gebhart/patrepeval huggingface dataset:
The many ways to cross the plasma membrane (2001)

The transfer into living cells of macromolecules, which monitor or modify molecule-specific intracellular processes, provides an efficient way to study the temporal and spatial regulation of protein systems that underlie basic cellular functions. Several methods have been developed for this purpose. Each of them has its characteristic advantages and disadvantages with respect to cell viability, transfer efficiency, general applicability, and technical requirements. We discuss current methodologies for the introduction of macromolecules, notably proteins, into cells in light of a new paper by Walev et al. (1) in a recent issue of PNAS in which a new protocol is provided for the reversible permeabilization of cells by using streptolysin-O. The function and interaction of many more novel proteins identified by the genome projects worldwide will have to be analyzed in the future. Therefore, transfer techniques that are easy to use, inexpensive, and suitable for automation such as the one described by Walev et al. (1) will become of superior importance.

Worldwide genomic and cDNA sequencing projects are now identifying new molecules every day. The genomic sequences of the most widely studied species , Saccharomyces cerevisiae, Caenorhabditis elegans , and Drosophila melanogaster , have recently been completed. The full genomic sequence of Homo sapiens will become available soon. An enormous task, and a great challenge, will now be to relate these sequences to functional data that may subsequently open new avenues of research toward the cure of diseases. Together with the methodological progress made in the past two decades in expressing and manipulating cloned genes in the test tube, these sequence data provide us with the necessary molecular tools to understand the connectivity and spatial organization of protein systems in their native environment, the living cell.

Common strategies in modern cell and molecular biology, which aim toward the identification of the role …
Silica Nanoparticle Architecture Determines Radiative Properties of Encapsulated Fluorophores (2008)

Silica nanoparticles with embedded fluorescent molecules are used in a variety of applications requiring the observation of single nanoprobes. We describe a class of fluorescent, core–shell silica nanoparticles with a radius of ∼15 nm, narrow particle size distribution, and controlled internal architecture. Particles covalently encapsulating multiple rhodamine molecules are over 20 times brighter than the single dye molecule in water. The photophysical behavior of rhodamine can be manipulated by small changes in the internal architecture of particles with otherwise similar composition, leading to 3-fold enhancement of quantum efficiency per dye with no observable energy transfer between neighboring dyes. This enhancement of quantum efficiency per dye is due to a uniform 2-fold enhancement in radiative rate and a variable reduction in nonradiative rate which varies inversely with the degree of rotational mobility of the dye allowed by the particle architecture. These results demonstrate a practical method for synthesizing highly fluorescent silica nanoparticles and an effective methodology for selectively modifying the photophysical properties of fluorophores.
Interleukin-6 induces hepcidin expression through STAT3 (2006)

Iron homeostasis is maintained through meticulous regulation of circulating hepcidin levels. Hepcidin levels that are inappropriately low or high result in iron overload or iron deficiency, respectively. Although hypoxia, erythroid demand, iron, and inflammation are all known to influence hepcidin expression, the mechanisms responsible are not well defined. In this report we show that the inflammatory cytokine interleukin-6 (IL-6) directly regulates hepcidin through induction and subsequent promoter binding of signal transducer and activator of transcription 3 (STAT3). STAT3 is necessary and sufficient for the IL-6 responsiveness of the hepcidin promoter. Our findings provide a mechanism by which hepcidin can be regulated by inflammation or, in the absence of inflammatory stimuli, by alternative mechanisms leading to STAT3 activation.
Construction of a representative cDNA library from prostatic intraepithelial neoplasia. (1996)

We report the construction of a plasmid-based cDNA library made from microdissected cells derived from prostatic intraepithelial neoplasia. Total RNA was extracted and converted to blunt-ended, double-stranded cDNA by oligo(dT)-mediated reverse transcription followed by linker addition. A linker-specific primer with UDG-compatible ends was used to amplify the cDNA and the resulting PCR product was subcloned. A total of 154 clones were sequenced and results indicated that 81.5% of the clones derived from either known genes, anonymous expressed sequence tags, or novel transcripts with very little redundancy of screened clones. These results demonstrate the feasibility of constructing complex representative cDNA libraries from specific microdissected cell populations that represent microscopic precursor stages of cancer progression. This method should facilitate identification of transcripts specifically expressed in cells of a distinct histological origin and tumorigenic stage.
Superoxide Protonation by Weak Acids in Imidazolium Based Ionic Liquids (2009)

