gebhart/patrepeval huggingface dataset:
Human cytomegalovirus persistence (2012)

Viral persistence is the rule following infection with all herpesviruses. The β-herpesvirus, human cytomegalovirus (HCMV), persists through chronic and latent states of infection. Both of these states of infection contribute to HCMV persistence and to the high HCMV seroprevalence worldwide. The chronic infection is poorly defined molecularly, but clinically manifests as low-level virus shedding over extended periods of time and often in the absence of symptoms. Latency requires long-term maintenance of viral genomes in a reversibly quiescent state in the immunocompetent host. In this review, we focus on recent advances in the biology of HCMV persistence, particularly with respect to the latent mode of persistence. Latently infected individuals harbour HCMV genomes in haematopoietic cells and maintain large subsets of HCMV-specific T-cells. In the last few years, impressive advances have been made in understanding virus-host interactions important to HCMV infection, many of which will profoundly impact HCMV persistence. We discuss these advances and their known or potential impact on viral latency. As herpesviruses are met with similar challenges in achieving latency and often employ conserved strategies to persist, we discuss current and future directions of HCMV persistence in the context of the greater body of knowledge regarding α- and γ-herpesviruses persistence.
Generation and characterization of nanobodies targeting PSMA for molecular imaging of prostate cancer (2014)

Nanobodies show attractive characteristics for tumor targeting in cancer diagnosis and therapy. A radiolabeled nanobody binding the prostate-specific membrane antigen (PSMA) could offer a noninvasive strategy to select prostate cancer patients eligible for PSMA-targeted therapies. We here describe the generation, production and in vivo evaluation of anti-PSMA nanobodies. Nanobodies were derived from heavy-chain-only antibodies, raised in immunized dromedaries. Binding characteristics were evaluated through ELISA and flow cytometry. Selected nanobodies were radiolabeled with (99m) Tc at their hexahistidine tail, after which cell binding capacity and internalization were evaluated on PSMA(pos) LNCaP and PSMA(neg) PC3 cell lines. In vivo tumor targeting was analyzed in both LNCaP and PC3 xenografted mice through SPECT/microCT and tissue sampling. A panel of 72 generated clones scored positive on ELISA, all contributing to three nanobody groups, of which group 3 dominated with 70 clones. ELISA and FACS analysis led to the selection of two dominant nanobodies. (99m) Tc-labeled PSMA6 and PSMA30 both showed specific binding on LNCAP cells, but not on PC3 cells. (99m) Tc-PSMA30 internalized significantly more in LNCaP cells compared to (99m) Tc-PSMA6. Higher absolute tumor uptake and tumor-to-normal organ ratios were observed for (99m) Tc-PSMA30 compared with (99m) Tc-PSMA6 and a (99m) Tc-control nanobody in LNCaP but not in PC3 tumor-bearing mice. PSMA30 nanobody has improved targeting characteristics both in vitro as well as in vivo compared with PSMA6 and the control nanobody, and was therefore selected as our in-house-developed lead compound for PSMA targeting.
Nitrophthaloyl and aminophthaloyl derivatives of amino acids (1968)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNitrophthaloyl and aminophthaloyl derivatives of amino acidsLyman R. Caswell and Kathryn Chia-Chi. YangCite this: J. Chem. Eng. Data 1968, 13, 2, 291–292Publication Date (Print):April 1, 1968Publication History Published online1 May 2002Published inissue 1 April 1968https://doi.org/10.1021/je60037a051Request reuse permissionsArticle Views84Altmetric-Citations3LEARN 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 InReddit PDF (172 KB) Get e-Alertsclose Get e-Alerts
Highly Selective Enrichment of Phosphorylated Peptides from Peptide Mixtures Using Titanium Dioxide Microcolumns (2005)

