gebhart/patrepeval huggingface dataset:
RNA recognition and regulation of HIV-1 gene expression by viral factor Tat. (1998)

Viral transcription factor Tat is a small nuclear protein containing a large number of basic amino acids. The tat gene consists of two exons but only the first encoding 72-amino acid polypeptide is necessary for protein activity. Since the second exon is poorly conservative the total number of amino acids among Tat proteins from different strains of HIV-1 varies from 86 to 130. Tat protein acts as trans-activator of HIV genome transcription. It is absolutely required for viral functioning. Tat increases processivity of RNA-polymerase II by abolition of transcription blockade, which appears after polycondensation of the first 60-70 nucleotides of either HIV mRNA, i.e., it acts as antiterminator. For manifestation of its activity Tat specifically binds to the double stranded RNA fragment called TAR which is located at the 5'-terminus of all HIV mRNAs. The TAR structure contains a hairpin and a side loop. The Tat-binding region includes only a site of the loop; manifestation of Tat activity in vivo requires the full TAR and additional cellular co-factors.
Migratory arrest of gonadotropin-releasing hormone neurons in transgenic mice. (1991)

Gonadotropin-releasing hormone (GnRH) is important in reproduction, although the mechanism of central hypogonadism in humans remains unclear. Because the GnRH neuron originates from the olfactory placode and migrates to the hypothalamus during development, central hypogonadism in humans could be caused by failure in normal migration of GnRH neurons to the hypothalamus. We report that in transgenic mice expression of the simian virus 40 T antigen, driven by the promoter of human GnRH gene, resulted in central hypogonadism due to an arrest in neuronal migration during development and tumor formation along the migratory pathway. This system appears to be an important animal model of hypogonadotropic hypogonadism in humans. Additionally, olfactory bulb tumors from these animals were dispersed, and a GnRH-secreting neuronal cell line (GN cell line) was established.
L‐type amino acid transporter 1 (LAT1) is frequently expressed in thymic carcinomas but is absent in thymomas (2009)

LAT1 is frequently expressed in thymic carcinomas but is absent in thymomas. Our results suggest that LAT1 expression might be an immunohistochemical marker for carcinomas, and could distinguish between thymomas and thymic carcinomas.
Receptor/Transporter-independent Targeting of Functional Peptides across the Plasma Membrane (2004)

Targeting of peptides, proteins, and other functional cargo into living cells is contingent upon efficient transport across the plasma membrane barrier. We have harnessed the signal sequence hydrophobic region (SSHR) to deliver functional cargoes to cultured cells and to experimental animals. We now report evidence that two chirally distinct forms of SSHR composed of all l or all d amino acids showed similar membrane-translocating activity as assessed by confocal microscopy, flow cytometry, and direct fluorescence measurement. An attached nuclear localization sequence ferried by the SSHR enantiomers displayed similar intracellular function by inhibiting inducible nuclear import of transcription factor nuclear factor kappa B and suppressing nuclear factor kappa B-dependent gene expression of cytokines. A nuclear localization sequence comprised of a positively charged cluster of amino acids was rapidly translocated by SSHR enantiomers to the interior of unilamellar phospholipid vesicles. These findings indicate that the SSHR translocates functional peptides directly through the plasma membrane phospholipid bilayer without involving chirally specific receptor/transporter mechanisms. This mechanism of SSHR translocation is suitable for facile delivery of biologically active peptides for cell-based and animal-based functional proteomic studies.
Cutting Edge: Rapamycin Augments Pathogen-Specific but Not Graft-Reactive CD8+ T Cell Responses (2010)

Recent evidence demonstrating that exposure to rapamycin during viral infection increased the quantity and quality of Ag-specific T cells poses an intriguing paradox, because rapamycin is used in transplantation to dampen, rather than enhance, donor-reactive T cell responses. In this report, we compared the effects of rapamycin on the Ag-specific T cell response to a bacterial infection versus a transplant. Using a transgenic system in which the Ag and the responding T cell population were identical in both cases, we observed that treatment with rapamycin augmented the Ag-specific T cell response to a pathogen, whereas it failed to do so when the Ag was presented in the context of a transplant. These results suggest that the environment in which an Ag is presented alters the influence of rapamycin on Ag-specific T cell expansion and highlights a fundamental difference between Ag presented by an infectious agent as compared with an allograft.
Strategy for catch and release of azide-tagged biomolecules utilizing a photolabile strained alkyne construct (2012)