The reactivity of the superoxide anion versus a series of substituted phenols was investigated in a common ionic liquid, 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([BMIm][TFSI]) and for comparison in dimethylformamide (+0.1 mol·L−1 of Bu4NPF6 as supporting electrolyte). On the whole, the mechanism of the reduction of O2 in the presence of the different phenols was found to be very similar in [BMIm][TFSI] and in DMF: A 2-electron mechanism involving a succession of electrochemical and protonation steps. These steps are accompanied by the production of the corresponding phenolate that was identified through its oxidation potential. The reactivities of the phenols were observed to slightly differ in the two media. A qualitative analysis of the voltammogram allows a classification of the reactivities of the superoxide as a function of the phenols. As previously found in organic solvents, the protonation of superoxide by phenol is an uphill reaction that is rendered possible thanks to a subsequent irreversible electron transfer. Its pKa is estimated to be around 4−5 units lower than that of unsubstituted phenol.
Transforming growth factor beta induces anchorage-independent growth of NRK fibroblasts via a connective tissue growth factor-dependent signaling pathway. (1997)

Connective tissue growth factor (CTGF) is a M(r)38,000 cysteine-rich peptide, the synthesis and secretion of which are selectively induced by transforming growth factor beta (TGF-beta). The relationship of CTGF to TGF-beta action on fibroblastic cells is not well understood. TGF-beta has the unique ability to stimulate the growth of normal fibroblasts in soft agar, a property of transformed cells. We have investigated whether CTGF can substitute for TGF-beta or whether CTGF action is essential for TGF-beta to stimulate anchorage-independent growth (AIG) of NRK fibroblasts. Our studies demonstrate that CTGF cannot induce AIG of NRK fibroblasts. However, CTGF synthesis and action are essential for the TGF-beta-induced AIG of NRK fibroblasts. Anti-CTGF antibodies specifically block TGF-beta-induced AIG but have no effect on platelet-derived growth factor or epidermal growth factor-induced growth in monolayer cultures and do not cross-react with platelet-derived growth factor or TGF-beta. Clones of NRK fibroblasts that express an antisense CTGF gene (NRK-ASCTGF), which blocks the expression of the endogenous CTGF gene, do not respond to TGF-beta in the AIG assay. The growth and morphology of the cells (NRK-ASCTGF) in monolayer culture are unaltered from the parent NRK cell line. The addition of recombinant CTGF to the NRK-ASCTGF clones in the presence of TGF-beta restores the AIG response of the cells. These studies demonstrate that the TGF-beta stimulation of NRK fibroblast AIG is dependent on events induced via the synergistic action of CTGF-dependent and CTGF-independent signaling pathways.
Chronic experimental myocardial infarction produces antinatriuresis by a renal nerve-dependent mechanism (2004)

The present study focused on the role of sympathetic renal nerve activity, in mediating congestive heart failure-induced sodium retention following experimental chronic myocardial infarction. Groups of male Wistar rats (240-260 g) were studied: sham-operated coronary ligation (CON3W, N = 11), coronary ligation and sham-operated renal denervation (INF3W, N = 19), 3 weeks of coronary ligation and sympathetic renal nerve denervation (INF3WDX, N = 6), sham-operated coronary ligation (N = 7), and 16 weeks of coronary ligation (INF16W, N = 7). An acute experimental protocol was used in which the volume overload (VO; 5% of body weight) was applied for 30 min after the equilibration period of continuous iv infusion of saline. Compared to control levels, VO produced an increase (P < 0.01, ANOVA) in urine flow rate (UFR; 570%) and urinary sodium excretion (USE; 1117%) in CON3W. VO induced a smaller increase (P < 0.01) in USE (684%) in INF3W. A similar response was also observed in INF16W. In INF3WDX, VO produced an immediate and large increase (P < 0.01) in UFR (547%) and USE (1211%). Similarly, in INF3W VO increased (P < 0.01) UFR (394%) and USE (894%). Compared with INF3W, VO induced a higher (P < 0.01) USE in INF3WDX, whose values were similar to those for CON3W. These results suggest that renal sympathetic activity may be involved in sodium retention induced by congestive heart failure. This premise is supported by the observation that in bilaterally renal denervated INF3WDX rats myocardial infarction was unable to reduce volume expansion-induced natriuresis. However, the mechanism involved in urinary volume regulation seems to be insensitive to the factors that alter natriuresis.
Novel HIF2A mutations disrupt oxygen sensing, leading to polycythemia, paragangliomas, and somatostatinomas (2013)

