gebhart/patrepeval huggingface dataset:
Expression and function of HLA‐A2.1 in transgenic mice (1989)

We have derived a number of transgenic mouse lines which express the human major histocompatibility complex class I gene HLA-A2.1. Two lines carry the complete human HLA-A2.1, the others bear a recombinant gene in which the HLA-A2.1 coding regions are fused to the H-2Kb promoter. Analysis of transgenic spleen cells by immunofluorescence demonstrates that these mouse cells express HLA-A2.1 on their surface in association with mouse beta 2-microglobulin (beta 2m), confirming that HLA-A2 does not require human beta 2m to be expressed at the cell surface. The cells contain more HLA mRNA than endogenous H-2 class I mRNA. There is also a large pool of non-beta 2m-associated HLA heavy chain inside the cell. In contrast the amount of HLA:beta 2m complex is low. Thus, in transgenic mice HLA-A2 seems to compete poorly with H-2 heavy chains for mouse beta 2m. The HLA-A2.1 transgenic mice do not produce influenza-virus-specific cytotoxic T cells (CTL) restricted to the HLA transgene, at least in sufficient numbers to be measured in a direct bulk CTL assay. The dominance of H-2-restricted clones may be the result of quantitative rather than qualitative factors. However, HLA-A2.1 transgenic spleen cells are effective in stimulating an allogeneic CTL response in normal mice. This response is not H-2 restricted. Cold target inhibition studies show that there are at least two populations of CTL, one of which is specific for HLA-A2.1 on mouse cells. This result suggests that at least some allo-CTL are directed against major histocompatibility complex plus "self-peptide".
Eye movements in reading and information processing: 20 years of research. (1998)

Recent studies of eye movements in reading and other information processing tasks, such as music reading, typing, visual search, and scene perception, are reviewed. The major emphasis of the review is on reading as a specific example of cognitive processing. Basic topics discussed with respect to reading are (a) the characteristics of eye movements, (b) the perceptual span, (c) integration of information across saccades, (d) eye movement control, and (e) individual differences (including dyslexia). Similar topics are discussed with respect to the other tasks examined. The basic theme of the review is that eye movement data reflect moment-to-moment cognitive processes in the various tasks examined. Theoretical and practical considerations concerning the use of eye movement data are also discussed.
The 5′ → 3′ exoribonuclease XRN1/Pacman and its functions in cellular processes and development (2012)

XRN1 is a 5' → 3' processive exoribonuclease that degrades mRNAs after they have been decapped. It is highly conserved in all eukaryotes, including homologs in Drosophila melanogaster (Pacman), Caenorhabditis elegans (XRN1), and Saccharomyces cerevisiae (Xrn1p). As well as being a key enzyme in RNA turnover, XRN1 is involved in nonsense-mediated mRNA decay and degradation of mRNAs after they have been targeted by small interfering RNAs or microRNAs. The crystal structure of XRN1 can explain its processivity and also the selectivity of the enzyme for 5' monophosphorylated RNA. In eukaryotic cells, XRN1 is often found in particles known as processing bodies (P bodies) together with other proteins involved in the 5' → 3' degradation pathway, such as DCP2 and the helicase DHH1 (Me31B). Although XRN1 shows little specificity to particular 5' monophosphorylated RNAs in vitro, mutations in XRN1 in vivo have specific phenotypes suggesting that it specifically degrades a subset of RNAs. In Drosophila, mutations in the gene encoding the XRN1 homolog pacman result in defects in wound healing, epithelial closure and stem cell renewal in testes. We propose a model where specific mRNAs are targeted to XRN1 via specific binding of miRNAs and/or RNA-binding proteins to instability elements within the RNA. These guide the RNA to the 5' core degradation apparatus for controlled degradation.
Ligand Affinity for Amino-Terminal and Juxtamembrane Domains of the Corticotropin Releasing Factor Type I Receptor:  Regulation by G-Protein and Nonpeptide Antagonists (2004)

