gebhart/patrepeval huggingface dataset:
Intravaginal Immunization of Mice with Recombinant Salmonella enterica Serovar Typhimurium Expressing Human Papillomavirus Type 16 Antigens as a Potential Route of Vaccination against Cervical Cancer (2008)

Cervical cancer, the second leading cause of cancer deaths in women, is the consequence of high-risk human papillomavirus (HPV) infections. Toward the development of therapeutic vaccines that can induce both innate and adaptive mucosal immune responses, we analyzed intravaginal (ivag) vaccine delivery of live attenuated Salmonella enterica serovar Typhimurium expressing HPV16L1 as a model antigen. Innate immune responses were examined in cervicovaginal tissues by determining gene expression patterns by microarray analysis using nylon membranes imprinted with cDNA fragments coding for inflammation-associated genes. At 24 h, a wide range of genes, including those for chemokines and Th1- and Th2-type cytokine and chemokine receptors were up-regulated in mice ivag immunized with Salmonella compared to control mice. However, the majority of transcripts returned to their steady-state levels 1 week after immunization, suggesting a transient inflammatory response. Indeed, cervicovaginal histology of immunized mice showed a massive, but transient, infiltration of macrophages and neutrophils, while T cells were still increased after 7 days. Ivag immunization also induced humoral and antitumor immune responses, i.e., serum and vaginal anti-HPV16VLP antibody titers similar to those induced by oral immunization, and significant protection in tumor protection experiments using HPV16-expressing C3 tumor cells. These results show that ivag immunization with live attenuated Salmonella expressing HPV16 antigens modulates the local mucosal gene expression pattern into a transient proinflammatory profile, elicits strong systemic and mucosal immunity against HPV16, and confers protection against HPV16 tumor cells subcutaneously implanted in mice. Examination of the efficacy with which ivag HPV16E7E6 Salmonella induces regression of tumors located in cervicovaginal tissue is warranted.
Steroidal Saponins from the Bark of Dracaena draco and Their Cytotoxic Activities (2003)

From the stem bark of Dracaena draco, three new compounds, namely, draconins A-C (1-3), were isolated, along with 17 known compounds. The structures of the new compounds isolated were elucidated on the basis of spectroscopic data interpretation. Several of the isolated compounds showed potent cytotoxic activities measured on the human leukemia cell line HL-60 (IC(50)'s from 2.0 to 9.7 microM at 72 h). The mechanism by which compounds 1 and 2 display their cytostatic properties is through induction of cell death by apoptosis, as evaluated by fluorescence microscopy and DNA fragmentation.
A New Antibacterial Sesquiterpene from Premna oligotricha (1993)

A novel sesquiterpene, 7 alpha-hydroxy-6, 11-cyclofarnes-3(15)-en-2-one [1], has been isolated from the aerial parts of Premna oligotricha (Verbenaceae) using an antimicrobial bioassay-guided isolation procedure. The sesquiterpene was identified on the basis of spectroscopic data and showed weak activity against Gram-positive bacteria Bacillus pumilus, Bacillus subtilis, Staphylococcus aureus, and Streptococcus faecalis.
Tissue Proteomics for the Next Decade? Towards a Molecular Dimension in Histology (2014)

The concept of tissues appeared more than 200 years ago, since textures and attendant differences were described within the whole organism components. Instrumental developments in optics and biochemistry subsequently paved the way to transition from classical to molecular histology in order to decipher the molecular contexts associated with physiological or pathological development or function of a tissue. In 1941, Coons and colleagues performed the first systematic integrated examination of classical histology and biochemistry when his team localized pneumonia antigens in infected tissue sections. Most recently, in the early 21(st) century, mass spectrometry (MS) has progressively become one of the most valuable tools to analyze biomolecular compounds. Currently, sampling methods, biochemical procedures, and MS instrumentations allow scientists to perform "in depth" analysis of the protein content of any type of tissue of interest. This article reviews the salient issues in proteomics analysis of tissues. We first outline technical and analytical considerations for sampling and biochemical processing of tissues and subsequently the instrumental possibilities for proteomics analysis such as shotgun proteomics in an anatomical context. Specific attention concerns formalin fixed and paraffin embedded (FFPE) tissues that are potential "gold mines" for histopathological investigations. In all, the matrix assisted laser desorption/ionization (MALDI) MS imaging, which allows for differential mapping of hundreds of compounds on a tissue section, is currently the most striking evidence of linkage and transition between "classical" and "molecular" histology. Tissue proteomics represents a veritable field of research and investment activity for modern biomarker discovery and development for the next decade.
Gram-Scale Synthesis of (+)-Spongistatin 1: Development of An Improved, Scalable Synthesis of the F-Ring Subunit, Fragment Union, and Final Elaboration (2008)