Hypoxia-inducible factors (HIFs) control the cellular response to hypoxia and, when dysregulated, contribute to tumorigenesis. Previously, we identified 2 gain-of-function somatic mutations in patients presenting with multiple paragangliomas or somatostatinomas, and polycythemia. Here, we report 2 additional unique HIF2A mutations, which disrupt the hydroxylation domain recognized by prolyl hydroxylase domain-2 containing protein, leading to stabilization of HIF-2α and increased expression of hypoxia-related genes.
Convenient Synthesis of 2‐Arylbenzimidazoles and 2,2′‐Diaryl‐bisbenzimidazoles. (2003)

Abstract For Abstract see ChemInform Abstract in Full Text.
Thermal Analysis Study of the Growth Kinetics of Carbon Nanotubes and Epitaxial Graphene Layers on Them (2009)

With the aim of improving the yield and purity of carbon nanotubes (CNTs), we have studied the chemical vapor deposition (CVD) growth of CNTs with Fe−Mo powder catalyst and acetylene precursor by using the technique of in situ simultaneous thermal analysis (STA). We could distinguish this way the rapid catalytic growth stage of CNTs and the slow epitaxial growth stage of graphitic impurities on the nanotubes, which were discovered to be graphene layers. Both reactions were first order, and the activation energies were determined to be 177 and 189 kJ/mol, respectively. In the rapid-growth stage, the growth of CNTs could be further tuned from kinetically controlled regime to gas-diffusion-controlled regime, where the CNTs exhibit a longer growth time and a higher yield, using appropriately shaped crucibles. These results are helpful for both elucidating the growth mechanism of CNTs and improving the quality of mass-produced CNTs.
A Structural Correlation Between Lentivirus Transmembrane Proteins and Natural Cytolytic Peptides (1991)

Although oncoviruses and lentiviruses replicate by similar mechanisms, they differ fundamentally in the usual fate of the infected host cell during productive natural infections. Oncoviruses typically establish persistent nonlytic infections in natural host cells, while lentivirus infections characteristically result in a variety of cytopathic effects ultimately leading to death of the target cell. Described here is a unique structural motif consisting of a strongly amphipathic and arginine-rich helical peptide segment in the carboxyl end of lentivirus TM proteins that is structurally similar to the family of cytolytic peptides produced as defensive agents by certain insects and amphibians. Also demonstrated is the lytic nature of synthetic peptides constructed from the transmembrane (TM) protein of human and simian immunodeficiency viruses (HIV and SIV). Thus, it appears that the cytopathic properties of lentiviruses may be in part attributed to the presence of lytic peptides within the TM protein, designated lentivirus lytic peptide (LLP) and that variations in this segment could account for some of the differences observed in the cytopathicity among variants of a particular lentivirus.
Organ‐specific autoantigens induce transforming growth factor‐β mRNA expression in mononuclear cells in multiple sclerosis and myasthenia gravis (1994)