Peptide ligands bind the CRF(1) receptor by a two-domain mechanism: the ligand's carboxyl-terminal portion binds the receptor's extracellular N-terminal domain (N-domain) and the ligand's amino-terminal portion binds the receptor's juxtamembrane domain (J-domain). Little quantitative information is available regarding this mechanism. Specifically, the microaffinity of the two interactions and their contribution to overall ligand affinity are largely undetermined. Here we measured ligand interaction with N- and J-domains expressed independently, the former (residues 1-118) fused to the activin IIB receptor's membrane-spanning alpha-helix (CRF(1)-N) and the latter comprising residues 110-415 (CRF(1)-J). We also investigated the effect of nonpeptide antagonist and G-protein on ligand affinity for N- and J-domains. Peptide agonist affinity for CRF(1)-N was only 1.1-3.5-fold lower than affinity for the whole receptor (CRF(1)-R), suggesting the N-domain predominantly contributes to peptide agonist affinity. Agonist interaction with CRF(1)-J (potency for stimulating cAMP accumulation) was 12000-1500000-fold weaker than with CRF(1)-R, indicating very weak direct agonist interaction with the J-domain. Nonpeptide antagonist affinity for CRF(1)-J and CRF(1)-R was indistinguishable, indicating the compounds bind predominantly the J-domain. Agonist activation of CRF(1)-J was fully blocked by nonpeptide antagonist, suggesting antagonism results from inhibition of agonist-J-domain interaction. G-protein coupling with CRF(1)-R (forming RG) increased peptide agonist affinity 92-1300-fold, likely resulting from enhanced agonist interaction with the J-domain rather than the N-domain. Nonpeptide antagonists, which bind the J-domain, blocked peptide agonist binding to RG, and binding of peptide antagonists, predominantly to the N-domain, was unaffected by R-G coupling. These findings extend the two-domain model quantitatively and are consistent with a simple equilibrium model of the two-domain mechanism: (1) The N-domain binds peptide agonist with moderate-to-high microaffinity, substantially increasing the local concentration of agonist and so allowing weak agonist-J-domain interaction. (2) Agonist-J-domain interaction is allosterically enhanced by receptor-G-protein interaction and inhibited by nonpeptide antagonist.
Analysis of Gangliosides Directly from Thin-Layer Chromatography Plates by Infrared Matrix-Assisted Laser Desorption/Ionization Orthogonal Time-of-Flight Mass Spectrometry with a Glycerol Matrix (2005)

A novel method is presented for direct coupling of high-performance thin-layer chromatography (HPTLC) with matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) for the analysis of biomolecules. A first key feature is the use of a liquid matrix (glycerol), which provides a homogeneous wetting of the silica gel and a simple and fast MALDI preparation protocol. A second is the use of an Er:YAG infrared laser, which ablates layers of approximately 10-microm thickness of analyte-loaded silica gel and provides a soft desorption/ionization of even very labile analyte molecules. The orthogonal time-of-flight mass spectrometer employed in this study, finally provides a high accuracy of the mass determination, which is independent of any irregularity of the silica gel surface. The analytical potential of the method is demonstrated by the compositional mapping of a native GM3 (II(3)-alpha-Neu5Ac-LacCer) ganglioside mixture from cultured Chinese hamster ovary cells. The analysis is characterized by a high relative sensitivity, allowing the simultaneous detection of various major and minor GM3 species directly from individual HPTLC analyte bands. The lateral resolution of the direct HPTLC-MALDI-MS analysis is defined by the laser focus diameter of currently approximately 200 microm. This allows one to determine mobility profiles of individual species with a higher resolution than by reading off the chromatogram by optical absorption. The fluorescent dye primuline was, furthermore, successfully tested as a nondestructive, MALDI-compatible staining agent.
Recombinant Vesicular Stomatitis Virus Transduction of Dendritic Cells Enhances Their Ability to Prime Innate and Adaptive Antitumor Immunity (2009)

Dendritic cell (DC)-based vaccines are a promising strategy for tumor immunotherapy due to their ability to activate both antigen-specific T-cell immunity and innate immune effector components, including natural killer (NK) cells. However, the optimal mode of antigen delivery and DC activation remains to be determined. Using M protein mutant vesicular stomatitis virus (DeltaM51-VSV) as a gene-delivery vector, we demonstrate that a high level of transgene expression could be achieved in approximately 70% of DCs without affecting cell viability. Furthermore, DeltaM51-VSV infection activated DCs to produce proinflammatory cytokines (interleukin-12, tumor necrosis factor-alpha, and interferon (IFN)alpha/beta), and to display a mature phenotype (CD40(high)CD86(high) major histocompatibility complex (MHC II)(high)). When delivered to mice bearing 10-day-old lung metastatic tumors, DCs infected with DeltaM51-VSV encoding a tumor-associated antigen mediated significant control of tumor growth by engaging both NK and CD8(+) T cells. Importantly, depletion of NK cells completely abrogated tumor destruction, indicating that NK cells play a critical role for this DC vaccine-induced therapeutic outcome. Our findings identify DeltaM51-VSV as both an efficient gene-delivery vector and a maturation agent allowing DC vaccines to overcome immunosuppression in the tumor-bearing host.
Ocean-bottom seismic measurements off the California coast (1964)

