gebhart/patrepeval huggingface dataset:
Identification of palmitoylated mitochondrial proteins using a bio‐orthogonal azido‐palmitate analogue (2007)

Increased levels of circulating saturated free fatty acids, such as palmitate, have been implicated in the etiology of type II diabetes and cancer. In addition to being a constituent of glycerolipids and a source of energy, palmitate also covalently attaches to numerous cellular proteins via a process named palmitoylation. Recognized for its roles in membrane tethering, cellular signaling, and protein trafficking, palmitoylation is also emerging as a potential regulator of metabolism. Indeed, we showed previously that the acylation of two mitochondrial proteins at their active site cysteine residues result in their inhibition. Herein, we sought to identify other palmitoylated proteins in mitochondria using a nonradioactive bio-orthogonal azido-palmitate analog that can be selectively derivatized with various tagged triarylphosphines. Our results show that, like palmitate, incorporation of azido-palmitate occurred on mitochondrial proteins via thioester bonds at sites that could be competed out by palmitoyl-CoA. Using this method, we identified 21 putative palmitoylated proteins in the rat liver mitochondrial matrix, a compartment not recognized for its content in palmitoylated proteins, and confirmed the palmitoylation of newly identified mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase. We postulate that covalent modification and perhaps inhibition of various mitochondrial enzymes by palmitoyl-CoA could lead to the metabolic impairments found in obesity-related diseases.
High-Throughput Screening of Surface Marker Expression on Undifferentiated and Differentiated Human Adipose-Derived Stromal Cells (2015)

Adipose tissue contains an abundant source of multipotent mesenchymal cells termed "adipose-derived stromal cells" (ASCs) that hold potential for regenerative medicine. However, the heterogeneity inherent to ASCs harvested using standard methodologies remains largely undefined, particularly in regards to differences across donors. Identifying the subpopulations of ASCs predisposed toward differentiation along distinct lineages holds value for improving graft survival, predictability, and efficiency. Human ASCs (hASCs) from three different donors were independently isolated by density-based centrifugation from adipose tissue and maintained in culture or differentiated along either adipogenic or osteogenic lineages using differentiation media. Undifferentiated and differentiated hASCs were then analyzed for the presence of 242 human surface markers by flow cytometry analysis. By comprehensively characterizing the surface marker profile of undifferentiated hASCs using flow cytometry, we gained novel insights into the heterogeneity underlying protein expression on the surface of cultured undifferentiated hASCs across different donors. Comparison of the surface marker profile of undifferentiated hASCs with hASCs that have undergone osteogenic or adipogenic differentiation allowed for the identification of surface markers that were upregulated and downregulated by osteogenic or adipogenic differentiation. Osteogenic differentiation induced upregulation of CD164 and downregulation of CD49a, CD49b, CD49c, CD49d, CD55, CD58, CD105, and CD166 while adipogenic differentiation induced upregulation of CD36, CD40, CD146, CD164, and CD271 and downregulation of CD49b, CD49c, CD49d, CD71, CD105, and CD166. These results lend support to the notion that hASCs isolated using standard methodologies represent a heterogeneous population and serve as a foundation for future studies seeking to maximize their regenerative potential through fluorescence-activated cell sorting-based selection before therapy.
A Model for Resonance-Assisted Hydrogen Bonding in Crystals and Its Graph Set Analysis (2001)

Resonance-assisted hydrogen bonding is treated by the simple quantum-mechanical model of a particle on a ring with different effective masses in the hydrogen bond and in the conjugated segment attached to its ends. The model is applied to an intramolecular hydrogen bond and extended to a hydrogen-bonded dimer and rings of arbitrary size up to an infinite chain of molecules, thus covering the main patterns of bonding identified by graph-set analysis. Analysis of intramolecular hydrogen bonding yields an electron effective mass in the hydrogen bond segment of about 34 electron masses. Conjugation always lowers the energy, but the lowering per molecule decreases with increasing ring size, that for the chain being one-third of that for the intramolecular hydrogen bond. This result rationalizes a predominance of intramolecular hydrogen bonds and dimer rings, given that geometrical factors also affect bonding.
Persistence of the Entire Epstein-Barr Virus Genome Integrated into Human Lymphocyte DNA (1984)

