gebhart/patrepeval huggingface dataset:
The complete sequence of the 8·2 kb segment left of MAT on chromosome III reveals five ORFs, including a gene for a yeast ribokinase (1990)

We report here the DNA sequence of a segment of chromosome III extending over 8.2 kb. The sequence was determined using the random clone strategy followed by oligonucleotide-directed sequencing. The segment contains five long open reading frames, YCR521, 522, 523, 524 and 526, with only short distances between them. YCR523 (333 codons) encodes a ribokinase, a new function for yeast. YCR526 originates inside the MAT cassette, which is in continuity with the present segment, and extends over 358 codons outside of MAT. YCR524 (923 codons) codes for a putative membrane protein. YCR521, 522 and 524, have each been disrupted by insertion of a URA3 cassette and are non-essential genes. An active ARS element is located within YCR523 or its vicinity.
Single Cell Multi-Omics Technology: Methodology and Application (2018)

In the era of precision medicine, multi-omics approaches enable the integration of data from diverse omics platforms, providing multi-faceted insight into the interrelation of these omics layers on disease processes. Single cell sequencing technology can dissect the genotypic and phenotypic heterogeneity of bulk tissue and promises to deepen our understanding of the underlying mechanisms governing both health and disease. Through modification and combination of single cell assays available for transcriptome, genome, epigenome, and proteome profiling, single cell multi-omics approaches have been developed to simultaneously and comprehensively study not only the unique genotypic and phenotypic characteristics of single cells, but also the combined regulatory mechanisms evident only at single cell resolution. In this review, we summarize the state-of-the-art single cell multi-omics methods and discuss their applications, challenges, and future directions.
Roles of programmed death-1 (PD-1)/PD-1 ligands pathway in the development of murine acute myocarditis caused by coxsackievirus B3 (2007)

Our findings strongly suggest that the PD-1/PD-L1 pathway played a pivotal role in suppressing myocardial inflammation and raise the possibility of immunotherapy by stimulating the PD-1/PD-L1 pathway to prevent myocardial damage in viral myocarditis.
Subtilisin. Stereochemical mechanism involving transition-state stabilization (1972)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSubtilisin. Stereochemical mechanism involving transition-state stabilizationJon D. Robertus, Joseph Kraut, Richard A. Alden, and Jens J. BirktoftCite this: Biochemistry 1972, 11, 23, 4293–4303Publication Date (Print):November 1, 1972Publication History Published online1 May 2002Published inissue 1 November 1972https://pubs.acs.org/doi/10.1021/bi00773a016https://doi.org/10.1021/bi00773a016research-articleACS PublicationsRequest reuse permissionsArticle Views805Altmetric-Citations284LEARN 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
Structural insights into the molecular mechanism of the m6A writer complex (2016)

Methylation of adenosines at the N(6) position (m(6)A) is a dynamic and abundant epitranscriptomic mark that regulates critical aspects of eukaryotic RNA metabolism in numerous biological processes. The RNA methyltransferases METTL3 and METTL14 are components of a multisubunit m(6)A writer complex whose enzymatic activity is substantially higher than the activities of METTL3 or METTL14 alone. The molecular mechanism underpinning this synergistic effect is poorly understood. Here we report the crystal structure of the catalytic core of the human m(6)A writer complex comprising METTL3 and METTL14. The structure reveals the heterodimeric architecture of the complex and donor substrate binding by METTL3. Structure-guided mutagenesis indicates that METTL3 is the catalytic subunit of the complex, whereas METTL14 has a degenerate active site and plays non-catalytic roles in maintaining complex integrity and substrate RNA binding. These studies illuminate the molecular mechanism and evolutionary history of eukaryotic m(6)A modification in post-transcriptional genome regulation.
REVIEW: Behavioural assessment of drug reinforcement and addictive features in rodents: an overview (2006)

