Table Of Contents Page, PNAS Volume 112, Number 40
This Week in PNAS
Letters (Online Only)
View the original article:
Measuring missing heritability: Inferring the contribution of common variants
This article has a reply:News Feature
View related content:
Core Concepts
View related content:
Commentaries
PNAS Plus Significance Statements
Perspective
The US biomedical research workforce does not currently mirror the nation’s population
demographically, despite numerous attempts to increase diversity. This imbalance is
limiting the promise of our biomedical enterprise for building knowledge and ...
Arthur M. Sackler Colloquium On Dark Matter Universe: On the Threshold of Discovery (Free Online)
Introduction
Most of the mass in the universe is in the form of dark matter—a new type of nonbaryonic
particle not yet detected in the laboratory or in other detection experiments. The
evidence for the existence of dark matter through its gravitational impact is clear
...
Colloquium Papers
The evidence for the dark matter (DM) of the hot big bang cosmology is about as good
as it gets in natural science. The exploration of its nature is now led by direct
and indirect detection experiments, to be complemented by advances in the full range
of ...
The cold dark matter (CDM) cosmological model has been remarkably successful in explaining
cosmic structure over an enormous span of redshift, but it has faced persistent challenges
from observations that probe the innermost regions of dark matter halos ...
I review the status of the model of dark matter as the neutralino of supersymmetry
in the light of constraints on supersymmetry given by the 7- to 8-TeV data from the
Large Hadron Collider (LHC).
The details of what constitutes the majority of the mass that makes up dark matter
in the Universe remains one of the prime puzzles of cosmology and particle physics
today—80 y after the first observational indications. Today, it is widely accepted
that ...
Indirect searches for products of dark matter annihilation and decay face the challenge
of identifying an uncertain and subdominant signal in the presence of uncertain backgrounds.
Two valuable approaches to this problem are (i) using analysis methods ...
In the late 20th century, cosmology became a precision science. Now, at the beginning
of the next century, the parameters describing how our universe evolved from the Big
Bang are generally known to a few percent. One key parameter is the total mass ...
Physical Sciences
Applied Physical Sciences
Gel electrophoresis is a powerful experimental method to probe the topology of DNA
and other biopolymers. Although there is a large body of experimental work that allows
us to accurately separate different topoisomers of a molecule, a full theoretical
...
A solar absorber, under the sun, is heated up by sunlight. In many applications, including
solar cells and outdoor structures, the absorption of sunlight is intrinsic for either
operational or aesthetic considerations, but the resulting heating is ...
Plasmonic cavities represent a promising platform for controlling light–matter interaction
due to their exceptionally small mode volume and high density of photonic states.
Using plasmonic cavities for enhancing light’s coupling to individual two-level ...
Mixing of complex fluids at low Reynolds number is fundamental for a broad range of
applications, including materials assembly, microfluidics, and biomedical devices.
Of these materials, yield stress fluids (and gels) pose the most significant challenges,
...
Astronomy
The cold dark matter (CDM) cosmological model has been remarkably successful in explaining
cosmic structure over an enormous span of redshift, but it has faced persistent challenges
from observations that probe the innermost regions of dark matter halos ...
Indirect searches for products of dark matter annihilation and decay face the challenge
of identifying an uncertain and subdominant signal in the presence of uncertain backgrounds.
Two valuable approaches to this problem are (i) using analysis methods ...
Chemistry
Lipid rafts are submicron proteolipid domains thought to be responsible for membrane
trafficking and signaling. Their small size and transient nature put an understanding
of their dynamics beyond the reach of existing techniques, leading to much ...
Earth, Atmospheric, and Planetary Sciences
The incorporation of C4 resources into hominin diet signifies increased dietary breadth within hominins and
divergence from the dietary patterns of other great apes. Morphological evidence indicates
that hominin diet became increasingly diverse by 4.2 ...
View related content:
The formation of Earth’s core left behind geophysical and geochemical signatures in
both the core and mantle that remain to this day. Seismology requires that the core
be lighter than pure iron and therefore must contain light elements, and the ...
Engineering
Raman spectroscopy is an important tool in understanding chemical components of various
materials. However, the excessive weight and energy consumption of a conventional
CCD-based Raman spectrometer forbids its applications under extreme conditions, ...
Thin sheets have long been known to experience an increase in stiffness when they
are bent, buckled, or assembled into smaller interlocking structures. We introduce
a unique orientation for coupling rigidly foldable origami tubes in a “zipper” fashion
...