A photolabile o-nitrobenzyl linker-cyclooctyne conjugate was prepared, immobilized on poly(methacrylate) beads and utilized as a trap for azide-functionalized compounds. These could be released by 365 nm UV light irradiation in high yield and purity. The "reagent-free" and time economic catch and release protocol was deemed useful for chemical proteomics applications.
Therapeutic activities of PHA-L4, the mitogenic isolectin of phytohemagglutinin. (1990)

Evidence is presented that suggests that PHA-L4 may exert the therapeutic effects of a theoretical ideal biological response modifier through its ability to do the following: to assist remission induction in certain malignancies, to exhibit direct antitumor cytotoxic effects, to enhance antineoplastic effect of radiation and chemotherapy, to decrease the liability to malignant transformation, to promote differentiation and restore normal growth responses in neoplastic cells, to manifest minimal liability to suppressor activity that would inhibit tumor rejection or antitumor cytotoxicity, to repress graft rejection and graft-versus-host responses and amplify the immunosuppressive effects of other agents in allograft transplantations, to display a direct protective effect against damage from radiation and chemotherapy, to stimulate normal myelopoiesis, to reinforce responses against various infections, to amplify tumor immunogenicity, and to attract mononuclear cells to sites of injection or local application.
Micelles of Imidazolium-Functionalized Polystyrene Diblock Copolymers Investigated with Neutron and Light Scattering (2003)

We synthesize a series of block copolymers comprising a polystyrene (PS) block and an imidazolium-functionalized PS (IL) block and characterize their assembly properties. We use small-angle neutron scattering and dynamic light scattering to determine the micelle size and shape in dilute solutions and to assess the micelle interactions in concentrated solutions. By studying a series of copolymers with fixed PS block length, we find that the length of the IL block governs the micelle dimensions. Our data suggest that these copolymers form elongated micelle structures where the IL block is extended in the micelle core. We find that these micelles can sequester water and that interactions between the micelles lead to structure factor peaks at elevated concentrations.
Extracellular Adenosine Triphosphate and Chronic Obstructive Pulmonary Disease (2010)

COPD is characterized by a strong and persistent up-regulation of extracellular ATP in the airways. Extracellular ATP appears to contribute to the pathogenesis of COPD by promoting inflammation and tissue degradation.
Cross-linked nucleic acids: Formation, structure, and biological function (2010)

Published data on the main types of reagents capable of introducing covalent interstrand cross links into nucleic acids (NA) are summarized in the present review. The reactivity of cross-linking agents, their preferred binding sites, and methods of determining the cross-link localization in a duplex are discussed. Cell response to DNA cross linking, namely, the blocking of replication and transcription, the initiation of reparation processes, and apoptotic death of the cell, are analyzed, as well as the use of cross-linking reagents in therapy and molecular biology.
Increased immunogenicity of tumor vaccines complexed with anti-Gal: studies in knockout mice for alpha1,3galactosyltransferase. (1999)

