bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional evolution of IGF2:IGF2R domain 11 binding generates novel structural interactions and a specific IGF2 antagonist
Authors: Frago Susana , Nicholls Ryan D. , Strickland Madeleine , Hughes Jennifer , Williams Christopher , Garner Lee , Surakhy Mirvat , Maclean Rory , Rezgui Dellel , Prince Stuart N. , Zaccheo Oliver J. , Ebner Daniel , Sanegre Sabina , Yu Sheng , Buffa Francesca M. , Crump Matthew P. , Hassan Andrew Bassim 
Published: May 2016

Significance
During 150 million years of mammalian evolution, the membrane-bound mannose 6-phosphate receptor evolved high-affinity binding loops for insulin-like growth factor 2. It remains unknown whether this highly evolved ligand interaction is optimal, and whether it can be further evolved. We addressed these questions using a mutation and selection strategy that incorporated surface display and protein structure. Multiple mutations of all the binding loops were identified and improved affinity by 100-fold when combined, yet retained IGF2 specificity. Structurally, IGF2 surface interactions with binding loops were reshaped, indicating that binding site evolution could not be predicted. High IGF2 affinity binding domains could selectively inhibit IGF2-dependent cell signaling, and may be applied in therapeutic IGF2 targeting in cancer.
A genetic method for dating ancient genomes provides a direct estimate of human generation interval in the last 45,000 years
Authors: Moorjani Priya , Sankararaman Sriram , Fu Qiaomei , Przeworski Molly , Patterson Nick , Reich David 
Published: May 2016

Significance
We report a method for dating ancient human samples that uses the recombination clock. To infer the age of ancient genomes, we take advantage of the shared history of Neanderthal gene flow into non-Africans that occurred around 50,000 y ago and measure the amount of “missing evolution” in terms of recombination breakpoints in the ancient genome compared with present-day samples. We show that this method provides age estimates that are highly correlated to radiocarbon dates, thus documenting the promise of this approach. By studying the linear relationship between the dates of Neanderthal admixture and the radiocarbon dates, we obtain, to our knowledge, the first direct estimate of the historical generation interval of 26–30 y.
Cryptic sequence features within the disordered protein p27
Kip1
regulate cell cycle signaling
Authors: Das Rahul K. , Huang Yongqi , Phillips Aaron H. , Kriwacki Richard W. , Pappu Rohit V. 
Published: May 2016

Significance
Intrinsically disordered regions (IDRs) of proteins are scaffolds for linear motifs that mediate protein–protein interactions and are the sites of posttranslational modifications. Using the cell cycle inhibitory protein p27 as an archetypal example, we show that the patterning of oppositely charged residues controls the conformational properties of IDRs. Charge patterning also encodes for auxiliary motifs within IDRs. We find that the functionalities of primary motifs are modulated by a combination of the net charge per residue within auxiliary motifs and their intra-IDR interactions that result from sequence-encoded charge patterning. These findings demonstrate that the sequences of IDRs are not just passive scaffolds for motifs. Instead, they encode features that regulate the functions of primary motifs.
Drift in ocean currents impacts intergenerational microbial exposure to temperature
Authors: Doblin Martina A. , van Sebille Erik 
Published: May 2016

Significance
Our current understanding of how marine biota are adapted to magnitudes, trends, and temporal patterns of variability in sea-surface temperature has arisen from examining long-term records at key ocean locations. However, floating plankton have a different perception of their habitat because they drift in ocean currents. Here we show that upper ocean microbes can be advected up to 3,500 km in latitude in 500 d, and that their operational temperatures exceed the in situ Eulerian temperature range by up to 10 °C, even in locations with strong seasonality. This result revises the present view of thermal exposure in the upper ocean, and provides a new framework for investigating climate change impacts on planktonic organisms.
Physical and situational inequality on airplanes predicts air rage
Authors: DeCelles Katherine A. , Norton Michael I. 
Published: May 2016

