An algorithm for protein engineering: simulations of recursive ensemble mutagenesis.

abstract：:Although de novo protein design is an important endeavor with implications for understanding protein folding, until now, structures have been determined for only a few 25- to 30-residue designed miniproteins. Here, the NMR solution structure of a complex 73-residue three-helix bundle protein, alpha3D, is reported. The...

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

authors： Walsh ST,Cheng H,Bryson JW,Roder H,DeGrado WF

更新日期：1999-05-11 00:00:00

abstract：:Cells are nonequilibrium systems that exchange matter and energy with the environment to sustain their metabolic needs. The nonequilibrium nature of this system presents considerable challenges to developing a general theory describing its behavior; however, when studied at appropriate spatiotemporal scales, the behav...

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

authors： Chang AY,Marshall WF

更新日期：2019-10-22 00:00:00

abstract：:Alzheimer's disease (AD) comprises multifactorial ailments for which current therapeutic strategies remain insufficient to broadly address the underlying pathophysiology. Epigenetic gene regulation relies upon multifactorial processes that regulate multiple gene and protein pathways, including those involved in AD. We...

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

authors： Volmar CH,Salah-Uddin H,Janczura KJ,Halley P,Lambert G,Wodrich A,Manoah S,Patel NH,Sartor GC,Mehta N,Miles NTH,Desse S,Dorcius D,Cameron MD,Brothers SP,Wahlestedt C

更新日期：2017-10-24 00:00:00

abstract：:Tentoxin, a natural cyclic tetrapeptide produced by phytopathogenic fungi from the Alternaria species affects the catalytic function of the chloroplast F(1)-ATPase in certain sensitive species of plants. In this study, we show that the uncompetitive inhibitor tentoxin binds to the alphabeta-interface of the chloroplas...

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

authors： Groth G

更新日期：2002-03-19 00:00:00

abstract：:Mice with a targeted deletion of beta3 integrin were used to examine the process by which tumor cells metastasize and destroy bone. Injection of B16 melanoma cells into the left cardiac ventricle resulted in osteolytic bone metastasis in 74% of beta3+/+ mice by 14 days. In contrast, only 4% of beta3-/- mice developed ...

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

authors： Bakewell SJ,Nestor P,Prasad S,Tomasson MH,Dowland N,Mehrotra M,Scarborough R,Kanter J,Abe K,Phillips D,Weilbaecher KN

更新日期：2003-11-25 00:00:00

abstract：:The biological basis underlying differentiation of naive (NAI) T cells into effector (EFFE) and memory (MEM) cells is incompletely understood. Furthermore, whether NAI T cells serially differentiate into EFFE and then MEM cells (linear differentiation) or whether they concurrently differentiate into either EFFE or MEM...

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

authors： Holmes S,He M,Xu T,Lee PP

更新日期：2005-04-12 00:00:00

abstract：:Smooth muscle cells use fibronectin to bind to type I and type III collagens but bind to type V collagen by a trypsin-resistant intrinsic glycoconjugate. The binding site on type V collagen is located in the alpha A chain. By using collagen-coated filters in a modified Boyden chamber assay for chemotaxis, it was obser...

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

authors： Grotendorst GR,Seppä HE,Kleinman HK,Martin GR

更新日期：1981-06-01 00:00:00

abstract：:The canonical function of the human telomerase protein (hTERT) is to synthesize telomeric DNA, but it has other biological activities, including enhancing cell proliferation, decreasing apoptosis, regulating DNA damage responses, and increasing cellular proliferative lifespan. The mechanistic relationships among these...

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

authors： Mukherjee S,Firpo EJ,Wang Y,Roberts JM

更新日期：2011-12-13 00:00:00

abstract：:The transcription factor Krüppel-like factor 2 (KLF2) is critical for normal trafficking of T lymphocytes, but its role in B cells is unclear. We report that B cell-specific KLF2 deficiency leads to decreased expression of the trafficking molecules CD62L and β7-integrin, yet expression of sphingosine-1 phosphate recep...

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

authors： Hart GT,Wang X,Hogquist KA,Jameson SC

更新日期：2011-01-11 00:00:00

abstract：:In a subclone derived from mouse L(tk-) cells, we found a plasmid present in a high copy number (greater than 5000 copies per cell) that was stably maintained extrachromosomally without any cytopathic effect to the host cells. This plasmid, termed L factor, has two forms: 5.3 and 5.5 kilobase pairs. DNA sequencing and...