Some psychoactive drugs are abused because of their ability to act as reinforcers. As a consequence behavioural patterns (such as drug-seeking/drug-taking behaviours) are promoted that ensure further drug consumption. After prolonged drug self-administration, some individuals lose control over their behaviour so that these drug-seeking/taking behaviours become compulsive, pervading almost all life activities and precipitating the loss of social compatibility. Thus, the syndrome of addictive behaviour is qualitatively different from controlled drug consumption. Drug-induced reinforcement can be assessed directly in laboratory animals by either operant or non-operant self-administration methods, by classical conditioning-based paradigms such as conditioned place preference or sign tracking, by facilitation of intracranial electric self-stimulation, or, alternatively by drug-induced memory enhancement. In contrast, addiction cannot be modelled in animals, at least as a whole, within the constraints of the laboratory. However, various procedures have been proposed as possible rodent analogues of addiction's major elements including compulsive drug seeking, relapse, loss of control/impulsivity, and continued drug consumption despite negative consequences. This review provides an extensive overview and a critical evaluation of the methods currently used for studying drug-induced reinforcement as well as specific features of addictive behaviour. In addition, comic strips that illustrate behavioural methods used in the drug abuse field are provided given for free download under http://www.zi-mannheim/psychopharmacology.de.
Identification and structural characterization of a mannose‐6‐phosphate containing oligomannosidic N‐glycan from human erythropoietin secreted by recombinant BHK‐21 cells (1995)

A sialidase resistant mono-charged N-glycan was isolated from glycosylation site I (Asn-24) of recombinant human erythropoietin expressed from baby hamster kidney (BHK-21) cells and constituted approximately 2-4% of the oligosaccharide material at this glycosylation site. Mass spectrometry and both 1- and 2-dimensional NMR techniques revealed a high mannose type structure (Man6) with a phospho-diesterbridged N-acetylglucosamine as follows: [formula: see text]
Concentration-Dependent Aggregation of CHAPS Investigated by NMR Spectroscopy (2010)

CHAPS (3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate) is a zwitterionic surfactant, which has been extensively used in various biological fields. In the present work, the concentration-dependent aggregation of the surfactant in deuterium oxide solution was investigated by NMR spectroscopy. We have found that two break points exist on the basis of the NMR parameters such as chemical shift difference (Delta delta), self-diffusion coefficient (D), and relaxation rates (R(1), R(2)). The first break point corresponds to the widely accepted normal critical micelle concentration (cmc). The second one is unexpected and ascribed to the second cmc, indicating that there is another type of micelle at higher concentrations. Further analysis using 1D selective NOESY with spin-diffusion quenching reveals that at the concentration above the second cmc CHAPS may form a two-layer spherical structure of micelles, with the aliphatic groups of CHAPS molecules in the inner layer interact with the steroid groups in the outer layer. The existence of two types of micelles has also been supported by our TEM experiment. The dependence of CHAPS micelle size on concentration explains why some proteins are soluble and stable only at concentrations above the second cmc. Therefore, our finding provides a basis for optimizing CHAPS concentration in functional and structural studies of membrane proteins.
Development of a serological test for tuberculosis. Problems and potential. (1994)

The secreted antigens of 24K and 38K and the hsp of 12K and 16K are valuable as reagents in a serodiagnostic assay for tuberculosis. A combination of the TB72 assay with either the 16K or 24K antigen gives the best sensitivity and specificity. Antigens isolated from mycobacterial cultures are valuable in a serological test. Peptides cannot be used as antigens. The value of antigens obtained with recombinant DNA techniques remains to be determined. In HIV-seronegative patients with TB serodiagnosis is a valuable test both in pulmonary and extrapulmonary TB. Unfortunately, the results in HIV-seropositive patients are rather disappointing. The use of likelihood ratios seems to increase the potential of serodiagnostic assays. The value of serodiagnosis should be judged in context with other diagnostic methods such as direct microscopy, bacteriological culture or skin tests. A serological test is especially valuable in cases where direct microscopy, polymerase chain reaction or skin testing is negative and allows antituberculous therapy to be started before results of culture are known.
Ligand Oxidations in High-Spin Nickel Thiolate Complexes and Zinc Analogues (2004)

