gebhart/patrepeval huggingface dataset:
Organization of kappa light chain genes in germ-line and somatic tissue. (1980)

We studied the organization of the kappa light chain genes in germ-line (sperm) and somatic (embryo) tissues. We constructed a plasmid containing a DNA insert coding for the kappa chain MOPC 167 and used the Southern blotting technique to determine the organization of kappa variable and constant region genes. In the haploid genome of the mouse there is only one constant region gene detectable and it has the same organization in sperm and embryo DNAs. There are several variable region genes in sperm and embryo that are related to the Vk167 gene. The organization of the V genes in sperm and embryo DNAs is identical. These results show that there is no rearrangement of variable region genes (or "minigenes") during early embryogenesis.
HLA-A, HLA-B, HLA-DRB1 Polymorphisms and Risk of Cervical Squamous Epithelial Cell Carcinoma: A Population Study in China (2013)

Cervical cancer is the second most common cancer in women. HLA class I and II alleles polymorphisms have been shown to associate with cervical cancer risk, but results varied among different populations. In this study, the HLA-A, -B, and -DRB1 alleles among 100 southern Chinese women with cervical squamous cell carcinoma (SCC) were compared to 254 controls. Our results showed that B*51:01:02 allele frequency was significantly higher in patients with SCC than that in healthy controls (P = 3.17x 10-5, Pc = 0.005, OR = 26.68). Statistical analysis also revealed a significantly decreased frequency of B*51:01:01 (P = 7.01x 10-4, Pc = 0.03, OR = 0.12) in patients with SCC when compared with healthy controls. These results indicate that HLA-B*51:01:02 may confer susceptibility to SCC and HLA-B*51:01:01 may contribute to the resistance to the development of SCC in Chinese women. None of the HLA-A-B or HLA-A-B-DRB1 haplotypes were significantly different in cases and controls after multiple testing corrections, implicating those individual allele associations are independent of the identified haplotypes. These results support the hypothesis that some HLA-B alleles could be involved with susceptibility for developing SCC.
Dyclonine rescues frataxin deficiency in animal models and buccal cells of patients with Friedreich's ataxia (2014)

Inherited deficiency in the mitochondrial protein frataxin (FXN) causes the rare disease Friedreich's ataxia (FA), for which there is no successful treatment. We identified a redox deficiency in FA cells and used this to model the disease. We screened a 1600-compound library to identify existing drugs, which could be of therapeutic benefit. We identified the topical anesthetic dyclonine as protective. Dyclonine increased FXN transcript and FXN protein dose-dependently in FA cells and brains of animal models. Dyclonine also rescued FXN-dependent enzyme deficiencies in the iron-sulfur enzymes, aconitase and succinate dehydrogenase. Dyclonine induces the Nrf2 [nuclear factor (erythroid-derived 2)-like 2] transcription factor, which we show binds an upstream response element in the FXN locus. Additionally, dyclonine also inhibited the activity of histone methyltransferase G9a, known to methylate histone H3K9 to silence FA chromatin. Chronic dosing in a FA mouse model prevented a performance decline in balance beam studies. A human clinical proof-of-concept study was completed in eight FA patients dosed twice daily using a 1% dyclonine rinse for 1 week. Six of the eight patients showed an increase in buccal cell FXN levels, and fold induction was significantly correlated with disease severity. Dyclonine represents a novel therapeutic strategy that can potentially be repurposed for the treatment of FA.
Double-Stranded RNA Adenosine Deaminases ADAR1 and ADAR2 Have Overlapping Specificities (2000)

