gebhart/patrepeval huggingface dataset:
Resolving voltage-dependent structural changes of a membrane photoreceptor by surface-enhanced IR difference spectroscopy (2008)

Membrane proteins are molecular machines that transport ions, solutes, or information across the cell membrane. Electrophysiological techniques have unraveled many functional aspects of ion channels but suffer from the lack of structural sensitivity. Here, we present spectroelectrochemical data on vibrational changes of membrane proteins derived from a single monolayer. For the seven-helical transmembrane protein sensory rhodopsin II, structural changes of the protein backbone and the retinal cofactor as well as single ion transfer events are resolved by surface-enhanced IR difference absorption spectroscopy (SEIDAS). Angular changes of bonds versus the membrane normal have been determined because SEIDAS monitors only those vibrations whose dipole moment are oriented perpendicular to the solid surface. The application of negative membrane potentials (DeltaV = -0.3 V) leads to the selective halt of the light-induced proton transfer at the stage of D75, the counter ion of the retinal Schiff base. It is inferred that the voltage raises the energy barrier of this particular proton-transfer reaction, rendering the energy deposited in the retinal by light excitation insufficient for charge transfer to occur. The other structural rearrangements that accompany light-induced activity of the membrane protein, are essentially unaffected by the transmembrane electric field. Our results demonstrate that SEIDAS is a generic approach to study processes that depend on the membrane potential, like those in voltage-gated ion channels and transporters, to elucidate the mechanism of ion transfer with unprecedented spatial sensitivity and temporal resolution.
Phylogenetic associations of human and simian T-cell leukemia/lymphotropic virus type I strains: evidence for interspecies transmission (1994)

Homologous env sequences from 17 human T-leukemia/lymphotropic virus type I (HTLV-I) strains from throughout the world and from 25 simian T-leukemia/lymphotropic virus type I (STLV-I) strains from 12 simian species in Asia and Africa were analyzed in a phylogenetic context as an approach to resolving the natural history of these related retroviruses. STLV-I exhibited greater overall sequence variation between strains (1 to 18% compared with 0 to 9% for HTLV-I), supporting the simian origin of the modern viruses in all species. Three HTLV-I phylogenetic clusters or clades (cosmopolitan, Zaire, and Melanesia) were resolved with phenetic, parsimony, and likelihood analytical procedures. Seven phylogenetic clusters of STLV-I were resolved with the most primitive (deeply rooted) divergence involving several STLV-I strains from Asian primate species. Combined analysis of HTLV-I and STLV-I revealed that neither STLV-I clusters nor HTLV-I clusters recapitulated host species specificity; rather, multiple clades from the same species were closer to clades from other species than to each other. We interpret these evolutionary associations as support for the occurrence of multiple discrete interspecies transmissions of ancestral viruses between primate species (including human) that led to recognizable phylogenetic clades that persist in modern species. Geographic concordance of divergent host species that harbor closely related viruses reinforces that physical feasibility for hypothesized interspecies virus transmission in the past and in the present.
Markedly Decreased Oxygen Tension in Transplanted Rat Pancreatic Islets Irrespective of the Implantation Site (2001)

In this study, we syngeneically transplanted islets to three different implantation sites of diabetic and nondiabetic rats, then 9-12 weeks later we measured the blood perfusion and compared the tissue partial pressure of oxygen (PO2) levels of these transplanted islets to endogenous islets. Modified Clark microelectrodes (outer tip diameter 2-6 microm) were used for the oxygen tension measurements, and islet transplant blood perfusion was recorded by laser-Doppler flowmetry (probe diameter 0.45 mm). The islet graft blood perfusion was similar in all islet grafts, irrespective of the implantation site. In comparison, the three implantation organs (the kidney cortex, liver, and spleen) differed markedly in their blood perfusion. There were no differences in islet graft blood perfusion between diabetic and nondiabetic recipients. Within native pancreatic islets, the mean PO2 was approximately 40 mmHg; however, all transplanted islets had a mean PO2 of approximately 5 mmHg. The oxygen tension of the grafts did not differ among the implantation sites. In diabetic recipients, an even lower PO2 level was recorded in the islet transplants. We conclude that the choice of implantation site seems less important than intrinsic properties of the transplanted islets with regard to the degree of revascularization and concomitant blood perfusion. Furthermore, the mean PO2 level in islets implanted to the kidney, liver, and spleen was markedly decreased at all three implantation sites when compared with native islets, especially in diabetic recipients. These results are suggestive of an insufficient oxygenization of revascularized transplanted islets, irrespective of the implantation site.
Tumoricidal activity of human monocytes activated in vitro by free and liposome-encapsulated human lymphokines. (1983)

