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Recognition of protein-linked glycans as a determinant of peptidase activity [Biochemistry]

PNAS Early Edition Articles - Tue, 01/17/2017 - 14:06
The vast majority of proteins are posttranslationally altered, with the addition of covalently linked sugars (glycosylation) being one of the most abundant modifications. However, despite the hydrolysis of protein peptide bonds by peptidases being a process essential to all life on Earth, the fundamental details of how peptidases accommodate posttranslational...

High Coulombic efficiency aluminum-ion battery using an AlCl3-urea ionic liquid analog electrolyte [Chemistry]

PNAS Early Edition Articles - Tue, 01/17/2017 - 14:06
In recent years, impressive advances in harvesting renewable energy have led to a pressing demand for the complimentary energy storage technology. Here, a high Coulombic efficiency (∼99.7%) Al battery is developed using earth-abundant aluminum as the anode, graphite as the cathode, and a cheap ionic liquid analog electrolyte made from...

Loss of GET pathway orthologs in Arabidopsis thaliana causes root hair growth defects and affects SNARE abundance [Plant Biology]

PNAS Early Edition Articles - Tue, 01/17/2017 - 14:06
Soluble N-ethylmaleimide–sensitive factor attachment protein receptor (SNARE) proteins are key players in cellular trafficking and coordinate vital cellular processes, such as cytokinesis, pathogen defense, and ion transport regulation. With few exceptions, SNAREs are tail-anchored (TA) proteins, bearing a C-terminal hydrophobic domain that is essential for their membrane integration. Recently, the...

Structure of eukaryotic CMG helicase at a replication fork and implications to replisome architecture and origin initiation [Biophysics and Computational Biology]

PNAS Early Edition Articles - Tue, 01/17/2017 - 14:06
The eukaryotic CMG (Cdc45, Mcm2–7, GINS) helicase consists of the Mcm2–7 hexameric ring along with five accessory factors. The Mcm2–7 heterohexamer, like other hexameric helicases, is shaped like a ring with two tiers, an N-tier ring composed of the N-terminal domains, and a C-tier of C-terminal domains; the C-tier contains...

Combating Parkinson’s disease-associated toxicity by modulating proteostasis [Commentaries]

PNAS Early Edition Articles - Tue, 01/17/2017 - 14:06
The incidence of age-associated neurodegenerative disease is growing rapidly, and it is expected to triple by 2050 (1). Currently, there are no cures or treatments that significantly modify disease progression. As researchers develop an in-depth understanding of the mechanisms of neurodegeneration, common features across different diseases are becoming apparent. Chief...

Uncovering hidden variation in polyploid wheat [Agricultural Sciences]

PNAS Early Edition Articles - Tue, 01/17/2017 - 14:06
Comprehensive reverse genetic resources, which have been key to understanding gene function in diploid model organisms, are missing in many polyploid crops. Young polyploid species such as wheat, which was domesticated less than 10,000 y ago, have high levels of sequence identity among subgenomes that mask the effects of recessive...

Conserved GTPase LepA (Elongation Factor 4) functions in biogenesis of the 30S subunit of the 70S ribosome [Biochemistry]

PNAS Early Edition Articles - Tue, 01/17/2017 - 14:06
The physiological role of LepA, a paralog of EF-G found in all bacteria, has been a mystery for decades. Here, we show that LepA functions in ribosome biogenesis. In cells lacking LepA, immature 30S particles accumulate. Four proteins are specifically underrepresented in these particles—S3, S10, S14, and S21—all of which...

Human transposon insertion profiling: Analysis, visualization and identification of somatic LINE-1 insertions in ovarian cancer [Genetics]

PNAS Early Edition Articles - Tue, 01/17/2017 - 14:06
Mammalian genomes are replete with interspersed repeats reflecting the activity of transposable elements. These mobile DNAs are self-propagating, and their continued transposition is a source of both heritable structural variation as well as somatic mutation in human genomes. Tailored approaches to map these sequences are useful to identify insertion alleles....

Transcriptomic, proteomic, and metabolomic landscape of positional memory in the caudal fin of zebrafish [Developmental Biology]

PNAS Early Edition Articles - Tue, 01/17/2017 - 14:06
Regeneration requires cells to regulate proliferation and patterning according to their spatial position. Positional memory is a property that enables regenerating cells to recall spatial information from the uninjured tissue. Positional memory is hypothesized to rely on gradients of molecules, few of which have been identified. Here, we quantified the...

Profile of David J. Thouless, J. Michael Kosterlitz, and F. Duncan M. Haldane, 2016 Nobel Laureates in Physics [Profiles]

PNAS Early Edition Articles - Tue, 01/17/2017 - 14:06
One of the most profound and mysterious facts in science is that abstract mathematics can beautifully describe various phenomena realized in the real world. The deep connection between geometry and physics, which dates back to ancient Greece, continues to surprise us and most remarkably has borne fruit as general relativity....

