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Noise decomposition of cellular signaling networks [Systems Biology]

PNAS Early Edition Articles - Mon, 11/17/2014 - 14:26
Experimental measurements of biochemical noise have primarily focused on sources of noise at the gene expression level due to limitations of existing noise decomposition techniques. Here, we introduce a mathematical framework that extends classical extrinsic–intrinsic noise analysis and enables mapping of noise within upstream signaling networks free of such restrictions....

NanoFlares for the detection of live tumor cells [Applied Biological Sciences]

PNAS Early Edition Articles - Mon, 11/17/2014 - 14:26
Metastasis portends a poor prognosis for cancer patients. Primary tumor cells disseminate through the bloodstream before the appearance of detectable metastatic lesions. The analysis of cancer cells in blood—so-called circulating tumor cells (CTCs)—may provide unprecedented opportunities for metastatic risk assessment and investigation. NanoFlares are nanoconstructs that enable live-cell detection of...

Hfq folds the rpoS mRNA leader [Biochemistry]

PNAS Early Edition Articles - Mon, 11/17/2014 - 14:26
The Sm-like protein Hfq (host factor Q-beta phage) facilitates regulation by bacterial small noncoding RNAs (sRNAs) in response to stress and other environmental signals. Here, we present a low-resolution model of Escherichia coli Hfq bound to the rpoS mRNA, a bacterial stress response gene that is targeted by three different...

Filopodia for probing substrate rigidity [Biophysics and Computational Biology]

PNAS Early Edition Articles - Mon, 11/17/2014 - 14:26
Rigidity sensing and durotaxis are thought to be important elements in wound healing, tissue formation, and cancer treatment. It has been challenging, however, to study the underlying mechanism due to difficulties in capturing cells during the transient response to a rigidity interface. We have addressed this problem by developing a...

A model for the generation of ER morphologies [Cell Biology]

PNAS Early Edition Articles - Mon, 11/17/2014 - 14:26
The peripheral endoplasmic reticulum (ER) forms different morphologies composed of tubules and sheets. Proteins such as the reticulons shape the ER by stabilizing the high membrane curvature in cross-sections of tubules and sheet edges. Here, we show that membrane curvature along the edge lines is also critical for ER shaping....

End of the Bronze Age not caused by climate change [Anthropology]

PNAS Early Edition Articles - Mon, 11/17/2014 - 14:26
The impact of rapid climate change on contemporary human populations is of global concern. To contextualize our understanding of human responses to rapid climate change it is necessary to examine the archeological record during past climate transitions. One episode of abrupt climate change has been correlated with societal collapse at...

Orientation of aromatic residues in prions [Chemistry]

PNAS Early Edition Articles - Mon, 11/17/2014 - 14:26
Structural conversion of one given protein sequence into different amyloid states, resulting in distinct phenotypes, is one of the most intriguing phenomena of protein biology. Despite great efforts the structural origin of prion diversity remains elusive, mainly because amyloids are insoluble yet noncrystalline and therefore not easily amenable to traditional...

Young capillary vessels rejuvenate aged islets [Medical Sciences]

PNAS Early Edition Articles - Mon, 11/17/2014 - 14:26
Pancreatic islets secrete hormones that play a key role in regulating blood glucose levels (glycemia). Age-dependent impairment of islet function and concomitant dysregulation of glycemia are major health threats in aged populations. However, the major causes of the age-dependent decline of islet function are still disputed. Here we demonstrate that...

Densovirus associated with sea-star wasting [Microbiology]

PNAS Early Edition Articles - Mon, 11/17/2014 - 14:26
Populations of at least 20 asteroid species on the Northeast Pacific Coast have recently experienced an extensive outbreak of sea-star (asteroid) wasting disease (SSWD). The disease leads to behavioral changes, lesions, loss of turgor, limb autotomy, and death characterized by rapid degradation (“melting”). Here, we present evidence from experimental challenge...

Global structural changes of MscL [Biophysics and Computational Biology]

PNAS Early Edition Articles - Mon, 11/17/2014 - 14:26
Mechanosensitive ion channels are sensors probing membrane tension in all species; despite their importance and vital role in many cell functions, their gating mechanism remains to be elucidated. Here, we determined the conditions for releasing intact mechanosensitive channel of large conductance (MscL) proteins from their detergents in the gas phase...