In a quest to develop an effective, scalable synthesis of (+)-spongistatin 1 ( 1), we devised a concise, third-generation scalable synthesis of (+)- 7, the requisite F-ring tetrahydropyran aldehyde, employing a proline-catalyzed cross-aldol reaction. Subsequent elaboration to (+)-EF Wittig salt (+)- 3, followed by union with advanced ABCD aldehyde (-)- 4, macrolactonization and global deprotection permitted access to >1.0 g of totally synthetic (+)-spongistatin 1 ( 1).
Abstract 13727: Effects of Ziltivekimab (ZILTI), a Novel Anti-Interleukin-6 Monoclonal Antibody, on Markers of Inflammation and Cardiovascular Risk in Patients With Chronic Kidney Disease on Hemodialysis (2019)

Introduction: Levels of the inflammatory cytokine IL-6 and its associated biomarker CRP, the production of which is predominantly stimulated by IL-6, are strongly correlated with CV outcomes in CKD...
Stage-Specific Regulation of Reprogramming to Induced Pluripotent Stem Cells by Wnt Signaling and T Cell Factor Proteins (2013)

Wnt signaling is intrinsic to mouse embryonic stem cell self-renewal. Therefore, it is surprising that reprogramming of somatic cells to induced pluripotent stem cells (iPSCs) is not strongly enhanced by Wnt signaling. Here, we demonstrate that active Wnt signaling inhibits the early stage of reprogramming to iPSCs, whereas it is required and even stimulating during the late stage. Mechanistically, this biphasic effect of Wnt signaling is accompanied by a change in the requirement of all four of its transcriptional effectors: T cell factor 1 (Tcf1), Lef1, Tcf3, and Tcf4. For example, Tcf3 and Tcf4 are stimulatory early but inhibitory late in the reprogramming process. Accordingly, ectopic expression of Tcf3 early in reprogramming combined with its loss of function late enables efficient reprogramming in the absence of ectopic Sox2. Together, our data indicate that the stepwise process of reprogramming to iPSCs is critically dependent on the stage-specific control and action of all four Tcfs and Wnt signaling.
Biological effects of radiofrequency/microwave radiation (2002)

Over the past 50 years, significant advances have been made in the characterization of radiofrequency/microwave (RF/MW) fields (3 kHz-300 GHz) and energy absorption, as well as in the quantification of biological responses of organisms exposed to this kind of electromagnetic energy. The known biological effects and hazards have been demonstrated to be largely thermal in nature. This paper reviews key developments in experimental and theoretical dosimetry, as well as confirmed biological effects that have formed the basis of ever more sophisticated human-exposure standards generated through the IEEE consensus process. It also suggests some potential benefits to mankind of systems based on the thermogenic character of RF/MW energy absorption.
Synthesis, Assembly, and Processing of Viral Proteins (1997)