View related content:
Transforming architectures inspired by origami
View related content:2015 Cozzarelli Prize recipients
Interview with 2015 Cozzarelli Prize Winners Glaucio Paulino and Evgueni Filipov
Environmental Sciences
Large responses of ecosystems to small changes in the conditions—regime shifts—are
of great interest and importance. In spatially extended ecosystems, these shifts may
be local or global. Using empirical data and mathematical modeling, we investigated
the ...
Physics
The evidence for the dark matter (DM) of the hot big bang cosmology is about as good
as it gets in natural science. The exploration of its nature is now led by direct
and indirect detection experiments, to be complemented by advances in the full range
of ...
I review the status of the model of dark matter as the neutralino of supersymmetry
in the light of constraints on supersymmetry given by the 7- to 8-TeV data from the
Large Hadron Collider (LHC).
The details of what constitutes the majority of the mass that makes up dark matter
in the Universe remains one of the prime puzzles of cosmology and particle physics
today—80 y after the first observational indications. Today, it is widely accepted
that ...
In the late 20th century, cosmology became a precision science. Now, at the beginning
of the next century, the parameters describing how our universe evolved from the Big
Bang are generally known to a few percent. One key parameter is the total mass ...
Next-generation flexible electronics require highly stretchable and transparent electrodes.
Few electronic conductors are both transparent and stretchable, and even fewer can
be cyclically stretched to a large strain without causing fatigue. Fatigue, ...
Using all-atom molecular dynamics (MD) simulations at constant water chemical potential
in combination with basic theoretical arguments, we study hydration-induced interactions
between two overall charge-neutral yet polar planar surfaces with different ...
Social Sciences
Anthropology
Salmon represented a critical resource for prehistoric foragers along the North Pacific
Rim, and continue to be economically and culturally important; however, the origins
of salmon exploitation remain unresolved. Here we report 11,500-y-old salmon ...
Psychological and Cognitive Sciences
We examined the application and review materials of three calls (n = 2,823) of a prestigious grant for personal research funding in a national full
population of early career scientists awarded by the Netherlands Organization for
Scientific Research (NWO)...
View related content:
Dutch research funding, gender bias, and Simpson’s paradox
This article has a reply:Reply to Albers: Acceptance of empirical evidence for gender disparities in Dutch research funding
Women are underrepresented in most high-level positions in organizations. Though a
great deal of research has provided evidence that bias and discrimination give rise
to and perpetuate this gender disparity, in the current research we explore another
...
Biological Sciences
Anthropology
The incorporation of C4 resources into hominin diet signifies increased dietary breadth within hominins and
divergence from the dietary patterns of other great apes. Morphological evidence indicates
that hominin diet became increasingly diverse by 4.2 ...
View related content:
Applied Biological Sciences
Enterohemorrhagic Escherichia coli (EHEC) is one of the leading causes of bacterial enteric infections worldwide, causing
∼100,000 illnesses, 3,000 hospitalizations, and 90 deaths annually in the United States
alone. These illnesses have been linked to ...
View related content:
Virus-like particles (VLPs) have been extensively explored as nanoparticle vehicles
for many applications in biotechnology (e.g., vaccines, drug delivery, imaging agents,
biocatalysts). However, amino acid sequence plasticity relative to subunit ...
Biochemistry
The Spt-Ada-Gcn5 acetyltransferase (SAGA) coactivator complex hyperacetylates histone
tails in vivo in a manner that depends upon histone 3 lysine 4 trimethylation (H3K4me3),
a histone mark enriched at promoters of actively transcribed genes. SAGA ...
Cyclooxygenase-2 (COX-2) oxygenates arachidonic acid (AA) and its ester analog, 2-arachidonoylglycerol
(2-AG), to prostaglandins (PGs) and prostaglandin glyceryl esters (PG-Gs), respectively.
Although the efficiency of oxygenation of these substrates by ...
This article has a correction:
Intercellular bridges are a conserved feature of spermatogenesis in mammalian germ
cells and derive from arresting cell abscission at the final stage of cytokinesis.
However, it remains to be fully understood how germ cell abscission is arrested in
the ...
Biophysics and Computational Biology
Gel electrophoresis is a powerful experimental method to probe the topology of DNA
and other biopolymers. Although there is a large body of experimental work that allows
us to accurately separate different topoisomers of a molecule, a full theoretical
...
We recently described general principles for designing ideal protein structures stabilized
by completely consistent local and nonlocal interactions. The principles relate secondary
structure patterns to tertiary packing motifs and enable design of ...