Oxidations of a trigonal-bipyramidal, high-spin Ni(II) dithiolate complex of a pentadentate, N3S2-donor ligand, N1,N9-bis(imino-2-mercaptopropane)-1,5,9-triazanonane) nickel(II), and the structurally analogous Zn(II) complex, lead to oxidations of the ligand. Oxidation of the Ni(II) complex with I2 produces a novel Ni(II) macrocyclic cationic complex containing a monodentate disulfide ligand (2). Crystals of the I3- salt of the complex form in the triclinic space group P(1) with cell dimensions a=8.508(3) A, b=9.681(2) A, c=14.066(4) A, angles alpha=90.97(2) degrees , beta=91.61(3) degrees , gamma=90.83(2) degrees , and Z=2. The structure was refined to R=6.31% and Rw=16.63% (I > 2sigma(I)). Oxidation of the Ni(II) complex with O2 leads to the formation of a novel pentadentate bis-iminothiocarboxylate complex with trigonal-bipyramidal geometry (3). This neutral product crystallizes in the monoclinic space group P21/c with cell dimensions a=13.625(3) A, b=7.605(5) A, c=14.902(4) A, angles alpha=gamma=90 degrees, beta=102.81(2) degrees , and Z=4. The structure was refined to R=7.18% and Rw=17.86% (I > 2sigma(I)). Oxidation of the Zn(II) dithiolate analogue with O2 leads to the formation of the Zn(II) complex of the pentadentate bis-iminothiocarboxylate ligand. The neutral complex is isomorphous with the Ni(II) complex and crystallizes in the monoclinic space group P2(1)/c with cell dimensions a=13.8465(4) A, b=7.6453(2) A, c=15.0165(6) A, angles alpha=gamma=90 degrees , beta=103.2140(11) degrees , and Z=4. The structure was refined to R=3.96% and Rw=9.45% (I > 2sigma(I)). Details of the crystal structures are reported. Kinetics of the O2 reactions show that the reactions of the Ni(II) and Zn(II) dithiolates follow the rate law, Rate=k2[1][O2], with k2=1.81 M(-1) s(-1) for the Ni(II) complex and k2=1.93 x 10(-2) M(-1) s(-1) for the Zn(II) complex. The O2 oxidation of the high-spin Ni(II) thiolate complex was found to follow a similar oxidation mechanism to those of low-spin Ni(II) complexes, which form transient persulfoxide intermediates that yield S-oxidation products. In the case of the high-spin system reported here, the transient persulfoxide intermediate gives rise to an alternative ligand oxidation product, a bis-iminothiocarboxylate complex, because of the reactivity of the ligand, which contains a methylene with acidic H atoms alpha to the thiolate sulfur. The proposed mechanism is supported by studies of the analogous Zn dithiolate complex, which gives rise to the analogous bis-iminothiocarboxylate product (5).
Recombinant human erythropoietin (rhEPO) treatment potentiates growth hormone (GH) response to growth hormone releasing hormone (GHRH) stimulation in hemodialysis patients. (1993)

On the basis of previously described effects of recombinant human erythropoietin (rhEPO) treatment on endocrine abnormalities present in uremia, we assessed the possible effect of treatment with rhEPO on growth hormone (GH) response to growth hormone releasing hormone (GHRH) in a group of uremic patients. Eight patients on maintenance hemodialysis for 12 to 228 months, not previously treated with rhEPO, were tested with 100 micrograms of GHRH i.v. in bolus before and after three months of rhEPO treatment (40 U/kg i.v. three times a week). Before treatment, the GH response to GHRH was characterized, in uremic patients, by remarkable differences in plasma GH values and in the pattern of response curve in single patients. The variability of GH response was not modified after rhEPO treatment; however, an overall potentiation of GH response with a significant increase of plasma GH (p = 0.017 at 15 min, p = 0.035 at 30 min after GHRH injection) was observed in the tests performed after treatment. rhEPO administration induced an evident improvement of anemia, blood hemoglobin concentration being 5.3-7.6 g/dl before and 9.1-11.3 g/dl after treatment; however a demonstrable correlation between the potentiation of GH response to GHRH and the increase of hemoglobin concentration was not observed.
Expression of folate receptors and heterogeneous nuclear ribonucleoprotein E1 in women with human papillomavirus mediated transformation of cervical tissue to cancer (2003)