Reversible phosphorylation of proteins regulates the majority of all cellular processes, e.g. proliferation, differentiation, and apoptosis. A fundamental understanding of these biological processes at the molecular level requires characterization of the phosphorylated proteins. Phosphorylation is often substoichiometric, and an enrichment procedure of phosphorylated peptides derived from phosphorylated proteins is a necessary prerequisite for the characterization of such peptides by modern mass spectrometric methods. We report a highly selective enrichment procedure for phosphorylated peptides based on TiO2microcolumns and peptide loading in 2,5-dihydroxybenzoic acid (DHB). The effect of DHB was a very efficient reduction in the binding of nonphosphorylated peptides to TiO2 while retaining its high binding affinity for phosphorylated peptides. Thus, inclusion of DHB dramatically increased the selectivity of the enrichment of phosphorylated peptides by TiO2. We demonstrated that this new procedure was more selective for binding phosphorylated peptides than IMAC using MALDI mass spectrometry. In addition, we showed that LC-ESI-MSMS was biased toward monophosphorylated peptides, whereas MALDI MS was not. Other substituted aromatic carboxylic acids were also capable of specifically reducing binding of nonphosphorylated peptides, whereas phosphoric acid reduced binding of both phosphorylated and nonphosphorylated peptides. A putative mechanism for this intriguing effect is presented.
Oxidative Conversion as a Means of Detecting Precursors to Perfluoroalkyl Acids in Urban Runoff (2012)

A new method was developed to quantify concentrations of difficult-to-measure and unidentified precursors of perfluoroalkyl carboxylic (PFCA) and sulfonic (PFSA) acids in urban runoff. Samples were exposed to hydroxyl radicals generated by thermolysis of persulfate under basic pH conditions and perfluoroalkyl acid (PFAA) precursors were transformed to PFCAs of related perfluorinated chain length. By comparing PFCA concentrations before and after oxidation, the concentrations of total PFAA precursors were inferred. Analysis of 33 urban runoff samples collected from locations around the San Francisco Bay, CA indicated that PFOS (2.6-26 ng/L), PFOA (2.1-16 ng/L), and PFHxA (0.9-9.7 ng/L) were the predominant perfluorinated compounds detected prior to sample treatment. Following oxidative treatment, the total concentrations of PFCAs with 5-12 membered perfluoroalkyl chains increased by a median of 69%, or between 2.8 and 56 ng/L. Precursors that produced PFHxA and PFPeA upon oxidation were more prevalent in runoff samples than those that produced PFOA, despite lower concentrations of their corresponding perfluorinated acids prior to oxidation. Direct measurements of several common precursors to PFOS and PFOA (e.g., perfluorooctanesulfonamide and 8:2 fluorotelomer sulfonate) accounted for less than 25% of the observed increase in PFOA, which increased by a median value of 37%. Exposure of urban runoff to sunlight, advanced oxidation processes, or microbes could result in modest, but measurable, increases in concentrations of PFCAs and PFSAs.
CD39 is a promising therapeutic antibody target for the treatment of soft tissue sarcoma. (2015)

Soft tissue sarcoma (STS) is a heterogenous tumor arising from the embryonic mesoderm represented by approximately 50 histological subtypes. Effective therapeutic intervention is lacking for recurrent, late stage and metastatic disease. CD39, a cell-surface ectonucleotidase, has previously been shown to be upregulated in hematological malignancies and various epithelial tumors, but not in STS. Here, we show by mass spectrometry and immunohistochemistry that CD39 is highly expressed in primary patient sarcoma samples. Moreover, CD39 nucleotidase activity is enhanced in fibrosarcoma compared with normal control cells. We demonstrate that an inhibitory monoclonal anti-CD39 antibody, abrogates CD39 enzymatic activity significantly and prolongs survival in a lethal metastatic patient-derived sarcoma model. Taken together, the data suggest CD39 is a novel therapeutic target for the treatment of STS.
Attenuated multimutated herpes simplex virus‐1 effectively treats prostate carcinomas with neural invasion while preserving nerve function (2008)

