Table Of Contents Page, PNAS Volume 107, Number 42
This Week in PNAS
Letters (Online Only)
Commentaries
QnAs
Feature Article
Elicitation of antibodies against targets that are immunorecessive, cryptic, or transient
in their native context has been a challenge for vaccine design. Here we demonstrate
the elicitation of structure-specific antibodies against the HIV-1 gp41 epitope ...
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Physical Sciences
Applied Physical Sciences
Optical imaging of single biomolecules and complexes in living cells provides a useful
window into cellular processes. However, the three-dimensional dynamics of most important
biomolecules in living cells remains essentially uncharacterized. The precise ...
Chemistry
A challenging target in the noncovalent synthesis of nanostructured functional materials
is the formation of uniform features that exhibit well-defined properties, e.g., precise
control over the aggregate shape, size, and stability. In particular, for ...
The potential for femtosecond to picosecond time-scale motions to influence the rate
of the intrinsic chemical step in enzyme-catalyzed reactions is a source of significant
controversy. Among the central challenges in resolving this controversy is the ...
Effective treatment of brain neurological disorders such as Alzheimer's disease, multiple
sclerosis, or tumors should be possible with drug delivery through blood–brain barrier
(BBB) or blood–brain tumor barrier (BTB) and targeting specific types of brain ...
Engineering
Fluorescent microbeads hold great promise for in vivo continuous glucose monitoring
with wireless transdermal transmission and long-lasting activity. The full potential
of fluorescent microbeads has yet to be realized due to insufficient intensity for
...
Environmental Sciences
Utility-scale large wind farms are rapidly growing in size and numbers all over the
world. Data from a meteorological field campaign show that such wind farms can significantly
affect near-surface air temperatures. These effects result from enhanced ...
The chemical history of dust particles in the atmosphere is crucial for assessing
their impact on both the Earth’s climate and ecosystem. So far, a number of studies
have shown that, in the vicinity of strong anthropogenic emission sources, Ca-rich
dust ...
Geology
The evolution of Earth’s biota is intimately linked to the oxygenation of the oceans
and atmosphere. We use the isotopic composition and concentration of molybdenum (Mo)
in sedimentary rocks to explore this relationship. Our results indicate two episodes
...
Geophysics
Freshwater discharge from the continents is a key component of Earth’s water cycle
that sustains human life and ecosystem health. Surprisingly, owing to a number of
socioeconomic and political obstacles, a comprehensive global river discharge observing
...
Physics
The visual system is challenged with extracting and representing behaviorally relevant
information contained in natural inputs of great complexity and detail. This task
begins in the sensory periphery: retinal receptive fields and circuits are matched
to ...
Social Sciences
Economic Sciences
Psychologists and economists take contradictory approaches to research on what psychologists
call happiness or subjective well-being, and economists call subjective utility. A
direct test of the most widely accepted psychological theory, set-point theory, ...
Social Sciences
Ending violent international conflicts requires understanding the causal factors that
perpetuate them. In the Israeli–Palestinian conflict, Israelis and Palestinians each
tend to see themselves as victims, engaging in violence only in response to attacks
...
Biological Sciences
Applied Biological Sciences
Nature frequently utilizes opposing factors to create a stable activator gradient
to robustly control pattern formation. This study employs a biomimicry approach, by
delivery of both angiogenic and antiangiogenic factors from spatially restricted zones
of ...
Biochemistry
The genomic revolution has identified therapeutic targets for a plethora of diseases,
creating a need to develop robust technologies for combination drug therapy. In the
present work, we describe a self-assembled polymeric nanoparticle (NP) platform to
...
Genome-wide mapping of nucleosomes generated by micrococcal nuclease (MNase) suggests
that yeast promoter and terminator regions are very depleted of nucleosomes, predominantly
because their DNA sequences intrinsically disfavor nucleosome formation. ...
HIV-1 and other enveloped viruses can be restricted by a host cellular protein called
BST2/tetherin that prevents release of budded viruses from the cell surface. Mature
BST2 contains a small cytosolic region, a predicted transmembrane helix, and an ...
