gebhart/patrepeval huggingface dataset:
Identification of Sites of Mannose 6-Phosphorylation on Lysosomal Proteins (2006)

Most newly synthesized soluble lysosomal proteins contain mannose 6-phosphate (Man-6-P), a specific carbohydrate modification that is recognized by Man-6-P receptors (MPRs) that direct targeting to the lysosome. A number of proteomic studies have focused on lysosomal proteins, exploiting the fact that Man-6-P-containing forms can be purified by affinity chromatography on immobilized MPRs. These studies have identified many known lysosomal proteins as well as many proteins not previously classified as lysosomal. The latter are of considerable biological interest with potential implications for lysosomal function and as candidates for lysosomal storage diseases of unknown etiology. However, a significant problem in interpreting the biological relevance of such proteins has been in distinguishing true Man-6-P glycoproteins from simple contaminants and from proteins associated with true Man-6-P glycoproteins (e.g. protease inhibitors and lectins). In this report, we describe a mass spectrometric approach to the verification of Man-6-phosphorylation based upon LC-MS of MPR-purified proteolytic glycopeptides. This provided a useful tool in validating novel MPR-purified proteins as true Man-6-P glycoproteins and also allowed identification of low abundance components not observed in the analysis of the total Man-6-P glycoprotein mixture. In addition, this approach allowed the global mapping of 99 Man-6-phosphorylation sites from 44 known lysosomal proteins purified from mouse and human brain. This information is likely to provide useful insights into protein determinants for this modification and may be of significant value in protein engineering approaches designed to optimize protein delivery to the lysosome in therapeutic applications such as gene and enzyme replacement therapies.
Fourteen years of plant proteomics reflected in Proteomics : Moving from model species and 2DE‐based approaches to orphan species and gel‐free platforms (2014)

In this article, the topic of plant proteomics is reviewed based on related papers published in the journal Proteomics since publication of the first issue in 2001. In total, around 300 original papers and 41 reviews published in Proteomics between 2000 and 2014 have been surveyed. Our main objective for this review is to help bridge the gap between plant biologists and proteomics technologists, two often very separate groups. Over the past years a number of reviews on plant proteomics have been published . To avoid repetition we have focused on more recent literature published after 2010, and have chosen to rather make continuous reference to older publications. The use of the latest proteomics techniques and their integration with other approaches in the "systems biology" direction are discussed more in detail. Finally we comment on the recent history, state of the art, and future directions of plant proteomics, using publications in Proteomics to illustrate the progress in the field. The review is organized into two major blocks, the first devoted to provide an overview of experimental systems (plants, plant organs, biological processes) and the second one to the methodology.
Processing of G4 DNA by Dna2 Helicase/Nuclease and Replication Protein A (RPA) Provides Insights into the Mechanism of Dna2/RPA Substrate Recognition (2008)

The polyguanine-rich DNA sequences commonly found at telomeres and in rDNA arrays have been shown to assemble into structures known as G quadruplexes, or G4 DNA, stabilized by base-stacked G quartets, an arrangement of four hydrogen-bonded guanines. G4 DNA structures are resistant to the many helicases and nucleases that process intermediates arising in the course of DNA replication and repair. The lagging strand DNA replication protein, Dna2, has demonstrated a unique localization to telomeres and a role in de novo telomere biogenesis, prompting us to study the activities of Dna2 on G4 DNA-containing substrates. We find that yeast Dna2 binds with 25-fold higher affinity to G4 DNA formed from yeast telomere repeats than to single-stranded DNA of the same sequence. Human Dna2 also binds G4 DNAs. The helicase activities of both yeast and human Dna2 are effective in unwinding G4 DNAs. On the other hand, the nuclease activities of both yeast and human Dna2 are attenuated by the formation of G4 DNA, with the extent of inhibition depending on the topology of the G4 structure. This inhibition can be overcome by replication protein A. Replication protein A is known to stimulate the 5'- to 3'-nuclease activity of Dna2; however, we go on to show that this same protein inhibits the 3'- to 5'-exo/endonuclease activity of Dna2. These observations are discussed in terms of possible roles for Dna2 in resolving G4 secondary structures that arise during Okazaki fragment processing and telomere lengthening.
Fluorescent Sensing of Pyrophosphate and Bis-carboxylates with Charge Neutral PET Chemosensors (2002)

