulator of p65RelA. Because p65RelA and ...
A variety of social behaviors like intermale aggression, fear, and mating rituals
are important for sustenance of a species. In mice, these behaviors have been implicated
to be mediated by peptide pheromones that are sensed by a class of G protein-coupled
...
Glucocorticoids (GCs) are used to treat pregnant women at risk for preterm delivery;
however, prenatal exposure to GCs may trigger adverse neurological side effects due
to reduced neural progenitor cell (NPC) proliferation. Whereas many established cell-...
Malignant tumors exhibit increased dependence on glycolysis, resulting in abundant
export of lactic acid, a hypothesized key step in tumorigenesis. Lactic acid is mainly
transported by two H+/lactate symporters, MCT1/MCT4, that require the ancillary ...
The MYC transcription factor is a master regulator of diverse cellular functions and
has been long considered a compelling therapeutic target because of its role in a
range of human malignancies. However, pharmacologic inhibition of MYC function has
...
The dynamic cellular reorganization needed for successful mitosis requires regulatory
cues that vary across microns. The chromosomal passenger complex (CPC) is a conserved
regulator involved in key mitotic events such as chromosome–microtubule attachment
...
Developmental Biology
To investigate the properties of metazoan replication origins, recent studies in cell
culture have adopted the strategy of identifying origins using genome-wide approaches
and assessing correlations with such features as transcription and histone ...
Retinoic acid (RA), an active vitamin A metabolite, is a key signaling molecule in
vertebrate embryos. Morphogenetic RA gradients are thought to be set up by tissue-specific
actions of retinaldehyde dehydrogenases (RALDHs) and catabolizing enzymes. ...
Evolution
Closely related species show a high degree of differences in gene expression, but
the functional significance of these differences remains unclear. Similarly, stress
responses in yeast typically involve differential expression of numerous genes, and
it is ...
Genetics
X chromosome inactivation (XCI) is the most dramatic example of epigenetic silencing
in eukaryotes. Once established, the inactivated X chromosome (Xi) remains silenced
throughout subsequent cell divisions. Though the initiation of XCI has been studied
...
The emerging amphibian disease chytridiomycosis is caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd). Amphibian populations and species differ in susceptibility to Bd, yet we know surprisingly little about the genetic basis of this natural ...
Immunology
IL-37, a newly described member of the IL-1 family, functions as a fundamental inhibitor
of innate inflammation and immunity. In the present study, we examined a role for
IL-37 during experimental colitis. A transgenic mouse strain was generated to ...
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Increasing evidence suggests that regulatory T cell (Treg) function is impaired in
chronic inflammatory diseases such as rheumatoid arthritis (RA). Here we demonstrate
that Tregs are unable to modulate the spontaneous production of TNF-α from RA synovial
...
Ipilimumab, a monoclonal antibody against cytotoxic T lymphocyte antigen 4 (CTLA-4),
has been shown to improve survival in patients with advanced metastatic melanoma.
It also enhances immunity to NY-ESO-1, a cancer/testis antigen expressed in a subset
of ...
In the nonobese diabetic (NOD) mouse model of type 1 diabetes (T1D), an insulin peptide
(B:9–23) is a major target for pathogenic CD4+ T cells. However, there is no consensus on the relative importance of the various
positions or “registers” this peptide ...
Although most self-reactive T cells are eliminated in the thymus, mechanisms to inactivate
or control T cells specific for extrathymic antigens are required and exist in the
periphery. By investigating the site in which autoreactive T cells are tolerized,
...
The salivary glands are important effector sites for IgA-mediated humoral immunity
to protect oral surfaces. Within murine submandibular glands (SMG), we identified
a memory CD8 T-cell population that exhibited a unique cell-surface phenotype distinct
...
A number of different classes of molecules function as structural matrices for effecting
innate and adaptive immunity. The most extensively characterized mediators of adaptive
immunity are the immunoglobulins and T-cell antigen receptors found in jawed ...
Medical Sciences
Focused ultrasound activation of systemically administered microbubbles is a noninvasive
and localized drug delivery method that can increase vascular permeability to large
molecular agents. Yet the range of acoustic parameters responsible for drug ...
The gene encoding the receptor for hyaluronan-mediated motility (RHAMM) is overexpressed
in many human cancers. However, it is unclear whether RHAMM plays a causal role in
tumor initiation or progression. Using somatic gene transfer in a mouse model of ...
The H19 gene, which localizes within a chromosomal region on human chromosome 11p15 that
is commonly lost in Wilms tumor (WT), encodes an imprinted untranslated RNA. However,
the biological significance of the H19 noncoding transcript remains unresolved ...