A major prerequisite for the success of tumor vaccines is their effective uptake by antigen-presenting cells (APCs) and transport of these APCs to the draining lymph nodes, where the processed and presented tumor-associated antigens activate tumor-specific naive T cells. We previously suggested that the immunogenicity of autologus tumor vaccines in humans may be augmented by engineering vaccinating tumor cell membranes to express alpha-galactosyl (alpha-gal) epitopes (i.e., Galalpha1,3Galbeta1,4GlcNAc-R). Subsequent in situ binding of natural anti-Gal IgG molecules to these epitopes would result in the formation of immune complexes that target tumor vaccines for uptake by APCs, via the interaction of the Fc portion of anti-Gal with Fcgamma receptors on APCs. This hypothesis was tested in a unique experimental animal model of knockout mice for alpha1,3galactosyltransferase (alpha1,3GT) and the mouse melanoma B16-BL6 (referred to here as BL6). Like humans, these mice lack alpha-gal epitopes and produce anti-GaL BL6 melanoma cels are highly tumorigenic, and like human tumor cells, they lack alpha-gal epitopes. Expression of alpha-gal epitopes on these melanoma cells was achieved by stable transfection with alpha,3GT cDNA. The transfected melanoma cells (termed BL6alphaGT) express approximately 2 x 10(6) alpha-gal epitopes per cell and readily form immune complexes with anti-Gal. Vaccination of the mice with 2 x 10(6) irradiated melanoma cells that express alpha-gal epitopes, followed by challenge with 0.5 x 10(6) live parental melanoma cells, resulted in protection for at least 2 months (i.e, no tumor growth) in one-third of the mice, whereas all mice immunized with irradiated parental melanoma cells developed tumors 21-26 days post-challenge. The proportion of protected mice doubled when the mice were immunized twice with irradiated melanoma cells expressing alpha-gal epitopes and challenged with 0.2 x 10(6) live BL6 cells. Histological studies on the developing tumors in challenged mice that were immunized with melanoma cells expressing alpha-gal epitopes demonstrated extensive infiltration of T lymphocytes and macrophages, whereas no mononuclear cell infiltrates were observed in tumors of mice immunized with parental tumor cells. Overall, these studies imply that immunization of alpha1,3GT knockout mice with BL6 melanoma cells that express alpha-gal epitopes elicits, in a proportion of the population, protective immune response against the same tumor lacking such epitopes. These studies further suggest that similar immunization of cancer patients with autologous tumor vaccines that are engineered to express alpha-gal epitopes may increase the immune response to autologous tumor-associated antigens and, thus, may elicit immune-mediated destruction of metastatic cells expressing these antigens.
Silent human immunodeficiency virus type 1 infection: a rare occurrence in a high-risk heterosexual population (1992)

A group of 58 heterosexual female partners (FP) of human immunodeficiency virus type 1 (HIV-1)-seropositive hemophiliacs was studied by conventional diagnostic methods such as enzyme-linked immunosorbent assay (ELISA) and Western blot analysis to examine whether any had acquired HIV-1 infection through sexual transmission. A subset of 29 FP were asked to answer a detailed questionnaire concerning their health, use of "safer sex" techniques, and other risk factors for HIV-1 infection. They also had additional blood drawn for CD4 cell analysis, viral cultures, nef, gag, and env immunoblots, and polymerase chain reaction (PCR) analysis to assess the occurrence of "silent" HIV-1 infection in a high-risk seronegative population. Among the 58 FP, three were found to be HIV-1-seropositive on first testing, with no new seroconversions occurring with subsequent testing in the remaining 55. Two seropositive FP had the additional testing and were found to have positive viral cultures, as well as positive PCR results. All of the seronegative FP (n = 24) who had additional testing were negative in viral culture, had negative immunoblots, and had no HIV-1 nucleic acid sequences detected by PCR. Thus, in this population, silent HIV-1 infection appears to be a rare occurrence and antibody testing seems to correlate with the more sensitive techniques of PCR and viral cultures.
Regeneration of herpesviruses from molecularly cloned subgenomic fragments (1988)

The ability to manipulate the genomes of herpesviruses is of eminent importance for obtaining insight into gene function and regulation of gene expression of these complex viruses. Here we report the use of in vivo overlap recombination to generate pseudorabies virus mutants. Cotransfection of up to five overlapping cloned subgenomic fragments, which together constitute the entire genomic information of pseudorabies virus, results in the efficient reconstitution of virus. This allows the efficient introduction of multiple well-defined mutations in herpesvirus genomes in a single step, without any selection or screening for a particular phenotype.
Amoebae as Training Grounds for Intracellular Bacterial Pathogens (2005)

Free-living amoebae are important predators that control microbial communities. They are ubiquitous and have been isolated from various natural sources such as soil, freshwater, salt water, dust, and air. Although their abundance in soil is only limited, they have been implicated in the stimulation
A charge-modulated FET for detection of biomolecular processes: conception, modeling, and simulation (2005)

A novel, solid-state sensor for charge detection in biomolecular processes is proposed. The device, called charge-modulated field-effect transistor, is compatible with a standard CMOS process, thus allowing fully electronic readout and large scale of integration of biosensors on a single chip. The detection mechanism is based on the field-effect modulation induced by electric charge changes related to the bioprocess. A model of the device was developed, to provide a manageable relationship between its output and geometric, design and process parameters. Extensive two- and three-dimensional simulations of the proposed structure validated the model and the working principle.
Wnt signaling and cancer (2000)

