gebhart/patrepeval huggingface dataset:
Identification of the Missing Links in Prokaryotic Pentose Oxidation Pathways (2006)

The pentose metabolism of Archaea is largely unknown. Here, we have employed an integrated genomics approach including DNA microarray and proteomics analyses to elucidate the catabolic pathway for D-arabinose in Sulfolobus solfataricus. During growth on this sugar, a small set of genes appeared to be differentially expressed compared with growth on D-glucose. These genes were heterologously overexpressed in Escherichia coli, and the recombinant proteins were purified and biochemically studied. This showed that D-arabinose is oxidized to 2-oxoglutarate by the consecutive action of a number of previously uncharacterized enzymes, including a D-arabinose dehydrogenase, a D-arabinonate dehydratase, a novel 2-keto-3-deoxy-D-arabinonate dehydratase, and a 2,5-dioxopentanoate dehydrogenase. Promoter analysis of these genes revealed a palindromic sequence upstream of the TATA box, which is likely to be involved in their concerted transcriptional control. Integration of the obtained biochemical data with genomic context analysis strongly suggests the occurrence of pentose oxidation pathways in both Archaea and Bacteria, and predicts the involvement of additional enzyme components. Moreover, it revealed striking genetic similarities between the catabolic pathways for pentoses, hexaric acids, and hydroxyproline degradation, which support the theory of metabolic pathway genesis by enzyme recruitment.
MRI in multiple sclerosis: correlation with expanded disability status scale (EDSS) (1999)

Magnetic resonance (MR) imaging is very sensitive in showing disseminated MS lesions. Subclinical MR progression occurs frequently, explaining why MR is now used to monitor treatment, even without measurable consequences, of new MR lesions to the patient at this moment. In the light of this clinico-radiological paradox, the significance of MR in MS is discussed, particularly in relation with the expanded disability status scale (EDSS). Gadolinium-enhancing lesions correlate with the occurrence of relapses, CSF myelin breakdown products and, in patients with relapsing-remitting disease, with higher EDSS. However, the predictive value of the frequency of enhancement for changes in EDSS is only weak. For conventional T2-weighted MR imaging, the cross-sectional correlation with EDSS varies between 0.15 and 0.60, and is limited mainly by the inherent lack of tissues specificity of T2-weighted images. Both T1 black holes and magnetisation transfer (MT) parameters show a better correlation with EDSS; it should be noted that lesions in which those abnormalities are found go through an initial phase of enhancement as well. For T1 black holes, a correlation up to 0.81 has been reported for SP patients. Post-mortem studies show that black holes and low MT ratios are in vivo markers of axonal loss. Preliminary data indicate that progressive atrophy also correlates with progression on the EDSS scale. More should be learned about the fate of new MR lesion with regards to development of axonal loss, which at present is difficult to predict in the enhancing stage. The existence of escape mechanisms, including remyelination, make a simple correlation with EDSS extremely unlikely, and perhaps not even desirable. Nevertheless, while the clinical effect of a given new lesion may be difficult to ascertain, the absence of (new) MR lesions is prognostically favourable, as will be the degree to which new lesions are prevented by treatment.
The Chemistry of Carbanions. XII. The Role of Copper in the Conjugate Addition of Organometallic Reagents1 (1966)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Chemistry of Carbanions. XII. The Role of Copper in the Conjugate Addition of Organometallic Reagents1Herbert O. House, William L. Respess, and George M. WhitesidesCite this: J. Org. Chem. 1966, 31, 10, 3128–3141Publication Date (Print):October 1, 1966Publication History Published online1 May 2002Published inissue 1 October 1966https://doi.org/10.1021/jo01348a012RIGHTS & PERMISSIONSArticle Views2137Altmetric-Citations277LEARN 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 InReddit PDF (2 MB) Get e-Alertsclose Get e-Alerts
An improved method for the in vitro evolution of aptamers and applications in protein detection and purification (2003)