Transfer of the RNA genome of a retrovirus from one cell to another requires its assembly within the structure of an infectious virion. Although most of the components of the retroviral particle have been identified (see Fig. 1 and Chapter 2), the molecular details of the assembly mechanisms are poorly understood. This may seem surprising since the number of distinct proteins contained in a retrovirus is small. What makes the process of assembly both difficult and interesting to study is its highly dynamic nature.An examination of the mature retroviral particle cannot fully explain the steps in assembly because these components are not those from which the particle was made. Rather, all of the structural proteins of the virion, with few exceptions, are derived from three polyproteins: Gag, Gag-Pro-Pol, and Env (Fig. 2). Each of these precursor proteins has special characteristics needed for specific steps in the assembly process, and each undergoes extensive changes along the way. In brief, the surface (SU) and transmembrane (TM) proteins found on the surface of the virion are initially synthesized as a single polypeptide, the Env glycoprotein, which is assembled into oligomeric complexes in the rough endoplasmic reticulum (RER), extensively modified, and then cleaved by a cell-encoded protease during transport to the surface of the cell. In some instances, further proteolytic processing of TM occurs after the particle is released. Likewise, the proteins found on the inside the virion (matrix, MA; capsid, CA; nucleocapsid, NC; protease, PR; reverse transcriptase, RT; integrase, IN) are initially linked within the Gag and Gag-Pro-Pol proteins. The Gag protein is sufficient for directing budding at the plasma membrane, and the Pro-Pol polyproteins are incorporated into the resulting particle because they are linked to Gag. Subsequent cleavage of the Gag and Gag-Pro-Pol proteins by the viral protease brings about new shapes and arrangements inside the nascent virion as the immature particle undergoes a metamorphosis into the mature, infectious retrovirus. Even the structure of the viral RNA, packaged into the virion through an interaction with Gag, changes during the budding and maturation process.
Letting Go of Papa's Hand: Music Education Without Music? (1996)

It seems to be the destiny of Music Education that it be tied in junior relationship with other subjects - Music of course, and more recently, Anthropology. Understood as Education in Music, the subject is assumed to concern itself with how music is taught and learned. The author suggests that Music Education should also be understood, in questions of research, as Education about Music, thus allowing it to make a more direct contribution to the Humanities, and in particular, to cultural studies. By way of a case-study, the article outlines the ways in which Education about Music influenced a generation of writers in 19th-century France, and spread itself 'secretly' into their literary work.
New Perspectives on Alzheimer's Disease (1986)

Significant progress has been made in refining diagnostic criteria for AD and in developing imaging approaches to exclude treatable disease and to assess some of the metabolic processes occurring in vivo in the brains of individuals with AD. However, as yet, no reliable diagnostic test is available. Although risk factors have been identified, the etiology of AD remains an enigma. The roles of familial, chromosomal, and genetic factors, toxins, and transmissible agents in the pathogenesis of this disease deserve intensive study. A variety of neurotransmitter systems are affected in the disease, and it seems likely that new approaches may identify additional systems at risk. Of particular importance will be studies on surviving neurons, since these cells will be targets for treatment. Neurons in certain parts of the brainstem, basal forebrain, amygdala, hippocampus, and neocortex show several types of cytoskeletal abnormalities, but mechanisms of cytoskeletal disorganization are not well understood, e.g. we do not have a clear idea of the sequence of cytoskeletal pathology, the time course of dysfunction of individual neurons, and consequences of these processes on cell function. In situ hybridization with radiolabeled nucleic acid probes and immunocytochemical approaches should provide information about levels of gene expression, protein compositions, and posttranslational modifications of normal and abnormal proteins in these cells. The relationships and sources of some of the abnormal proteins (e.g. those associated with PHF, 15-nm straight filaments, plaque amyloid, and vascular amyloid) can be clarified by new approaches of protein chemistry (purification and sequencing) and molecular biology (recombinant DNA techniques). Finally, investigations of animal models that recapitulate certain features of AD should provide new insights into the nature, mechanisms, and consequences of cellular pathology of specific systems. These models may be useful for imaging studies similar to those used in human patients and for developing and testing new therapeutic approaches that eventually may be useful for treating this all-too-common disorder of the central nervous system.
Estrogen promotes chemotherapeutic drug resistance by a mechanism involving Bcl-2 proto-oncogene expression in human breast cancer cells. (1995)