Many cancers can cause disability and pain by invading nerves. In particular, prostate carcinoma has a high propensity for neural invasion (NI) at an early stage. Attempted surgical treatment of tumors with NI often leads to erectile dysfunction and deteriorated quality of life. Therefore, there is a need for novel modalities that will selectively target cancer cells while preserving neural function. Herpes simplex viruses (HSVs) have a natural trophism for peripheral nerves. We hypothesized that oncolytic therapy using HSV engineered to minimize neurotoxicity would be appropriate for this clinical setting. Attenuated HSV (NV1023) injected to sciatic nerves of nude mice had no toxic effect on nerve function (n=30). NV1023 had significant oncolytic effect on prostate carcinoma cells (PC3, DU145, and LNCap) in vitro. An in vivo model of NI was established by implanting prostate carcinoma cells in the sciatic nerves of nude mice. Mice were treated with NV1023 or saline 7 days after establishment of tumors. Significant reduction in tumor size and inhibition of NI was found 6-8 wk after treatment (P<0.005). All animals treated with saline developed complete paralysis <5 wk post-treatment, whereas most NV1023-treated animals had preserved nerve function >12 wk after treatment (P<0.0001). We conclude that oncolytic therapy effectively treats prostate carcinomas with NI in an in vivo murine model while preserving neural function. These findings may hold significant clinical implications for patients with prostate cancer or other neurotrophic tumors.
Spectroscopic diagnosis of bladder cancer with elastic light scattering (1995)

A diagnostic algorithm for distinguishing malignant from nonmalignant tissue based on the values of the slopes over the wavelength range 330-370 nm has a sensitivity of 100% and specificity of 97% for the limited number of patients in this study.
Adenovirus-Mediated Gene Transfer of Herpes Simplex Virus Thymidine Kinase in an Ascites Model of Human Breast Cancer (1996)

In this study, the growth of locally disseminated breast cancer was modeled using a human breast cancer cell line, MDA-MB-435A, adapted to grow as an ascites tumor in athymic mice. Ex vivo infection of MDA-MB-435A cells with adenovirus containing the herpes simplex virus thymidine kinase gene (HSV-tk) were injected into the intraperitoneal cavity of athymic mice. Ganciclovir (GCV) treatment resulted in prolonged median survival (117 vs. 34 days, p < 0.001) compared to untreated or control animals. Adenovirus containing HSV-tk also demonstrated therapeutic activity after in vivo transduction resulting in prolongation of median survival after GCV treatment (32 vs. 25 days, p < 0.001). However, compared to ex vivo treatment, the effect was modest. In an attempt to increase survival, the viral dose was increased three-fold. Instead of prolonging survival, the increased dose resulted in more toxic deaths. Necropsy demonstrated that the most significant histologic abnormality was marked, diffuse, cytomegalic changes in the liver. Polymerase chain reaction (PCR) analysis of hepatic DNA demonstrated the presence of the virus in the affected tissue. Similar host toxicity and hepatic abnormalities were seen in non-tumor-bearing mice treated with ADV/RSV-tk plus GCV. In conclusion, adenoviral vectors can successfully transfer genes in vivo to cancer cells growing as ascites tumors. Transduction with HSV-tk followed by GCV treatment can prolong survival in this model system of disseminated disease, however toxicity can be substantial. Further refinement in targeting expression of HSV-tk will be required to enhance the therapeutic benefit.
Outcome of Immunization of Cynomolgus Monkeys with Recombinant Semliki Forest Virus Encoding Human Immunodeficiency Virus Type 1 Envelope Protein and Challenge with a High Dose of SHIV-4 Virus (1997)

Infection of macaques with chimeric simian-human immunodeficiency viruses (SHIVs) allows evaluation of HIV-1 envelope vaccines. SHIV-4 is based on SIVmac239 but carries the env, tat, and rev genes of HIV-1IIIB. In this study we used Semliki Forest virus (SFV) RNA vectors to express the envelope protein gp160 of HIV-1IIIB in cynomolgus macaques. Monkeys were immunized four times with recombinant suicide SFV. Whereas two of four monkeys showed T cell-proliferative responses, only one monkey had demonstrable levels of antibodies to HIV-1 gp41 and gp120 as shown by enzyme-linked immunosorbent assay (ELISA) and Western blot. The vaccinated monkeys and four control animals were challenged with 10,000 MID100 (100% minimum infectious doses) of cell-free monkey cell-grown SHIV-4 virus. As demonstrated by virus isolation, all macaques became infected after challenge. All vaccinated monkeys showed an HIV-1-specific anamnestic T cell-proliferative response. Three of four vaccines had developed HIV-1-Env-specific antibodies 2 weeks after challenge whereas none of the four controls showed any detectable immune response at this time point. Furthermore, three of four vaccinated monkeys had no demonstrable viral antigenemia and low viral load as opposed to one of the four naive control animals.
Intravascular strain imaging: experiments on an inhomogeneous phantom (2002)

