SFXN1 is a mitochondrial serine transporter required for one-carbon metabolism
One-carbon metabolism generates the one-carbon units required to synthesize many critical metabolites, including nucleotides. The pathway has cytosolic and mitochondrial branches, and a key step is the entry, through an unknown mechanism, of serine into mitochondria, where it is converted into glycine and formate. In a CRISPR-based genetic screen in human cells for genes of the mitochondrial pathway, we found sideroflexin 1 (SFXN1), a multipass inner mitochondrial membrane protein of unclear function. Like cells missing mitochondrial components of one-carbon metabolism, those null for SFXN1 are defective in glycine and pur...
Source: ScienceNOW - November 15, 2018 Category: Science Authors: Kory, N., Wyant, G. A., Prakash, G., uit de Bos, J., Bottanelli, F., Pacold, M. E., Chan, S. H., Lewis, C. A., Wang, T., Keys, H. R., Guo, Y. E., Sabatini, D. M. Tags: Biochemistry, Cell Biology, Online Only r-articles Source Type: news
Response to Comment on "Predicting reaction performance in C-N cross-coupling using machine learning"
We demonstrate that the chemical-feature model described in our original paper is distinguishable from the nongeneralizable models introduced by Chuang and Keiser. Furthermore, the chemical-feature model significantly outperforms these models in out-of-sample predictions, justifying the use of chemical featurization from which machine learning models can extract meaningful patterns in the dataset, as originally described. (Source: ScienceNOW)
Source: ScienceNOW - November 15, 2018 Category: Science Authors: Estrada, J. G., Ahneman, D. T., Sheridan, R. P., Dreher, S. D., Doyle, A. G. Tags: Chemistry, Computers, Mathematics t-comment Source Type: news
Comment on "Predicting reaction performance in C-N cross-coupling using machine learning"
Ahneman et al. (Reports, 13 April 2018) applied machine learning models to predict C–N cross-coupling reaction yields. The models use atomic, electronic, and vibrational descriptors as input features. However, the experimental design is insufficient to distinguish models trained on chemical features from those trained solely on random-valued features in retrospective and prospective test scenarios, thus failing classical controls in machine learning. (Source: ScienceNOW)
Source: ScienceNOW - November 15, 2018 Category: Science Authors: Chuang, K. V., Keiser, M. J. Tags: Chemistry, Computers, Mathematics t-comment Source Type: news
Molecular, spatial, and functional single-cell profiling of the hypothalamic preoptic region
The hypothalamus controls essential social behaviors and homeostatic functions. However, the cellular architecture of hypothalamic nuclei—including the molecular identity, spatial organization, and function of distinct cell types—is poorly understood. Here, we developed an imaging-based in situ cell-type identification and mapping method and combined it with single-cell RNA-sequencing to create a molecularly annotated and spatially resolved cell atlas of the mouse hypothalamic preoptic region. We profiled ~1 million cells, identified ~70 neuronal populations characterized by distinct neuromodulatory signatures ...
Source: ScienceNOW - November 15, 2018 Category: Science Authors: Moffitt, J. R., Bambah-Mukku, D., Eichhorn, S. W., Vaughn, E., Shekhar, K., Perez, J. D., Rubinstein, N. D., Hao, J., Regev, A., Dulac, C., Zhuang, X. Tags: Neuroscience, Online Only r-articles Source Type: news
In vivo modeling of human neuron dynamics and Down syndrome
Harnessing the potential of human stem cells for modeling the physiology and diseases of cortical circuitry requires monitoring cellular dynamics in vivo. We show that human induced pluripotent stem cell (iPSC)–derived cortical neurons transplanted into the adult mouse cortex consistently organized into large (up to ~100 mm3) vascularized neuron-glia territories with complex cytoarchitecture. Longitudinal imaging of>4000 grafted developing human neurons revealed that neuronal arbors refined via branch-specific retraction; human synaptic networks substantially restructured over 4 months, with balanced rates of syna...