Microbiology
Many species of Proteobacteria communicate by using LuxI-LuxR–type quorum-sensing systems that produce and detect
acyl-homoserine lactone (acyl-HSL) signals. Most of the known signals are straight-chain
fatty acyl-HSLs, and evidence indicates that LuxI ...
Nitrification is a core process in the global nitrogen cycle that is essential for
the functioning of many ecosystems. The discovery of autotrophic ammonia-oxidizing
archaea (AOA) within the phylum Thaumarchaeota has changed our perception of the ...
Numerous pathogens of humans, animals, and plants are transmitted by specific arthropod
vectors. However, understanding the mechanisms governing these pathogen–vector interactions
is hampered, in part, by the lack of easy-to-use analytical tools. We ...
Neuroscience
Synaptic cell adhesion molecules, including the neurexin ligands, neuroligins (NLs)
and leucine-rich repeat transmembrane proteins (LRRTMs), are thought to organize synapse
assembly and specify synapse function. To test the synaptic role of these ...
In recent years the study of resting state brain networks (RSNs) has become an important
area of neuroimaging. The majority of studies have used functional magnetic resonance
imaging (fMRI) to measure temporal correlation between blood-oxygenation-level–...
Neurogenesis requires mechanisms that coordinate early cell-fate decisions, migration,
and terminal differentiation. Here, we show that the transcriptional repressor, repressor
element 1 silencing transcription factor (REST), regulates radial migration ...
Whereas the neurodegeneration associated with various polyglutamine (polyQ) diseases
has prompted extensive studies of polyQ-induced cell death, the neuronal loss that
typically appears during late stages of the diseases may not account for the preceding
...
Rhythmic brain activity is thought to reflect, and to help organize, spike activity
in populations of neurons during on-going behavior. We report that during learning,
a major transition occurs in task-related oscillatory activity in the ventromedial
...
Although physiological data on microcircuits involving a few inhibitory neurons in
the mammalian cerebral cortex are available, data on the quantitative relation between
inhibition and excitation in cortical circuits involving thousands of neurons are
...
BDNF is produced from many transcripts that display distinct subcellular localization,
suggesting that spatially restricted effects occur as a function of genetic and physiological
regulation. Different BDNF 5′ splice variants give a restricted ...
Miraculin (MCL) is a homodimeric protein isolated from the red berries of Richadella dulcifica. MCL, although flat in taste at neutral pH, has taste-modifying activity to convert
sour stimuli to sweetness. Once MCL is held on the tongue, strong sweetness ...
Once their safety is confirmed, human-induced pluripotent stem cells (hiPSCs), which
do not entail ethical concerns, may become a preferred cell source for regenerative
medicine. Here, we investigated the therapeutic potential of transplanting hiPSC-...
Physiology
The mechanisms through which dietary restriction enhances health and longevity in
diverse species are unclear. The transsulfuration pathway (TSP) is a highly conserved
mechanism for metabolizing the sulfur-containing amino acids, methionine and cysteine.
...
Plant Biology
Light is critical for supplying carbon to the energetically expensive, nitrogen-fixing
symbiosis between legumes and rhizobia. Here, we show that phytochrome B (phyB) is
part of the monitoring system to detect suboptimal light conditions, which normally
...
The autoregulatory loops of the circadian clock consist of feedback regulation of
transcription/translation circuits but also require finely coordinated cytoplasmic
and nuclear proteostasis. Although protein degradation is important to establish steady-...
Psychological and Cognitive Sciences
Defocus blur is nearly always present in natural images: Objects at only one distance
can be perfectly focused. Images of objects at other distances are blurred by an amount
depending on pupil diameter and lens properties. Despite the fact that defocus is
...
Systems Biology
Gene expression networks are complicated by the assortment of regulatory factors that
bind DNA and modulate transcription combinatorially. Single-cell measurements can
reveal biological mechanisms hidden by population averages, but their value has not
...
Correction
Cover image: Pictured is a confocal microscopy image of two T cells, green, in the process of actively invading a hepatocyte, red. Volker Benseler et al. describe an efficient mechanism by which naïve CD8 T cells that react to the body’s own antigens are rapidly eliminated in the liver after invading hepatocytes. Blocking this process causes these autoreactive T cells to accumulate and leads to the development of autoimmune hepatitis. The findings suggest that this kind of “suicidal” cell invasion serves as a mechanism to delete autoreactive T cells and prevent autoimmunity. See the article by Benseler et al. on pages 16735–16740. Image courtesy of Michelle Vo.
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