[reaction: see text] The fluorescent photoinduced electron transfer (PET) chemosensors 2 and 3 were designed for the recognition of anions possessing two binding sides such as dicarboxylates and pyrophosphate; the anion recognition in DMSO takes place through the two charge neutral thiourea receptor sites with concomitant PET quenching of the anthracene moiety. The anion binding of acetate, phosphate, and pyrophosphate to 2 and 3 was also evaluated by using 1H NMR in DMSO-d6.
Reversals in regiospecificity. The reactivity of vinylogous amides toward bis-electrophiles (1977)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTReversals in regiospecificity. The reactivity of vinylogous amides toward bis-electrophilesGregory B. Bennett, W. Ronald J. Simpson, Robert B. Mason, Robert J. Strohschein, and Ruth MansukhaniCite this: J. Org. Chem. 1977, 42, 2, 221–225Publication Date (Print):January 1, 1977Publication History Published online1 May 2002Published inissue 1 January 1977https://pubs.acs.org/doi/10.1021/jo00422a009https://doi.org/10.1021/jo00422a009research-articleACS PublicationsRequest reuse permissionsArticle Views212Altmetric-Citations25LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Mycobacterium wolinskyi sp. nov. and Mycobacterium goodii sp. nov., two new rapidly growing species related to Mycobacterium smegmatis and associated with human wound infections: a cooperative study from the International Working Group on Mycobacterial Taxonomy (1999)

Previous investigations demonstrated three taxonomic groups among 22 clinical isolates of Mycobacterium smegmatis. These studies were expanded to 71 clinical isolates, of which 35 (49%) (group 1) were identical to five ATCC reference strains including the type strain ATCC 19420T. Twenty-eight isolates (39%) were group 2, and eight isolates (11%) were group 3. Isolates of groups 2 and 3 were most often associated with post-traumatic or post-surgical wound infections including osteomyelitis, were susceptible to sulfamethoxazole, amikacin, imipenem and the tetracyclines, variably resistant to clarithromycin, and susceptible (group 1), intermediately resistant (group 2) or resistant (group 3) to tobramycin. The three groups were similar by routine biochemical and growth characteristics, but had different mycolic acid dimethoxy-4-coumarinylmethyl ester elution patterns by HPLC and different PCR-restriction enzyme patterns of a 439 bp fragment of the hsp-65 gene. Group 3 isolates differed from group 1 by 18 bp by 16S rRNA sequencing and exhibited < 25% homology by DNA-DNA hybridization, being most closely related to Mycobacterium mageritense. The 16S rRNA of group 1 and group 2 isolates differed by only 3 bp, but by DNA-DNA hybridization they exhibited only 40% homology. The following names are proposed: Mycobacterium goodii sp. nov. for group 2 isolates (type strain ATCC 700504T = MO69T), Mycobacterium wolinskyi sp. nov. for group 3 isolates (type strain ATCC 700010T = MO739T) and Mycobacterium smegmatis sensu stricto for group 1 isolates.
Investigating nonlinear femtosecond pulse propagation with frequency-resolved optical gating (1999)

Frequency-resolved optical gating (FROG) is used to investigate nonlinear pulse propagation in normally dispersive media. We present high-dynamic-range measurements of broad-bandwidth femtosecond pulses that result from nonlinear propagation in fused silica and compare these measurements with a (3+1)-dimensional modified nonlinear Schrodinger equation. We also demonstrate the ability of FROG to provide information about a noninstantaneous nonlinearity in methanol. In this case, the instantaneous nonlinear index and the time response of the noninstantaneous nonlinearity are used as fit parameters in a (1+1)-dimensional model.
p53 as a target for cancer vaccines: recombinant canarypox virus vectors expressing p53 protect mice against lethal tumor cell challenge. (1996)