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

authors： Kusano T,Uehara H,Saito H,Segawa K,Oishi M

更新日期：1987-04-01 00:00:00

abstract：:The most common monogenic cause of small-vessel disease leading to ischemic stroke and vascular dementia is the neurodegenerative syndrome cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), which is associated with mutations in the Notch 3 receptor. CADASIL pathology ...

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

authors： Arboleda-Velasquez JF,Manent J,Lee JH,Tikka S,Ospina C,Vanderburg CR,Frosch MP,Rodríguez-Falcón M,Villen J,Gygi S,Lopera F,Kalimo H,Moskowitz MA,Ayata C,Louvi A,Artavanis-Tsakonas S

更新日期：2011-05-24 00:00:00

abstract：:Nucleotide excision repair proteins have been implicated in genetic recombination by experiments in Saccharomyces cerevisiae and Drosophila melanogaster, but their role, if any, in mammalian cells is undefined. To investigate the role of the nucleotide excision repair gene ERCC1, the hamster homologue to the S. cerevi...

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

authors： Sargent RG,Rolig RL,Kilburn AE,Adair GM,Wilson JH,Nairn RS

更新日期：1997-11-25 00:00:00

abstract：:The [A] allele of SNP rs965513 in 9q22 has been consistently shown to be highly associated with increased papillary thyroid cancer (PTC) risk with an odds ratio of ∼1.8 as determined by genome-wide association studies, yet the molecular mechanisms remain poorly understood. Previously, we noted that the expression of t...

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

authors： He H,Li W,Liyanarachchi S,Srinivas M,Wang Y,Akagi K,Wang Y,Wu D,Wang Q,Jin V,Symer DE,Shen R,Phay J,Nagy R,de la Chapelle A

更新日期：2015-05-12 00:00:00

abstract：:Substance P prohormones were identified in the caudate nucleus, hypothalamus, and substantia nigra of human brain. A polypeptide fraction of acidic brain extracts was fractionated on Sephadex G-50. The lyophilized fractions were sequentially treated with trypsin and a substance P-degrading enzyme with strong preferenc...

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

authors： Nyberg F,le Grevés P,Terenius L

更新日期：1985-06-01 00:00:00

abstract：:The Cu,Zn superoxide dismutase (SOD) was examined earlier and found to behave in a very unclock-like manner despite (accepted point mutation, or PAM) corrections for multiple replacements per site. Depending upon the time span involved, rates could differ 5-fold. We have sought to determine whether the data might be c...

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

authors： Fitch WM,Ayala FJ

更新日期：1994-07-19 00:00:00

abstract：:We present evidence of rapid and reliable associative learning by the terrestrial mollusc, Limax maximus. Slugs were exposed once to a pairing of a highly attractive food odor (potato or carrot) and a saturated solution of quinidine sulfate, a bitter-tasting plant substance. In comparison with control slugs, the expos...

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

authors： Sahley C,Gelperin A,Rudy JW

更新日期：1981-01-01 00:00:00

abstract：:If X(1), X(2),... are independent random variables with zero expectation and finite variances, the cumulative sums S(n) are, on the average, of the order of magnitude S(n), where S(n) (2) = E(S(n) (2)). The occasional maxima of the ratios S(n)/S(n) are surprisingly large and the problem is to estimate the extent of th...

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

authors： Feller W

更新日期：1969-07-01 00:00:00

abstract：:A full-length cDNA clone encoding a purified augmenter of liver regeneration (ALR) factor prepared from the cytosol of weanling rat livers was isolated. The 1.2-kb cDNA included a 299-bp 5' untranslated region, a 375-bp coding region, and a 550-bp 3' untranslated region. It encoded a protein consisting of 125 amino ac...

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

authors： Hagiya M,Francavilla A,Polimeno L,Ihara I,Sakai H,Seki T,Shimonishi M,Porter KA,Starzl TE

更新日期：1994-08-16 00:00:00

abstract：:Although prostate cancer (CaP) is the most frequently diagnosed malignant tumor and the second leading cause of cancer deaths in American men, the mechanisms explaining the development and progression of CaP remain largely unknown. Recent studies have shown that some aberrantly expressed microRNAs (miRNAs) are involve...

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

authors： Shi XB,Xue L,Yang J,Ma AH,Zhao J,Xu M,Tepper CG,Evans CP,Kung HJ,deVere White RW

更新日期：2007-12-11 00:00:00

abstract：:Interleukin 3 (IL-3) is a hematopoietic growth factor that supports the proliferation and differentiation of early hematopoietic-lineage progenitors. By using growth factor-dependent cell lines, IL-3 has been shown to induce the appearance of several phosphotyrosine-containing proteins, including a 140-kDa cell surfac...