These results are consistent with a hypothesis that reduced hnRNP-E1 expression may be permissive for HPV proliferation and progression to cervical cancer, and support the need for prospective longitudinal studies of hnRNP-E1 expression in HPV-16 infected women.
Global control of aberrant splice-site activation by auxiliary splicing sequences: evidence for a gradient in exon and intron definition (2007)

Auxiliary splicing signals play a major role in the regulation of constitutive and alternative pre-mRNA splicing, but their relative importance in selection of mutation-induced cryptic or de novo splice sites is poorly understood. Here, we show that exonic sequences between authentic and aberrant splice sites that were activated by splice-site mutations in human disease genes have lower frequencies of splicing enhancers and higher frequencies of splicing silencers than average exons. Conversely, sequences between authentic and intronic aberrant splice sites have more enhancers and less silencers than average introns. Exons that were skipped as a result of splice-site mutations were smaller, had lower SF2/ASF motif scores, a decreased availability of decoy splice sites and a higher density of silencers than exons in which splice-site mutation activated cryptic splice sites. These four variables were the strongest predictors of the two aberrant splicing events in a logistic regression model. Elimination or weakening of predicted silencers in two reporters consistently promoted use of intron-proximal splice sites if these elements were maintained at their original positions, with their modular combinations producing expected modification of splicing. Together, these results show the existence of a gradient in exon and intron definition at the level of pre-mRNA splicing and provide a basis for the development of computational tools that predict aberrant splicing outcomes.
Transient functional expression of alphaVbeta 3 on vascular cells during wound repair. (1996)

During early granulation tissue formation of wound repair, new capillaries invade the fibrin clot, a process that undoubtedly requires an interaction of vascular cells with the wound provisional matrix composed mainly of fibrin, fibronectin, and vitronectin. Integrin alphaVbeta3 is the vascular cell receptor for these wound-associated adhesive proteins. Therefore, we investigated the expression of this receptor on new capillaries of healing full-thickness cutaneous porcine wounds. During granulation tissue formation, alphaVbeta3 was expressed specifically on capillary sprouts invading the central fibrin clot whereas the closely related integrin alphaVbeta5 failed to localize to these cells. Cyclic peptides or antibody antagonists of alphaVbeta3 specifically inhibited granulation tissue formation in a transient manner during the period of invasive angiogenesis. Immunolocalization studies revealed that alphaVbeta3 became aggregated and lost from sprouting vessels after treatment with a peptide antagonist. In contrast, beta 1 integrins were not modulated by this treatment. Once granulation tissue filled the wound and invasive angiogenesis terminated, the alphaVbeta3 showed little or no expression in the granulation tissue microvasculature. These data demonstrate that integrin alphaVbeta3 plays a fundamental, but transient, role during invasive angiogenesis and granulation tissue formation in a healing wound.
Coupling complement regulators to immunoglobulin domains generates effective anti-complement reagents with extended half-lifein vivo (2002)

