gebhart/patrepeval huggingface dataset:
Purified yeast protein farnesyltransferase is structurally and functionally similar to its mammalian counterpart (1993)

Protein farnesyltransferase (FTase) catalyses the addition of a farnesyl group to a cysteine within the so-called 'CAAX box' at the C-terminus of various proteins. In the present paper we report purification of Saccharomyces cerevisiae FTase to near-homogeneity. This was accomplished by constructing a yeast strain overproducing FTase approx. 100-fold. The purified enzyme was a heterodimer of approx. 90 kDa and consisted of 43 kDa and 34 kDa subunits. The 43 kDa subunit was shown to be the product of the DPR1 gene by using antibody raised against baculovirus-produced DPR1 polypeptide. The purified enzyme required Mg2+, showed a pH optimum of 7.8 and was most active at 50 degrees C. The Km values for farnesyl pyrophosphate and GST-CIIS (glutathione S-transferase fused to the C-terminal 12 amino acids of yeast RAS2 protein), KmFpp and KmGST CIIS, were 8.1 and 5.1 microM respectively. The enzyme was capable of farnesylating GST-CIIL (the same as GST-CIIS, except that the C-terminal serine is changed to leucine), a substrate protein for the enzyme geranylgeranyltransferase, although with a higher apparent Km than for GST-CIIS. Like its mammalian counterpart, yeast FTase activity was inhibited by peptides containing the C-terminal CAAX sequence (that is, one where C = cysteine, A = aliphatic amino acid and X = any amino acid). These results provide direct evidence for the idea that the yeast and mammalian FTases are structurally and functionally very similar.
Multiple traps created with an inclined dual-fiber system (2009)

Multiple optical traps allow one to manipulate multiple particles simultaneously, to characterize interactions in colloidal systems, and to assemble particles into complex structures. Most of the current multiple optical traps are realized with microscope objective-based optical tweezers, which are bulky in size. In this article, we created multiple optical traps with an inclined dual-fiber optical tweezers setup. One 3D trap and two 2D traps were formed at different vertical levels with adjustable separations and positions. We demonstrated that this fiber-based trapping system can be used as a simple block to perform multiple functions, such as particle grouping, separation, and stacking. Moreover, we found that multiple beads can be trapped and stacked up in three dimensions. Compared with those formed with objective-based optical tweezers, the multiple traps presented here are small in size and independent of the objective or the substrate, and hence hold the promise to be integrated in microfluidic systems. This fiber-based multiple traps can be used for on-chip parallel manipulation, particle separation, and characterization of interactions of colloidal and biological systems.
Neonatal Fc Receptor: From Immunity to Therapeutics (2010)

The neonatal Fc receptor (FcRn), also known as the Brambell receptor and encoded by Fcgrt, is a MHC class I like molecule that functions to protect IgG and albumin from catabolism, mediates transport of IgG across epithelial cells, and is involved in antigen presentation by professional antigen presenting cells. Its function is evident in early life in the transport of IgG from mother to fetus and neonate for passive immunity and later in the development of adaptive immunity and other functions throughout life. The unique ability of this receptor to prolong the half-life of IgG and albumin has guided engineering of novel therapeutics. Here, we aim to summarize the basic understanding of FcRn biology, its functions in various organs, and the therapeutic design of antibody- and albumin-based therapeutics in light of their interactions with FcRn.
MYB58 and MYB63 Are Transcriptional Activators of the Lignin Biosynthetic Pathway during Secondary Cell Wall Formation in Arabidopsis (2009)