Atrial natriuretic peptide regulates adipose tissue accumulation in adult atria [Medical Sciences]

PNAS Early Edition Articles - Tue, 01/17/2017 - 14:06
The abundance of epicardial adipose tissue (EAT) is associated with atrial fibrillation (AF), the most frequent cardiac arrhythmia. However, both the origin and the factors involved in EAT expansion are unknown. Here, we found that adult human atrial epicardial cells were highly adipogenic through an epithelial–mesenchymal transition both in vitro...

The NBS-LRR architectures of plant R-proteins and metazoan NLRs evolved in independent events [Evolution]

PNAS Early Edition Articles - Tue, 01/17/2017 - 14:06
There are intriguing parallels between plants and animals, with respect to the structures of their innate immune receptors, that suggest universal principles of innate immunity. The cytosolic nucleotide binding site–leucine rich repeat (NBS-LRR) resistance proteins of plants (R-proteins) and the so-called NOD-like receptors of animals (NLRs) share a domain architecture...

Evolution of antibiotic resistance is linked to any genetic mechanism affecting bacterial duration of carriage [Evolution]

PNAS Early Edition Articles - Tue, 01/17/2017 - 14:06
Understanding how changes in antibiotic consumption affect the prevalence of antibiotic resistance in bacterial pathogens is important for public health. In a number of bacterial species, including Streptococcus pneumoniae, the prevalence of resistance has remained relatively stable despite prolonged selection pressure from antibiotics. The evolutionary processes allowing the robust coexistence...

Harmonic template neurons in primate auditory cortex underlying complex sound processing [Neuroscience]

PNAS Early Edition Articles - Tue, 01/17/2017 - 14:06
Harmonicity is a fundamental element of music, speech, and animal vocalizations. How the auditory system extracts harmonic structures embedded in complex sounds and uses them to form a coherent unitary entity is not fully understood. Despite the prevalence of sounds rich in harmonic structures in our everyday hearing environment, it...

Eight-coordinate fluoride in a silicate double-four-ring [Chemistry]

PNAS Early Edition Articles - Tue, 01/17/2017 - 14:06
Fluoride, nature’s smallest anion, is capable of covalently coordinating to eight silicon atoms. The setting is a simple and common motif in zeolite chemistry: the box-shaped silicate double-four-ring (D4R). Fluoride seeks its center. It is the strain of box deformation that keeps fluoride in the middle of the box, and...

Mitochondrial fusion dynamics is robust in the heart and depends on calcium oscillations and contractile activity [Physiology]

PNAS Early Edition Articles - Tue, 01/17/2017 - 14:06
Mitochondrial fusion is thought to be important for supporting cardiac contractility, but is hardly detectable in cultured cardiomyocytes and is difficult to directly evaluate in the heart. We overcame this obstacle through in vivo adenoviral transduction with matrix-targeted photoactivatable GFP and confocal microscopy. Imaging in whole rat hearts indicated mitochondrial...

Loss of astrocyte cholesterol synthesis disrupts neuronal function and alters whole-body metabolism [Physiology]

PNAS Early Edition Articles - Tue, 01/17/2017 - 14:06
Cholesterol is important for normal brain function. The brain synthesizes its own cholesterol, presumably in astrocytes. We have previously shown that diabetes results in decreased brain cholesterol synthesis by a reduction in sterol regulatory element-binding protein 2 (SREBP2)-regulated transcription. Here we show that coculture of control astrocytes with neurons enhances...

Myofibril breakdown during atrophy is a delayed response requiring the transcription factor PAX4 and desmin depolymerization [Cell Biology]

PNAS Early Edition Articles - Tue, 01/17/2017 - 14:06
A hallmark of muscle atrophy is the excessive degradation of myofibrillar proteins primarily by the ubiquitin proteasome system. In mice, during the rapid muscle atrophy induced by fasting, the desmin cytoskeleton and the attached Z-band–bound thin filaments are degraded after ubiquitination by the ubiquitin ligase tripartite motif-containing protein 32 (Trim32)....

{beta}-Catenin haploinsufficiency promotes mammary tumorigenesis in an ErbB2-positive basal breast cancer model [Cell Biology]

PNAS Early Edition Articles - Tue, 01/17/2017 - 14:06
Aberrant activation of β-catenin through its activity as a transcription factor has been observed in a large proportion of human malignancies. Despite the improved understanding of the β-catenin signaling pathway over the past three decades, attempts to develop therapies targeting β-catenin remain challenging, and none of these targeted therapies have...

Stress granule-associated protein G3BP2 regulates breast tumor initiation [Cell Biology]

PNAS Early Edition Articles - Tue, 01/17/2017 - 14:06
Breast tumors contain tumorigenic cancer cells, termed “tumor-initiating cells” (TICs), which are capable of both replenishing themselves and giving rise to populations of nontumorigenic breast cancer cells (non-TICs). However, the molecular mechanisms responsible for breast tumor initiation remain poorly understood. Here we describe a chemical screening strategy to identify small...
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