The entire Epstein-Barr virus genome is integrated into Burkitt tumor cell DNA at the terminal direct repeat sequence of the virus. There is no homology between the GC-rich (G, guanine; C, cytosine) terminal repeat and the AT-rich (A, adenine; T, thymine) cell sequences with which it has recombined. More than 15 kilobases of cell DNA have been deleted and 236 base pairs are duplicated at one virus-cell junction site.
Vascular endothelial growth factor-C (VEGF-C) is a more specific risk factor for lymph node metastasis than VEGF-D in submucosal colorectal cancer. (2007)

These results may suggest that VEGF-C is a more specific risk factor for lymph node metastasis than VEGF-D in submucosal colorectal cancer.
Biological and Clinical Implications of Heat Shock Protein 27000 (Hsp27): a Review (1993)

Heat shock and other environmental and pathophysiologic stresses stimulate synthesis of heat shock proteins (Hsps). These proteins enable the cell to survive and recover from stressful conditions by as yet uncompletely understood mechanisms. Hsp27 is an important small Hsp (molecular weight, 27,000) found in human cells--both cancer cells and normal cells. This protein, besides its putative role in thermotolerance, is of special clinical interest because of recent data suggesting it may also play a role in drug resistance. In adults, Hsp27 is found particularly in several cell types such as breast, uterus, cervix, placenta, skin, and platelets. Although low-molecular-weight (small) Hsps have been found to be involved in embryogenesis of Xenopus and Drosophila, they have not been detected in human fetal organs. Regulation of expression of the Hsp gene (also known as HSPB1) has been considered a paradigm of gene regulation and is actively being studied in both prokaryotes and eukaryotes. In prokaryotes, the major Hsp genes are transcriptionally regulated by positively and negatively acting transcription factors. In eukaryotes, the genes encoding Hsps contain a regulatory DNA motif (inverted repeats of the pentameric sequence nGAAn) known as the heat shock element. Hsp27 may function as a molecular chaperone and in signal transduction pathways of different cell regulators, and Hsp27 and other Hsps may be active in development of resistance to stressful conditions and agents including cytotoxic drugs. Study findings indicate that some but not all estrogen-positive breast cancers express Hsp27, and overexpression of Hsp27 has been associated with both good and poor prognosis. In endometrial carcinomas, the presence of Hsp27 is correlated with the degree of tumor differentiation as well as with the presence of estrogen and progesterone receptors. Studies suggest, however, that detection of Hsp27 should not be considered to be a method for identifying hormone-responsive tumors or detecting estrogen receptors. Hsp27 seems to be a biochemical marker of estrogenic endometrial response. In patients with cervical cancer, Hsp27 is predominantly expressed in well-differentiated and moderately differentiated squamous cell carcinomas. In addition, expression of Hsp27 seems to be a negative prognostic factor for gastric cancer. Different isoforms of Hsp27 have been found in lymphoid tissue of patients with acute lymphoblastic leukemia, and the protein has also been associated with viral infections. These aspects are summarized and discussed in the present review.
Targeting Human Papillomavirus Type 16 E7 to the Endosomal/Lysosomal Compartment Enhances the Antitumor Immunity of DNA Vaccines against Murine Human Papillomavirus Type 16 E7-Expressing Tumors (1999)