As a part of the Vela Uniform program seismograms were recorded between December 19, 1961, and April 1, 1962, from instruments placed on the ocean bottom off the California coast in water depths up to 1.2 km. Three components of velocity and water pressure were recorded digitally. During the test period a total of five underground nuclear blasts originating from the Nevada test site and several small unidentified seismic events were recorded by the ocean-bottom seismometer. Recordings of pressure and vertical velocity in the frequency range of 0.5 to 5 cps for three nuclear blasts were of sufficient quality for detailed analysis. Spectral analyses were performed on several of these nuclear blast seismograms and the noise data immediately preceding them. These were compared with similar analyses of the same events obtained from a land station in the southern California area. The results indicated that signal-to-noise ratio is slightly poorer on the ocean bottom in 1.2 km of water than on a land station at the same range. The absolute noise level appears to be higher at the deep water sites relative to the land station; however, the ocean-bottom noise level is near the continental ‘average’ of Brune and Oliver for the samples investigated. Finally, the simultaneous recording of pressure and velocity appears to afford a distinct advantage in the identification and classification of arrivals recorded on the ocean bottom because of the P-V relationship that exists for the various propagation modes.
Cloning and developmental expression of the ecdysone receptor gene from the spruce budworm, choristoneura fumiferana (1995)

Degenerate oligonucleotides were designed on the basis of conserved amino acid sequences in the DNA and ligand-binding regions of the members of the steroid hormone receptor superfamily. Using these oligonucleotides in RNA-PCR, a cDNA fragment was isolated from the spruce budworm, Choristoneura fumiferana. Comparison of the deduced amino acid sequence of this cDNA fragment with the members of the steroid hormone receptor superfamily suggested that this PCR fragment is a region of the ecdysone receptor from C. fumiferana. Using this cDNA fragment as a probe, 10 clones were isolated from a cDNA library that was constructed using the RNA from 4- and 5-day old embryos of C. fumiferana. Two cDNA clones (1.3 and 3 kb) that overlap and show amino acid identity with Drosophila melanogaster ecdysone receptor B-1 isoform (DmEcR) were characterized and sequenced. The longest open reading frame had 539 codons and covered the complete EcR coding region. The deduced amino acid sequence of this open reading frame had all five of the regions typical for a steroid hormone nuclear receptor. The C domain or DNA binding region showed the highest identity wit EcR proteins from D. melanogaster, Chironomus tendons, Aedes aegypti, Manduca sexta, and Bombyx mori. The A/B region, D domain or hinge region, E domain, or ligand binding region also showed significant amino acid similarity with the EcR proteins from the five insects mentioned above. The C. fumiferana ecdysteroid receptor (CfEcR) cDNA probe detected a 6.0-kb mRNA that was present throughout the development of C. fumiferana. The CfEcR mRNA increases in abundance at the time of the ecdysteroid peak during the molting phase in the embryonic, larval and pupal stages but remains low during the intermolt period. In the 6th instar larvae, the 6-kb CfEcR mRNA was detected in the epidermis, fat body, and midgut and maximum expression was observed during the prepupal peak of ecdysteroids in the hemolymph. CfEcR mRNA was induced in ecdysone treated CF-203 cells as well in the epidermis and midgut of larvae that were fed the nonsteroidal ecdysteroid agonist, RH-5992. The induction occurred within an hour and reached maximum levels around 3 hr, after which it decreased to the basal level by 6 hr. In vitro transcription and translation of the CfEcR cDNA yielded a 67-Kda protein that bound to the ecdysone response element (EcRE) as a heterodimer, along with the ultraspiracle protein.
Microbiology and Treatment of Acute Apical Abscesses (2013)