It has previously been shown that SECONDARY WALL-ASSOCIATED NAC DOMAIN PROTEIN1 (SND1) is a key transcription factor regulating secondary cell wall formation, including the biosynthesis of cellulose, xylan, and lignin. In this study, we show that two closely related SND1-regulated MYB transcription factors, MYB58 and MYB63, are transcriptional regulators specifically activating lignin biosynthetic genes during secondary wall formation in Arabidopsis thaliana. MYB58 and MYB63 are phylogenetically distinct from previously characterized MYBs shown to be associated with secondary wall formation or phenylpropanoid metabolism. Expression studies showed that MYB58 and MYB63 are specifically expressed in fibers and vessels undergoing secondary wall thickening. Dominant repression of their functions led to a reduction in secondary wall thickening and lignin content. Overexpression of MYB58 and MYB63 resulted in specific activation of lignin biosynthetic genes and concomitant ectopic deposition of lignin in cells that are normally unlignified. MYB58 was able to activate directly the expression of lignin biosynthetic genes and a secondary wall-associated laccase (LAC4) gene. Furthermore, the expression of MYB58 and MYB63 was shown to be regulated by the SND1 close homologs NST1, NST2, VND6, and VND7 and their downstream target MYB46. Together, our results indicate that MYB58 and MYB63 are specific transcriptional activators of lignin biosynthesis in the SND1-mediated transcriptional network regulating secondary wall formation.
Intravascular-Catheter-Related Infections (2003)

The past few decades have witnessed the advent of many medical advancements, which undoubtedly have aided health care professionals and ameliorated the suffering of many critically ill patients. Among these advancements are intravascular catheters, which have become indispensable for the administration of medications, especially chemotherapeutic agents, intravenous antibiotics, blood products, parenteral nutritional solutions, and fluids; for monitoring critically ill patients haemodynamically; and for providing access for haemodialysis (Flowers et al., 1989). The use of such devices is associated with an increased risk for catheter-related infections, such as local catheter site infection, thrombophlebitis, catheter-related bloodstream infections (CR-BSI), endocarditis, metastatic infections such as osteomyelitis, arthritis, endophthalmitis, and distant organ abscesses (Arnow, Quimosing, and Beach, 1993). Our understanding of the process that leads to CR-BSI has evolved over the years, and now the role of bacterial biofilms in this process is certainly undeniable.
Predictive Molecular Markers of Response to Epidermal Growth Factor Receptor(EGFR) Family-Targeted Therapies (2010)

Constitutive activation of the EGFR/RAS/PI3K cell-signaling pathway that may occur through molecular aberrations in core pathway components occurs in many solid tumours, including colorectal cancer(CRC), non-small-cell lung cancer(NSCLC) and breast cancer. Predictive biomarkers of response to therapeutics targeting this pathway are necessary to select patients more likely to respond, and importantly, to avoid treating patients likely to suffer a worse outcome with therapy compared to standard of care. Determination of EGFR by immunohistochemistry(IHC) is not strongly predictive of response to EGFR-targeted therapy in CRC and NSCLC. EGFR gene mutations in the tyrosine kinase(TK) binding domain are predictive of response to EGFR tyrosine kinase inhibitors(TKIs) in NSCLC, and the acquisition of a point mutation in a gene encoding an amino acid in an adjacent area, T790M, is predictive of resistance. However, novel irreversible EGFR inhibitors such as BIBW-2992 and HKI-272 may retain activity in tumours with T790M mutations. It is well established in CRC that mutations in KRAS are predictive of resistance to EGFR pathway inhibition, and may predict for a poorer outcome with therapy. Other potentially useful biomarkers of resistance to EGFR-targeted therapy in the process of clinical validation include mutations in BRAF, PTEN loss and PI3KCA mutations, nuclear factor-kappa beta(NF-Κβ) pathway activity, and expression of alternative EGFR ligands. Functional genomics elucidation of drug resistance pathways using RNA interference (RNAi) techniques may provide novel therapeutic approaches in disease resistant to EGFR pathway targeting and accelerate predictive biomarker development.
Iodine requirements during pregnancy, lactation and the neonatal period and indicators of optimal iodine nutrition (2007)

Pregnant women and young infants, but especially the second group, are more sensitive to the effects of an iodine deficiency (ID) than the general population because their serum thyroid-stimulating hormone (TSH) and thyroxine are increased and decreased, respectively, for degrees of ID that do not seem to affect thyroid function in the general population. Systematic neonatal thyroid screening using primary TSH could be the most sensitive indicator to monitor the process of ID control.
Multidrug resistance and its reversal. (1998)