DNA vaccination is an attractive approach for tumor immunotherapy because of its stability and simplicity of delivery. Advances demonstrate that helper T cell responses play a critical role in initiating immune responses. The aim of the current study is to test whether targeting HPV-16 E7 to the endosomal/lysosomal compartment can enhance the potency of DNA vaccines. We linked the lysosome-associated membrane protein 1 (LAMP-1) to HPV-E7 to construct a chimeric DNA, Sig/E7/LAMP-1 DNA. For in vivo tumor prevention experiments, mice were vaccinated with E7 DNA or Sig/E7/LAMP-1 DNA via gene gun, followed by tumor challenge. For in vivo tumor regression experiments, mice were first challenged with tumor cells and then vaccinated with E7-DNA or Sig/E7/LAMP-1 DNA. Intracellular cytokine staining with flow cytometry analysis, cytotoxic T lymphocyte (CTL) assays, enzyme-linked immunoabsorbent assay (ELISA), and enzyme-linked immunospot (ELISPOT) assays were used for in vitro E7-specific immunological studies. In both tumor prevention and tumor regression assays, Sig/E7/LAMP-1 DNA generated greater antitumor immunity than did wild-type E7 DNA. In addition, mice vaccinated with Sig/E7/LAMP-1 DNA had greater numbers of E7-specific CD4+ helper T cells, higher E7-specific CTL activity, and greater numbers of CD8+ T cell precursors than did mice vaccinated with Sig/E7 or wild-type E7 DNA. Sig/E7 generated a stronger E7-specific antibody response than did Sig/E7/LAMP-1 or wild-type E7 DNA. Our results indicate that linkage of the antigen gene to an endosomal/lysosomal targeting signal may greatly enhance the potency of DNA vaccines.
Use of Inhaled Insulin in a Basal/Bolus Insulin Regimen in Type 1 Diabetic Subjects (2005)

Inhaled insulin may provide an alternative for the management of type 1 diabetes as part of a basal/bolus strategy in patients who are unwilling or unable to use preprandial insulin injections.
A 2.5Gb/s Burst-Mode CDR based on a 1/8th rate Dual Pulse Ring Oscillator (2007)

A 2.5Gb/s burst-mode CDR uses a 1/8 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">th</sup> rate ring oscillator with two pulses running simultaneously that are phase independent. One pulse sets the delay of the ring by phase locking it to a reference. The other pulse tracks the phase of the incoming data. Phase acquisition is instantaneous from a single data edge. Run length tolerance is greater than 72 bits. The 0.6mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> 0.13μm CMOS chip includes a CML-to-CMOS input buffer, PLL with on-chip loop filter, PRBS checker, 1:8 demux and 8 output buffers. It has 2.7UI <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">PP</sub> jitter tolerance at 100kHz and consumes 42mW from a single 1.2V supply.
Catching a SPY: Using the SpyCatcher-SpyTag and Related Systems for Labeling and Localizing Bacterial Proteins (2019)

The SpyCatcher-SpyTag system was developed seven years ago as a method for protein ligation. It is based on a modified domain from a <i>Streptococcus pyogenes</i> surface protein (SpyCatcher), which recognizes a cognate 13-amino-acid peptide (SpyTag). Upon recognition, the two form a covalent isopeptide bond between the side chains of a lysine in SpyCatcher and an aspartate in SpyTag. This technology has been used, among other applications, to create covalently stabilized multi-protein complexes, for modular vaccine production, and to label proteins (e.g., for microscopy). The SpyTag system is versatile as the tag is a short, unfolded peptide that can be genetically fused to exposed positions in target proteins; similarly, SpyCatcher can be fused to reporter proteins such as GFP, and to epitope or purification tags. Additionally, an orthogonal system called SnoopTag-SnoopCatcher has been developed from an <i>S. pneumoniae</i> pilin that can be combined with SpyCatcher-SpyTag to produce protein fusions with multiple components. Furthermore, tripartite applications have been produced from both systems allowing the fusion of two peptides by a separate, catalytically active protein unit, SpyLigase or SnoopLigase. Here, we review the current state of the SpyCatcher-SpyTag and related technologies, with a particular emphasis on their use in vaccine development and in determining outer membrane protein localization and topology of surface proteins in bacteria.
The Real Facts of Life. c. 1850–1940. By Margaret Jackson. Pp. 206. (Taylor & Francis, London, 1994.) £12.95. (1995)

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Bacteria associated with false-positive most-probable-number coliform test results for shellfish and estuaries (1981)

Aerobic and facultatively anaerobic bacteria isolated from false-positive, presumptive, total coliform, most-probable-number tests of Chesapeake Bay oyster, water, and sediment samples were characterized and then classified by numerical taxonomy. A total of 538 bacterial strains clustered into 17 phena, the predominant groups of which were Enterobacteriaceae (including Escherichia coli), Aeromonas spp., and Bacillus spp. Bacillus spp. were recovered most frequently from sediment samples. Gas-producing strains which were not members of the Enterobacteriaceae were not isolated during this study. However, disproportionately large numbers of atypical and anaerogenic lactose-fermenting strains were encountered. We concluded that no single, specific bacterial group can be identified as being responsible for the false-positive reaction in the presumptive coliform test. Instead, the false-positive reaction is a result of complex interactions among various genera, representing predominantly bacteria other than coliforms.
The transforming growth factor beta receptors types I, II, and III form hetero-oligomeric complexes in the presence of ligand. (1993)