Adenosine deaminases that act on RNA (ADARs) deaminate adenosines to produce inosines within RNAs that are largely double-stranded (ds). Like most dsRNA binding proteins, the enzymes will bind to any dsRNA without apparent sequence specificity. However, once bound, ADARs deaminate certain adenosines more efficiently than others. Most of what is known about the intrinsic deamination specificity of ADARs derives from analyses of Xenopus ADAR1. In addition to ADAR1, mammalian cells have a second ADAR, named ADAR2; the deamination specificity of this enzyme has not been rigorously studied. Here we directly compare the specificity of human ADAR1 and ADAR2. We find that, like ADAR1, ADAR2 has a 5' neighbor preference (A approximately U > C = G), but, unlike ADAR1, also has a 3' neighbor preference (U = G > C = A). Simultaneous analysis of both neighbor preferences reveals that ADAR2 prefers certain trinucleotide sequences (UAU, AAG, UAG, AAU). In addition to characterizing ADAR2 preferences, we analyzed the fraction of adenosines deaminated in a given RNA at complete reaction, or the enzyme's selectivity. We find that ADAR1 and ADAR2 deaminate a given RNA with the same selectivity, and this appears to be dictated by features of the RNA substrate. Finally, we observed that Xenopus and human ADAR1 deaminate the same adenosines on all RNAs tested, emphasizing the similarity of ADAR1 in these two species. Our data add substantially to the understanding of ADAR2 specificity, and aid in efforts to predict which ADAR deaminates a given editing site adenosine in vivo.
A "turnkey" optoelectronic oscillator with low acceleration sensitivity (2002)

We present the experimental results on the acceleration sensitivity of the first fully packaged optoelectronic oscillator module operating at 11 GHz. We demonstrate a fiber delay line package technique that reduces the acceleration sensitivity of the module by 40 times. With measured acceleration sensitivity less than 1.5/spl times/10(-10)/g, this oscillator is believed to have the lowest acceleration sensitivity of any oscillator operating at 10 GHz and above.
Synthesis of ara-doridosine, a new arabinosyl nucleoside resistant to adenosine deaminase. X-Ray structure determination of 6-N,9(N)-diacetyl-1 (N)-methylisoguanine (1985)

9-(β-D-Arabinofuranosyl)-1-(N)-methylisoguanine (2)(ara-doridosine) has been prepared via two stereochemically complementary synthetic routes, one of which utilized a recently described, novel nucleoside-base rearrangement reaction. The structural determination of several intermediates, some with unusual tautomeric forms stabilized by hydrogen bonding, was facilitated by use of 13C–1H long-range coupling values. An X-ray diffraction analysis and a mass-spectral isotope fragmentation experiment also facilitated the structure elucidation of the key intermediates, 6-N,9(N)-diacetyl-1 (N)-methylisoguanine (6) and 6-N-methylisoguanine (7). respectively. The potential long acting antiviral agent (2) has been shown to be resistant to the enzyme adenosine deaminase.
HOVERGEN: a database of homologous vertebrate genes (1994)

Comparison of homologous genes is a major step for many studies related to genome structure, function or evolution. Similarity search programs easily find genes homologous to a given sequence. However, only very tedious manual procedures allow the retrieval of all sets of homologous genes sequenced for a given set of species. Moreover, this search often generates errors due to the complexity of data to be managed simultaneously: phylogenetic trees, alignments, taxonomy, sequences and related information. HOVERGEN helps to solve these problems by integrating all this information. HOVERGEN corresponds to GenBank sequences from all vertebrate species, with some data corrected, clarified, or completed, notably to address the problem of redundancy. Coding sequences have been classified in gene families. Protein multiple alignments and phylogenetic trees have been calculated for each family. Sequences and related information have been structured in an ACNUC database which permits complex selections. A graphical interface has been developed to visualize and edit trees. Genes are displayed in color, according to their taxonomy. Users have directly access to all information attached to sequences and to multiple alignments simply by clicking on genes. This graphical tool gives thus a rapid and simple access to all data necessary to interpret homology relationships between genes. HOVERGEN allows the user to easily select sets of homologous vertebrate genes, and thus is particularly useful for comparative sequence analysis, or molecular evolution studies.
Adapting to network and client variation using infrastructural proxies: lessons and perspectives (1998)

Today's Internet clients vary widely with respect to both hardware and software properties: screen size, color depth, effective bandwidth, processing power, and the ability to handle different data formats. The order-of-magnitude span of this variation is too large to hide at the network level, making application-level techniques necessary. We show that on-the-fly adaptation by transformational proxies is a widely applicable, cost-effective, and flexible technique for addressing all these types of variations. To support this claim, we describe our experience with data-type-specific distillation (lossy compression) in a variety of applications. We also argue that placing adaptation machinery in the network infrastructure, rather than inserting it into end servers, enables incremental deployment and amortization of operating costs. To this end, we describe a programming model for large-scale interactive Internet services and a scalable cluster-based framework that has been in production use at UC Berkeley since April 1997. We present a detailed examination of TranSend, a scalable transformational Web proxy deployed on our cluster framework, and give descriptions of several handheld-device applications that demonstrate the wide applicability of the proxy-adaptation philosophy.
Interpreting the molecular biology and clinical behavior of multiple myeloma in the context of global gene expression profiling (2003)