Significance
We suggest that physical and situational inequality are built into people’s everyday environments—such as the modern airplane—and that exposure to these forms of inequality can trigger antisocial behavior. Analyses reveal that air rage is more common in economy class on airplanes, where inequality is physically present, and in both economy and first class when inequality is situationally salient. We extend research demonstrating that the salience of inequality decreases prosocial behavior by higher class individuals, showing that temporary exposure to physical and situational inequality predicts antisocial behavior among individuals in both higher and lower classes. Moreover, we explore a novel predictor of inequality-induced antisocial behavior—the design of physical environments—augmenting research on macrostructural forms of inequality.
Living biofouling-resistant membranes as a model for the beneficial use of engineered biofilms
Authors: Wood Thammajun L. , Guha Rajarshi , Tang Li , Geitner Michael , Kumar Manish , Wood Thomas K. 
Published: May 2016

Significance
Biofouling is a significant problem for membrane-based systems because it reduces flow and increases energy consumption. This work shows a previously unreported approach to prevent membrane biofouling by using a beneficial biofilm. The beneficial strain was engineered to have a dispersal “feedback circuit,” based on secretion and uptake of a communication signal, limiting its own biofilm formation by self-monitoring and selective dispersal. The beneficial strain was also engineered to produce nitric oxide, which prevents biofilm formation by harmful bacteria; biofouling by the two most prevalent organisms was shown to be controlled by the beneficial strain. Moreover, the beneficial biofilm was engineered to produce an evolved epoxide hydrolase to enable it to remove the environmental pollutant epichlorohydrin.
Spontaneous recovery of superhydrophobicity on nanotextured surfaces
Authors: Prakash Suruchi , Xi Erte , Patel Amish J. 
Published: May 2016

Significance
Due to its aversion to the hydrophobic surface texture, a water droplet makes minimal contact with, and readily rolls off of, a superhydrophobic surface, conferring it with beneficial properties such as water repellency and self-cleaning. However, the surface texture can readily wet in response to conditions such as elevated pressures, leading to a breakdown of superhydrophobicity that is widely believed to be irreversible. By using specialized molecular simulations to study surfaces with nanoscale texture, here we find that the dewetting of the surface texture is strongly influenced by water density fluctuations. Furthermore, an understanding of the dewetting pathways allows us to design novel surface textures on which fluctuations can facilitate a spontaneous recovery of superhydrophobicity.
Structure of a prereaction complex between the nerve agent sarin, its biological target acetylcholinesterase, and the antidote HI-6
Authors: Allgardsson Anders , Berg Lotta , Akfur Christine , Hörnberg Andreas , Worek Franz , Linusson Anna , Ekström Fredrik J. 
Published: May 2016

Significance
Enzymatic reactions can be difficult to study using X-ray crystallography, because conformations and reacting species are temporally and spatially averaged, and many reactions proceed to completion before intermediates can be trapped. Here, we describe the combined use of diffusion trap cryocrystallography, density functional theory calculations, and kinetic measurements to investigate the reactivation of the essential cholinergic enzyme acetylcholinesterase by the nerve agent antidote HI-6 after covalent inhibition by the nerve agent sarin. We have determined prereaction conformations of HI-6 and propose that the reactivating cleavage of the enzyme–sarin bond is preceded by a change in the sarin adduct’s binding pose. The structures presented in this work will facilitate additional mechanistic analysis and the development of novel antidotes.
Strain-enhanced stress relaxation impacts nonlinear elasticity in collagen gels
Authors: Nam Sungmin , Hu Kenneth H. , Butte Manish J. , Chaudhuri Ovijit 
Published: May 2016

SignificanceThe extracellular matrix is a complex assembly of structural proteins that provides physical support and biochemical signaling to cells within our tissues. One of the key structural components of the extracellular matrix is collagen, and matrices of collagen exhibit remarkable mechanical properties. Their resistance to deformation is enhanced as deformation is increased over short timescales, a behavior termed strain stiffening, yet they exhibit some characteristics of viscous fluids at longer timescales. Strikingly, we show that the strain stiffening of collagen matrices is coupled with their liquid-like behavior: at greater deformations, these matrices become stiffer but then flow more rapidly to relax this increase in stiffness. These complex mechanical behaviors are likely to be relevant to cellular interactions with these matrices.
Peptidoglycan-linked protein A promotes T cell-dependent antibody expansion duringStaphylococcus aureusinfection
Authors: Kim Hwan Keun , Falugi Fabiana , Missiakas Dominique M. , Schneewind Olaf 
Published: May 2016