Source: ScienceNOW - November 15, 2018 Category: Science Authors: Real, R., Peter, M., Trabalza, A., Khan, S., Smith, M. A., Dopp, J., Barnes, S. J., Momoh, A., Strano, A., Volpi, E., Knott, G., Livesey, F. J., De Paola, V. Tags: Neuroscience, Online Only r-articles Source Type: news
Technology Feature | Protein expression, revisited
Source: ScienceNOW - November 15, 2018 Category: Science Authors: Smith, C. Tags: opms-sups Source Type: news
Programmed DNA destruction by miniature CRISPR-Cas14 enzymes
CRISPR-Cas systems provide microbes with adaptive immunity to infectious nucleic acids and are widely employed as genome editing tools. These tools use RNA-guided Cas proteins whose large size (950 to 1400 amino acids) has been considered essential to their specific DNA- or RNA-targeting activities. Here we present a set of CRISPR-Cas systems from uncultivated archaea that contain Cas14, a family of exceptionally compact RNA-guided nucleases (400 to 700 amino acids). Despite their small size, Cas14 proteins are capable of targeted single-stranded DNA (ssDNA) cleavage without restrictive sequence requirements. Moreover, tar...
Source: ScienceNOW - November 15, 2018 Category: Science Authors: Harrington, L. B., Burstein, D., Chen, J. S., Paez-Espino, D., Ma, E., Witte, I. P., Cofsky, J. C., Kyrpides, N. C., Banfield, J. F., Doudna, J. A. Tags: Biochemistry, Microbiology reports Source Type: news
Small-molecule inhibitor of OGG1 suppresses proinflammatory gene expression and inflammation
The onset of inflammation is associated with reactive oxygen species and oxidative damage to macromolecules like 7,8-dihydro-8-oxoguanine (8-oxoG) in DNA. Because 8-oxoguanine DNA glycosylase 1 (OGG1) binds 8-oxoG and because Ogg1-deficient mice are resistant to acute and systemic inflammation, we hypothesized that OGG1 inhibition may represent a strategy for the prevention and treatment of inflammation. We developed TH5487, a selective active-site inhibitor of OGG1, which hampers OGG1 binding to and repair of 8-oxoG and which is well tolerated by mice. TH5487 prevents tumor necrosis factor–α–induced OGG1...
Source: ScienceNOW - November 15, 2018 Category: Science Authors: Visnes, T., Cazares-Körner, A., Hao, W., Wallner, O., Masuyer, G., Loseva, O., Mortusewicz, O., Wiita, E., Sarno, A., Manoilov, A., Astorga-Wells, J., Jemth, A.-S., Pan, L., Sanjiv, K., Karsten, S., Gokturk, C., Grube, M., Homan, E. J., Hanna, B. Tags: Chemistry, Immunology reports Source Type: news
Protein assemblies ejected directly from native membranes yield complexes for mass spectrometry
Membrane proteins reside in lipid bilayers and are typically extracted from this environment for study, which often compromises their integrity. In this work, we ejected intact assemblies from membranes, without chemical disruption, and used mass spectrometry to define their composition. From Escherichia coli outer membranes, we identified a chaperone-porin association and lipid interactions in the β-barrel assembly machinery. We observed efflux pumps bridging inner and outer membranes, and from inner membranes we identified a pentameric pore of TonB, as well as the protein-conducting channel SecYEG in association wit...
Source: ScienceNOW - November 15, 2018 Category: Science Authors: Chorev, D. S., Baker, L. A., Wu, D., Beilsten-Edmands, V., Rouse, S. L., Zeev-Ben-Mordehai, T., Jiko, C., Samsudin, F., Gerle, C., Khalid, S., Stewart, A. G., Matthews, S. J., Grünewald, K., Robinson, C. V. Tags: Biochemistry reports Source Type: news
Quantifying reputation and success in art
In areas of human activity where performance is difficult to quantify in an objective fashion, reputation and networks of influence play a key role in determining access to resources and rewards. To understand the role of these factors, we reconstructed the exhibition history of half a million artists, mapping out the coexhibition network that captures the movement of art between institutions. Centrality within this network captured institutional prestige, allowing us to explore the career trajectory of individual artists in terms of access to coveted institutions. Early access to prestigious central institutions offered l...
Source: ScienceNOW - November 15, 2018 Category: Science Authors: Fraiberger, S. P., Sinatra, R., Resch, M., Riedl, C., Barabasi, A.-L. Tags: Computers, Mathematics reports Source Type: news
Beyond the molecular movie: Dynamics of bands and bonds during a photoinduced phase transition
Ultrafast nonequilibrium dynamics offer a route to study the microscopic interactions that govern macroscopic behavior. In particular, photoinduced phase transitions (PIPTs) in solids provide a test case for how forces, and the resulting atomic motion along a reaction coordinate, originate from a nonequilibrium population of excited electronic states. Using femtosecond photoemission, we obtain access to the transient electronic structure during an ultrafast PIPT in a model system: indium nanowires on a silicon(111) surface. We uncover a detailed reaction pathway, allowing a direct comparison with the dynamics predicted by ...