Human peripheral blood mononuclear cells from normal donors obtained by separation on a Percoll gradient were incubated with free or liposome-entrapped lymphokines produced from concanavalin A-stimulated lymphocytes and then were tested for cytotoxic activity against tumor cells. The treated monocytes lysed tumorigenic melanoma and glioblastoma target cells, but had no effect on three types of nontumorigenic target cells. The activation of monocytes to become tumoricidal was caused by macrophage-activating factor (MAF) and not by contamination with endotoxins, concanavalin A, or interferon. The endocytosis of liposomes containing MAF, but not of those containing control supernatants, led to the activation of cytotoxic properties in the monocytes. Activation by liposome-encapsulated MAF was very efficient and required less than 1/800th of the amount of free MAF necessary to achieve the same levels of cytotoxicity. Thus, the encapsulation of mitogen-induced MAF in liposomes could provide an effective approach for the activation of blood monocytes in situ.
Industrial Microorganisms : Basic and Applied Molecular Genetics (1993)

Morphological and Physiological Differentiation in Streptomyces coelicolor Global Regulatory Mechanisms Gene Transfer and Mapping Regulation of Transcription and Translation Emerging Microbial Systems Genetics of Secondary Metabolite Biosynthesis I Heterologous Gene Expression and Secretion Genetics of Secondary Metabolite Biosynthesis II
An expedient and high-yielding method for the solid-phase synthesis of diverse 1,4-benzodiazepine-2,5-diones (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAn expedient and high-yielding method for the solid-phase synthesis of diverse 1,4-benzodiazepine-2,5-dionesConstantine G. Boojamra, Kristina M. Burow, and Jonathan A. EllmanCite this: J. Org. Chem. 1995, 60, 18, 5742–5743Publication Date (Print):September 1, 1995Publication History Published online1 May 2002Published inissue 1 September 1995https://pubs.acs.org/doi/10.1021/jo00123a001https://doi.org/10.1021/jo00123a001research-articleACS PublicationsRequest reuse permissionsArticle Views517Altmetric-Citations132LEARN 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-AlertscloseSupporting Info (2)»Supporting Information Supporting Information Get e-Alerts
Neonatal gene transfer leads to widespread correction of pathology in a murine model of lysosomal storage disease (1999)

For many inborn errors of metabolism, early treatment is critical to prevent long-term developmental sequelae. We have used a gene-therapy approach to demonstrate this concept in a murine model of mucopolysaccharidosis type VII (MPS VII). Newborn MPS VII mice received a single intravenous injection with 5.4 x 10(6) infectious units of recombinant adeno-associated virus encoding the human beta-glucuronidase (GUSB) cDNA. Therapeutic levels of GUSB expression were achieved by 1 week of age in liver, heart, lung, spleen, kidney, brain, and retina. GUSB expression persisted in most organs for the 16-week duration of the study at levels sufficient to either reduce or prevent completely lysosomal storage. Of particular significance, neurons, microglia, and meninges of the central nervous system were virtually cleared of disease. In addition, neonatal treatment of MPS VII mice provided access to the central nervous system via an intravenous route, avoiding a more invasive procedure later in life. These data suggest that gene transfer mediated by adeno-associated virus can achieve therapeutically relevant levels of enzyme very early in life and that the rapid growth and differentiation of tissues does not limit long-term expression.
The Gene for High Bone Mass (2002)