Multiple myeloma (MM) is a rare but uniformly fatal malignancy of antibody-secreting plasma cells (PCs). Although several key molecular events in disease initiation or progression have been confirmed (e.g. FGFR3/MMSET activation) or implicated (e.g. chromosome 13 deletion), the mechanisms of MM development remain enigmatic. Importantly, although generally being indistinguishable morphologically, MM exhibits a tremendous degree of variability in clinical course, with some patients surviving only months and others many years. However, current laboratory parameters can account for no more than 20% of this outcome variability. Furthermore, the means by which current drugs impart their anti-MM effect are also mostly unknown. In addition, the mechanisms by which MM cells contribute to serious comorbidities, such as osteopenia and/or focal lytic lesions of bone, are also poorly understood. Finally, very little knowledge exists concerning the molecular events leading to benign hyperplasia and/or overt malignancy of PCs. Given that abnormal gene expression lies at the heart of most, if not all, cancers, high-throughput global gene expression profiling has become a powerful tool for investigating molecular biology and clinical behavior of diseases. Here, we discuss recent progress made in addressing many of the above issues through the molecular dissection of the transcriptome of normal PCs and MM.
Differential Expression of Two hemA mRNAs Encoding Glutamyl-tRNA Reductase Proteins in Greening Cucumber Seedlings (1996)

The first committed step of porphyrin synthesis in higher plants is the reduction of glutamyl-tRNA to glutamate 1-semialdehyde. This reaction is catalyzed by glutamyl-tRNA reductase, which is encoded by hemA genes. Two hemA cDNA clones (hemA1 and hemA2) were obtained from cucumber (Cucumis sativus) cotyledons by the PCR and cDNA library screening. They showed significant homology with published hemA sequences. Southern blot analysis of cucumber genomic DNA revealed that these genes are located at different loci and that there is another gene similar to the hemA genes. Accumulation of hemA1 mRNA was detected primarily in cotyledons and hypocotyls of greening cucumber seedlings, whereas that of hemA2 mRNA was detected in all tissues examined. Illumination of cucumber seedlings increased markedly the accumulation of hemA1 mRNA, but it did not induce remarkable changes in that of hemA2 mRNA. These findings suggest that hemA1 mRNA was accumulated in response to the demand of Chl synthesis in photosynthesizing tissues, whereas hemA2 mRNA was expressed in response to the demand of the synthesis of porphyrins other than chlorophylls.
Autoacylation of G Protein α Subunits (1996)

The palmitoylation or S-acylation of at least some G protein alpha subunits is a dynamic process that is regulated in vivo by the activation of associated receptors. Highly purified, myristoylated Gialpha1 and other G protein alpha subunits react spontaneously with palmitoyl-CoA in vitro to form thioesterified proteins. This reaction requires native Gialpha1 and occurs exclusively at Cys3, the same residue that is palmitoylated in vivo. The reaction proceeds to completion, and its rate is roughly equal to the rate of loss of palmitate observed in pulse-chase experiments in vivo. The rate of autoacylation is significantly enhanced by the G protein betagamma subunit complex. Autoacylation may play a role in the dynamic thioesterification of some cellular proteins.
Sperm-zona interaction and recombinant DNA technology (1997)

Recombinant DNA technology has revolutionized our understanding of many biological systems. However, such techniques and their application have not been fully exploited in the study of sperm zona interaction. Using examples from other biological systems, we ourline several experimental approaches that are likely to significantly enhance our understanding of the gamete recognition process.
Inhibition of malignant transformation in vitro by inhibitors of poly(ADP-ribose) synthesis. (1984)