The p53 protein is an attractive target for immunotherapy, because mutations in the p53 gene are the most common genetic alterations found in human tumors. These mutations result in high levels of p53 protein in the tumor cell, whereas the expression level of wild-type p53 in nonmalignant tissue is usually much lower. Several canarypox virus recombinants expressing human or murine p53 in wild-type or mutant form were constructed. Immunization with these viruses protected BALB/c mice from a challenge with an isogenic and highly tumorigenic mouse fibroblast tumor cell line expressing high levels of mutant p53. The tumor protection was equally effective regardless of whether wild-type or mutant p53 was used for the immunization, indicating that the immunologic response was not dependent on any particular p53 mutation and that immunization with this live virus vaccine works effectively against mutant p53 protein expressed in a tumor cell. In tumors escaping immunologic rejection, the expression of the p53 protein was commonly down-regulated.
Concomitant expression ofE. colicytosine deaminase and uracil phosphoribosyltransferase improves the cytotoxicity of 5-fluorocytosine (1998)

The prodrug activation system formed by the E. coli codA gene encoding cytosine deaminase (CD) and 5-fluorocytosine (5-FC) developed for selective cancer chemotherapy suffers from a sensitivity limitation in many tumour cells. In an attempt to improve the CD/5-FC suicide association, we combined the E. coli upp gene encoding uracil phosphoribosyltransferase (UPRT) with codA gene to create the situation prevailing in E. coli, a bacterium very efficient in metabolising 5-FC. The constitutive expression of the two genes cloned on an E. coli-animal cell shuttle plasmid either in a linked or in a fused configuration was evaluated in E. coli strains selected and engineered to mimic the 5-FC metabolism encountered in mammalian cells. The simultaneous expression of codA and upp genes generated a cooperative effect resulting in a dramatic increase in 5-FC sensitivity of cells compared to the expression of codA alone. Furthermore, it was shown that the association of UPRT with CD facilitated the uptake of 5-FC, in the situation where the drug penetrates cells by passive diffusion as in mammalian cells, by directly channeling 5-fluorouracil, the product of CD, to 5-fluoroUMP, the product of UPRT.
Trehalose Protects from Aggravation of Amyloid Pathology Induced by Isoflurane Anesthesia in APPswe Mutant Mice (2012)

There is an open controversy about the role of surgery and anesthesia in the pathogenesis of Alzheimer's disease (AD). Clinical studies have shown a high prevalence of these procedures in subjects with AD but the interpretation of these studies is difficult because of the co-existence of multiple variables. Experimental studies in vitro and in vivo have shown that small molecular weight volatile anesthetics enhance amyloidogenesis in vitro and produce behavioral deficits and brain lesions similar to those found in patients with AD. We examined the effect of co-treatment with trehalose on isoflurane-induced amyloidogenesis in mice. WT and APP(swe) mice, of 11 months of age, were exposed to 1% isoflurane, 3 times, for 1.5 hours each time and sacrificed 24 hours after their last exposure to isoflurane. The right hemi-brain was used for histological analysis and the contra-lateral hemi-brain used for biochemical studies. In this study, we have shown that repetitive exposure to isoflurane in pre-symptomatic mature APP(swe) mice increases apoptosis in hippocampus and cerebral cortex, enhances astrogliosis and the expression of GFAP and that these effects are prevented by co-treatment with trehalose, a disaccharide with known effects as enhancer of autophagy. We have also confirmed that in our model the co-treatment with trehalose increases the expression of autophagic markers as well as the expression of chaperones. Cotreatment with trehalose reduces the levels of β amyloid peptide aggregates, tau plaques and levels of phospho-tau. Our study, therefore, provides new therapeutic avenues that could help to prevent the putative pro-amyloidogenic properties of small volatile anesthetics.
Tyrosine Kinase Etk/BMX Is Up-regulated in Human Prostate Cancer and Its Overexpression Induces Prostate Intraepithelial Neoplasia in Mouse (2006)