The molecular basis of the function of transporters is a problem of significant importance,
and the emerging structural information has not yet been converted to a full understanding
of the corresponding function. This work explores the molecular origin ...
Glycoside hydrolase (GH) enzymes apply acid/base chemistry to catalyze the decomposition
of complex carbohydrates. These ubiquitous enzymes accept protons from solvent and
donate them to substrates at close to neutral pH by modulating the pKa values of ...
Regulated intramembrane proteolysis (RIP) is a conserved mechanism crucial for numerous
cellular processes, including signaling, transcriptional regulation, axon guidance,
cell adhesion, cellular stress responses, and transmembrane protein fragment ...
Charged particles are increasingly used in cancer radiotherapy and contribute significantly
to the natural radiation risk. The difference in the biological effects of high-energy
charged particles compared with X-rays or γ-rays is determined largely by ...
Although protein folding and stability have been well explored under simplified conditions
in vitro, it is yet unclear how these basic self-organization events are modulated
by the crowded interior of live cells. To find out, we use here in-cell NMR to ...
Cell Biology
Microvillus inclusion disease (MVID) is a rare intestinal enteropathy with an onset
within a few days to months after birth, resulting in persistent watery diarrhea.
Mutations in the myosin Vb gene (MYO5B) have been identified in the majority of MVID ...
The 427-kDa protein dystrophin is expressed in striated muscle where it physically
links the interior of muscle fibers to the extracellular matrix. A range of mutations
in the DMD gene encoding dystrophin lead to a severe muscular dystrophy known as ...
Regulated degradation of proteins by the proteasome is often critical to their function
in dynamic cellular pathways. The molecular clock underlying mammalian circadian rhythms
relies on the rhythmic expression and degradation of its core components. ...
Developmental Biology
Lnx2 ubiquitin ligase is essential for exocrine cell differentiation in the early zebrafish pancreas
The gene encoding the E3 ubiquitin ligase Ligand of Numb protein-X (Lnx)2a is expressed
in the ventral-anterior pancreatic bud of zebrafish embryos in addition to its expression
in the brain. Knockdown of Lnx2a by using an exon 2/intron 2 splice ...
The suspensor is a temporary supporting structure of proembryos. It has been proposed
that suspensor cells also possess embryogenic potential, which is suppressed by the
embryo as an effect of the embryo–suspensor interaction. However, data to support
...
Ecology
In agroecosystems worldwide, bats are voracious predators of crop pests and may provide
services to farmers worth billions of U.S. dollars. However, such valuations make
untested assumptions about the ecological effect of bats in agroecosystems. ...
Evolution
Phenotypic capacitance refers to the ability of a genome to accumulate mutations that
are conditionally hidden and only reveal phenotype-altering effects after certain
environmental or genetic changes. Capacitance has important implications for the ...
Genetics
Large-scale tumor sequencing projects enabled the identification of many new cancer
gene candidates through computational approaches. Here, we describe a general method
to detect cancer genes based on significant 3D clustering of mutations relative to
the ...
Contrary to the pattern seen in mammalian sex chromosomes, where most Y-linked genes
have X-linked homologs, the Drosophila X and Y chromosomes appear to be unrelated. Most of the Y-linked genes have autosomal
paralogs, so autosome-to-Y transposition must ...
This article has a correction:
The microbial world presents a complex palette of opportunities and dangers to animals,
which have developed surveillance and response strategies to hints of microbial intent.
We show here that the mitochondrial homeostatic response pathway of the ...
The free-living flatworm, Macrostomum lignano has an impressive regenerative capacity. Following injury, it can regenerate almost
an entirely new organism because of the presence of an abundant somatic stem cell
population, the neoblasts. This set of ...
Immunology and Inflammation
Beta cells from nondiabetic mice transfer secretory vesicles to phagocytic cells.
The passage was shown in culture studies where the transfer was probed with CD4 T
cells reactive to insulin peptides. Two sets of vesicles were transferred, one containing
...
Neuroinflammation is associated with a broad spectrum of neurodegenerative and psychiatric
diseases. The core process in neuroinflammation is activation of microglia, the innate
immune cells of the brain. We measured the neuroinflammatory response ...
Successful induction of B-cell activation and memory depends on help from CD4+ T cells. Invariant natural killer T (iNKT) cells (glycolipid-specific, CD1d-restricted
innate lymphocytes) provide both cognate (direct) and noncognate (indirect) helper
...