SignificanceStaphylococcus aureusinfection of humans is associated with immunoglobulin expansions but not with the development of immunity against recurrent disease. The mechanism whereby staphylococci manipulate the host immune system to block adaptive immunity is not known. We show here thatS. aureusinfection of mice is also associated with immunoglobulin expansions and that staphylococcal protein A (SpA), a molecule that cross-links B-cell receptors, is both necessary and sufficient for this immune evasion mechanism. Further, SpA requires covalent linkage to bacterial peptidoglycan and CD4 T-cell help to manipulate the immunoglobulin responses of infected hosts. Our results provide insights into microbial signaling mechanisms for B-cell activation and antibody development.
Extreme cellular adaptations and cell differentiation required by a cyanobacterium for carbonate excavation
Authors: Guida Brandon Scott , Garcia-Pichel Ferran 
Published: May 2016

SignificanceMicroorganisms can play a significant role as agents of erosion. Euendolithic cyanobacteria, photosynthetic microorganisms that bore their way into carbonate substrates, are among the most important bioerosive agents known. The mechanism by which they dissolve and excavate carbonate rocks has remained a mystery for decades, but is now known to involve calcium transport from cell to cell. Herein we show that the mechanism involves two adaptations unprecedented in prokaryotic biology: the polar placement of calcium and proton transporting enzymes in a manner that is coordinated between cells and the differentiation of a novel type of cell that is able to accumulate calcium at levels some 500-fold those found in normal cells.
DNA-based nanoparticle tension sensors reveal that T-cell receptors transmit defined pN forces to their antigens for enhanced fidelity
Authors: Liu Yang , Blanchfield Lori , Ma Victor Pui-Yan , Andargachew Rakieb , Galior Kornelia , Liu Zheng , Evavold Brian , Salaita Khalid 
Published: May 2016

Significance
T cells protect the body against pathogens and cancer by recognizing specific foreign peptides on the cell surface. Because antigen recognition occurs at the junction between a migrating T cell and an antigen-presenting cell (APC), it is likely that cellular forces are generated and transmitted through T-cell receptor (TCR)-ligand bonds. Here we develop a DNA-based nanoparticle tension sensor producing the first molecular maps of TCR-ligand forces during T cell activation. We find that TCR forces are orchestrated in space and time, requiring the participation of CD8 coreceptor and adhesion molecules. Loss or damping of TCR forces results in weakened antigen discrimination, showing that T cells harness mechanics to optimize the specificity of response to ligand.
Mode of action uncovered for the specific reduction of methane emissions from ruminants by the small molecule 3-nitrooxypropanol
Authors: Duin Evert C. , Wagner Tristan , Shima Seigo , Prakash Divya , Cronin Bryan , Yáñez-Ruiz David R. , Duval Stephane , Rümbeli Robert , Stemmler René T. , Thauer Rudolf Kurt , Kindermann Maik 
Published: May 2016

Significance
Methane emission from the ruminant livestock sector—a by-product from enteric fermentation of plant biomass in the ruminant digestive system—is produced by methanogenic archaea and represents not only a significant amount of anthropogenic greenhouse gases contributing to climate change but also an energy loss and a reduction in feed efficacy. The present study elucidates the development and the unique mode of action of the highly specific inhibitor 3-nitrooxypropanol (3-NOP), which is targeting the nickel enzyme methyl-coenzyme M reductase in rumen archaea that catalyzes the methane-forming reaction. At the very low effective concentrations recently applied in vivo (dairy and beef cattle), 3-NOP appears to inhibit only methanogens and thus to be attractive for development as a feed supplement.
Control of active liquid crystals with a magnetic field
Authors: Guillamat Pau , Ignés-Mullol Jordi , Sagués Francesc 
Published: May 2016