One of the key components of proteomics initiatives is the production of high affinity ligands or probes that specifically recognize protein targets in assays that detect and capture proteins of interest. Particularly versatile probes with tremendous potential for use as affinity molecules are aptamers. Aptamers are short single-stranded DNA or RNA sequences that are selected in vitro based on affinity for a target molecule. Aptamers offer advantages over traditional antibody-based affinity molecules in their ease of production, regeneration and stability, largely due to the chemical properties of nucleic acids versus amino acids. We describe an improved in vitro selection protocol that relies on magnetic separations for DNA aptamer production that is relatively easy and scalable without the need for expensive robotics. We demonstrate the ability of aptamers that recognize thyroid transcription factor 1 (TTF1) to bind their target protein with high affinity and specificity, and detail their uses in a number of assays. The TTF1 aptamers were characterized using surface plasmon resonance, and shown to be useful for enzyme-linked assays, western blots and affinity purification.
(—)‐nicotine produces conditioned place preference in Lewis, but not Fischer 344 rats (1997)

In this study, we sought to determine if Fischer 344 (F344) and Lewis rats showed different conditioned place preference (CPP) responses to subcutaneously administered (—)-nicotine. Lewis rats displayed a CPP response to (—)-nicotine after five pairings, whereas F344 rats showed no preference for nicotine compared to vehicle. After 10 pairings, the F344 rats showed a conditioned place aversion to (—)-nicotine, whereas the Lewis rats still displayed a significant CPP response. These results suggest that the differences in appetitiveness shown between Lewis and F344 rats to other drugs of abuse extend also to (—)-nicotine. Synapse 26:93–94, 1997. © 1997 Wiley-Liss, Inc.
A triple helix stabilizes the 3′ ends of long noncoding RNAs that lack poly(A) tails (2012)

The MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) locus is misregulated in many human cancers and produces an abundant long nuclear-retained noncoding RNA. Despite being transcribed by RNA polymerase II, the 3' end of MALAT1 is produced not by canonical cleavage/polyadenylation but instead by recognition and cleavage of a tRNA-like structure by RNase P. Mature MALAT1 thus lacks a poly(A) tail yet is expressed at a level higher than many protein-coding genes in vivo. Here we show that the 3' ends of MALAT1 and the MEN β long noncoding RNAs are protected from 3'-5' exonucleases by highly conserved triple helical structures. Surprisingly, when these structures are placed downstream from an ORF, the transcript is efficiently translated in vivo despite the lack of a poly(A) tail. The triple helix therefore also functions as a translational enhancer, and mutations in this region separate this translation activity from simple effects on RNA stability or transport. We further found that a transcript ending in a triple helix is efficiently repressed by microRNAs in vivo, arguing against a major role for the poly(A) tail in microRNA-mediated silencing. These results provide new insights into how transcripts that lack poly(A) tails are stabilized and regulated and suggest that RNA triple-helical structures likely have key regulatory functions in vivo.
Asymptotically Optimal Approximation of Single Qubit Unitaries by Clifford andTCircuits Using a Constant Number of Ancillary Qubits (2013)

Decomposing unitaries into a sequence of elementary operations is at the core of quantum computing. Information theoretic arguments show that approximating a random unitary with precision ε requires Ω(log(1/ε)) gates. Prior to our work, the state of the art in approximating a single qubit unitary included the Solovay-Kitaev algorithm that requires O(log(3+δ)(1/ε)) gates and does not use ancillae and the phase kickback approach that requires O(log(2)(1/ε)loglog(1/ε)) gates but uses O(log(2)(1/ε)) ancillae. Both algorithms feature upper bounds that are far from the information theoretic lower bound. In this Letter, we report an algorithm that saturates the lower bound, and as such it guarantees asymptotic optimality. In particular, we present an algorithm for building a circuit that approximates single qubit unitaries with precision ε using O(log(1/ε)) Clifford and T gates and employing up to two ancillary qubits. We connect the unitary approximation problem to the problem of constructing solutions corresponding to Lagrange's four-square theorem, and thereby develop an algorithm for computing an approximating circuit using an average of O(log(2)(1/ε)loglog(1/ε)) operations with integers.
Some recent advances in the synthesis of polycyclic imidazole-containing marine natural products (2007)