The cellulose synthesizing terminal complex consisting of subunits A, B, C, and D
in Acetobacter xylinum spans the outer and inner cell membranes to synthesize and extrude glucan chains,
which are assembled into subelementary fibrils and further into a ...
Trichloroethylene (TCE) is one of the most widespread environmental contaminants,
which is metabolized to N-acetyl-S-1,2-dichlorovinyl-l-cysteine (NA-DCVC) before being excreted in the urine. Alternatively, NA-DCVC can
be deacetylated by aminoacylase 3 (...
Microbial niches contain toxic chemicals capable of forcing organisms into periods
of intense natural selection to afford survival. Elucidating the mechanisms by which
microbes evade environmental threats has direct relevance for understanding and ...
Biophysics and Computational Biology
Optical imaging of single biomolecules and complexes in living cells provides a useful
window into cellular processes. However, the three-dimensional dynamics of most important
biomolecules in living cells remains essentially uncharacterized. The precise ...
Elicitation of antibodies against targets that are immunorecessive, cryptic, or transient
in their native context has been a challenge for vaccine design. Here we demonstrate
the elicitation of structure-specific antibodies against the HIV-1 gp41 epitope ...
View related content:
The potential for femtosecond to picosecond time-scale motions to influence the rate
of the intrinsic chemical step in enzyme-catalyzed reactions is a source of significant
controversy. Among the central challenges in resolving this controversy is the ...
Local conformational changes in primer-template (P/T) DNA are involved in the selective
incorporation of dNTP by DNA polymerases (DNAP). Here we use near UV CD and fluorescence
spectra of pairs of base analogue probes, substituted either at the primer ...
The robustness of proteins against point mutations implies that only a small subset
of residues determines functional properties. We test this prediction using photoactive
yellow protein (PYP), a 125-residue prototype of the PER-ARNT-SIM (PAS) domain ...
Cell Biology
That tumors cause changes in surrounding tissues is well documented, but whether they
also affect distant tissues is uncertain. Such knowledge may be important in understanding
the relationship between cancer and overall patient health. To address this ...
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Long-distance inflammatory and genotoxic impact of cancer in vivo
In mammalian testes, the blood–testis barrier (BTB) or Sertoli cell barrier created
by specialized junctions between Sertoli cells near the basement membrane confers
an immunological barrier by sequestering the events of meiotic division and postmeiotic
...
Heme proteins play essential roles in biology, but little is known about heme transport
inside mammalian cells or how heme is inserted into soluble proteins. We recently
found that nitric oxide (NO) blocks cells from inserting heme into several proteins,
...
Tight junctions (TJs) play a key role in mediating paracellular ion reabsorption in
the kidney. The paracellular pathway in the collecting duct of the kidney is a predominant
route for transepithelial chloride reabsorption that determines the ...
Developmental Biology
Phagocytosis of apoptotic cells requires recognition of cell corpses followed by internalization
and enclosure within plasma membrane-derived phagosomes. Phagosomes undergo maturation
to generate phagolysosomes in which cell corpses are degraded; however, ...
Translational repression mediated by RNA-binding proteins or micro RNAs has emerged
as a major regulatory mechanism for fine-tuning important biological processes. In
Caenorhabditis elegans, translational repression of the key sex-determination gene tra-2 ...
Dorsoventral cell fate in the Drosophila embryo is specified by activation of the Toll receptor, leading to a ventral-to-dorsal
gradient across nuclei of the NF-κB transcription factor Dorsal. Toll receptor has
been investigated genetically, molecularly, ...
Evolution
The evolution of Earth’s biota is intimately linked to the oxygenation of the oceans
and atmosphere. We use the isotopic composition and concentration of molybdenum (Mo)
in sedimentary rocks to explore this relationship. Our results indicate two episodes
...
Pleiotropy refers to the phenomenon of a single mutation or gene affecting multiple
distinct phenotypic traits and has broad implications in many areas of biology. Due
to its central importance, pleiotropy has also been extensively modeled, albeit with
...
Although metazoan body plans are remarkably diverse, the structure and function of
many embryonic regulatory genes are conserved because large changes would be detrimental
to development. However, the fushi tarazu (ftz) gene has changed dramatically ...