Source: ScienceNOW - November 15, 2018 Category: Science Authors: Nicholson, C. W., Lücke, A., Schmidt, W. G., Puppin, M., Rettig, L., Ernstorfer, R., Wolf, M. Tags: Physics reports Source Type: news
Wafer-scale single-crystal hexagonal boron nitride film via self-collimated grain formation
Although polycrystalline hexagonal boron nitride (PC-hBN) has been realized, defects and grain boundaries still cause charge scatterings and trap sites, impeding high-performance electronics. Here, we report a method of synthesizing wafer-scale single-crystalline hBN (SC-hBN) monolayer films by chemical vapor deposition. The limited solubility of boron (B) and nitrogen (N) atoms in liquid gold promotes high diffusion of adatoms on the surface of liquid at high temperature to provoke the circular hBN grains. These further evolve into closely packed unimodal grains by means of self-collimation of B and N edges inherited by e...
Source: ScienceNOW - November 15, 2018 Category: Science Authors: Lee, J. S., Choi, S. H., Yun, S. J., Kim, Y. I., Boandoh, S., Park, J.-H., Shin, B. G., Ko, H., Lee, S. H., Kim, Y.-M., Lee, Y. H., Kim, K. K., Kim, S. M. Tags: Materials Science reports Source Type: news
Light-driven fine chemical production in yeast biohybrids
Inorganic-biological hybrid systems have potential to be sustainable, efficient, and versatile chemical synthesis platforms by integrating the light-harvesting properties of semiconductors with the synthetic potential of biological cells. We have developed a modular bioinorganic hybrid platform that consists of highly efficient light-harvesting indium phosphide nanoparticles and genetically engineered Saccharomyces cerevisiae, a workhorse microorganism in biomanufacturing. The yeast harvests photogenerated electrons from the illuminated nanoparticles and uses them for the cytosolic regeneration of redox cofactors. This pro...
Source: ScienceNOW - November 15, 2018 Category: Science Authors: Guo, J., Suastegui, M., Sakimoto, K. K., Moody, V. M., Xiao, G., Nocera, D. G., Joshi, N. S. Tags: Materials Science, Molecular Biology reports Source Type: news
Reversible self-assembly of superstructured networks
We report on hydrogels of peptide-DNA conjugates and peptides that organize into superstructures of intertwined filaments that disassemble upon the addition of molecules or changes in charge density. Experiments and simulations demonstrate that this response requires large-scale spatial redistribution of molecules directed by strong noncovalent interactions among them. Simulations also suggest that the chemically reversible structures can only occur within a limited range of supramolecular cohesive energies. Storage moduli of the hydrogels change reversibly as superstructures form and disappear, as does the phenotype of ne...
Source: ScienceNOW - November 15, 2018 Category: Science Authors: Freeman, R., Han, M., Alvarez, Z., Lewis, J. A., Wester, J. R., Stephanopoulos, N., McClendon, M. T., Lynsky, C., Godbe, J. M., Sangji, H., Luijten, E., Stupp, S. I. Tags: Chemistry, Materials Science reports Source Type: news
Templated nanofiber synthesis via chemical vapor polymerization into liquid crystalline films
Extrusion, electrospinning, and microdrawing are widely used to create fibrous polymer mats, but these approaches offer limited access to oriented arrays of nanometer-scale fibers with controlled size, shape, and lateral organization. We show that chemical vapor polymerization can be performed on surfaces coated with thin films of liquid crystals to synthesize organized assemblies of end-attached polymer nanofibers. The process uses low concentrations of radical monomers formed initially in the vapor phase and then diffused into the liquid-crystal template. This minimizes monomer-induced changes to the liquid-crystal phase...