Acute apical abscess is the most common form of dental abscess and is caused by infection of the root canal of the tooth. It is usually localized intraorally, but in some cases the apical abscess may spread and result in severe complications or even mortality. The reasons why dental root canal infections can become symptomatic and evolve to severe spreading and sometimes life-threatening abscesses remain elusive. Studies using culture and advanced molecular microbiology methods for microbial identification in apical abscesses have demonstrated a multispecies community conspicuously dominated by anaerobic bacteria. Species/phylotypes commonly found in these infections belong to the genera Fusobacterium, Parvimonas, Prevotella, Porphyromonas, Dialister, Streptococcus, and Treponema. Advances in DNA sequencing technologies and computational biology have substantially enhanced the knowledge of the microbiota associated with acute apical abscesses and shed some light on the etiopathogeny of this disease. Species richness and abundance and the resulting network of interactions among community members may affect the collective pathogenicity and contribute to the development of acute infections. Disease modifiers, including transient or permanent host-related factors, may also influence the development and severity of acute abscesses. This review focuses on the current evidence about the etiology and treatment of acute apical abscesses and how the process is influenced by host-related factors and proposes future directions in research, diagnosis, and therapeutic approaches to deal with this disease.
Bone formation in coralline hydroxyapatite: Effects of pore size studied in rabbits (1994)

We analyzed osseous reactions in the rabbit femoral condyle to coralline hydroxyapatite bone substitutes of various pore sizes by radiology and histology. The results were compared to bone repair of empty cavities and to integration of allografts. Spontaneous bone repair of the empty cavities took approximately 12 weeks, while integration of the cryopreserved allografts occurred after 9 weeks. However, no signs of new bone formation were found with the 200 microns pore size hydroxyapatite. In contrast, there was substantial production of bone within the 500 microns pore size implants at 12 and 26 weeks. Our results indicate that the pore size of the coralline hydroxyapatite influenced the development of bone in the implants in the cancellous bone bed of the rabbit femoral condyle. The results also show that spontaneous bone repair should be taken into consideration when the integration of implants is evaluated.
Inhibition of the VEGF receptor 2 combined with chronic hypoxia causes cell death‐dependent pulmonary endothelial cell proliferation and severe pulmonary hypertension (2001)

Our understanding of the pathobiology of severe pulmonary hypertension, usually a fatal disease, has been hampered by the lack of information of its natural history. We have demonstrated that, in human severe pulmonary hypertension, the precapillary pulmonary arteries show occlusion by proliferated endothelial cells. Vascular endothelial growth factor (VEGF) and its receptor 2 (VEGFR-2) are involved in proper maintenance, differentiation, and function of endothelial cells. We demonstrate here that VEGFR-2 blockade with SU5416 in combination with chronic hypobaric hypoxia causes severe pulmonary hypertension associated with precapillary arterial occlusion by proliferating endothelial cells. Prior to and concomitant with the development of severe pulmonary hypertension, lungs of chronically hypoxic SU5416-treated rats show significant pulmonary endothelial cell death, as demonstrated by activated caspase 3 immunostaining and TUNEL. The broad caspase inhibitor Z-Asp-CH2-DCB prevents the development of intravascular pulmonary endothelial cell growth and severe pulmonary hypertension caused by the combination of SU5416 and chronic hypoxia.
Projections from the cervical enlargement to the cerebellar nuclei in the rat, studied by anterograde axonal tracing (1997)

Spinocerebellar projections from the cervical enlargement originate from neurons in the medial part of lamina VI and the central part of lamina VII. In the present study, the topographic projections of the cervical enlargement to the cerebellar nuclei were examined by anterograde tracing with biotinylated dextran in the rat. Following injections of the tracer into the spinal cord at levels between the C5 and T1 segments, anterogradely labeled axons and terminals were immunohistochemically demonstrated in the cerebellar nuclei. Unilateral injections revealed that projections are bilateral, but predominantly ipsilateral, to the cells of origin. Labeled axons entered the media nucleus from its rostrodorsal and rostromedial aspects. Labeled terminals were distributed to dorsal and medial parts of the middle subdivision at its rostral levels and to medial parts of the caudomedial subdivision of the medial nucleus. Most axons terminated in the middle subdivision. Single axons were seen to course rostrocaudally in the medial nucleus and give off terminal axons to both subdivisions. A few labeled terminals were seen in the dorsolateral protuberance of the medial nucleus, and in the anterior interpositus and the posterior interpositus nuclei. No labeled terminals were seen in the lateral cerebellar nucleus. The present study demonstrates that spinocerebellar neurons in laminae VI and VII of the cervical enlargement project to dorsomedial areas of the medial nucleus at rostral levels, bilaterally but predominantly ipsilaterally. It is suggested that these areas specifically receive cutaneous and muscular input related to the forelimb movement.
Genes Associated with Fast Glioma Cell Migration In Vitro and In Vivo (2006)

