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PAPD5-dependent degradation pathway of miR-21 [Medical Sciences]

PNAS Early Edition Articles - Mon, 07/21/2014 - 13:05
Next-generation sequencing experiments have shown that microRNAs (miRNAs) are expressed in many different isoforms (isomiRs), whose biological relevance is often unclear. We found that mature miR-21, the most widely researched miRNA because of its importance in human disease, is produced in two prevalent isomiR forms that differ by 1 nt...

Subpolar cell wall addition in mycobacteria [Microbiology]

PNAS Early Edition Articles - Mon, 07/21/2014 - 13:05
Mycobacteria are surrounded by a complex multilayered envelope and elongate at the poles. The principles that organize the coordinated addition of chemically diverse cell wall layers during polar extension remain unclear. We show that enzymes mediating the terminal cytosolic steps of peptidoglycan, arabinogalactan, and mycolic acid synthesis colocalize at sites...

Allosteric eIF4E/eIF4G inhibition by 4EGI-1 [Biochemistry]

PNAS Early Edition Articles - Mon, 07/21/2014 - 13:05
The interaction of the eukaryotic translation initiation factor eIF4E with the initiation factor eIF4G recruits the 40S ribosomal particle to the 5′ end of mRNAs, facilitates scanning to the AUG start codon, and is crucial for eukaryotic translation of nearly all genes. Efficient recruitment of the 40S particle is particularly...

Lateral flagella and directional persistence [Environmental Sciences]

PNAS Early Edition Articles - Mon, 07/21/2014 - 13:05
As numerous bacterial species, Shewanella putrefaciens CN-32 possesses a complete secondary flagellar system. A significant subpopulation of CN-32 cells induces expression of the secondary system under planktonic conditions, resulting in formation of one, sometimes two, filaments at lateral positions in addition to the primary polar flagellum. Mutant analysis revealed that...

Exoplanet populations with NASA's Kepler Mission [Perspectives]

PNAS Early Edition Articles - Mon, 07/21/2014 - 13:05
The Kepler Mission is exploring the diversity of planets and planetary systems. Its legacy will be a catalog of discoveries sufficient for computing planet occurrence rates as a function of size, orbital period, star type, and insolation flux. The mission has made significant progress toward achieving that goal. Over 3,500...

Formate-dependent energy conservation [Microbiology]

PNAS Early Edition Articles - Mon, 07/21/2014 - 13:05
Thermococcus onnurineus NA1 is known to grow by the anaerobic oxidation of formate to CO2 and H2, a reaction that operates near thermodynamic equilibrium. Here we demonstrate that this reaction is coupled to ATP synthesis by a transmembrane ion current. Formate oxidation leads to H+ translocation across the cytoplasmic membrane...

Dissection of Semaphorin reverse signaling [Developmental Biology]

PNAS Early Edition Articles - Mon, 07/21/2014 - 13:05
Semaphorin family proteins are well-known axon guidance ligands. Recent studies indicate that certain transmembrane Semaphorins can also function as guidance receptors to mediate axon–axon attraction or repulsion. The mechanisms by which Semaphorin reverse signaling modulates axon-surface affinity, however, remain unknown. In this study, we reveal a novel mechanism underlying upregulation...

A phage protein inhibiting TFP assembly [Microbiology]

PNAS Early Edition Articles - Mon, 07/21/2014 - 13:05
Type IV pili (TFPs) are required for bacterial twitching motility and for phage infection in the opportunistic human pathogen Pseudomonas aeruginosa. Here we describe a phage-encoded protein, D3112 protein gp05 (hereafter referred to as Tip, representing twitching inhibitory protein), whose expression is necessary and sufficient to mediate the inhibition of...

Genome editing eradicates HIV-1 [Medical Sciences]

PNAS Early Edition Articles - Mon, 07/21/2014 - 13:05
AIDS remains incurable due to the permanent integration of HIV-1 into the host genome, imparting risk of viral reactivation even after antiretroviral therapy. New strategies are needed to ablate the viral genome from latently infected cells, because current methods are too inefficient and prone to adverse off-target effects. To eliminate...

Hydrogen production in an obligate aerobe [Environmental Sciences]

PNAS Early Edition Articles - Mon, 07/21/2014 - 13:05
Oxygen availability is a major factor and evolutionary force determining the metabolic strategy of bacteria colonizing an environmental niche. In the soil, conditions can switch rapidly between oxia and anoxia, forcing soil bacteria to remodel their energy metabolism accordingly. Mycobacterium is a dominant genus in the soil, and all its...