Abstract The nonreceptor tyrosine kinase Etk/BMX was originally identified from the human prostate xenograft CWR22. Here, we report that Etk is up-regulated in human prostate tumor specimens surveyed. Knocking down Etk expression by a specific small interfering RNA (siRNA) in prostate cancer cells attenuates cell proliferation, suggesting an essential role of Etk for prostate cancer cell survival and growth. Targeted expression of Etk in mouse prostate epithelium results in pathologic changes resembling human prostatic intraepithelial neoplasia, indicating that up-regulation of Etk may contribute to prostate cancer development. A marked increase of luminal epithelial cell proliferation was observed in the Etk transgenic prostate, which may be attributed in part to the elevated activity of Akt and signal transducers and activators of transcription 3 (STAT3). More interestingly, the expression level of acetyltransferase cyclic AMP–responsive element binding protein–binding protein (CBP) is also increased in the Etk transgenic prostate as well as in a prostate cancer cell line overexpressing Etk, concomitant with elevated histone 3 acetylation at lysine 18 (H3K18Ac). Down-modulation of Etk expression by a specific siRNA leads to a decrease of H3 acetylation in prostate cancer cell lines. Our data suggest that Etk may also modulate chromatin remodeling by regulating the activity of acetyltransferases, such as CBP. Given that Etk may exert its effects in prostate through modulation of multiple signaling pathways altered in human prostate cancer, the Etk transgenic mouse model may be a useful tool for studying the functions of Etk and identification of new molecular markers and drug targets relevant to human diseases. (Cancer Res 2006; 66(16): 8058-64)
Coherent beam control with an all-dielectric transformation optics based lens (2016)

Transformation optics (TO) concept well known for its huge possibility in patterning the path of electromagnetic waves is exploited to design a beam steering lens. The broadband directive in-phase emission in a desired off-normal direction from an array of equally fed radiators is numerically and experimentally reported. Such manipulation is achieved without the use of complex and bulky phase shifters as it is the case in classical phased array antennas. The all-dielectric compact low-cost lens prototype presenting a graded permittivity profile is fabricated through three-dimensional (3D) polyjet printing technology. The array of radiators is composed of four planar microstrip antennas realized using standard lithography techniques and is used as excitation source for the lens. To validate the proposed lens, we experimentally demonstrate the broadband focusing properties and in-phase directive emissions deflected from the normal direction. Both the far-field radiation patterns and the near-field distributions are measured and reported. Measurements agree quantitatively and qualitatively with numerical full-wave simulations and confirm the corresponding steering properties. Such experimental validation paves the way to inexpensive easy-made all-dielectric microwave lenses for beam forming and collimation.
An Engineered Tetrahymena tRNAGln for in Vivo Incorporation of Unnatural Amino Acids into Proteins by Nonsense Suppression (1996)

A new tRNA, THG73, has been designed and evaluated as a vehicle for incorporating unnatural amino acids site-specifically into proteins expressed in vivo using the stop codon suppression technique. The construct is a modification of tRNAGln(CUA) from Tetrahymena thermophila, which naturally recognizes the stop codon UAG. Using electrophysiological studies of mutations at several sites of the nicotinic acetylcholine receptor, it is established that THG73 represents a major improvement over previous nonsense suppressors both in terms of efficiency and fidelity of unnatural amino acid incorporation. Compared with a previous tRNA used for in vivo suppression, THG73 is as much as 100-fold less likely to be acylated by endogenous synthetases of the Xenopus oocyte. This effectively eliminates a major concern of the in vivo suppression methodology, the undesirable incorporation of natural amino acids at the suppression site. In addition, THG73 is 4-10-fold more efficient at incorporating unnatural amino acids in the oocyte system. Taken together, these two advances should greatly expand the range of applicability of the in vivo nonsense suppression methodology.
Combined N- and C-Terminal Truncation of Human Apolipoprotein A-I Yields a Folded, Functional Central Domain (2005)