In coronary arteries, knowing the relative stiffness of atherosclerotic lesions can help physicians select the most appropriate therapeutic modality. Because soft material supports larger strains than hard, measurements of this quantity can distinguish tissue of differing stiffness. In a previous paper, we described techniques for computing displacements and strains in coronary arteries using an integrated angioplasty and imaging catheter. Here, we demonstrate that hard and soft materials in a tissue-mimicking phantom can be differentiated with this device. Because tissue motion cannot be distinguished from catheter motion a priori, we perform all computations in the coordinate system centered at the balloon's geometric center. This reference frame depends only on balloon shape and is independent of catheter motion. A correlation-based, phase-sensitive speckle tracking algorithm has been developed to compute strain. Maximum phantom displacement was greater than 25 /spl mu/m, and the maximum radial, normal strain was about 4.0 percent.
Defective stimulus-response coupling in human monocytes infected with Leishmania donovani is associated with altered activation and translocation of protein kinase C. (1992)

Stimulus-response coupling through protein kinase C (PKC) was shown to be defective in mononuclear phagocytes (M phi) infected with Leishmania donovani. Phorbol 12-myristate 13-acetate (PMA)-induced oxidative burst activity and protein phosphorylation were markedly attenuated in infected M phi. These results were not explained either by quantitative alterations in amounts of PKC or by altered phorbol ester binding but were related to defects in kinase activation. Analysis in vitro of the kinetic properties of PKC from infected M phi revealed an approximately 2-fold increase in the concentration of 1,2-dioleoyl-rac-glycerol required to achieve half-maximal kinase activation. Evidence for abnormal PKC activation in vivo was reflected by attenuation of PMA-induced translocation of enzyme to the particulate fraction of infected cells. These results provide direct evidence that infection with Leishmania inhibits activation of, and therefore intracellular signaling dependent on, PKC. Inhibition of stimulus-response coupling through PKC provides a basis for understanding impairment of cellular activation by Leishmania and may contribute to chronic infection.
Human Immunodeficiency Virus Type 1 Vpr Alters Bone Marrow Cell Function (1999)

Vpr, a 96 amino acid protein, encoded by the human immunodeficiency virus type I (HIV-1), is important for efficient infection of mononuclear phagocytic cells. These cells are abundant in whole bone marrow, which can easily be cultured in vitro to support hematopoiesis. Our experiments indicate that Vpr plays a role in the potent activation of murine and human mononuclear phagocytic cells within a hematopoietic microenvironment. In murine cultures, avid erythrophagocytosis is triggered by transduction of marrow cells with supernatant derived from PA317 cells transfected with a murine retroviral delivery vector bearing a Vpr expression cassette. Supernatants derived from cells transfected with the same vector carrying sequences for the expression of other relevant viral and nonviral proteins do not induce erythrophagocytosis to any marked degree. The effect on human marrow cells is similar, where treatment promotes adhesion of mononuclear phagocytic cells to culture plates in association with other nucleated and nonnucleated cells that undergo subsequent engulfment. The differential effects of Vpr point and deletion mutants in both marrow culture systems fortify the view that the effect is specific to HIV-1 Vpr. Addition of low molar quantities of purified Vpr to marrow cultures is also capable of promoting cell adhesion and phagocytosis, suggesting that extracellular Vpr is the effector of the phenomenon. Accelerated phagocytosis is a hallmark of promonocyte, monocyte, and macrophage activation and its occurrence within a hematopoietic microenvironment may account for critical in vivo pathogenic features of HIV-1 infection. First, activation of mononuclear phagocytes may promote productive viral infection; and second, premature phagocytosis could provide, at least in part, a molecular explanation for the induction of the idiopathic cytopenias that are typical of individuals infected with HIV-1.
Effects of daminozide on somatic embryogenesis from immature and mature embryos of wheat. (2009)