The regulation of cell growth and survival can be subverted by a variety of genetic defects that alter transcriptional programs normally responsible for controlling cell number. High throughput analysis of these gene expression patterns should ultimately lead to the identification of minimal expression profiles that will serve as common denominators in assigning a cancer to a given category. In the course of defining the common denominators, though, we should not be too surprised to find that cancers within a single category may nevertheless exhibit seemingly disparate genetic defects. The wnt pathway has already provided an outstanding example of this. We now know of three regulatory genes in this pathway that are mutated in primary human cancers and several others that promote experimental cancers in rodents (Fig. 1). In all of these cases the common denominator is the activation of gene transcription by -catenin. The resulting gene expression profile should provide us with a signature common to those cancers carrying defects in the wnt pathway. In this review, the wnt pathway will be covered from the perspective of cancer, with emphasis placed on molecular defects known to promote neoplastic transformation in humans and in animal models.
Die gemischte Guerbet‐Reaktion zwischen cyclischen und acyclischen Alkoholen (1980)

Abstract Auf Grund der mechanistischen Verwandtschaft zur Aldolkondensation sollten in einer gemischten Guerbet‐Reaktion sekundäre cyclische Alkohole durch primäre Alkohole alkyliert werden. Neben der erwarteten Hauptreaktion wurde folgendes festgestellt: Der cyclische Alkohol kondensiert leicht mit sich selbst. Diese Reaktion tritt bevorzugter ein als die Selbstkondensation des primären acyclischen Alkohols. Besitzt der cyclische Alkohol zwei unsubstituierte Methylengruppen in Nachbarschaft zur Hydroxymethylgruppe, so findet bevorzugt die Alkylierung beider Positionen statt. Das Endprodukt ist ein Gemisch aus Alkoholen und Ketonen.
A review of oral diabetic medication (2010)

We have an ever increasing awareness of the importance of tight glycaemic control in the management of type 2 diabetes mellitus. Over the past decade a number of new medicines have become available for the management of type 2 diabetes. We need to have a good knowledge of these agents to optimise patient therapy and meet previously unattained treatment goals. This article reviews the different classes of diabetic medication including their mode of action, efficacy, pharmacokinetics and safety profile.
Kondensierte Indole aus 2‐Chlorindolaldehyd‐(3) (1972)

Abstract Aus 2‐Oxindolen lassen sich mit dem Vilsmeier‐Reagens 2‐Chlorindol‐3‐aldehyde darstellen, während 2– bzw. 3‐Pyrrolone zu 2– bzw. 3‐Hydroxypyrrolaldehyden führen. Unter gleichen Bedingungen reagieren Succinimid, N‐Phenylsuccinimid und 1‐Phenyl‐2,3,‐dimethylpyrrolon‐(5) nicht. Aus 2‐Chlorindolaldehyd‐(3) sind durch Umsetzung mit bifunktionellen Verbindungen kondensierte Indolderivate zugänglich.
Early‐eye morphogenesis in the zebrafish, Brachydanio rerio (1994)

Early eye morphogenesis in the zebrafish between 12 and 36 hours postfertilization was studied by light- and scanning electron microscopy. Overall, early eye morphogenesis in the zebrafish is similar to that of other vertebrates even though the optic primordia evaginate from the forebrain as solid masses of cells. After initial evagination (6-7 somite stage [SS]), the optic primordia take on a wing-like shape (8-9 SS). Subsequently, they bend ventrally and rotate slightly in an anterior direction (10-12 SS). These changes serve to bring the primordia from a horizontal to a more vertical orientation in relation to the embryonic neural axis. Invagination commences from the center of each primordium (14 SS) and progresses symmetrically out towards the periphery (14-20 SS). The choroid fissure forms by an involution along the anterior region of the eyecup (18-20 SS). By 24 hours postfertilization (pf), the eyecups are well formed. Between 24 and 36 hours pf, the eyes rotate further in relation to the axis of the embryo, and this repositions the choroid fissue to a typical ventral location by 36 hours pf. Because of the two rotations of the eye during early morphogenesis, particularly the later one, the anterior-posterior orientation of the emerging optic primordium ultimately becomes the ventral-dorsal axis of the completed eyecup.
Drug Delivery Into the Eye With the Use of Ultrasound (2004)

Application of 880-kHz ultrasound provided up to 10-fold enhancement in the delivery of a hydrophilic compound through the cornea while producing minor changes in the corneal epithelium.
Essential pro-Bmp roles of crossveinless 2 in mouse organogenesis (2006)