SignificanceActive liquid crystals are aqueous in vitro suspensions of cytoskeletal proteins that self-assemble into elongated fibers and develop sustained flows at the continuous expense of ATP. When they condense on soft interfaces, the aligned fibers organize into nonequilibrium analogs of passive liquid crystals. However, proteins do not respond to external electromagnetic fields, unlike liquid crystals, which are readily reconfigured inside devices. We demonstrate a reversible and biocompatible experimental protocol to align an active liquid crystal with a uniform magnetic field, allowing the transition between turbulent and laminar flow regimes. The active liquid crystal senses the interfacial viscous anisotropy of a lamellar hydrophobic liquid crystal, not unlike the adaptation of cells to the mechanical features of their environment.
Hsp70 biases the folding pathways of client proteins
Authors: Sekhar Ashok , Rosenzweig Rina , Bouvignies Guillaume , Kay Lewis E. 
Published: May 2016

Significance
Hsp70 (70-kDa heat shock protein) chaperones bind cognate substrates to prevent their aggregation and guide them toward their correctly folded, functional states. Here we use NMR spectroscopy to understand how this is achieved by studying a complex of Hsp70 with a folding competent substrate. Using an NMR experiment presented here, we show that long-range transient contacts are established in the unfolded, unbound state of the substrate. These contacts are greatly attenuated in the bound form of the substrate that also exists as an unfolded ensemble. Our results establish that Hsp70 binding can significantly bias the folding mechanism of client substrate molecules toward pathways where secondary structure is first generated, followed by the establishment of longer-range interactions in a distance-dependent fashion.
Aquaporin gene therapy corrects Sjögren’s syndrome phenotype in mice
Authors: Lai Zhennan , Yin Hongen , Cabrera-Pérez Javier , Guimaro Maria C. , Afione Sandra , Michael Drew G. , Glenton Patricia , Patel Ankur , Swaim William D. , Zheng Changyu , Nguyen Cuong Q. , Nyberg Fred , Chiorini John A. 
Published: May 2016

Significance
Recent reports of increases in the prevalence and incidence of autoimmune diseases make this disease group a pressing public health concern. Patients suffering from Sjögren’s syndrome experience debilitating oral and ocular dryness due to dysfunction within the salivary and lacrimal glands. Due to our lack of knowledge regarding the underlying mechanisms, no effective treatments are available and affected organs gradually degenerate. In this study, we identify the loss of water permeability as a mechanism associated with xerostomia in a subset of patients. We demonstrate that a novel therapy, aquaporin 1 replacement, can increase the water permeability of the gland and restore fluid movement while relieving the dry mouth and eye phenotypes associated with this disease in addition to disease-associated inflammation.
Imaging through plasmonic nanoparticles
Authors: Tanzid Mehbuba , Sobhani Ali , DeSantis Christopher J. , Cui Yao , Hogan Nathaniel J. , Samaniego Adam , Veeraraghavan Ashok , Halas Naomi J. 
Published: May 2016

Significance
How is an image transmitted through a material consisting of subwavelength structures? We use two distinct methods to obtain quantitative answers to that question. The first, structural similarity index, is a method related to human perception, initially developed to quantify transmitted image quality following image compression in digital image transmission systems. The second method treats the medium as an optical component itself, where we determine the spatial frequency content of the image transmitted by the medium. This study opens the door to analyzing images transmitted through particulate media that absorb and/or scatter light, which applies generally to imaging systems whose components are composed of subwavelength structures, such as those composed of random particulates or nanoengineered flat-optics metasurface lenses.
Preventing diet-induced obesity in mice by adipose tissue transformation and angiogenesis using targeted nanoparticles
Authors: Xue Yuan , Xu Xiaoyang , Zhang Xue-Qing , Farokhzad Omid C. , Langer Robert 
Published: May 2016