This Highlight describes some of the recent synthetic work on imidazole-containing alkaloids isolated from marine sponges. Target molecules have been chosen which demonstrate synthetic strategies leading towards metabolites containing intact imidazole moieties as well as systems bearing modified imidazole rings.
A study of renaturation of reduced hen egg white lysozyme. Enzymically active intermediates formed during oxidation of the reduced protein. (1976)

The material obtained from reduced hen egg white lysozyme after complete air oxidation at pH 8.0 and 37 degrees has yielded, by gel filtration on a Bio-Gel P-30 column, enzymically active species and an enzymically inactive form which eluted sooner than the active species but later than expected for a dimer of lysozyme. Reduced lysozyme also elutes at the same position as this inactive material. Examination of the fragments produced on CNBr cleavage of the inactive form indicates that at least 24% of the population contains incorrect disulfide bonds involving half-cystine residues 6, 30, 115, and 127. Tryptophan fluorescence and the intrinsic viscosity of the inactive form show an enlarged molecular domain with a disordered conformation. The yield of the inactive form increases as the oxidation of reduced lysozyme is accelerated using cupric ion. In the presence of 4 X 10(-5) M cupric ion, reduced lysozyme forms almost quantitatively the inactive form, which is almost completely converted to the native form by sulfhydryl-disulfide interchange catalyzed by thiol groups of either reduced lysozyme or beta-mercaptoethanol. The material trapped by alkylation of the free sulfhydryl groups with [1-14C]iodoacetic acid during the early stage of air oxidation of reduced lysozyme was fractionated by gel filtration to permit separation of the active species from the inactive form. Ion exchange chromatography of the active species yielded completely renatured lysozyme and three major enzymically active radioactive derivatives. Two of these derivatives contained approximately 2 mol of S-carboxymethylcysteine. Isolation and characterization of radioactive tryptic peptides from each of the three active forms, permitted the identification of Cys 6 and Cys 127, Cys 76 and 94, and Cys 80 as the sulfhydryl groups alkylated in these three incompletely oxidized, partially active forms. Thus, it appears that the interatomic interactions maintaining the compact three-dimensional structure of native lysozyme are operational even when one of these three native disulfide bonds between Cys 6 and Cys 127, Cys 76 and Cys 94, and Cys 64 and 80 is open.
Antibody Treatment of Ebola and Sudan Virus Infection via a Uniquely Exposed Epitope within the Glycoprotein Receptor-Binding Site (2016)

Previous efforts to identify cross-neutralizing antibodies to the receptor-binding site (RBS) of ebolavirus glycoproteins have been unsuccessful, largely because the RBS is occluded on the viral surface. We report a monoclonal antibody (FVM04) that targets a uniquely exposed epitope within the RBS; cross-neutralizes Ebola (EBOV), Sudan (SUDV), and, to a lesser extent, Bundibugyo viruses; and shows protection against EBOV and SUDV in mice and guinea pigs. The antibody cocktail ZMapp™ is remarkably effective against EBOV (Zaire) but does not cross-neutralize other ebolaviruses. By replacing one of the ZMapp™ components with FVM04, we retained the anti-EBOV efficacy while extending the breadth of protection to SUDV, thereby generating a cross-protective antibody cocktail. In addition, we report several mutations at the base of the ebolavirus glycoprotein that enhance the binding of FVM04 and other cross-reactive antibodies. These findings have important implications for pan-ebolavirus vaccine development and defining broadly protective antibody cocktails.
Insulin increases NADH/NAD+ redox state, which stimulates guanylate cyclase in vascular smooth muscle (2002)

We conclude that insulin increases cGMP production in VSMC with iNOS by raising the cell NADH/NAD+ redox state, which may increase the availability of iNOS-derived NO.
Adoptive transfer of experimental allergic encephalomyelitis after in vitro treatment with recombinant murine interleukin-12. Preferential expansion of interferon-gamma-producing cells and increased expression of macrophage-associated inducible nitric oxide synthase as immunomodulatory mechanisms. (1996)