Recent studies have shown that the Bcl-2 protein suppresses programmed cell death or apoptosis induced by a variety of stimuli including chemotherapeutic drugs. Because estrogen promotes the survival of estrogen-dependent breast cancer cells in vivo, we investigated whether estrogen might regulate levels of Bcl-2 gene expression in an estrogen-responsive human breast cancer cell line. Estrogen receptor-positive MCF-7 human breast cancer cells cultured in the presence of estrogen express the 8.5-kb Bcl-2 mRNA transcript. Depletion of estrogen from the medium results in loss of expression of the mRNA, whereas reexposure to estrogen markedly induces the Bcl-2 transcript. The changes in Bcl-2 mRNA are paralleled by changes in Bcl-2 protein levels. Estrogen-induced increases in Bcl-2 are significantly inhibited by inclusion of the pure antiestrogen ICI 164,384 in the medium. The Bax protein that heterodimerizes with Bcl-2 and promotes cell death is expressed in MCF-7 cells grown in the presence of estrogen and is unaffected by culture in estrogen-free medium. Estrogen depletion doubles the sensitivity of MCF-7 cells to the cytotoxic effects of Adriamycin compared with cells cultured in medium supplemented with estrogen, consistent with a decrease in the Bcl-2 levels. MCF-7 cells treated simultaneously with estrogen and ICI 164,384 exhibit markedly lower resistance to Adriamycin compared with cells treated with estrogen alone. In the absence of estrogen, MCF-7 cells transfected with Bcl-2 expression plasmids display a marked increase in resistance to Adriamycin. In the presence of estrogen, MCF-7 cells expressing Bcl-2 antisense transcripts are rendered twice as sensitive to acute Adriamycin cytotoxicity as a control clone. We conclude that estrogen can promote resistance of estrogen receptor bearing human breast cancer cells to chemotherapeutic drugs through a mechanism that involves regulation of the Bcl-2 proto-oncogene.
Genome Engineering with Targetable Nucleases (2014)

Current technology enables the production of highly specific genome modifications with excellent efficiency and specificity. Key to this capability are targetable DNA cleavage reagents and cellular DNA repair pathways. The break made by these reagents can produce localized sequence changes through inaccurate nonhomologous end joining (NHEJ), often leading to gene inactivation. Alternatively, user-provided DNA can be used as a template for repair by homologous recombination (HR), leading to the introduction of desired sequence changes. This review describes three classes of targetable cleavage reagents: zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and CRISPR/Cas RNA-guided nucleases (RGNs). As a group, these reagents have been successfully used to modify genomic sequences in a wide variety of cells and organisms, including humans. This review discusses the properties, advantages, and limitations of each system, as well as the specific considerations required for their use in different biological systems.
High‐grade surface osteosarcoma (2008)

High-grade surface osteosarcoma is an extremely rare subtype of osteosarcoma. The current series demonstrates good overall survival for patients with this tumor. Metastatic disease and limb-sacrificing surgery were associated with a worse prognosis. Wide surgical excision and chemotherapy might improve the outcome.
N-Linked Glycosylation of Folded Proteins by the Bacterial Oligosaccharyltransferase (2006)

N-linked protein glycosylation is found in all domains of life. In eukaryotes, it is the most abundant protein modification of secretory and membrane proteins, and the process is coupled to protein translocation and folding. We found that in bacteria, N-glycosylation can occur independently of the protein translocation machinery. In an in vitro assay, bacterial oligosaccharyltransferase glycosylated a folded endogenous substrate protein with high efficiency and folded bovine ribonuclease A with low efficiency. Unfolding the eukaryotic substrate greatly increased glycosylation. We propose that in the bacterial system, glycosylation sites are located in flexible parts of folded proteins, whereas the eukaryotic cotranslational glycosylation evolved to a mechanism presenting the substrate in a flexible form before folding.
Fast production of homogeneous recombinant RNA—towards large-scale production of RNA (2012)

In the past decades, RNA molecules have emerged as important players in numerous cellular processes. To understand these processes at the molecular and atomic level, large amounts of homogeneous RNA are required for structural, biochemical and pharmacological investigations. Such RNAs are generally obtained from laborious and costly in vitro transcriptions or chemical synthesis. In 2007, a recombinant RNA technology has been described for the constitutive production of large amounts of recombinant RNA in Escherichia coli using a tRNA-scaffold approach. We demonstrate a general applicable extension to the described approach by introducing the following improvements: (i) enhanced transcription of large recombinant RNAs by T7 RNA polymerase (high transcription rates, versatile), (ii) efficient and facile excision of the RNA of interest from the tRNA-scaffold by dual cis-acting hammerhead ribozyme mediated cleavage and (iii) rapid purification of the RNA of interest employing anion-exchange chromatography or affinity chromatography followed by denaturing polyacrylamide gel electrophoresis. These improvements in the existing method pave the tRNA-scaffold approach further such that any (non-)structured product RNA of a defined length can cost-efficiently be obtained in (multi-)milligram quantities without in vitro enzymatic manipulations.
The relationship between clinically confirmed cobalamin deficiency and serum methylmalonic acid (1990)