Genetics
A set of currently known alleles increasing the risk for coronary artery disease,
cancer, and type 2 diabetes as identified by genome-wide association studies was tested
for compatibility with human longevity. Here, we show that nonagenarian siblings from
...
O6-alkylG adducts are highly mutagenic due to their capacity to efficiently form O6-alkylG:T mispairs during replication, thus triggering G→A transitions. Mutagenesis
is largely prevented by repair strategies such as reversal by alkyltransferases or
...
The central feature of standard eukaryotic translation initiation is small ribosome
subunit loading at the 5′ cap followed by its 5′ to 3′ scanning for a start codon.
The preferred start is an AUG codon in an optimal context. Elaborate cellular machinery
...
Immunology
The brain is not routinely surveyed by lymphocytes and is defined as an immuno-privileged
site. However, viral infection of the brain results in the infiltration and long-term
persistence of pathogen-specific CD8+ T cells. These cells survive without ...
NF-κB is a key transcription factor involved in the regulation of T-cell activation
and proliferation upon engagement of the T-cell receptor (TCR). T cells that lack
the IκB kinase (IKKβ) are unable to activate NF-κB, and rapidly undergo apoptosis
upon ...
Early embryos of many organisms develop outside the mother and are immediately confronted
with myriads of potential colonizers. How these naive developmental stages control
and shape the bacterial colonization is largely unknown. Here we show that early ...
Immune-mediated pulmonary diseases are a significant public health concern. Analysis
of leukocyte behavior in the lung is essential for understanding cellular mechanisms
that contribute to normal and diseased states. Here, we used two-photon imaging to
...
Characterization of mononuclear phagocytic cells in medaka fish transgenic for a cxcr3a:gfp reporter
Chemokines and chemokine receptors are key evolutionary innovations of vertebrates.
They are involved in morphogenetic processes and play an important role in the immune
system. Based on an analysis of the chemokine receptor gene family in teleost genomes,...
The early events that determine the decision between lymphocyte tolerance and activation
are not well-understood. Using a model of systemic self-antigen recognition by CD4+ T cells, we show, using single-cell biochemical analyses, that tolerance is ...
Medical Sciences
Bioterrorism poses a daunting challenge to global security and public health in the
21st century. Variola major virus, the etiological agent of smallpox, and Bacillus anthracis, the bacterial pathogen responsible for anthrax, remain at the ...
Unknown molecular responses to sarcomere protein gene mutations account for pathologic
remodeling in hypertrophic cardiomyopathy (HCM), producing myocyte growth and increased
cardiac fibrosis. To determine if hypertrophic signals activated myocyte ...
Epstein Barr virus latent membrane protein 1 (LMP1) induces NF-κB activation through
transformation effector sites (TES) 1 and 2, both of which are critical for B-lymphocyte
transformation. TES2 principally activates canonical NF-κB, which we confirm is ...
Mutations in WNK1 and WNK4 lead to familial hyperkalemic hypertension (FHHt). Because FHHt associates net positive
Na+ balance together with K+ and H+ renal retention, the identification of WNK1 and WNK4 led to a new paradigm to explain
how aldosterone ...
To examine the role of breast cancer stem cells (BCSCs) in metastasis, we generated
human-in-mouse breast cancer orthotopic models using patient tumor specimens, labeled
with optical reporter fusion genes. These models recapitulate human cancer features
...
Cardiac failure occurs when the heart fails to adapt to chronic stresses. Reactive
oxygen species (ROS)-dependent signaling is implicated in cardiac stress responses,
but the role of different ROS sources remains unclear. Here we report that NADPH oxidase-...
Microbiology
Bacterial nanowires are extracellular appendages that have been suggested as pathways
for electron transport in phylogenetically diverse microorganisms, including dissimilatory
metal-reducing bacteria and photosynthetic cyanobacteria. However, there has ...
Intestinal health requires the coexistence of eukaryotic self with the gut microbiota
and dysregulated host-microbial interactions can result in intestinal inflammation.
Here, we show that colitis improved in T-bet−/−Rag2−/− mice that consumed a fermented ...
The anaerobic acetogenic bacterium Acetobacterium woodii carries out a unique type of Na+-motive, anaerobic respiration with caffeate as electron acceptor, termed “caffeate
respiration.” Central, and so far the only identified membrane-bound reaction in ...
