Prediction of intracellular exposure bridges the gap between target- and cell-based drug discovery.

abstract：:Little is known about the catalytic mechanism of the recently discovered ThyX family of flavin-dependent thymidylate synthases that are required for thymidylate (deoxythymidine 5'-monophosphate) synthesis in a large number of microbial species. Using a combination of site-directed mutagenesis and biochemical measureme...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Leduc D,Graziani S,Lipowski G,Marchand C,Le Maréchal P,Liebl U,Myllykallio H

更新日期：2004-05-11 00:00:00

abstract：:Several findings suggest that signals from tyrosine kinases are transduced, at least in part, through ras proteins. These findings include (i) blockage of the transforming activity of constitutively active tyrosine kinases by inhibiting ras function and (ii) genetic screens in Caenorhabditis elegans and in Drosophila ...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Bowtell D,Fu P,Simon M,Senior P

更新日期：1992-07-15 00:00:00

abstract：:Expression systems based on the Escherichia coli arabinose operon P(BAD) promoter exhibit the all-or-nothing (autocatalytic) induction of expression that was first documented in the lac operon. Under conditions of subsaturating levels of inducer, some of the cells of the population are fully induced, whereas other cel...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Morgan-Kiss RM,Wadler C,Cronan JE Jr

更新日期：2002-05-28 00:00:00

abstract：:Cellular factors tightly regulate the architecture of bundles of filamentous cytoskeletal proteins, giving rise to assemblies with distinct morphologies and physical properties, and a similar control of the supramolecular organization of nanotubes and nanorods in synthetic materials is highly desirable. However, it is...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Needleman DJ,Ojeda-Lopez MA,Raviv U,Miller HP,Wilson L,Safinya CR

更新日期：2004-11-16 00:00:00

abstract：:The equations of motion of the coupled electron-phonon system are integrated in real time for the model of polyacetylene recently proposed. To illustrate the physical behavior of this nonlinear system we consider the time evolution starting from three physically relevant configurations: (i) end generated soliton, (ii)...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Su WP,Schrieffer JR

更新日期：1980-10-01 00:00:00

abstract：:Protein kinase C (PKC) phosphorylation stimulates the cystic fibrosis transmembrane conductance regulator (CFTR) channel and enhances its activation by protein kinase A (PKA) through mechanisms that remain poorly understood. We have examined the effects of mutating consensus sequences for PKC phosphorylation and repor...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Chappe V,Hinkson DA,Howell LD,Evagelidis A,Liao J,Chang XB,Riordan JR,Hanrahan JW

更新日期：2004-01-06 00:00:00

abstract：:The Ritz upper bound to eigenvalues of Hermitian operators is essential for many applications in science. It is a staple of quantum chemistry and physics computations. The lower bound devised by Temple in 1928 [G. Temple, Proc. R. Soc. A Math. Phys. Eng. Sci. 119, 276-293 (1928)] is not, since it converges too slowly....

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Martinazzo R,Pollak E

更新日期：2020-07-14 00:00:00

abstract：:In 1950, Barbara McClintock published a Classic PNAS article, "The origin and behavior of mutable loci in maize," which summarized the evidence leading to her discovery of transposition. The article described a number of genome alterations revealed through her studies of the Dissociation locus, the first mobile geneti...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Fedoroff NV

更新日期：2012-12-11 00:00:00

abstract：:To investigate protein folding dynamics in terms of compactness, we developed a continuous-flow mixing device to make small-angle x-ray scattering measurements with the time resolution of 160 micros and characterized the radius of gyration (R(g)) of two folding intermediates of cytochrome c (cyt c). The early intermed...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Akiyama S,Takahashi S,Kimura T,Ishimori K,Morishima I,Nishikawa Y,Fujisawa T

更新日期：2002-02-05 00:00:00

abstract：:The surface layer of the oceans and other aquatic environments contains many bacteria that range in activity, from dormant cells to those with high rates of metabolism. However, little experimental evidence exists about the activity of specific bacterial taxa, especially rare ones. Here we explore the relationship bet...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Campbell BJ,Yu L,Heidelberg JF,Kirchman DL

更新日期：2011-08-02 00:00:00

abstract：:Four different human cell lines transformed by simian virus 40 (SV40) were tested for their tumorigenicity in athymic nude mice. Two of these lines, W18Va2 and GM52VA, were found to be tumorigenic when inoculated at a concentration of 1 x 10(7) cells per mouse. The other two cell lines, LN-SV and GM54VA, were found to...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Koprowski H,Croce CM