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

authors： Isfort RJ,Stevens D,May WS,Ihle JN

更新日期：1988-11-01 00:00:00

abstract：:NRSF/REST is a protein that silences transcription of a number of genes that contain a DNA element called the neuron-restrictive silencer element (NRSE). During embryogenesis, REST is expressed ubiquitously in nonneural cells, but is down-regulated during differentiation of neural progenitors into neurons. REST is als...

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

authors： Koenigsberger C,Chicca JJ 2nd,Amoureux MC,Edelman GM,Jones FS

更新日期：2000-02-29 00:00:00

abstract：:Drug discovery in psychiatry has been limited to chemical modifications of compounds originally discovered serendipitously. Therefore, more mechanism-oriented strategies of drug discovery for mental disorders are awaited. Schizophrenia is a devastating mental disorder with synaptic disconnectivity involved in its path...

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

authors： Hayashi-Takagi A,Araki Y,Nakamura M,Vollrath B,Duron SG,Yan Z,Kasai H,Huganir RL,Campbell DA,Sawa A

更新日期：2014-04-29 00:00:00

abstract：:Fluoxetine (Prozac) inhibited the membrane currents elicited by serotonin (5-hydroxytryptamine; 5HT) in Xenopus oocytes expressing either cloned 5HT2C receptors or 5HT receptors encoded by rat cortex mRNA. Responses of 5HT2C receptors, elicited by nM concentrations of 5HT, were rapidly and reversibly blocked by microm...

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

authors： Ni YG,Miledi R

更新日期：1997-03-04 00:00:00

abstract：:The liver provides for long-term energy needs of the body by converting excess carbohydrate into fat for storage. Insulin is one factor that promotes hepatic lipogenesis, but there is increasing evidence that glucose also contributes to the coordinated regulation of carbohydrate and fat metabolism in liver by mechanis...

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

authors： Iizuka K,Bruick RK,Liang G,Horton JD,Uyeda K

更新日期：2004-05-11 00:00:00

abstract：:Paracoccidioidomycosis, a disease caused by Paracoccidioides brasiliensis, which is endemic to Latin America, is much more common in men than women, suggesting a role for hormonal factors. We recently showed that two other yeasts possess steroid binding proteins and postulated that these receptor-like molecules repres...

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

authors： Loose DS,Stover EP,Restrepo A,Stevens DA,Feldman D

更新日期：1983-12-01 00:00:00

abstract：:The Golgi apparatus is a membrane-bounded organelle with the characteristic shape of a series of stacked flat cisternae. During mitosis in mammalian cells, the Golgi apparatus is once fragmented into small vesicles and then reassembled to form the characteristic shape again in each daughter cell. The mechanism and det...

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

authors： Tachikawa M,Mochizuki A

更新日期：2017-05-16 00:00:00

abstract：:The exotoxins produced by certain strains of Staphylococcus aureus are able to stimulate powerful polyclonal proliferative responses and to induce nonresponsiveness by clonal deletion of T lymphocytes expressing the appropriate T-cell antigen receptor V beta gene products. This paper examines the ability of S. aureus ...

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

authors： O'Hehir RE,Lamb JR

更新日期：1990-11-01 00:00:00

abstract：:Fas, a member of the tumor necrosis factor receptor family, can induce apoptosis when activated by Fas ligand binding or anti-Fas antibody crosslinking. Genetic studies have shown that a defect in Fas-mediated apoptosis resulted in abnormal development and function of the immune system in mice. A point mutation in the...

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

authors： Chu K,Niu X,Williams LT

更新日期：1995-12-05 00:00:00

abstract：:An obstacle in the utilization of catalytic Abs for selective prodrug activation in cancer therapy has been systemic tumor targeting. Here we report the generation of catalytic Abs that effectively target tumor cells with undiminished prodrug activation capability. Ab conjugates were prepared by covalent conjugation o...

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

authors： Abraham S,Guo F,Li LS,Rader C,Liu C,Barbas CF 3rd,Lerner RA,Sinha SC

更新日期：2007-03-27 00:00:00

abstract：:A closed duplex DNA molecule relaxed and containing nucleosomes has a different linking number from the same molecule relaxed and without nucleosomes. What does this say about the structure of the nucleosome? A mathematical study of this question is made, representing the DNA molecule by a ribbon. It is shown that the...

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

authors： Fuller FB

更新日期：1978-08-01 00:00:00