Multiple sclerosis (MS) is characterized by patchy accumulations of inflammatory cells combined with demyelination. There are mononuclear cells in blood and cerebrospinal fluid of patients with MS that produce interferon-gamma and interleukin-4 in response to myelin basic protein (MBP) and proteolipid protein (PLP). Here we describe autoantigen-induced production of transforming growth factor-beta (TGF-beta). This multifunctional cytokine has inhibitory effects on the growth, differentiation, and effector functions of activated T cells. Blood and cerebrospinal fluid cells were exposed in short-term cultures to MBP and PLP and, after hybridization with complementary DNA oligonucleotide probes, they were evaluated for TGF-beta mRNA expression. Patients with MS had higher numbers of MBP- and PLP-responsive TGF-beta mRNA expressing cells in blood compared with control patients with other neurological diseases or myasthenia gravis and a five- and threefold further increment in their cerebrospinal fluid. In blood of patients with myasthenia gravis, where the acetylcholine receptor (AChR) is a target for autoaggressive immunity, there were increased levels of AChR-responsive TGF-beta mRNA expressing cells. Thymectomized myasthenia gravis patients showed higher levels of TGF-beta mRNA expressing cells compared with patients not thymectomized. Numbers of cells responding to AChR in MS and MBP in myasthenia gravis did not differ from numbers found in absence of antigen. Patients with other neurological diseases showed infrequent and low responses to MBP, PLP, and AChR. Diseases with presumed autoimmune pathogenesis are associated with organ-specific autoantigen-induced TGF-beta production, which is increased after thymectomy.
Effects of ribosome inactivating proteins on insect development – differences between Lepidoptera and Coleoptera (1990)

Abstract Ricin and saporin represent two different classes of ribosome inactivating proteins (RIPs), or cytotoxins, present in plant seeds. The toxicity of these substances to several eukaryotic organisms is widely known, as is their intracellular mode of inhibitory action on the ribosomes. However virtually nothing is known of the effects of these substances on insects. In this paper we report on systematic studies which indicate that RIPs can be extremely toxic to insects although the effects are variable with different insect orders. Specifically, two Coleopteran species were extremely susceptible to the effects of both RIP's with average LD 50 values of less than 10 −2 % (dry weight). The studies also indicate that resistance to the toxic effects, exhibited by Lepidopteran insects, may be due in part to the protease complements of the insect guts which are capable of hydrolysing the RIPs, thus eliminating them before they are absorbed and can exert their effects within the insects cells. Résumé Influence de deux protéines inactivant les ribosomes sur le développement des insectes: différences entre lépidoptères et coléoptères La ricine et la saporine des graines de plantes représentent deux classes différentes de protéines inactivant les ribosomes (RIPs), ou cytotoxines. La toxicité de ces substances pour plusieurs eucaryotes est bien connue, de même que le processus intracellulaire de leur activité inhibitrice des ribosomes. Cependant, on ne connaît pratiquement rien de leurs effets sur les insectes. Dans cet article, nour relatons des travaux systématiques qui montrent que les RIPs peuvent être extrêmement toxiques pour les insectes, bien que leurs effets varient suivant les ordres d'insectes. Particulièrement, deux espèces de coléoptères sont extrêmement sensibles aux effets des deux RIPs avec des DL 50 inférieures à 10 −2 % du poids sec. Ces travaux indiquent aussi que la résistance des lépidoptères à ces effets toxiques peut être due en partie à la présence dans leur intestin de protéases susceptibles d'hydrolyser les RIPs, et de les éliminer ainsi avant leur absorption et avant qu'elles ne puissent exercer leurs effets dans les cellules des insectes.
Active and inactive conformations of the epidermal growth factor receptor (2004)

The members of the EGFR (epidermal growth factor receptor) family of RTKs (receptor tyrosine kinases), also known as the ErbB or HER family, have been implicated in many human cancers. Structural studies of the EGFR extracellular region (sEGFR) have led to the proposal of a novel mechanism for ligand-induced receptor dimerization. In this model EGF binding induces a dramatic conformational change in EGFR, exposing a dimerization site that is normally occluded in the inactivated conformation, and thus promoting the formation of an entirely receptor-mediated dimer. It is well established that antibodies against the extracellular region of EGFR that prevent ligand binding and/or receptor signalling can inhibit tumour growth in vivo. At least five such anti-EGFR antibodies are currently in clinical trials and one, C225/cetuximab (Erbitux), was recently approved in the U.S. and Europe for use in advanced colorectal cancers. Recent structural studies of ErbB2 in complex with anti-ErbB2 antibodies (trastuzumab/Herceptin and pertuzumab/Omnitarg) have provided significant insights into how these drugs function. There have been no such studies for similar EGFR-targeted drugs to date. The implications of this model for the possible mechanisms of antibody-mediated inhibition of EGFR are discussed.
Therapeutic developments in multiple sclerosis (2000)