更新日期：1977-03-01 00:00:00

abstract：:Gene conversion and conversion-associated reciprocal recombination have been studied in various Saccharomyces cerevisiae hybrids. In a sample of 11,023 unselected meiotic tetrads, 907 conversions were observed at the arg4, thr3, his1, and SUP6 loci. Of these conversions, 445 (or 49.1%) were associated with reciprocal ...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Hurst DD,Fogel S,Mortimer RK

更新日期：1972-01-01 00:00:00

abstract：:Past research found that the ingestion of glucose can enhance self-control. It has been widely assumed that basic physiological processes underlie this effect. We hypothesized that the effect of glucose also depends on people's theories about willpower. Three experiments, both measuring (experiment 1) and manipulating...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Job V,Walton GM,Bernecker K,Dweck CS

更新日期：2013-09-10 00:00:00

abstract：:Although aquaporin 5 (AQP5) is the major water channel expressed in alveolar type I cells in the lung, its actual role in the lung is a matter of considerable speculation. By using immunohistochemical staining, we show that AQP5 expression in mouse lung is not restricted to type I cells, but is also detected in alveol...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Krane CM,Fortner CN,Hand AR,McGraw DW,Lorenz JN,Wert SE,Towne JE,Paul RJ,Whitsett JA,Menon AG

更新日期：2001-11-20 00:00:00

abstract：:Formulas are derived for the effect of size on a free-swimming microbe's ability to follow chemical, light, or temperature stimuli or to disperse in random directions. The four main assumptions are as follows: (i) the organisms can be modeled as spheres, (ii) the power available to the organism for swimming is proport...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Dusenbery DB

更新日期：1997-09-30 00:00:00

abstract：:Protein tyrosine phosphorylation in purified synaptic vesicles from rat forebrain has been studied in the presence of Mn2+ and orthovanadate. High levels of endogenous protein tyrosine phosphorylation were observed. Four major phosphoproteins, with apparent molecular masses of 105, 94, 38, and 30 kDa, were shown to co...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Pang DT,Wang JK,Valtorta F,Benfenati F,Greengard P

更新日期：1988-02-01 00:00:00

abstract：:The tremendous pandemic potential of coronaviruses was demonstrated twice in the past few decades by two global outbreaks of deadly pneumonia. The coronavirus spike (S) glycoprotein initiates infection by promoting fusion of the viral and cellular membranes through conformational changes that remain largely uncharacte...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Walls AC,Tortorici MA,Snijder J,Xiong X,Bosch BJ,Rey FA,Veesler D

更新日期：2017-10-17 00:00:00

abstract：:Activation of the cascade of proteolytic caspases has been identified as the final common pathway of apoptosis in diverse biological systems. We have isolated a gene, termed MRIT, that possesses overall sequence homology to FLICE (MACH), a large prodomain caspase that links the aggregated complex of the death domain r...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Han DK,Chaudhary PM,Wright ME,Friedman C,Trask BJ,Riedel RT,Baskin DG,Schwartz SM,Hood L

更新日期：1997-10-14 00:00:00

abstract：:Cognitive studies of memory processes demonstrate that memory for stimuli is a function of how they are encoded; stimuli processed semantically are better remembered than those processed in a perceptual or shallow fashion. This study investigates the neural correlates of this cognitive phenomenon. Twelve subjects perf...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Kapur S,Craik FI,Tulving E,Wilson AA,Houle S,Brown GM

更新日期：1994-03-15 00:00:00

abstract：:In the mitochondrial genome of the hemichordate Balanoglossus carnosus, the codon AAA, which is assigned to lysine in most metazoans but to asparagine in echinoderms, is absent. Furthermore, the lysine tRNA gene carries an anticodon substitution that renders its gene product unable to decode AAA codons, whereas the as...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Castresana J,Feldmaier-Fuchs G,Pääbo S

更新日期：1998-03-31 00:00:00

abstract：:Free hydrogen (H2) is a basal energy source underlying chemosynthetic activity within igneous ocean crust. In an attempt to systematically account for all H2 within young oceanic lithosphere (<10 Ma) near the Mid-Ocean Ridge (MOR), we construct a box model of this environment. Within this control volume, we assess abi...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Worman SL,Pratson LF,Karson JA,Schlesinger WH