In an adoptive transfer model of experimental allergic encephalomyelitis, stimulation of lymph node cells with proteolipid protein and recombinant murine interleukin (rmIL)-12 before cell transfer accelerated the onset and exacerbates clinical disease. In vitro stimulation with proteolipid protein in the presence of rmIL-12 was associated with an increase in interferon-gamma-producing cells and a decrease in IL-4-producing cells, indicating a preferential expansion of Th1 effector cells. This was supported by the finding that severe disease with rapid onset could be transferred with as few as 10 x 10(6) rmIL-12-stimulated lymph node cells. Immunohistochemical analysis confirmed that the accelerated onset of disease after in vitro stimulation with rmIL-12 coincided with an acute inflammatory response in the central nervous system. At peak disease, both control and rmIL-12 treatment groups exhibited extensive cellular infiltration with characteristic perivascular cuffing. No notable differences in either the cellular composition or cytokine expression within the lesions were seen between groups. However, the frequency of macrophages that stained positively for inducible nitric oxide synthase was increased in animals challenged with rmIL-12-treated lymph node cells. The results suggest that, in addition to promoting the preferential expansion of interferon-gamma-producing cells by rmIL-12 in vitro, secondary in vivo effects leading to macrophage activation and inducible nitric oxide synthase expression may contribute to the severe and protracted course of central nervous system inflammation in this model.
Intrinsic mineralization defect inHyp mouse osteoblasts (1998)

X-linked hypophosphatemia (XLH) is caused by inactivating mutations of PEX, an endopeptidase of uncertain function. This defect is shared by Hyp mice, the murine homologue of the human disease, in which a 3' Pex deletion has been documented. In the present study, we report that immortalized osteoblasts derived from the simian virus 40 (SV40) transgenic Hyp mouse (TMOb-Hyp) have an impaired capacity to mineralize extracellular matrix in vitro. Compared with immortalized osteoblasts from the SV40 transgenic normal mouse (TMOb-Nl), osteoblast cultures from the SV40 Hyp mouse exhibit diminished 45Ca accumulation into extracellular matrix (37 +/- 6 vs. 1,484 +/- 68 counts . min-1 . microgram protein-1) and reduced formation of mineralization nodules. Moreover, in coculture experiments, we found evidence that osteoblasts from the SV40 Hyp mouse produce a diffusible factor that blocks mineralization of extracellular matrix in normal osteoblasts. Our findings indicate that abnormal PEX in osteoblasts is associated with the accumulation of a factor(s) that inhibits mineralization of extracellular matrix in vitro.
[Dry powdered formoterol, twice a day versus aerosolized salbutamol, four times a day, in patients with stable asthma]. (1999)

That formoterol is a safe, efficacious and long-acting Beta 2 agonist which can be administered twice daily.
TP53Mutations and Survival in Squamous-Cell Carcinoma of the Head and Neck (2007)

Disruptive TP53 mutations in tumor DNA are associated with reduced survival after surgical treatment of squamous-cell carcinoma of the head and neck.
P‐cadherin expression in breast carcinoma indicates poor survival (1999)