Malignant transformation in vitro of hamster embryo cells and mouse C3H 10T 1/2 cells by x-rays, ultraviolet light, and chemical carcinogens was inhibited by benzamide and by 3-aminobenzamide at concentrations that are specific for inhibition of poly(ADP-ribose) formation. These compounds slow the ligation stage of repair of x-ray and alkylation damage but not of ultraviolet light damage. At high concentrations they also inhibited de novo synthesis of DNA purines and DNA methylation by S-adenosylmethionine. The suppression of transformation by the benzamides is in striking contrast to their reported effectiveness in enhancing sister chromatid exchange, mutagenesis, and killing in cells exposed to alkylating agents. Our results suggest that mechanisms regulating malignant transformation are different from those regulating DNA repair, sister chromatid exchange, and mutagenesis and may be associated with changes in gene regulation and expression caused by alterations in poly(ADP-ribosyl)ation.
Interaction between human tRNA synthetases involves repeated sequence elements. (1996)

Aminoacyl-tRNA synthetases (tRNA synthetases) of higher eukaryotes form a multiprotein complex. Sequence elements that are responsible for the protein assembly were searched by using a yeast two-hybrid system. Human cytoplasmic isoleucyl-tRNA synthetase is a component of the multi-tRNA synthetase complex and it contains a unique C-terminal appendix. This part of the protein was used as bait to identify an interacting protein from a HeLa cDNA library. The selected sequence represented the internal 317 amino acids of human bifunctional (glutamyl- and prolyl-) tRNA synthetase, which is also known to be a component of the complex. Both the C-terminal appendix of the isoleucyl-tRNA synthetase and the internal region of bifunctional tRNA synthetase comprise repeating sequence units, two repeats of about 90 amino acids, and three repeats of 57 amino acids, respectively. Each repeated motif of the two proteins was responsible for the interaction, but the stronger interaction was shown by the native structures containing multiple motifs. Interestingly, the N-terminal extension of human glycyl-tRNA synthetase containing a single motif homologous to those in the bifunctional tRNA synthetase also interacted with the C-terminal motif of the isoleucyl-tRNA synthetase although the enzyme is not a component of the complex. The data indicate that the multiplicity of the binding motif in the tRNA synthetases is necessary for enhancing the interaction strength and may be one of the determining factors for the tRNA synthetases to be involved in the formation of the multi-tRNA synthetase complex.
Processing of mutated proinsulin with tetrabasic cleavage sites to mature insulin reflects the expression of furin in nonendocrine cell lines (1993)

Furin is a mammalian propeptide-processing endoprotease in nonendocrine cells and has been demonstrated to be present in virtually all nonendocrine cells, including fibroblasts, epithelial cells, and hepatocytes. Furin cleaves the concensus processing site -Arg-4-X-3-Lys/Arg-2-Arg-1 decreases X+1-. Some subunit-containing precursor proteins, including an insulin receptor precursor, possess an additional basic residue at position -3, thus forming a tetrabasic processing site. This implies that a tetrabasic processing site must be easily cleavable in nonendocrine cells. We created a mutant proinsulin DNA with a peptide structure comprised of B- and A-chains linked to the C-peptide by a pair of tetrabasic residues, in the following order: B-chain-Arg-Arg-Lys-Arg-C peptide-Arg-Arg-Lys-Arg-A-chain. The native proinsulin structure was B-chain-Arg-Arg-C-peptide-Lys-Arg-A-chain. Both the native and mutant proinsulins were expressed in the following four cell lines: a monkey kidney-derived cell line (COS-7), a Chinese hamster ovary-derived cell line (CHO), a human liver cancer-derived cell line (HepG2), and a mouse fibroblast-like cell line (NIH3T3). We used these cell lines because they contain different quantities of furin mRNA, ranking as follows: NIH3T3 > HepG2 > COS > CHO. When mutant insulin was expressed in these cells, the conversion of proinsulin to mature insulin was approximately 85% in NIH3T3, 70% in HepG2, 60% in COS, and 50% in CHO. The conversion correlated well with the furin expression in each cell line as measured by the density of its Northern blot band. Moreover, in CHO, the cell line with the lowest furin expression, coexpression of mutant proinsulin with furin resulted in complete conversion of proinsulin to mature insulin.
Expression and characterization of antimicrobial peptides Retrocyclin‐101 and Protegrin‐1 in chloroplasts to control viral and bacterial infections (2010)