The mass, density, and architecture of the skeleton are adapted to enable it to perform its mechanical, protective, and metabolic functions. Osteoporosis is a condition of lost adaptation characterized by decreased skeletal mass and density and increased skeletal fragility. Many diseases result in increased bone density, including osteopetrosis and Paget’s disease, but deformities or bony lesions with decreased skeletal integrity usually accompany these conditions. We have identified a kindred with high bone mass (HBM) yet normally shaped bones. Linkage analysis localized the gene for the HBM trait to chromosome 11 (11q12–13). Subsequent physical mapping and mutation analysis have identified the cause as a point mutation in the LDL receptor-related protein 5 (Lrp5) gene that results in a valine substitution for glycine at position 171 in the protein. This protein is important in the Wnt signaling pathway. The authors have hypothesized that the Lrp5 gene/pathway is part of the mechanism by which bone senses mechanical load. Increased bone strength, HBM, and a phenotype resembling our human kindred develop in transgenic mice carrying the human Lrp5 gene with the HBM mutation. Recent data indicate that the HBM mutation reduces the threshold for response of the skeleton to mechanical load resulting in an overadaptation to normal mechanical loads. This discovery has opened the door to understanding one of the most important paradigms in bone biology, how bones respond and adapt to mechanical loading. Understanding the mechanosensation path-way and its regulation will lead us to new treatments for osteoporosis.
Frequency Specific Modulation of Human Somatosensory Cortex (2011)

Oscillatory neuronal activities are commonly observed in response to sensory stimulation. However, their functional roles are still the subject of debate. One-way to probe the roles of oscillatory neural activities is to deliver alternating current to the cortex at biologically relevant frequencies and examine whether such stimulation influences perception and cognition. In this study, we tested whether transcranial alternating current stimulation (tACS) over the primary somatosensory cortex (SI) could elicit tactile sensations in humans in a frequency-dependent manner. We tested the effectiveness of tACS over SI at frequency bands ranging from 2 to 70 Hz. Our results show that stimulation in alpha (10-14 Hz) and high gamma (52-70 Hz) frequency range produces a tactile sensation in the contralateral hand. A weaker effect was also observed for beta (16-20 Hz) stimulation. These findings highlight the frequency dependency of effective tACS over SI with the effective frequencies corresponding to those observed in previous electroencephalography/magnetoencephalography studies of tactile perception. Our present study suggests that tACS could be used as a powerful online stimulation technique to reveal the causal roles of oscillatory brain activities.
Electric-Field-Driven Fluid Flow Around Nano Particles (2004)

Recently there has been significant progress in assembling an array of individual carbon nanotubes (CNTs) on microfabricated electrodes using the Composite Electric-field Guided Assembly (CEGA) method. This technology allows for integrating individual nano components with micro/nano systems, and should find application in areas such as sensors and NEMS devices. For realizing this as a viable technology, it is crucial to understand the electric-field-driven flow around the nanostructures being deposited. We previously discovered that the flow patterns that are present can lead to deposition of a periodic array CNTs. Here, we present recent experimental observations and the results of modeling/simulation on the electric-field-driven flow around CNTs. The results suggest that this method of assembling nanostructures be used for integration with an accuracy approaching tens of nanometers.
Stem cell factor, interleukin-3, and interleukin-6 promote retroviral- mediated gene transfer into murine hematopoietic stem cells (1992)