BACKGROUND The cadherin family of cell-cell adhesion molecules and their associated proteins, the catenins, are essential to embryonic development and the maintenance of adult tissues. During development, the homotypic interaction of a particular cadherin with an identical cadherin expressed on a neighboring cell results in the sorting of cells to form distinctive tissues. Cadherins are believed to be tumor suppressors, and their altered expression and function have been associated with tumor development. METHODS The authors examined the expression of P-cadherin, E-cadherin, and N-cadherin, and α-catenin and β-catenin in 183 cases of invasive breast carcinoma by immunohistochemistry on paraffin sections using specific antibodies and a steam-based antigen retrieval method. RESULTS P-cadherin was positive in 95 cases and negative in 88 cases of breast carcinoma. Positive P-cadherin expression in breast carcinoma showed a strong correlation with poor patient prognosis. Five years after surgery, 90% of the patients with P-cadherin negative tumors were alive in contrast to only 59% of patients with P-cadherin positive tumors. The difference in survival reached statistical significance (P = 0.0001) as early as 2 years after surgical treatment. Expression of N-cadherin, α-catenin, and β-catenin did not correlate with patient survival. Multivariable statistical analyses of the data showed that expression of P-cadherin was independent of tumor size and lymph node metastases, but correlated inversely with estrogen/progesterone receptor status. In ductal carcinomas, positive P-cadherin expression correlated with a higher histologic grade. In contrast, expression of E-cadherin was low in high grade ductal carcinomas but negative tumors were uncommon. Negative or low E-cadherin expression did not correlate with poor survival. In lobular carcinomas, E-cadherin expression frequently was negative or low, and P-cadherin always was negative. CONCLUSIONS Expression of P-cadherin in breast carcinoma is associated strongly with poor survival and constitutes an independent prognostic predictor. P-cadherin expression is a better indicator of clinical outcome than alterations in the expression of E-cadherin, N-cadherin, α-catenin, or β-catenin. Cancer 1999;86:1263–72. © 1999 American Cancer Society.
Multiple colors by fluorescence in situ hybridization using ratio-labelled DNA probes create a molecular karyotype (1992)

Fluorescence in situ hybridization (FISH) is now widely used for the localization of genomic DNA fragments, and the identification of chromosomes by painting. We now show that half of the chromosomal complement can be painted in twelve different colors by using human chromosome specific libraries carrying three distinct labels mixed in multiple ratios. The photographs are in 'real' color rather than 'colorized'. The painting technique described here can be used for the identification of small or complex chromosomal rearrangements and marker chromosomes in humans or in any other species for which well defined chromosome specific libraries exist in a laboratory equipped with a conventional fluorescence microscope. The versatility of this novel cytogenetic technology may well constitute an advancement comparable to the introduction of chromosome banding and high resolution analysis of chromosomes in prometaphase.
Novel kidney cancer immunotherapy based on the granulocyte-macrophage colony-stimulating factor and carbonic anhydrase IX fusion gene. (2003)

Our results suggest that the fusion protein GMCA-9 is capable of generating an immune response both in vitro and in vivo. Additional studies will confirm the utility of ex vivo GMCA-9-transduced DCs as a kidney cancer vaccine.
Potential of IL-1, IL-18 and Inflammasome Inhibition for the Treatment of Inflammatory Skin Diseases (2017)

In 2002, intracellular protein complexes known as the inflammasomes were discovered and were shown to have a crucial role in the sensing of intracellular pathogen- and danger-associated molecular patterns (PAMPs and DAMPs). Activation of the inflammasomes results in the processing and subsequent secretion of the pro-inflammatory cytokines IL-1β and IL-18. Several autoinflammatory disorders such as cryopyrin-associated periodic syndromes and Familial Mediterranean Fever have been associated with mutations of genes encoding inflammasome components. Moreover, the importance of IL-1 has been reported for an increasing number of autoinflammatory skin diseases including but not limited to deficiency of IL-1 receptor antagonist, mevalonate kinase deficiency and PAPA syndrome. Recent findings have revealed that excessive IL-1 release induced by harmful stimuli likely contributes to the pathogenesis of common dermatological diseases such as acne vulgaris or seborrheic dermatitis. A key pathogenic feature of these diseases is IL-1β-induced neutrophil recruitment to the skin. IL-1β blockade may therefore represent a promising therapeutic approach. Several case reports and clinical trials have demonstrated the efficacy of IL-1 inhibition in the treatment of these skin disorders. Next to the recombinant IL-1 receptor antagonist (IL-1Ra) Anakinra and the soluble decoy Rilonacept, the anti-IL-1α monoclonal antibody MABp1 and anti-IL-1β Canakinumab but also Gevokizumab, LY2189102 and P2D7KK, offer valid alternatives to target IL-1. Although less thoroughly investigated, an involvement of IL-18 in the development of cutaneous inflammatory disorders is also suspected. The present review describes the role of IL-1 in diseases with skin involvement and gives an overview of the relevant studies discussing the therapeutic potential of modulating the secretion and activity of IL-1 and IL-18 in such diseases.