Cross-resistance between different cytostatic agents which are structurally and functionally dissimilar is a common phenomenon called multidrug resistance (MDR). The best characterized mechanism of MDR involves P-glycoprotein. However, this does not completely explain MDR. Within the last few years, two new genes that can confer MDR have been identified (MRP and LRP). Furthermore, topoisomerase II has been associated with a special form of MDR. During the past several years, considerable interest has been shown in strategies to reverse MDR by using pharmacological compounds, monoclonal antibodies, immunotoxins, bispecific antibodies, antisense oligodeoxynucleotides, ribozymes, and albumin-conjugated drugs in in vitro and in vivo assays. All these experimental assays demonstrated that MDR can be circumvented. Two agents that have received the most attention in the clinic are verapamil and cyclosporin A. Despite some promising results (especially in hematological malignancies), the results obtained in the treatment of solid tumors with modulators have so far been quite disappointing. This may be explained by the fact that the MDR phenotype alone does not completely account for the resistance of human cancer. Several other resistance-related proteins (e.g., glutathione S-transferase, metallothionein, O6-alkylguanine-DNA-alkyltransferase, thymidylate synthase, dihydrofolate reductase, heat shock proteins) can be also expressed in resistant tumors. Additionally, cell proliferation, vascularization and apoptosis are involved in resistance.
[Characterization of propofol binding to plasma proteins and possible interactions]. (1995)

The binding of propofol to plasma proteins seems unlikely to cause drug interactions in clinical practice.
LPXTG Protein InlJ, a Newly Identified Internalin Involved in Listeria monocytogenes Virulence (2005)

Listeria monocytogenes expresses surface proteins covalently anchored to the peptidoglycan by sortase enzymes. Inactivation of srtA attenuates Listeria virulence in mice (H. Bierne, S. K. Mazmanian, M. Trost, M. G. Pucciarelli, G. Liu, P. Dehoux, L. Jansch, F. Garcia-del Portillo, O. Schneewind, and P. Cossart, Mol. Microbiol. 43:869-881, 2002). We show here that an srtA mutant is more attenuated than an internalin mutant in orally infected guinea pigs and transgenic mice expressing human E-cadherin (hEcad mice), indicating the involvement of other SrtA substrates, LPXTG proteins, in food-borne listeriosis. Data recently generated with a listerial DNA macroarray identified two LPXTG protein-encoding genes present in the genomes of L. monocytogenes strains and absent from all other Listeria species, inlI (lmo0333) and inlJ (lmo2821). They also revealed two other LPXTG protein-encoding genes, ORF29 and ORF2568, present only in a subclass of L. monocytogenes serovars, including the epidemic serovar 4b. We report here that an inlJ deletion mutant, in contrast to inlI and ORF29 mutants, is significantly attenuated in virulence after intravenous infection of mice or oral inoculation of hEcad mice. Interestingly, a DeltaORF2568 strain showed a slight increase in virulence. inlJ encodes a leucine-rich repeat (LRR) protein that is structurally related to the listerial invasion factor internalin. However, the consensus sequence of the InlJ LRR defines a novel subfamily of cysteine-containing LRRs in bacteria. In conclusion, this postgenomic approach identified InlJ as a new virulence factor among the proteins belonging to the internalin family in L. monocytogenes.
Genetic analysis of temperature-sensitive lethal mutants of Salmonella typhimurium. (1989)

We have isolated 440 mutants of Salmonella typhimurium that show temperature-sensitive growth on complex medium at 44 degrees. Approximately 16% of the mutations in these strains have been mapped to 17 chromosomal locations; two of these chromosomal locations seem to include several essential genes. Genetic analysis of the mutations suggests that the collection saturates the genes readily mutable to a ts lethal phenotype in S. typhimurium. Physiological characteristics of the ts lethal mutants were tested: 6% of the mutants can grow at high temperature under anaerobic conditions, 17% can grow when the medium includes 0.5 M KCl, and 9% of the mutants die after a 2-hr incubation at the nonpermissive temperature. Most ts lethal mutations in this collection probably affect genes required for growth at all temperatures (not merely during high temperature growth) since Tn10 insertions that cause a temperature-sensitive lethal phenotype are rare.
Underlying physics of the thermochemical E model in describing low-field time-dependent dielectric breakdown in SiO2 thin films (1998)