Recently there have been considerable advances made in the treatment of multiple sclerosis. For the first time since its initial clinical description in the 1800s, there are now available several medications which unequivocally exert favourable clinical effects through the lowering of the biological activity of the human illness. The therapeutic efficacy of IFN-beta preparations seems particularly well established in this regard on the basis of five large, independent, trials of this agent. These trials have demonstrated remarkably consistent reductions in both attack rates and disability levels using a combination of clinical and magnetic resonance imaging outcome measures. The therapeutic benefit of glatiramer acetate also has been well established, although there is less available data on this agent than there is for interferon. It is important to recognise, however, that, although these agents represent an important first step in the management of patients with multiple sclerosis, they are only partial therapies. In order to actually cure the illness or even to substantially improve patient outcome we need considerably better agents than we have currently. Nevertheless, it is likely that, with improved knowledge of the role that interferon beta plays in the pathogenesis of multiple sclerosis and with better understanding of the mechanism by which glatiramer acetate exerts its therapeutic effect, greatly improved therapeutic agents will be available in the future. In addition, it seems likely that, in the future (by analogy to the experience in oncology), we will begin utilising combinations of therapies in order to better control the biological activity of this debilitating disease. Such combination therapy will almost certainly include combinations of partially effective agents as well as combinations of these agents with other medications (e.g., the immunosuppressive drugs) which, by themselves, have only been demonstrated to exert marginal clinical benefits on the course of illness. Moreover, it also seems likely that, increasingly, therapeutic strategies that enhance or promote myelin repair will become a major focus of clinical research in this area.
Requirements for the Assembly and Release of Newcastle Disease Virus-Like Particles (2006)

Paramyxoviruses, such as Newcastle disease virus (NDV), assemble in and bud from plasma membranes of infected cells. To explore the role of each of the NDV structural proteins in virion assembly and release, virus-like particles (VLPs) released from avian cells expressing all possible combinations of the nucleoprotein (NP), membrane or matrix protein (M), an uncleaved fusion protein (F-K115Q), and hemagglutinin-neuraminidase (HN) protein were characterized for densities, protein content, and efficiencies of release. Coexpression of all four proteins resulted in the release of VLPs with densities and efficiencies of release (1.18 to 1.16 g/cm(3) and 83.8% +/- 1.1%, respectively) similar to those of authentic virions. Expression of M protein alone, but not NP, F-K115Q, or HN protein individually, resulted in efficient VLP release, and expression of all different combinations of proteins in the absence of M protein did not result in particle release. Expression of any combination of proteins that included M protein yielded VLPs, although with different densities and efficiencies of release. To address the roles of NP, F, and HN proteins in VLP assembly, the interactions of proteins in VLPs formed with different combinations of viral proteins were characterized by coimmunoprecipitation. The colocalization of M protein with cell surface F and HN proteins in cells expressing all combinations of viral proteins was characterized. Taken together, the results show that M protein is necessary and sufficient for NDV budding. Furthermore, they suggest that M-HN and M-NP interactions are responsible for incorporation of HN and NP proteins into VLPs and that F protein is incorporated indirectly due to interactions with NP and HN protein.
Purines. X. Reactivities of Methyl Groups on 9-Phenylpurines: Condensation with an Aldehyde or an Ester, and Oxidation with Selenium Dioxide. (1992)

The condensation of a methyl group at the 6- of 8-position on the 9H-purine ring with benzaldehyde and ethyl benzoate in the presence of sodium hydride occurred to give the styryl- (4a, b) and phenacyl-9H-purines (5a, b and 6a, b). Conversion of the metyl group into a formyl group was achieved by treatment with selenium dioxide in dioxane, giving the 9H-purinecarboxaldehydes (7a, b and 8a, b).