Complement activation and subsequent generation of inflammatory molecules and membrane attack complex contributes to the pathology of a number of inflammatory and degenerative diseases, including arthritis, glomerulonephritis and demyelination. Agents that specifically inhibit complement activation might prove beneficial in the treatment of these diseases. Soluble recombinant forms of the naturally occurring membrane complement regulatory proteins (CRP) have been exploited for this purpose. We have undertaken to design better therapeutics based on CRP. Here we describe the generation of soluble, recombinant CRP comprising rat decay accelerating factor (DAF) or rat CD59 expressed as Fc fusion proteins, antibody-like molecules comprising two CRP moieties in place of the antibody Fab arms (CRP-Ig). Reagents bearing DAF on each arm (DAF-Ig), CD59 on each arm (CD59-Ig) and a hybrid reagent containing both DAF and CD59 were generated. All three reagents inhibited C activation in vitro. Compared with soluble CRP lacking Fc domains, activity was reduced, but was fully restored by enzymatic release of the regulator from the Ig moiety, implicating steric constraints in reducing functional activity. In vivo studies showed that DAF-Ig, when compared to soluble DAF, had a much extended half-life in the circulation in rats and concomitantly caused a sustained reduction in plasma complement activity. When given intra-articularly to rats in a model of arthritis, DAF-Ig significantly reduced severity of disease. The data demonstrate the potential of CRP-Ig as reagents for sustained therapy of inflammatory disorders, including arthritis, but emphasize the need for careful design of fusion proteins to retain function.
Atomic layer deposition of copper thin film using Cu<sup>II</sup>(diketoiminate)<inf>2</inf> and H<inf>2</inf> (2009)

We report for the first time the atomic layer deposition (ALD) of Cu film using alternating exposures to Cu <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">II</sup> (diketoiminate) <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> and H <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> . The influences of deposition temperature on the properties of the deposited film were investigated at 140-220degC. Minimum sheet resistance and continuous film surface on Pt substrate were obtained at 180-200degC. The resistivity of 17-nm-thick ALD Cu film was ~7 muOmegamiddotcm.
Advances in the biology and therapy of diffuse large B-cell lymphoma: moving toward a molecularly targeted approach (2005)

Diffuse large B-cell lymphoma (DLBCL) displays striking heterogeneity at the clinical, genetic, and molecular levels. Clinical prognostic models can define a population at high risk for relapse following empiric chemotherapy, although such models do not account for underlying biologic differences among tumors. Commonly observed genetic abnormalities that likely contribute to pathogenesis include translocations of BCL6, BCL2, cMYC, and FAS(CD95) mutations, and aberrant somatic hypermutation. Despite recent advances in empiric chemotherapy, including interval reduction of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) and the incorporation of anti-CD20 monoclonal antibodies, a significant proportion of patients still die of their disease. Gene expression profiling has shed light on the molecular heterogeneity within DLBCL by highlighting similarities between subsets of tumors and normal B cells, identifying features associated with unfavorable responses to empiric combination chemotherapy, and defining robust subtypes with comprehensive transcriptional signatures. Such strategies have suggested distinct routes to lymphomagenesis and have identified promising rational therapeutic targets. Additional novel therapies under investigation include those targeting BCL6 and BCL2, as well as development of novel monoclonal antibody-based therapies. Our increasing molecular understanding of the heterogeneous subsets within DLBCL will likely improve the current empiric therapy of DLBCL by identifying rational therapeutic targets in specific disease subtypes.
Mutational Analysis of BRAF in Fine Needle Aspiration Biopsies of the Thyroid: A Potential Application for the Preoperative Assessment of Thyroid Nodules (2004)

BRAF mutations are common in conventional PTCs, and they are specific for PTC. A BRAF mutation can be reliably detected in cells aspirated from a thyroid nodule suggesting a role for this marker in the preoperative evaluation of thyroid nodules.
Two-dimensional birefringence imaging in biological tissue by polarization-sensitive optical coherence tomography (1997)

Using a low-coherence Michelson interferometer, we measure two-dimensional images of optical birefringence in bovine tendon as a function of depth. Polarization-sensitive detection of the signal formed by interference of backscattered light from the sample and a mirror in the reference arm give the optical phase delay between light that is propagating along the fast and slow axes of the birefringent tendon. Images showing the change in birefringence in response to laser irradiation are presented. The technique permits rapid noncontact investigation of tissue structural properties through two-dimensional imaging of birefringence.
Method for the Determination of Total Homocysteine in Plasma and Urine by Stable Isotope Dilution and Electrospray Tandem Mass Spectrometry (1999)

The sensitivity and specificity of tandem mass spectrometry are well suited to perform high-volume analysis of tHcy. Reagents are inexpensive and sample preparation of a batch of 40 specimens is completed in less than 1 h and is amenable to automation.