The underlying physics behind the success of the thermochemical E model in describing time-dependent dielectric breakdown (TDDB) in SiO2 thin films is presented. Weak bonding states can be broken by thermal means due to the strong dipolar coupling of intrinsic defect states with the local electric field in the dielectric. This dipole-field coupling serves to lower the activation energy required for thermal bond-breakage and accelerates the dielectric degradation process. A temperature-independent field acceleration parameter γ and a field-independent activation energy ΔH can result when different types of disturbed bonding states are mixed during TDDB testing of SiO2 thin films. While γ for each defect type alone has the expected 1/T dependence and ΔH shows a linear decrease with electric field, a nearly temperature-independent γ and a field-independent ΔH can result when two or more types of disturbed bonding states are mixed. The good agreement between long-term TDDB data and the thermochemical model suggest strongly that the oxygen vacancy is an important intrinsic defect for breakdown and that field, not current, is the primary cause of TDDB under low-field conditions.
New Applications of Polyfunctional Organometallic Compounds in Organic Synthesis (2000)

In the second half of the twentieth century much effort was invested in the preparation of highly reactive polar organometallic reagents. The high reactivity of these reagents precluded the presence of many functional groups and often good chemoselectivities and stereoselectivities could only by achieved by transmetalation reactions. The synthesis of increasingly complex target molecules and the desire to avoid tedious protection-deprotection steps has led inevitably to the use of functionalized organometallic reagents in retrosynthesis. In the last fifteen years, the generation of organic derivatives of numerous metals and metalloids (Li, Mg, B, Zn, Sn) was investigated. In this review the most important preparations and applications of organometallic reagents in organic synthesis will be covered, with particular emphasis on organozinc reagents.
Autoregulation of the splicing of transcripts from the transformer-2 gene of Drosophila. (1991)

The Drosophila transformer-2 gene uses alternative promoters and splicing patterns to generate four different mRNAs that together encode three putative RNA-binding polypeptides. The transformer-2 products expressed in somatic tissues function to regulate the RNA splicing of the sex determination gene doublesex, whereas products expressed in the male germ line play an unknown, but essential, role in spermatogenesis. Two alternatively spliced transformer-2 transcripts, each encoding a different putative RNA-binding protein, are found only in the male germ line. These male germ line-specific mRNAs differ from each other by the presence or absence of a single intron called M1. We show that M1-containing transcripts make up a majority of transformer-2 germ-line transcripts in wild-type males but fail to accumulate in males homozygous for transformer-2 null mutations. Germ-line transformation experiments using a variety of reporter gene constructs demonstrate that specific polypeptide products of the transformer-2 gene itself normally repress M1 splicing in the male germ line. Thus, in addition to its role in the sex-specific control of doublesex RNA splicing in somatic tissues, the transformer-2 gene also regulates the splicing of its own transcripts in the male germ line. We propose that this autoregulatory function may serve in negative feedback control of transformer-2 activity during spermatogenesis. The finding that transformer-2 controls multiple splicing decisions suggests that a variety of different alternative splicing choices could be regulated by a relatively limited number of trans-acting factors.
General Theory of Mortality and Aging (1960)

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Dynamic Docking of Myosin and Actin Observed with Resonance Energy Transfer (2002)

Atomic models of myosin subfragment-1 (S1) and the actin filament are docked together using resonance energy-transfer data from both pre- and postpowerstroke conditions. The quality of the resulting best fits discriminated between neck-region orientations of the S1 for a given set of experimental conditions. For measurements of the postpowerstroke states in the presence of ADP, resonance energy-transfer data alone are sufficient to dock the atomic models and provide evidence that S1 exists with at least two neck-region orientations under these conditions. To dock the prepowerstroke state, resonance energy-transfer data were used in combination with previous chemical cross-linking data to determine that a neck-region orientation similar to that of a proposed prepowerstroke state best fit the data. The resulting models determined independently from electron microscopy compare favorably with micrographs from the recent literature. The docking models by resonance energy transfer suggest that the larger movements in the light-chain binding domain are accompanied by twisting and rotating movements of the catalytic domain, causing a tilt of approximately 30 degrees during the weak-to-strong transition. This transition provides the displacement necessary to support motility and force generation.
Synthesis of functionalized benzyl amines by the reductive alkylation of heterocyclic and heteroaromatic amines with arylaldehydes and preparation of the intermediates for new synthetic biomolecules (2008)