Significance
Obesity has been recognized by the American Medical Association to be a disease affecting significant portions of the population and is related to an expansion and proliferation of white adipose tissue (WAT) in the body. The primary function of WAT is to store energy, whereas brown adipose tissue (BAT) generates heat through energy expenditure. Transforming WAT into BAT is of tremendous interest for obesity treatment. Herein, we describe a targeted nanoparticle approach encapsulating either a PPARgamma activator or a prostaglandin E2 analog, each of which induces adipose tissue transformation and angiogenesis, facilitating the transformation of WAT into BAT. Targeted nanoparticles show antiobesity effects compared with free drug and the nontargeted nanoparticle controls in a mouse model.
Development of potent small-molecule inhibitors to drug the undruggable steroid receptor coactivator-3
Authors: Song Xianzhou , Chen Jianwei , Zhao Mingkun , Zhang Chengwei , Yu Yang , Lonard David M. , Chow Dar-Chone , Palzkill Timothy , Xu Jianming , O’Malley Bert W. , Wang Jin 
Published: May 2016

Significance
Steroid receptor coactivator-3 (SRC-3) sits at the nexus of many intracellular signaling pathways critical for cancer formation and proliferation. Although the oncogenic role of SRC-3 has been well established in breast and other cancers, coactivators are usually considered as “undruggable” because of their large and flexible structures. Herein, we developed SI-2 as a new class of potent small-molecule inhibitors for SRC-3. SI-2 can selectively reduce the transcriptional activities and the protein concentrations of SRC-3 in cells and significantly inhibit primary tumor growth in a breast cancer mouse model. This work not only has the potential to improve breast cancer treatment, but also to provide a viable strategy to target often “undruggable but important” protein targets without ligand-binding sites.
Cell wall structure and biogenesis inAspergillusspecies
Authors: Yoshimi Akira , Miyazawa Ken , Abe Keietsu 
Published: May 2016

AbstractAspergillus species are among the most important filamentous fungi from the viewpoints of industry, pathogenesis, and mycotoxin production. Fungal cells are exposed to a variety of environmental stimuli, including changes in osmolality, temperature, and pH, which create stresses that primarily act on fungal cell walls. In addition, fungal cell walls are the first interactions with host cells in either human or plants. Thus, understanding cell wall structure and the mechanism of their biogenesis is important for the industrial, medical, and agricultural fields. Here, we provide a systematic review of fungal cell wall structure and recent findings regarding the cell wall integrity signaling pathways in aspergilli. This accumulated knowledge will be useful for understanding and improving the use of industrial aspergilli fermentation processes as well as treatments for some fungal infections.
Wasabi leaf extracts attenuate adipocyte hypertrophy through PPARγ and AMPK
Authors: Oowatari Yasuo , Ogawa Tetsuro , Katsube Takuya , Iinuma Kiyohisa , Yoshitomi Hisae , Gao Ming 
Published: May 2016

AbstractHypertrophy of adipocytes in obese adipose tissues causes metabolic abnormality by adipocytokine dysregulation, which promotes type 2 diabetes mellitus, hypertension, and dyslipidemia. We investigated the effects of wasabi (Wasabia japonica Matsum) leaf extracts on metabolic abnormalities in SHRSP.Z-Leprfa/IzmDmcr rats (SHRSP/ZF), which are a model of metabolic syndrome. Male SHRSP/ZF rats aged 7 weeks were divided into two groups: control and wasabi leaf extract (WLE) groups, which received water or oral treatment with 4 g/kg/day WLE for 6 weeks. WLE improved the body weight gain and high blood pressure in SHRSP/ZF rats, and the plasma triglyceride levels were significantly lower in the WLE group. Adipocyte hypertrophy was markedly prevented in adipose tissue. The expression of PPARγ and subsequent downstream genes was suppressed in the WLE group adipose tissues. Our data suggest that WLE inhibits adipose hypertrophy by suppressing PPARγ expression in adipose tissue and stimulating the AMPK activity by increased adiponectin.