A combined N- and C-terminal truncation variant of human apolipoprotein A-I (apoA-I) was designed, expressed in Escherichia coli, isolated, and characterized. Hydrodynamic experiments yielded a weight average molecular weight of 34000, indicating apoA-I-(44−186) exists in solution predominantly as a dimer. An axial ratio of 4.2 was calculated for the dimer based on sedimentation velocity experiments. Far-UV circular dichroism spectroscopy of apoA-I-(44−186) in buffer indicated the presence of 65% α-helix secondary structure. Guanidine hydrochloride denaturation experiments yielded a transition midpoint of 0.5 M for apoA-I-(44−186). ApoA-I-(44−186) induced solubilization of dimyristoylphosphatidylcholine vesicles at a rate comparable to that of full-length apoA-I, displayed lipoprotein binding ability, and was an acceptor of ABCA1-mediated cholesterol efflux from cultured macrophages. Fluorescence quenching studies with KI indicate that the three Trp residues in apoA-I-(44−186) are shielded from the aqueous environment. Taken together, the data indicate that lipid-free apoA-I-(44−186) adopts a folded conformation in solution that possesses lipid binding capability. The central region of apoA-I appears to adopt a globular amphipathic α-helix bundle organization that is stabilized by intramolecular and/or intermolecular helix−helix interactions. Lipid association likely results in a conformational adaptation wherein helix−helix contacts are substituted for helix−lipid interactions.
Effects of Excitative and Sedative Music on Subjective and Physiological Relaxation (1997)

Previous investigations using heart rate as a measure have not clarified the excitative-sedative effects of music. One of the sources of this failure was considered to be use of the index of heart rate. The present purpose was to examine the excitative-sedative effect of music on indices of the sympathetic and the parasympathetic nervous activities through spectral analysis of heart rate. The presented stimuli were three excitative musical pieces and three sedative ones. Subjective feelings about music were measured by an adjective checklist concerning musical activity. Heart-rate variabilities divided into two components of Low Frequency, mainly affected by the sympathetic nervous system and of High Frequency, mainly affected by the parasympathetic nervous system. Six types of heart-rate indices were employed: (1) mean increments from posttrial base, (2) coefficient of variances of heart rate, (3) mean powers of Low Frequency, (4) coefficient of component variances of Low Frequency, (5) mean powers of High Frequency, and (6) coefficient of component variances of High Frequency. From the factor analysis based on responses to an adjective checklist, there was a single major activity factor. Activity scores showed some were high during excitative pieces and others low during sedative ones. For heart rate, excitative-sedative effects of music were observed only in indices related to High Frequency. This result suggests that musical effect was observed in measures of the parasympathetic nervous system but not in the sympathetic nervous system.
An assessment of the use of Implanon® in three community services (2002)

The three services have been reassured that they are providing a good standard of care to clients requesting Implanon and that their 'real life' 6- and 12-month continuation rates are reasonable.
Specificity of antisense oligonucleotides in vivo. (1992)

Antisense oligonucleotides are widely used as inhibitors of gene expression in cultured cells and have been proposed as potential therapeutic agents, but it is not known to what extent they are specific for their intended target RNAs. Statistical considerations indicate that if oligonucleotides can form hybrids with mRNA molecules in vivo by means of short or imperfect regions of complementarity, then the specificity of oligonucleotides as antisense reagents will be greatly compromised. We have used Xenopus oocytes as a model system in which to investigate the potential specificity of antisense oligonucleotides in vivo. We injected perfect and partially matched antisense oligonucleotides into oocytes and measured the resulting degradation of the target RNA in each case. On the basis of the extent to which antisense oligonucleotides can cause cleavage of RNAs at imperfectly matched target sites, we conclude that in this system it is probably not possible to obtain specific cleavage of an intended target RNA without also causing at least the partial destruction of many nontargeted RNAs.