Superhard iron tetraboride under high pressure [Physics]

PNAS Early Edition Articles - Mon, 11/17/2014 - 14:26
First principles–based electronic structure calculations of superhard iron tetraboride (FeB4) under high pressure have been undertaken in this study. Starting with a “conventional” superconducting phase of this material under high pressure leads to an unexpected phase transition toward a semiconducting one. This transition occurred at 53.7 GPa, and this pressure...

Triclosan promotes liver fibrosis and tumor growth [Environmental Sciences]

PNAS Early Edition Articles - Mon, 11/17/2014 - 14:26
Triclosan [5-chloro-2-(2,4-dichlorophenoxy)phenol; TCS] is a synthetic, broad-spectrum antibacterial chemical used in a wide range of consumer products including soaps, cosmetics, therapeutics, and plastics. The general population is exposed to TCS because of its prevalence in a variety of daily care products as well as through waterborne contamination. TCS is linked...

Hormonal contraceptives and marriage [Psychological and Cognitive Sciences]

PNAS Early Edition Articles - Mon, 11/17/2014 - 14:26
How are hormonal contraceptives (HCs) related to marital well-being? Some work suggests HCs suppress biological processes associated with women’s preferences for partner qualities reflective of genetic fitness, qualities that may be summarized by facial attractiveness. Given that realizing such interpersonal preferences positively predicts relationship satisfaction, any changes in women’s preferences...

Uncleaved caspase-1 is active in response to LT [Immunology and Inflammation]

PNAS Early Edition Articles - Mon, 11/17/2014 - 14:26
Inflammasomes are caspase-1–activating multiprotein complexes. The mouse nucleotide-binding domain and leucine rich repeat pyrin containing 1b (NLRP1b) inflammasome was identified as the sensor of Bacillus anthracis lethal toxin (LT) in mouse macrophages from sensitive strains such as BALB/c. Upon exposure to LT, the NLRP1b inflammasome activates caspase-1 to produce mature...

Pattern formation of photoactivated polymers [Applied Physical Sciences]

PNAS Early Edition Articles - Mon, 11/17/2014 - 14:26
Since the pioneering work of Turing on the formation principles of animal coat patterns [Turing AM (1952) Phil Trans R Soc Lond B 237(641):37–72], such as the stripes of a tiger, great effort has been made to understand and explain various phenomena of self-assembly and pattern formation. Prominent examples are...

New decades in age and the search for meaning [Psychological and Cognitive Sciences]

PNAS Early Edition Articles - Mon, 11/17/2014 - 14:26
Although humans measure time using a continuous scale, certain numerical ages inspire greater self-reflection than others. Six studies show that adults undertake a search for existential meaning when they approach a new decade in age (e.g., at ages 29, 39, 49, etc.) or imagine entering a new epoch, which leads...

APE1 is dispensable for S-region cleavage in CSR [Immunology and Inflammation]

PNAS Early Edition Articles - Mon, 11/17/2014 - 14:26
Activation-induced cytidine deaminase (AID) is essential for antibody diversification, namely somatic hypermutation (SHM) and class switch recombination (CSR). The deficiency of apurinic/apyrimidinic endonuclease 1 (Ape1) in CH12F3-2A B cells reduces CSR to ∼20% of wild-type cells, whereas the effect of APE1 loss on SHM has not been examined. Here we...

Atmospheric turbulence and inertia-gravity waves [Earth, Atmospheric, and Planetary Sciences]

PNAS Early Edition Articles - Mon, 11/17/2014 - 14:26
Midlatitude fluctuations of the atmospheric winds on scales of thousands of kilometers, the most energetic of such fluctuations, are strongly constrained by the Earth’s rotation and the atmosphere’s stratification. As a result of these constraints, the flow is quasi-2D and energy is trapped at large scales—nonlinear turbulent interactions transfer energy...

Harm to others outweighs harm to self [Psychological and Cognitive Sciences]

PNAS Early Edition Articles - Mon, 11/17/2014 - 14:26
Concern for the suffering of others is central to moral decision making. How humans evaluate others’ suffering, relative to their own suffering, is unknown. We investigated this question by inviting subjects to trade off profits for themselves against pain experienced either by themselves or an anonymous other person. Subjects made...

Fast high-resolution 3D TIRF microscopy [Biophysics and Computational Biology]

PNAS Early Edition Articles - Mon, 11/17/2014 - 14:26
Total internal reflection fluorescence microscopy (TIRFM) is the method of choice to visualize a variety of cellular processes in particular events localized near the plasma membrane of live adherent cells. This imaging technique not relying on particular fluorescent probes provides a high sectioning capability. It is, however, restricted to a...
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