We here report essential roles of the Bmp-binding protein crossveinless 2 (Cv2; Bmper) in mouse organogenesis. In the null Cv2 mutant mouse, gastrulation occurs normally, but a number of defects are found in Cv2-expressing tissues such as the skeleton. Cartilage differentiation by Bmp4 treatment is reduced in cultured Cv2(-/-) fibroblasts. Moreover, the defects in the vertebral column and eyes of the Cv2(-/-) mouse are substantially enhanced by deleting one copy of the Bmp4 gene, suggesting a pro-Bmp role of Cv2 in the development of these organs. In addition, the Cv2(-/-) mutant exhibits substantial defects in Bmp-dependent processes of internal organ formation, such as nephron generation in the kidney. This kidney hypoplasia is synergistically enhanced by the additional deletion of Kcp (Crim2) which encodes a pro-Bmp protein structurally related to Cv2. This study demonstrates essential pro-Bmp functions of Cv2 for locally restricted signal enhancement in multiple aspects of mammalian organogenesis.
The human breast carcinoma cell line SW 613-S: an experimental system to study tumor heterogeneity in relation to c-myc amplification, growth factor production and other markers (review). (1990)

Amplification of the c-myc gene has been frequently reported in breast carcinomas. However the precise function of the c-myc protein is still unknown and the nature of the selective advantage offered to a cell by an overexpression of such a protein is unclear. We are addressing this question using the SW 613-S human breast carcinoma cell line as a model system. This cell line harbours an amplified c-myc gene and a mutated c-Ki-ras gene. By various criteria the amplified c-myc gene of SW613-S cells appears undistinguishable from a normal human c-myc gene. The SW613-S cell line is heterogeneous: it contains cells with a high level of amplification and carrying the extra copies of the c-myc gene in double minute chromosomes (DMs) and cells with few c-myc genes integrated into chromosomes. DM-containing cells are progressively lost upon in vitro cultivation but are selected for during in vivo growth, as tumors in nude mice, or by cultivating the cells in a chemically defined, serum-free medium or under conditions preventing anchorage. Clones with different levels of amplification and different chromosomal localization of the c-myc copies were isolated from the SW 613-S cell population. Those with a high level of amplification and expression of the c-myc gene are tumorigenic in nude mice, whereas those with a low level are not. Introduction of c-myc gene copies by transfection confers tumorigenicity to the nontumorigenic clones, indicating that a high level of amplification of the c-myc gene contributes to the tumorigenic phenotype of SW 613-S cells. Tumorigenic clones grow unattached, are able to proliferate in a chemically defined medium, and produce high levels of several growth factors (e.g. TGF-alpha, IGF2). Nontumorigenic clones are more dependent upon anchorage for growth, show a restricted growth in defined medium, and produce low or undetectable level of the growth factors tested. We have identified several genes, besides c-myc, the expression level of which is markedly different in the two types of clones. TGF-alpha, IGF2, PDGF-A, int-2, cytokeratins K8 and K18 and ferritin H chain are overexpressed in tumorigenic clones. In contrast, c-erbB1 (EGF receptor), c-jun, vimentin and p53 are expressed at a higher level in the nontumorigenic clones. Finally the major histocompatibility class I antigens, ferritin L chain, TGF-beta and c-Ki-ras, are examples of genes expressed at the same level in both types of clones.(ABSTRACT TRUNCATED AT 400 WORDS)
Expression of CD44 in articular cartilage is associated with disease severity in knee osteoarthritis (2013)

Objectives To investigate CD44 levels in articular cartilage of knee osteoarthritis (OA) and the relationship between CD44 and severity of the disease. Methods All 50 cartilage tissues included normal and OA cartilage, and were ascribed to the following four groups on the basis of modified Mankin score: normal, mild lesions, moderate lesions and severe lesions. CD44 levels in articular cartilage were assessed by immunohistochemical methods. Results CD44 levels were detected in all four groups. The difference in average gray value of CD44 expression showed statistical significance when compared between each group (P < 0.05). In addition, CD44 expression in each group correlated with disease severity, according to the modified Mankin score (ρ = −0.848, P < 0.01). Conclusions CD44 in articular cartilage is associated with progressive knee OA joint damage.