Retrocyclin-101 (RC101) and Protegrin-1 (PG1) are two important antimicrobial peptides that can be used as therapeutic agents against bacterial and/or viral infections, especially those caused by the HIV-1 or sexually transmitted bacteria. Because of their antimicrobial activity and complex secondary structures, they have not yet been produced in microbial systems and their chemical synthesis is prohibitively expensive. Therefore, we created chloroplast transformation vectors with the RC101 or PG1 coding sequence, fused with GFP to confer stability, furin or Factor Xa cleavage site to liberate the mature peptide from their fusion proteins and a His-tag to aid in their purification. Stable integration of RC101 into the tobacco chloroplast genome and homoplasmy were confirmed by Southern blots. RC101 and PG1 accumulated up to 32%-38% and 17%∼26% of the total soluble protein. Both RC101 and PG1 were cleaved from GFP by corresponding proteases in vitro, and Factor Xa-like protease activity was observed within chloroplasts. Confocal microscopy studies showed location of GFP fluorescence within chloroplasts. Organic extraction resulted in 10.6-fold higher yield of RC101 than purification by affinity chromatography using His-tag. In planta bioassays with Erwinia carotovora confirmed the antibacterial activity of RC101 and PG1 expressed in chloroplasts. RC101 transplastomic plants were resistant to tobacco mosaic virus infections, confirming antiviral activity. Because RC101 and PG1 have not yet been produced in other cell culture or microbial systems, chloroplasts can be used as bioreactors for producing these proteins. Adequate yield of purified antimicrobial peptides from transplastomic plants should facilitate further preclinical studies.
Chemi- and bio-luminescence of coelenterazine analogues with phenyl homologues at the C-2 position (1992)

A series of phenyl homologues of coelenterazine substituted at the C-2 position were synthesized and their bio- and chemi-luminescence properties were investigated including the measurement of chemiluminescence spectra in various media. The light emitting species of each analogue was found to be a neutral form of a coelenteramide derivative in diethylene glycol dimethyl ether (DGM) containing a trace amount of acetate buffer (pH 5.60), while a monoanion was found only in dimethyl sulfoxide (DMSO) and a dianion was observed in DMSO containing a trace amount of aqueous sodium hydroxide. Based on pseudo first-order reaction kinetics, chemiluminescence rate constants were obtained in DGM containing a trace amount of acetate buffer. Each of the synthetic coelenterazine analogues was incorporated into recombinant apoaequorin to obtain a series of semi-synthetic aequorins. Measurements of bioluminescence activities of the aequorins revealed that a benzyl group in the C-2 position was essential for efficient luminescence activity. A two-step incubation procedure was used to determine why some analogues gave less luminescence activity than the benzyl analogue and natural coelenterazine.
Acidity Adjustment of HZSM-5 Zeolites by Dealumination and Realumination with Steaming and Citric Acid Treatments (2006)

This article describes a novel method for acidity adjustment of HZSM-5 zeolites with steaming and citric acid treatments and demonstrates the realumination effect of citric acid on HZSM-5 zeolites dealuminated by steaming. A series of modified HZSM-5 zeolites were prepared by streaming and/or acid treatments and characterized by means of X-ray diffraction (XRD), X-ray fluorescence spectroscopy (XRF), (27)Al MAS NMR spectroscopy, hydroxyl infrared spectroscopy (OH-IR), pyridine-adsorbed infrared spectroscopy, and N(2) adsorption in the present investigation. The results showed that compared with single HCl or citric acid treatment, steaming treatment, and steaming/HCl treatments, citric acid treatment after steaming exclusively increased the amount of framework Al due to reinsertion of extraframework Al into the defective sites of the steamed HZSM-5 framework. This realumination effect of the citric acid treatment on the steamed HZSM-5 zeolite, which is reported here for the first time to the best of our knowledge, could nearly recover the pore structure of the steamed zeolite to that of the parent HZSM-5 zeolite and appropriately tailor the amount and strength of different acid sites, which sheds light on optimizing the physicochemical properties of HZSM-5 zeolites. It was also found that the steaming treatment prior to the citric acid treatment was the precondition of the realumination of HZSM-5 zeolites, suggesting that the lattice defect sites generated during steaming were necessary for citric acid to work.