The efficiency of retroviral-mediated gene transfer into hematopoietic stem cells (HSC) is dependent on the survival and self-renewal of HSC in vitro during retroviral infection. We have examined the effect of prestimulation of bone marrow with various cytokines, including the product of the Steel gene, Steel factor or stem cell factor (SCF) (the ligand for the c-kit receptor) on the efficiency of retroviral transduction of the human adenosine deaminase (hADA) cDNA into murine HSC. Bone marrow cells were prestimulated for 48 hours with hematopoietic growth factors, then cocultivated with the packaging cell line producing the ZipPGK-ADA simplified retrovirus for an additional 48 hours with continued growth factor exposure. Nonadherant cells from these cocultures were injected into lethally irradiated recipients. The content of day 12 colony-forming unit-spleen (CFU-S12) in SCF/interleukin 6 (IL-6)-prestimulated and cocultured bone marrow was more than threefold greater than that of IL-3/IL-6-prestimulated bone marrow cells. All mice receiving bone marrow cells infected with the PGK-ADA virus after prestimulation with IL-3/IL-6 or SCF/IL-6 demonstrated hADA expression in the peripheral blood after full hematopoietic reconstitution. While all recipients of IL-3/IL-6-prestimulated bone marrow expressed hADA at 4 months posttransplant, in three independent experiments examining a total of 33 mice, in most recipients of SCF/IL-6-prestimulated and infected bone marrow cells, the expression of human enzyme was higher than IL-3/IL-6 mice. Southern blot analysis of DNA from hematopoietic tissues from these same mice prepared at least 4 months posttransplantation also demonstrated a higher infection efficiency of HSC as measured by proviral integration patterns and genome copy number analysis. These results suggest that the higher level of hADA expression seen in mice receiving marrow prestimulated with SCF/IL-6 before retroviral infection is due to more efficient infection of reconstituting HSC. Other growth factor combinations were also studied; however, prestimulation with SCF/IL-6 or IL-3/IL-6 appeared optimal. Using retroviral-mediated gene transfer and viral integration patterns, Steel factor (SCF) in combination with IL-6 appears to increase the survival and self-renewal of reconstituting hematopoietic stem cells and proves useful in effecting expression of foreign genes in transplant recipients. Such pretreatment may also be useful in the application of retroviral transfer methods to human cells.
p53 Basic C Terminus Regulates p53 Functions through DNA Binding Modulation of Subset of Target Genes (2012)

The p53 gene encodes a transcription factor that is composed of several functional domains: the N-terminal transactivation domain, the central sequence-specific DNA binding domain, the tetramerization domain, and the highly basic C-terminal regulatory domain (CTD). The p53 CTD is a nonspecific DNA binding domain that is subject to extensive post-translational modifications. However, the functional significance of the p53 CTD remains unclear. The role of this domain in the regulation of p53 functions is explored by comparing the activity of ectopically expressed wild-type (WT) p53 protein to that of a truncated mutant lacking the 24 terminal amino acids (Δ24). Using quantitative real time PCR and chromatin Immuno-Precipitation experiments, a p53 CTD deletion is shown to alter the p53-dependent induction of a subset of its target genes due to impaired specific DNA binding. Moreover, p53-induced growth arrest and apoptosis both require an intact p53 CTD. These data indicate that the p53 CTD is a positive regulator of p53 tumor suppressor functions.
Phage Display Libraries as a Source of Tumour-Targeting Agents (2001)

One way to improve the therapeutic index of anti-cancer agents would be to target them to the tumour site, thereby sparing normal tissues. Tumour targeting approaches heavily rely on the availability of specific binding molecules, recognising markers which are selectively expressed in the tumour environment. The display of antibody repertoires on the surface of filamentous phage, together with efficient selection-amplification schemes, allows the isolation of good-quality human antibodies against virtually any molecular target. This article illustrates how antibody phage technology has been used in our laboratory for the isolation of tumour targeting agents. Furthermore, we present recent developments in the display of repertoires of small globular proteins on filamentous phage, aimed at the isolation of specific binding molecules with molecular weight &lt; 10000 Dalton.
Design of a novel class of protein‐based magnetic resonance imaging contrast agents for the molecular imaging of cancer biomarkers (2013)