With the object of synthesis of benzyl derivatives of heterocyclic amines, we have investigated the reaction of amines 1, 2, 10-12 and arylaldehydes 3, 4 in the presence of different reducing agents. The improved procedure for the reductive alkylation of heterocycle containing primary amines or heterocyclic secondary amines has been elaborated for synthesis of new benzyl derivatives 7-9 and 16-18. These benzyl amines have been obtained in 50-75% yields by direct reductive amination of arylaldehydes with sodium borohydride -acetic acid reducing system.
Stereochemistry of the Inhibition of δ‐Chymotrypsin with Optically Active cis‐Decaline‐Type Organophosphates: 31P‐NMR studies (1998)

Abstract Investigation of the inhibition of δ‐chymotrypsin with the four novel, optically active, axially and equatorially substituted cis ‐3‐(2,4‐dinitrophenoxy)‐2,4‐dioxa‐3λ 5 ‐phosphabicyclo[4.4.0]decan‐3‐ones (= 3‐(2,4‐dinitrophenoxy)hexahydro‐4 H ‐1,3,2‐benzodioxaphosphorin 2‐oxides) showed only the equatorially substituted enantiomer (−)‐ 4b to be an irreversible inhibitor of the enzyme, and (−)‐ 4b at pH 7.8 revealed a quickly rising resonance at −2.49 ppm assigned to the hydrolysis product 8 and later, while inhibition proceeded, a second one at −4.08 ppm. attributed to the δ‐chymotrypsin adduct 7 ( Scheme 3 ). Comparision of the latter signal with the 31 P‐NMR chemical shifts of the covalent phosphoserine model compounds (−)‐ 6a (−5.67 ppm, axial substitution) and (+)‐ 6b (−4.02 ppm, equatorial substitution) suggests that the inhibition proceeded via neat retention of the configuration at the P‐atom of (−)‐ 4b yielding the equatorially substituted covalent Ser 195 adduct 7 .
Inhibition of Interferon-Gamma May Suppress Allograft Reactivity by T Lymphocytes in Vitro and in Vivo (1985)

The addition to mixed-leukocyte reactions of monoclonal antibodies to interferon-gamma abrogated alloantigen recognition and induction of cytotoxic T lymphocytes by inducing early and highly effective suppressor T lymphocytes. This inhibitory activity was not confined to in vitro models, since daily injection of the antibodies into CBA/J mice blocked the usual rejection of allogenic tumor cells.
Tyrosine Phosphorylation of the vav Proto-Oncogene Product in Activated B Cells (1992)

Activation of B lymphocytes by engagement of their immunoglobulin M antigen receptors results in phosphorylation of a number of proteins on tyrosine residues. One such protein is p95vav, the product of the vav proto-oncogene. Tyrosine phosphorylation of p95vav occurred within seconds of immunoglobulin M cross-linking and was independent of other events induced during stimulation of B cells, such as protein kinase C activation, guanosine triphosphate-binding protein signaling, and calcium mobilization. Moreover, engagement of antigen receptors induced the rapid (approximately 5 seconds) and transient (approximately 60 seconds) association of p95vav with a 70-kilodalton tyrosine-phosphorylated protein, Vap-1, an interaction mediated by the Src homology 2 domain of p95vav. These results suggest that the vav proto-oncogene participates in the signaling processes that mediate the antigen-induced activation of B lymphocytes.
A rapid method for the preparation of amino acid resin esters for merrifield solid‐phase peptide synthesis (1973)

Abstract An improved method for the preparation of Merrifield resin esters is presented. This method is rapid, is free of racemization, and is not complicated by a quaternization side reaction. Chloromethylated resin beads, t ‐butoxycarbonyl amino acid, and potassium t ‐butoxide are heated at 80 °C in dimethylsulfoxide for one‐half hour to yield resin esters of suitable substitution for solid‐phase petide synthesis. All twenty of the BOC protected common amino acids were esterified to the resin by this method. Resin substitution values lie in the range of 0.13 meq/g (BOC‐Glu (NH 2 )) to 0.66 meq/g (BOC/Pro), with most of the amino acids yielding 0.3–0.4 meq/g (on a resin containing 0.8 meq Cl/g).