Over a 1-year period, we examined 42 consecutive patients with low serum cobalamin levels detected by primary screening test (S-protein binder, RIA). In 31 patients (74%) clinical cobalamin deficiency was confirmed, whereas the remaining 11 patients (26%) were characterized clinically as non-cobalamin deficient. The serum methylmalonic acid level was higher than 0.34 mumol l-1 (3 SD above the mean in normal controls) in 30 of the 31 clinically characterized cobalamin-deficient subjects, and below this level in 10 of the 11 non-deficient patients. We conclude that the serum methylmalonic acid assay provides an appropriate means of discrimination between cobalamin deficiency and non-cobalamin deficiency (efficiency = 0.95), and we recommend that the assay be adopted as the standard test for diagnosis of tissue cobalamin deficiency.
A Meningococcal Factor H Binding Protein Mutant That Eliminates Factor H Binding Enhances Protective Antibody Responses to Vaccination (2011)

Certain pathogens recruit host complement inhibitors such as factor H (fH) to evade the immune system. Microbial complement inhibitor-binding molecules can be promising vaccine targets by eliciting Abs that neutralize this microbial defense mechanism. One such Ag, meningococcal factor H-binding protein (fHbp), was used in clinical trials before the protein was discovered to bind fH. The potential effect of fH binding on vaccine immunogenicity had not been assessed in experimental animals because fHbp binds human fH specifically. In this study, we developed a human fH transgenic mouse model. Transgenic mice immunized with fHbp vaccine had 4- to 8-fold lower serum bactericidal Ab responses than those of control mice whose native fH did not bind the vaccine. In contrast, Ab responses were unimpaired in transgenic mice immunized with a control meningococcal group C polysaccharide-protein conjugate vaccine. In transgenic mice, immunization with an fH nonbinding mutant of fHbp elicited Abs with higher bactericidal activity than that of fHbp vaccination itself. Abs elicited by the mutant fHbp more effectively blocked fH binding to wild-type fHbp than Abs elicited by fHbp that bound fH. Thus, a mutant fHbp vaccine that does not bind fH but that retains immunogenicity is predicted to be superior in humans to an fHbp vaccine that binds human fH. In the case of mutant fHbp vaccination, the resultant Ab responses may be directed more at epitopes in or near the fH binding site, which result in greater complement-mediated serum bactericidal activity; these epitopes may be obscured when human fH is bound to the wild-type fHbp vaccine.
Regulation of the Pancreatic Islet-Specific Gene BETA2 ( neuroD ) by Neurogenin 3 (2000)

The BETA2 (neuroD) gene is expressed in endocrine cells during pancreas development and is essential for proper islet morphogenesis. The objective of this study is to identify potential upstream regulators of the BETA2 gene during pancreas development. We demonstrated that the expression of neurogenin 3 (ngn3), an islet- and neuron-specific basic-helix-loop-helix transcription factor, partially overlaps that of BETA2 during early mouse development. More importantly, overexpression of ngn3 can induce the ectopic expression of BETA2 in Xenopus embryos and stimulate the endogenous RNA of BETA2 in endocrine cell lines. Furthermore, overexpression of ngn3 could cause a dose-dependent activation on the 1.0-kb BETA2 promoter in islet-derived cell lines. Deletion and mutation analyses revealed that two proximal E box sequences, E1 and E3, could bind to ngn3-E47 heterodimer and mediate ngn3 activation. Based on these results, we hypothesize that ngn3 is involved in activating the expression of BETA2 at an early stage of islet cell differentiation through the E boxes in the BETA2 promoter.