Identification of genes mediating glioma invasion promotes the understanding of glia motility and might result in biologically based therapeutic approaches. Most experimental studies have been performed in vitro, although glial cells typically undergo marked phenotypic change following placement into cell culture. To evaluate migration mechanisms operating in vitro versus in vivo, we used C6 rat glioblastoma cells for selecting highly migratory cells in a monolayer migration assay as well as in brains of nude mice, and analyzed in each paradigm the expression profiles of these "fast" cells versus those of the original "slow" cells using oligonucleotide microarrays comprising 8832 genes. In vitro, 516 (10.6%) of 4848 expressed genes were regulated (i.e., differentially expressed in fast versus slow cells); 916 genes were expressed only in vitro, including 142 (15.5%) regulated genes. In vivo, 245 (6.1%) of 4044 expressed genes were regulated; 112 genes were expressed only in vivo, including 25 (22.3%) regulated genes, none of them having a known relation to glioma invasion. Of 730 regulated genes, only 31 (4.2%) were regulated in parallel in vitro and in vivo, most of them having a known relation to (glioma) invasion. Our data provide new molecular entry points for identifying glioma invasion genes operating exclusively in the brain. They further suggest that genes underlying glia cell motility are strikingly different in vitro and in vivo.
Toward a Third Generation of Cholinesterase Inhibitors (1991)

The finding of a severely damaged and underactive cholinergic system in the brain of AD patients has led to clinical trials of new cholinomimetics including cholinesterase inhibitors (ChEI) (see Becker and Giacobini, 1988a,b). Based on available experimental and clinical information (Giacobini and Becker, 1989; Pomponi et al., 1990), an ideal ChEI suitable for symptomatic treatment of memory and cognitive impairment in AD should satisfy the following requirements: a) produce a long-term acetylcholinesterase (AChE) inhibition in brain with a steady-state phase of increased cortical ACh; b) not inhibit acetylcholine (ACh) synthesis or release in nerve endings; and c) produce only mild side effects at therapeutic doses. Such requirements have not been met by the ChEI used so far (Becker and Giacobini, 1988a,b). We have studied a number of new ChEI (Giacobini and Becker, 1989) and based on our experimental results in animals, we have proposed three new ChEI for experimental therapy of Alzheimer disease (AD), heptyl-physostigmine (HEP), a physostigmine (PHY) derivative, metrifonate (MTF) and huperzine A (HUP-A) (Hallak and Giacobini, 1987, 1989; DeSarno et al., 1989; Tang et al., 1989). All three compounds are in clinical trials. Both MTF and HEP have a low level of toxicity in humans and only at the 60–80% of plasma butyrylcholinesterase (BuChE) level of inhibition, peripheral side effects are present. No central side effects have been recorded.
A multivariate analysis of patients with brain tumors treated with ATN-RNA. (2009)

Glioblastoma multiforme (GBM) is the most common form of malignant glioma, characterized by genetic instability, intratumoral histopathological variability, and unpredictable clinical behavior. Malignant gliomas express preferentially a number of surface markers that may be exploited as therapeutic targets, such as tenascin-C, an extracellular matrix glycoprotein contributes to tumor cell adhesion, invasion, migration and proliferation. Disappointing results in the treatment of gliomas with surgery, radiation and chemotherapy have fuelled a search for new treatment modalities. Here we present the data for 46 patients suffering from brain tumor. They were resected and treated with dsRNA (ATN-RNA) complementary to the sequence of tenascin-C mRNA. MRI and CT follow up studies showed growth tumor delay or lack of its recurrence symptoms, due to inhibition of TN-C synthesis. A significant improvement in overall survival (OS) was observed without loosing of the quality of life (QOL) of patients. This novel therapy based on RNA interference shows a big therapeutical potential. To our knowledge intervention with RNAi (iRNAi) is the first protocol of application of RNAi in human disease treatment.