Magnetic resonance imaging (MRI) of disease biomarkers, especially cancer biomarkers, could potentially improve our understanding of the disease and drug activity during preclinical and clinical drug treatment and patient stratification. MRI contrast agents with high relaxivity and targeting capability to tumor biomarkers are highly required. Extensive work has been done to develop MRI contrast agents. However, only a few limited literatures report that protein residues can function as ligands to bind Gd(3+) with high binding affinity, selectivity, and relaxivity. In this paper, we focus on reporting our current progress on designing a novel class of protein-based Gd(3+) MRI contrast agents (ProCAs) equipped with several desirable capabilities for in vivo application of MRI of tumor biomarkers. We will first discuss our strategy for improving the relaxivity by a novel protein-based design. We then discuss the effect of increased relaxivity of ProCAs on improving the detection limits for MRI contrast agent, especially for in vivo application. We will further report our efforts to improve in vivo imaging capability and our achievement in molecular imaging of cancer biomarkers with potential preclinical and clinical applications.
Bone grafting: Role of histocompatibility in transplantation (1985)

Abstract The role of histocompatibility matching in bone allografting was studied in two canine bone graft models. In a cancellous ulnar segmental replacement model, frozen bone allografts exchanged between closely matched dogs were significantly better incorporated by radiographic and histologic criteria than were strongly incompatible grafts. Frozen allograts from disparate donors in recipients receiving immunosuppression appeared indistinguishable 6 months later from those in the untreated closely matched groups and from fresh autografts. Fresh vascularized orthotopically placed fibular bone grafts were evaluated by quantitative blood flow assessment, microangiography, and fluorochrome histomorphometry. Revascularized grafts exchanged between untreated closely matched dogs demonstrated preservation of blood flow and a pattern of repair that was delayed by not otherwise different than vascularized autografts. These results suggest that fresh vascularized grafts in the Judiciously matched or immunosuppressed recipient offer attractive clinical possibilities.
Hypermutagenesis of RNA using human immunodeficiency virus type 1 reverse transcriptase and biased dNTP concentrations. (1994)

The finding of G-->A hypermutated retroviral genomes in which up to 40% of guanines may be substituted by adenines was proposed to result from the depletion of the intracellular dCTP concentration and suggested a means to hypermutagenize nucleic acids. Using a RNA/reverse transcriptase ratio of approximately 1:30, comparable to that within the retroviral replication complex, G-->A hypermutants were produced in a simple in vitro reaction using highly biased dNTP concentrations--i.e., a low ratio of [dCTP]/[dTTP]. Up to 38% of G residues could be substituted, the proportion being inversely proportional to the concentration of dCTP. As G-->A hypermutation resulted from elongation beyond multiple rG.dT mismatches, U-->C hypermutants resulting from multiple rU.dG mismatches were sought, and found, during cDNA synthesis using low [dATP] and high [dGTP]. Mixed G-->A and U-->C hypermutants could also be produced under conditions of low [dCTP] plus low [dATP] and high [dTTP] plus high [dGTP]. Hypermutagenesis should allow jumping through, and subsequent exploration of, sequence space to a greater degree than heretofore and, in conjunction with genetic screening, might be of use in the search of proteins or ribozymes with novel or enhanced properties.
Targeting Cell Surface Receptors with Ligand-Conjugated Nanocrystals (2002)

To explore the potential for use of ligand-conjugated nanocrystals to target cell surface receptors, ion channels, and transporters, we explored the ability of serotonin-labeled CdSe nanocrystals (SNACs) to interact with antidepressant-sensitive, human and Drosophila serotonin transporters (hSERT, dSERT) expressed in HeLa and HEK-293 cells. Unlike unconjugated nanocrystals, SNACs were found to dose-dependently inhibit transport of radiolabeled serotonin by hSERT and dSERT, with an estimated half-maximal activity (EC(50)) of 33 (dSERT) and 99 microM (hSERT). When serotonin was conjugated to the nanocrystal through a linker arm (LSNACs), the EC(50) for hSERT was determined to be 115 microM. Electrophysiology measurements indicated that LSNACs did not elicit currents from the serotonin-3 (5HT(3)) receptor but did produce currents when exposed to the transporter, which are similar to those elicited by antagonists. Moreover, fluorescent LSNACs were found to label SERT-transfected cells but did not label either nontransfected cells or transfected cells coincubated with the high-affinity SERT antagonist paroxetine. These findings support further consideration of ligand-conjugated nanocrystals as versatile probes of membrane proteins in living cells.