Medical Sciences
Plasma consists of DNA released from multiple tissues within the body. Using genome-wide
bisulfite sequencing of plasma DNA and deconvolution of the sequencing data with reference
to methylation profiles of different tissues, we developed a general ...
Adult T-cell leukemia (ATL) develops in individuals infected with human T-cell lymphotropic
virus-1 (HTLV-1). Presently there is no curative therapy for ATL. HTLV-1–encoded protein
Tax (transactivator from the X-gene region) up-regulates Bcl-xL (B-cell ...
Most therapeutic agents are excluded from entering the central nervous system by the
blood–brain barrier (BBB). Receptor mediated transcytosis (RMT) is a common mechanism
used by proteins, including transferrin (Tf), to traverse the BBB. Here, we prepared
...
Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide.
Recent high-throughput analyses of genomic alterations revealed several driver genes
and altered pathways in GC. However, therapeutic applications from genomic data are
...
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Some anecdotal
reports suggest that ASD is related to exposure to ethyl mercury, in the form of the
vaccine preservative, thimerosal, and/or receiving the measles, mumps, rubella (...
Microbiology
SecDF interacts with the SecYEG translocon in bacteria and enhances protein export
in a proton-motive-force-dependent manner. Vibrio alginolyticus, a marine-estuarine bacterium, contains two SecDF paralogs, V.SecDF1 and V.SecDF2.
Here, we show that the ...
Paramyxoviruses include many important animal and human pathogens. Most paramyxoviruses
have two integral membrane proteins: fusion protein (F) and attachment proteins hemagglutinin,
hemagglutinin–neuraminidase, or glycoprotein (G), which are critical for ...
The rod shape of most bacteria requires the actin homolog, MreB. Whereas MreB was
initially thought to statically define rod shape, recent studies found that MreB dynamically
rotates around the cell circumference dependent on cell wall synthesis. However, ...
Neuroscience
Although anatomy is often the first step in assigning functions to neural structures,
it is not always clear whether architecturally distinct regions of the brain correspond
to operational units. Whereas neuroarchitecture remains relatively static, ...
Human pluripotent stem cell-based in vitro models that reflect human physiology have
the potential to reduce the number of drug failures in clinical trials and offer a
cost-effective approach for assessing chemical safety. Here, human embryonic stem
(ES) ...
The present study investigated the cortical large-scale functional network underpinning
audiovisual integration via magnetoencephalographic recordings. The reorganization
of this network related to long-term musical training was investigated by comparing
...
Physiology
Stromal interacting molecule (STIM) and Orai proteins constitute the core machinery
of store-operated calcium entry. We used transmission and freeze–fracture electron
microscopy to visualize STIM1 and Orai1 at endoplasmic reticulum (ER)–plasma membrane
(...
Nav channels are essential for metazoan membrane depolarization, and Nav channel dysfunction is directly linked with epilepsy, ataxia, pain, arrhythmia, myotonia,
and irritable bowel syndrome. Human Nav channelopathies are primarily caused by variants ...
Plant Biology
Ubiquitination is a signal for various cellular processes, including for endocytic
degradation of plasma membrane cargos. Ubiquitinating as well as deubiquitinating
enzymes (DUBs) can regulate these processes by modifying the ubiquitination status
of ...
Meiosis halves diploid genomes to haploid and is essential for sexual reproduction
in eukaryotes. Meiotic recombination ensures physical association of homologs and
their subsequent accurate segregation and results in the redistribution of genetic
...
Corrections (Online Only)
SI Corrections (Online Only)
Cover image: Pictured is a composite image of a colliding pair of clusters of galaxies; the image shows gravitational lensing observations of the mass distribution made by the Hubble Space Telescope (blue) and the gas distribution made by the Chandra X-ray Observatory (pink). Collisions between clusters of galaxies, such as the one occurring in this galactic cluster, provide an opportunity to study how dark matter particles, which compose most of the mass of the colliding clusters, interact with each other. Observations suggest that dark matter interacts only weakly with visible matter and with other dark matter particles, a finding that constrains the possible compositions of dark matter. See the Introduction to the Dark Matter Universe: On the Threshold of Discovery Sackler Colloquium by Neta A. Bahcall on pages 12243–12245. Image courtesy of NASA, ESA, and STScI.
Advertisement
Recent Issues
Submit to PNAS
Submit to the Proceedings of the National Academy of Sciences (PNAS) and have your research discovered by millions of researchers in the Biological, Physical, and Social Sciences.
Submit your manuscript