Source: ScienceNOW - November 15, 2018 Category: Science Authors: Cheng, K. C. K., Bedolla-Pantoja, M. A., Kim, Y.-K., Gregory, J. V., Xie, F., de France, A., Hussal, C., Sun, K., Abbott, N. L., Lahann, J. Tags: Materials Science reports Source Type: news
Heterobiaryl synthesis by contractive C-C coupling via P(V) intermediates
We present an alternative approach to metal-catalyzed cross-coupling to make heterobiaryls using contractive phosphorus C–C couplings, also termed phosphorus ligand coupling reactions. The process starts by regioselective phosphorus substitution of the C–H bonds para to nitrogen in two successive heterocycles; ligand coupling is then triggered via acidic alcohol solutions to form the heterobiaryl bond. Mechanistic studies imply that ligand coupling is an asynchronous process involving migration of one heterocycle to the ipso position of the other around a central pentacoordinate P(V) atom. The strategy can be a...
Source: ScienceNOW - November 15, 2018 Category: Science Authors: Hilton, M. C., Zhang, X., Boyle, B. T., Alegre-Requena, J. V., Paton, R. S., McNally, A. Tags: Chemistry r-articles Source Type: news
Dominant effect of relative tropical Atlantic warming on major hurricane occurrence
Here we explore factors potentially linked to the enhanced major hurricane activity in the Atlantic Ocean during 2017. Using a suite of high-resolution model experiments, we show that the increase in 2017 major hurricanes was not primarily caused by La Niña conditions in the Pacific Ocean but rather triggered mainly by pronounced warm sea surface conditions in the tropical North Atlantic. Further, we superimpose a similar pattern of North Atlantic surface warming on data for long-term increasing sea surface temperature (a product of increases in greenhouse gas concentrations and decreases in aerosols) to show that t...
Source: ScienceNOW - November 15, 2018 Category: Science Authors: Murakami, H., Levin, E., Delworth, T. L., Gudgel, R., Hsu, P.- C. Tags: Atmospheric Science, Geochemistry, Geophysics r-articles Source Type: news
Swifter, higher, stronger: Whats on the menu?
The exploits of elite athletes delight, frustrate, and confound us as they strive to reach their physiological, psychological, and biomechanical limits. We dissect nutritional approaches to optimal performance, showcasing the contribution of modern sports science to gold medals and world titles. Despite an enduring belief in a single, superior "athletic diet," diversity in sports nutrition practices among successful athletes arises from the specificity of the metabolic demands of different sports and the periodization of training and competition goals. Pragmatic implementation of nutrition strategies in real-worl...
Source: ScienceNOW - November 15, 2018 Category: Science Authors: Burke, L. M., Hawley, J. A. Tags: Physiology special/review Source Type: news
The gut microbiota at the intersection of diet and human health
Diet affects multiple facets of human health and is inextricably linked to chronic metabolic conditions such as obesity, type 2 diabetes, and cardiovascular disease. Dietary nutrients are essential not only for human health but also for the health and survival of the trillions of microbes that reside within the human intestines. Diet is a key component of the relationship between humans and their microbial residents; gut microbes use ingested nutrients for fundamental biological processes, and the metabolic outputs of those processes may have important impacts on human physiology. Studies in humans and animal models are be...
Source: ScienceNOW - November 15, 2018 Category: Science Authors: Gentile, C. L., Weir, T. L. Tags: Physiology special/review Source Type: news
A time to fast
Nutrient composition and caloric intake have traditionally been used to devise optimized diets for various phases of life. Adjustment of meal size and frequency have emerged as powerful tools to ameliorate and postpone the onset of disease and delay aging, whereas periods of fasting, with or without reduced energy intake, can have profound health benefits. The underlying physiological processes involve periodic shifts of metabolic fuel sources, promotion of repair mechanisms, and the optimization of energy utilization for cellular and organismal health. Future research endeavors should be directed to the integration of a b...
Source: ScienceNOW - November 15, 2018 Category: Science Authors: Di Francesco, A., Di Germanio, C., Bernier, M., de Cabo, R. Tags: Physiology special/review Source Type: news
Dietary fat: From foe to friend?
For decades, dietary advice was based on the premise that high intakes of fat cause obesity, diabetes, heart disease, and possibly cancer. Recently, evidence for the adverse metabolic effects of processed carbohydrate has led to a resurgence in interest in lower-carbohydrate and ketogenic diets with high fat content. However, some argue that the relative quantity of dietary fat and carbohydrate has little relevance to health and that focus should instead be placed on which particular fat or carbohydrate sources are consumed. This review, by nutrition scientists with widely varying perspectives, summarizes existing evidence...
Source: ScienceNOW - November 15, 2018 Category: Science Authors: Ludwig, D. S., Willett, W. C., Volek, J. S., Neuhouser, M. L. Tags: Physiology special/review Source Type: news