Neuroscience
Effective treatment of brain neurological disorders such as Alzheimer's disease, multiple
sclerosis, or tumors should be possible with drug delivery through blood–brain barrier
(BBB) or blood–brain tumor barrier (BTB) and targeting specific types of brain ...
The visual system is challenged with extracting and representing behaviorally relevant
information contained in natural inputs of great complexity and detail. This task
begins in the sensory periphery: retinal receptive fields and circuits are matched
to ...
Sleep and wakefulness are regulated primarily by inhibitory interactions between the
hypothalamus and brainstem. The expression of the states of rapid eye movement (REM)
sleep and non-REM (NREM) sleep also are correlated with the activity of groups of
REM-...
MicroRNAs (miRNAs) are a class of small, noncoding RNAs that function as posttranscriptional
regulators of gene expression. Many miRNAs are expressed in the developing brain and
regulate multiple aspects of neural development, including neurogenesis, ...
Visual working memory (VWM) is a remarkable skill dependent on the brain's ability
to construct and hold an internal representation of the world for later comparison
with an external stimulus. The prefrontal cortex (PFC) and basal ganglia (BG) interact
...
Long-term memory relies on modulation of synaptic connections in response to experience.
This plasticity involves trafficking of AMPA receptors (AMPAR) and alteration of spine
morphology. Arc, a gene induced by synaptic activity, mediates the endocytosis ...
Recent findings identified electroencephalography (EEG) microstates as the electrophysiological
correlates of fMRI resting-state networks. Microstates are defined as short periods
(100 ms) during which the EEG scalp topography remains quasi-stable; that ...
The mechanisms underlying memory formation in the hippocampal network remain a major
unanswered aspect of neuroscience. Although high-frequency activity appears essential
for plasticity, salience for memory formation is also provided by activity in ...
Intrinsic or resting state functional connectivity MRI and structural covariance MRI
have begun to reveal the adult human brain's multiple network architectures. How and
when these networks emerge during development remains unclear, but understanding ...
Generation of supramolecular architectures through controlled linking of suitable
building blocks can offer new perspectives to medicine and applied technologies. Current
linking strategies often rely on chemical methods that have limitations and cannot
...
Pharmacology
We have shown that the potent phosphodiesterase-5 (PDE-5) inhibitor sildenafil (Viagra)
induces a powerful effect on reduction of infarct size following ischemia/reperfusion
injury and improvement of left ventricular dysfunction in the failing heart after
...
Physiology
Rett syndrome (RTT) is an autism spectrum disorder caused by mutations in the X-linked
gene that encodes the transcription factor methyl-CpG-binding protein 2 (MeCP2). A
major debilitating phenotype in affected females is frequent apneas, and heterozygous
...
Plant Biology
Diatoms are prominent phytoplanktonic organisms that contribute around 40% of carbon
assimilation in the oceans. They grow and perform optimally in variable environments,
being able to cope with unpredictable changes in the amount and quality of light.
...
Salicylic acid (SA) is a defense hormone required for both local and systemic acquired
resistance (SAR) in plants. Pathogen infections induce SA synthesis through up-regulating
the expression of Isochorismate Synthase 1 (ICS1), which encodes a key enzyme ...
Systems Biology
Body fat distribution is an important predictor of the metabolic consequences of obesity,
but the cellular mechanisms regulating regional fat accumulation are unknown. We assessed
the changes in adipocyte size (photomicrographs) and number in response to ...
Cover image: Pictured is antibody 2F5 (blue) superimposed onto its mimic, antibody 11F10 (orange and purple). 2F5, which can neutralize HIV-1 (gray), is hard for the immune system to elicit, partly because the recognized part of HIV-1 changes shape. Gilad Ofek et al. have developed a technique for placing the antibody-recognized epitope of 2F5 in a protein scaffold. Animals inoculated with 2F5-epitope scaffolds produced antibodies that induced flexible versions of the 11F10 epitope (red) to adopt a shape similar to that of the 2F5 epitope (white). The findings demonstrate a strategy for designing better vaccines. See the feature article by Ofek et al. on pages 17880–17887. Image courtesy of Jonathan Stuckey (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD).
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