Transforming growth factors beta (TGF-beta s) are disulfide-linked dimers. In Rat-1 cells both radioiodinated TGF-beta 1 and -beta 2 bind to and can be chemically cross-linked to type I and II receptors (which are thought to mediate effects of cell growth suppression and gene activation), to type III proteoglycan receptors, and to a novel approximately 50-kDa protein. After detergent solubilization of cells that were cross-linked with radioiodinated TGF-beta, antibodies specific for the type II receptor precipitated labeled receptor types I and III as well as type II. In these cells, the type III receptor is the predominant TGF-beta-binding protein, and antibodies specific for it precipitate mainly this cross-linked receptor. Thus, in the presence of TGF-beta ligand, receptor types II and III and types II and I form heteromeric complexes. The majority of the type III receptor does not associate with receptor types I and II, probably reflecting the relative amounts of the three receptors on the surface of Rat-1 cells. Since TGF-beta 1 but not TGF-beta 2 binds to the exoplasmic domain of the type II receptor in the absence of the type III receptor, and since both TGF-beta 1 and -beta 2 bind with high affinity to the type III receptor, we suggest that TGF-beta 2, and possibly TGF-beta 1, bind initially to the type III receptor. The TGF-beta 2-type III receptor complex would then interact with a type II receptor, thus modulating the affinity of the type II receptor for TGF-beta 2.
The Importance of Dynamic Effects on the Enzyme Activity (2005)

Onconase (ONC), a member of the RNase A superfamily extracted from oocytes of Rana pipiens, is an effective cancer killer. It is currently used in treatment of various forms of cancer. ONC antitumor properties depend on its ribonucleolytic activity that is low in comparison with other members of the superfamily. The most damaging side effect from Onconase treatment is renal toxicity, which seems to be caused by the unusual stability of the enzyme. Therefore, mutants with reduced thermal stability and/or increased catalytic activity may have significant implications for human cancer chemotherapy. In this context, we have determined the crystal structures of two Onconase mutants (M23L-ONC and C87S,des103-104-ONC) and performed molecular dynamic simulations of ONC and C87S,des103-104-ONC with the aim of explaining on structural grounds the modifications of the activity and thermal stability of the mutants. The results also provide the molecular bases to explain the lower catalytic activity of Onconase compared with RNase A and the unusually high thermal stability of the amphibian enzyme.
Antibody-dependent cellular cytotoxicity-inducing antibodies against human immunodeficiency virus. Presence at different clinical stages. (1987)

The presence of antibodies mediating antibody-dependent cellular cytotoxicity (ADCC) against human immunodeficiency virus (HIV)-infected target cells was investigated with 170 sera from patients with varying severity of HIV infection. Approximately 40% of sera from individuals representing all stages of infection were ADCC-positive when tested against HTLV-IIIB infected 0937 clone 2 target cells. The positive sera had higher HIV antibody titers as measured by enzyme-linked immunosorbent assay compared with ADCC-negative sera. ADCC titers were lower in patients with acquired immune deficiency syndrome than in asymptomatic carriers. This decline in ADCC titer was not correlated with a general decrease of HIV antibodies. No correlation between the CD4:CD8 lymphocyte ratio and ADCC activity was found. The possible beneficial effect of ADCC-inducing antibodies early in infection is discussed in relation to the effect of ADCC-inducing antibodies in other retrovirus systems and to the nature of lentivirus infections.
mRNA as a Versatile Tool for Exogenous Protein Expression (2012)