Mechanism of inhibition by IF1 [Biochemistry]

PNAS Early Edition Articles - Mon, 07/21/2014 - 13:05
The hydrolysis of ATP by the ATP synthase in mitochondria is inhibited by a protein called IF1. Bovine IF1 has 84 amino acids, and its N-terminal inhibitory region is intrinsically disordered. In a known structure of bovine F1-ATPase inhibited with residues 1–60 of IF1, the inhibitory region from residues 1–50...

Family intervention reduces youth inflammation [Psychological and Cognitive Sciences]

PNAS Early Edition Articles - Mon, 07/21/2014 - 13:05
Children of low socioeconomic status (SES) are at elevated risk for health problems across the lifespan. Observational studies suggest that nurturant parenting might offset some of these health risks, but their design precludes inferences about causal direction and clinical utility. Here we ask whether a psychosocial intervention, focused improving parenting,...

Modeling electrogenicity upon charge translocation [Biophysics and Computational Biology]

PNAS Early Edition Articles - Mon, 07/21/2014 - 13:05
Measurements of voltage changes in response to charge separation within membrane proteins can offer fundamental information on mechanisms of charge transport and displacement processes. A recent example is provided by studies of cytochrome c oxidase. However, the interpretation of the observed voltage changes in terms of the number of charge...

Oceanographic dynamics and the last interglacial [Earth, Atmospheric, and Planetary Sciences]

PNAS Early Edition Articles - Mon, 07/21/2014 - 13:05
The last interglacial interval was terminated by the inception of a long, progressive glaciation that is attributed to astronomically influenced changes in the seasonal distribution of sunlight over the earth. However, the feedbacks, internal dynamics, and global teleconnections associated with declining northern summer insolation remain incompletely understood. Here we show...

Protein stability in living cells [Biochemistry]

PNAS Early Edition Articles - Mon, 07/21/2014 - 13:05
The intracellular milieu differs from the dilute conditions in which most biophysical and biochemical studies are performed. This difference has led both experimentalists and theoreticians to tackle the challenging task of understanding how the intracellular environment affects the properties of biopolymers. Despite a growing number of in-cell studies, there is...

PI(4,5)P2-meditated activation mechanism of FAK [Biochemistry]

PNAS Early Edition Articles - Mon, 07/21/2014 - 13:05
Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase (NRTK) with key roles in integrating growth and cell matrix adhesion signals, and FAK is a major driver of invasion and metastasis in cancer. Cell adhesion via integrin receptors is well known to trigger FAK signaling, and many of the players...

PhoPR deficiency in animal tubercle strains [Microbiology]

PNAS Early Edition Articles - Mon, 07/21/2014 - 13:05
Although the bovine tuberculosis (TB) agent, Mycobacterium bovis, may infect humans and cause disease, long-term epidemiological data indicate that humans represent a spill-over host in which infection with M. bovis is not self-maintaining. Indeed, human-to-human transmission of M. bovis strains and other members of the animal lineage of the tubercle...

Bioactive protein hydrogels [Biochemistry]

PNAS Early Edition Articles - Mon, 07/21/2014 - 13:05
Protein-based hydrogels have emerged as promising alternatives to synthetic hydrogels for biomedical applications, owing to the precise control of structure and function enabled by protein engineering. Nevertheless, strategies for assembling 3D molecular networks that carry the biological information encoded in full-length proteins remain underdeveloped. Here we present a robust protein...

Defining allosteric effects in KIX complexes [Biophysics and Computational Biology]

PNAS Early Edition Articles - Mon, 07/21/2014 - 13:05
Allosteric binding events play a critical role in the formation and stability of transcriptional activator–coactivator complexes, perhaps in part due to the often intrinsically disordered nature of one or more of the constituent partners. The kinase-inducible domain interacting (KIX) domain of the master coactivator CREB binding protein/p300 is a conformationally...

53BP1 interacts with methylated pRb [Biochemistry]

PNAS Early Edition Articles - Mon, 07/21/2014 - 13:05
The retinoblastoma tumor suppressor protein pRb is a key regulator of cell cycle progression and mediator of the DNA damage response. Lysine methylation at K810, which occurs within a critical Cdk phosphorylation motif, holds pRb in the hypophosphorylated growth-suppressing state. We show here that methyl K810 is read by the...
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