The influence of daminozide, an inhibitor of gibberellins biosynthesis, on the somatic embryogenesis in immature and mature embryo derived from tissue cultures of wheat was investigated. Low concentrations of daminozide (0.064-0.127 mM) positively affected the somatic embryogenic capacity of immature embryos (cv. ‘Andros’) cultured on the medium supplemented with either 2,4-dichlorophenoxyacetic acid (2,4-D) or dicamba or para chlorophenoxyacetic acid ( p-CPA). The higher concentration of daminozide (0.51-1.02 mM) reduced the regeneration of shoots. The modification of exogenous/endogenous ratio of gibberellins by application of exogenous GA 3 did not remove the effect of daminozide. On the contrary, its combination with GA 3 inhibited the somatic embryogenesis and resulted in the supression of the development of somatic embryos. The supplement of 0.127 mM daminozide to 2,4-D containing medium increased the embryogenic competence of immature embryos of eleven Russian spring and winter varieties. For ten varieties the number of shoots produced per callus did not differ statistically from the control medium; one variety showed the increase of shoot number. In contrast with immature wheat embryos, mature ones (cv. Tajoznaja) did not response to daminozide supplementation either of the inductive or the different- tiative media. The present observations provide a method to increase the embryogenesis efficiency for wheat commercial varieties which immature embryos display low embryogenic potential. Abbereviations: 2,4-D_ 2,4-dichlorophenoxyacetic acid; p-CPA_ para chlorophenoxyacetic acid; GA 3_ gibberellic acid; GAs _ gibberellins; ABA_ abscisic acid.
Transposable element Mu1 is found in multiple copies only in Robertson's Mutator maize lines. (1984)

An approximately 1.4 kb fragment of DNA called Mu1, mutationally inserted into the Adh1 locus of maize in a Robertson's Mutator plant, has been cloned. The instability of the mutation induced by this element, the nature of the Robertson's Mutator system, and terminal inverted repeats indicate that the 1.4 kb insert is a transposable element. All Robertson's Mutator corn lines have Mu1-like elements, at copy numbers of 10-70 per diploid genome. The basic size of these multiple interspersed copies is generally the same. The elements are found on different genomic restriction fragments in closely related individuals, indicating a high degree of mobility. Aside from the one corn line identified by Robertson in the mid-1970s as Mutator, all maize lines tested, plus several near and remote corn relatives, have no detectable DNA which cross-hybridizes strongly with Mu1.
Adsorption and Hybridization of Oligonucleotides on Mercaptoacetic Acid-Capped CdSe/ZnS Quantum Dots and Quantum Dot−Oligonucleotide Conjugates (2006)

Interest in the unique optical properties of quantum dots (QDs) has resulted in the development QD-bioconjugates for imaging and diagnostics. Although these applications are numerous, considerably less is known about the interactions between QDs and biomolecules. In this work, we describe hydrogen-bonding interactions between oligonucleotides and CdSe/ZnS quantum dots capped with mercaptoacetic acid ligands. The strength of the interactions can be modulated by changes in the pH and ionic strength, the addition of formamide, and differences between ssDNA and dsDNA. Fluorescence resonance energy transfer experiments have shown that conjugated oligonucleotides adopt a conformation that lies across the surface of the QD. The hydrogen-bonding interactions also affect the kinetics of hybridization with QD-DNA conjugates and the thermal stability of QD-conjugated dsDNA. The former is analogous to conventional solid-phase hybridization, where stronger oligonucleotide adsorption leads to faster kinetics. With respect to the latter, interactions with the QD surface can sharpen the melt transition and alter the melt temperature of dsDNA. These effects are largely absent when adsorptive interactions are minimized.
Role of NifS in maturation of glutamine phosphoribosylpyrophosphate amidotransferase (1997)

Glutamine phosphoribosylpyrophosphate amidotransferase from Bacillus subtilis is synthesized as an inactive precursor that requires two maturation steps: incorporation of a [4Fe-4S] center and cleavage of an 11-residue NH2-terminal propeptide. Overproduction from a multicopy plasmid in Escherichia coli leads to the formation of soluble proenzyme and mature enzyme forms as well as a small fraction of insoluble proenzyme. Heterologous expression of Azotobacter vinelandii nifS from a compatible plasmid increased the maturation of the soluble proenzyme three- to fourfold without influencing the content of the insoluble fraction. These results support a role for NifS in heterologous Fe-S cluster assembly and enzyme maturation.