更新日期：2020-06-16 00:00:00

abstract：:gp130 is a common signal-transducing receptor component for the interleukin 6 family of cytokines functioning in, for example, immune, hematopoietic, and nervous systems. In this study, to investigate the physiological functions of gp130 and to determine the pathological consequences of impaired gp130 signals, we have...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Kumanogoh A,Marukawa S,Kumanogoh T,Hirota H,Yoshida K,Lee IS,Yasui T,Yoshida K,Taga T,Kishimoto T

更新日期：1997-03-18 00:00:00

abstract：:Two RNA fractions have been isolated and purified from both oncogenic and nononcogenic strains of Agrobacterium tumefaciens. Both RNAs are capable of inducing the formation of transplantable tumors when introduced at wound sites in stems of Datura stramonium plants. One of these RNA fractions was found to be bound to ...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Beljanski M,Aaron-da Cunha MI,Beljanski MS,Manigault P,Bourgarel P

更新日期：1974-05-01 00:00:00

abstract：:Chlorarachniophytes are amoeboid algae with unusual chloroplasts. Instead of the usual two membranes that surround the chloroplasts of plants, green algae, and red algae, the chloroplasts of chlorarachniophytes have four bounding membranes. The extra membranes may reflect an unusual origin of chlorarachniophyte chloro...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： McFadden GI,Gilson PR,Hofmann CJ,Adcock GJ,Maier UG

更新日期：1994-04-26 00:00:00

abstract：:The photoproduct of carbon monoxide myoglobin generated at 4 K and lower has a resonance Raman spectrum characteristic of a high-spin heme but in which the high-frequency core size-sensitive lines are at lower frequency than those in the deoxy preparation. Such differences are not detected in the photoproduct generate...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Rousseau DL,Argade PV

更新日期：1986-03-01 00:00:00

abstract：:Methionine sulfoxide reductase A (MsrA) catalyzes the reduction of methionine sulfoxide to methionine and is specific for the S epimer of methionine sulfoxide. The enzyme participates in defense against oxidative stresses by reducing methionine sulfoxide residues in proteins back to methionine. Because oxidation of me...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Lim JC,You Z,Kim G,Levine RL

更新日期：2011-06-28 00:00:00

abstract：:The skeletal muscle L-type Ca2+ channel is a complex of five subunits that is specifically localized in the triad. Its primary function is the rapid activation of Ca2+ release from cytoplasmic stores in a process called excitation-contraction coupling. To study the role of alpha1S-beta1a interactions in the incorporat...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Neuhuber B,Gerster U,Döring F,Glossmann H,Tanabe T,Flucher BE

更新日期：1998-04-28 00:00:00

abstract：:Persephin (Pspn), a recently cloned member of the transforming growth factor-beta superfamily (TGF-beta) and glial cell line-derived neurotrophic factor (GDNF) subfamily, is distributed throughout the nervous system at extremely low levels and is thought to function as a survival factor for midbrain dopaminergic and s...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Tomac AC,Agulnick AD,Haughey N,Chang CF,Zhang Y,Bäckman C,Morales M,Mattson MP,Wang Y,Westphal H,Hoffer BJ

更新日期：2002-07-09 00:00:00

abstract：:Global climate change is expected to have broad ecological consequences for species and communities. Attempts to forecast these consequences usually assume that changes in air or water temperature will translate into equivalent changes in a species' organismal body temperature. This simple change is unlikely because a...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Gilman SE,Wethey DS,Helmuth B

更新日期：2006-06-20 00:00:00

abstract：:The ubiquitous gasotransmitter hydrogen sulfide (H2S) has been recognized to play a crucial role in human health. Using cystathionine γ-lyase (CSE)-deficient mice, we demonstrate an unexpected role of H2S in Mycobacterium tuberculosis (Mtb) pathogenesis. We showed that Mtb-infected CSE-/- mice survive longer than WT m...

journal_title：Proceedings of the National Academy of Sciences of the United States of America

authors： Rahman MA,Cumming BM,Addicott KW,Pacl HT,Russell SL,Nargan K,Naidoo T,Ramdial PK,Adamson JH,Wang R,Steyn AJC

更新日期：2020-03-24 00:00:00