Several viral and non-viral vectors have been developed for exogenous protein expression in specific cells. Conventionally, this purpose is achieved through the use of recombinant DNA. But mainly due to the risks associated with permanent genetic alteration of cells, safety and ethical concerns have been raised for the use of DNA-based vectors in human clinical therapy. In the last years, synthetic messenger RNA has emerged as powerful tool to deliver genetic information. RNA vectors exhibit several advantages compared to DNA and are particularly interesting for applications that require transient gene expression. RNA stability and translation efficiency can be increased by cis-acting structural elements in the RNA such as the 5'-cap, the poly(A)-tail, untranslated regions and the sequence of the coding region. Here we review recent developments in the optimization of messenger RNA as vector for modulation of protein expression emphasizing on stability, transfection and immunogenicity. In addition, we summarize current pre-clinical and clinical studies using RNA-based vectors for immunotherapy, T cell, stem cell as well as gene therapy.
Gold nanoparticles as assisted matrices for the detection of biomolecules in a high-salt solution through laser desorption/ionization mass spectrometry (2009)

Citrate-capped gold nanoparticles (AuNPs) serve as matrices for the determination of biomolecules in a high-salt solution through matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). In the case of using 2,5-dihydroxybenzoic acid (2,5-DHB) as a matrix, the signal intensities of neutral steroids were severely suppressed in a high-salt solution. A high concentration of NaCl caused the formation of the sodium adduct ions during the desorption/ionization process, resulting in a decrease of the signal intensities of the protonated ions. In comparison, by applying AuNP-assisted LDI-TOF-MS, the signal intensities of neutral steroids remained almost constant when the concentration of NaCl was increased to 500 mM. Because the use of citrate-capped AuNPs as matrices primarily offers alkali metal ion adducts, AuNP matrices have a higher tolerance to high NaCl concentrations relative to that of 2,5-DHB matrices. The relevant phenomena are also discovered in the case of analysis of neutral carbohydrate, monosialoganglioside, indolamine, and angiotensin I. The quantification of small molecules in a high-salt solution has been accomplished by AuNP-assisted LDI-TOF-MS coupled to a unique sample preparation, in which samples are deposited onto the sample plate before AuNPs. The present method has been further applied to the determination of urea, creatinine, uric acid, and glucose in a urine sample.
Cellular tensegrity: defining new rules of biological design that govern the cytoskeleton (1993)

ABSTRACT “…organization exists in the living organism, and this organization is not something fundamentally mystical and unamenable to scientific attack, but rather the basic problem confronting the biologist.” Joseph Needham (Terry Lectures, Yale University, 1936)
Photoinduced superconductivity in YSr(x)Ba(2-x)Cu3O(y) films (1996)

The effects of photoinduced hole doping on YSrxBa2-xCu3Oy thin films are studied. Previously persistent photoinduced conductivity (PPC) and Tc enhancement have been observed in YBa2Cu3Oy with y ＜ 7. We show that these persistent photoinduced effects are absent in YSrxBa2-xCu3Oy films with an oxygen content y ＜ 7 if the oxygen deficiency is caused by Sr doping, not by insufficient oxygenation. However, upon laser illumination, substantial increase of T, and normal state conductivity are observed in YSrxBa2-xCu3Oy films annealed in reduced oxygen pressure. The conductivity decreases and relaxes back to its original values the temperature approaches room temperature during the warm-up process. The relaxation of PPC is much faster than that observed in YBa2Cu3Oy. We attribute these differences to the smaller lattice constants of YSrxBa2-xCu3Oy.
A general class of preconditioners for statistical iterative reconstruction of emission computed tomography (1997)

A major drawback of statistical iterative image reconstruction for emission computed tomography is its high computational cost. The ill-posed nature of tomography leads to slow convergence for standard gradient-based iterative approaches such as the steepest descent or the conjugate gradient algorithm. In this paper new theory and methods for a class of preconditioners are developed for accelerating the convergence rate of iterative reconstruction. To demonstrate the potential of this class of preconditioners, a preconditioned conjugate gradient (PCG) iterative algorithm for weighted least squares reconstruction (WLS) was formulated for emission tomography. Using simulated positron emission tomography (PET) data of the Hoffman brain phantom, it was shown that the convergence rate of the PCG can reduce the number of iterations of the standard conjugate gradient algorithm by a factor of 2-8 times depending on the convergence criterion.