gebhart/patrepeval huggingface dataset:
Expression of alternatively spliced epidermal growth factor-like domains in aggrecans of different species. Evidence for a novel module (1993)

The carboxyl-terminal globular domain of human aggrecan has been shown previously to contain an alternatively spliced epidermal growth factor (EGF)-like module. We have used reverse transcription/polymerase chain reactions on cartilage-derived RNAs to investigate the heterogeneity in the EGF-like domain content of aggrecans from five species (mouse, rat, dog, bovine, and human). A novel alternatively spliced EGF-like module was detected in human aggrecan, establishing the presence of two of these domains. Highly homologous domains are present in aggrecans of other species, and the expression of these modules is identical (4-8%). They share significant homology with EGF-like domains of differentiation proteins and coagulation factors and have a putative calcium binding site. In contrast to this novel domain (EGF2), the previously described EGF-like module (EGF1) is expressed at a high level exclusively in human aggrecan. The expression of the two EGF-like domains in human aggrecan appears to be independent. Although the function of these domains is not understood, the uniform expression of the EGF2 domain may indicate a general role of this aggrecan module, while the expression of the EGF1 domain may reflect species specificity.
Toll-like receptor-4 is required for intestinal response to epithelial injury and limiting bacterial translocation in a murine model of acute colitis (2005)

Inflammatory bowel disease (IBD) arises from a dysregulated mucosal immune response to luminal bacteria. Toll-like receptor (TLR)4 recognizes LPS and transduces a proinflammatory signal through the adapter molecule myeloid differentiation marker 88 (MyD88). We hypothesized that TLR4 participates in the innate immune response to luminal bacteria and the development of colitis. TLR4-/- and MyD88-/- mice and littermate controls were given 2.5% dextran sodium sulfate (DSS) for 5 or 7 days followed by a 7-day recovery. Colitis was assessed by weight loss, rectal bleeding, and histopathology. Immunostaining was performed for macrophage markers, chemokine expression, and cell proliferation markers. DSS treatment of TLR4-/- mice was associated with striking reduction in acute inflammatory cells compared with wild-type mice despite similar degrees of epithelial injury. TLR4-/- mice experienced earlier and more severe bleeding than control mice. Similar results were seen with MyD88-/- mice, suggesting that this is the dominant downstream pathway. Mesenteric lymph nodes from TLR4-/- and MyD88-/- mice more frequently grew gram-negative bacteria. Altered neutrophil recruitment was due to diminished macrophage inflammatory protein-2 expression by lamina propria macrophages in TLR4-/- and MyD88-/- mice. The similarity in crypt epithelial damage between TLR4-/- or MyD88-/- and wild-type mice was seen despite decreased epithelial proliferation in knockout mice. TLR4 through the adapter molecule MyD88 is important in intestinal response to injury and in limiting bacterial translocation. Despite the diversity of luminal bacteria, other TLRs do not substitute for the role of TLR4 in this acute colitis model. A defective innate immune response may result in diminished bacterial clearance and ultimately dysregulated response to normal flora.
Adeno-associated Virus (AAV) Assembly-Activating Protein Is Not an Essential Requirement for Capsid Assembly of AAV Serotypes 4, 5, and 11 (2016)

Assembly-activating protein (AAP) is a recently discovered adeno-associated virus (AAV) protein that promotes capsid assembly and provides new opportunities for research in assembly. Previous studies on AAV serotype 2 (AAV2) showed that assembly takes place in the nucleolus and is dependent on AAP and that capsids colocalize with AAP in the nucleolus during the assembly process. However, through the investigation of 12 different AAV serotypes (AAV1 to -12), we find that AAP is not an essential requirement for capsid assembly of AAV4, -5, and -11, and AAP, assembled capsids, and the nucleolus do not colocalize for all the serotypes. In addition, we find that there are both serotype-restricted and serotype-promiscuous AAPs in their assembly roles. These findings challenge widely held beliefs about the importance of the nucleolus and AAP in AAV assembly and show the heterogeneous nature of the assembly process within the AAV family.
Mutational Analysis of the vacA Promoter Provides Insight into Gene Transcription in Helicobacter pylori (1999)

Analysis of 12 Helicobacter pylori promoters indicates the existence of a consensus -10 hexamer (TAtaaT) but little conservation of -35 sequences. In this study, mutations in either the H. pylori vacA -10 region or the -35 region resulted in decreased vacA transcription and suggested that an extended -10 motif is utilized. Thus, despite the lack of a -35 consensus sequence for H. pylori promoters, the -35 region plays a functional role in vacA transcription.
Electromagnetic propagation in periodic stratified media I General theory* (1977)

The propagation of electromagnetic radiation in periodically stratified media is considered. Media of finite, semi-infinite, and infinite extent are treated. A diagonalization of the unit cell translation operator is used to obtain exact solutions for the Bloch waves, the dispersion relations, and the band structure of the medium. Some new phenomena with applications to integrated optics and laser technology are presented.
KIT activation is a ubiquitous feature of gastrointestinal stromal tumors. (2001)

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, and they are generally resistant to chemotherapy and radiation therapy. Most GISTs express the KIT receptor tyrosine kinase protein, and a subset of GISTs contain activating mutations within the KIT juxtamembrane region. We evaluated 48 GISTs, including 10 benign, 10 borderline, and 28 malignant cases, to determine whether KIT expression and activation are general properties of these tumors. Immunohistochemical KIT expression was demonstrated in each case. Somatic KIT mutations were found in 44 tumors (92%), of which 34 (71%) had juxtamembrane region mutations. Other GISTs had KIT mutations in the extracellular region (n = 6) and in two different regions in the tyrosine kinase domain (n = 4). Contrary to previous reports, KIT mutations were not identified preferentially in higher-grade tumors: indeed, they were found in each of 10 histologically benign GISTs. Notably, mutations in all KIT domains were associated with high-level KIT activation/phosphorylation, and KIT activation was also demonstrated in the four GISTs that lacked detectable KIT genomic and cDNA mutations. These studies underscore the role of KIT activation in GIST pathogenesis, and they suggest that activated KIT might represent a universal therapeutic target in GISTs.
Total and biologically active CD154 in patients with SLE (2009)

CD154, a member of the tumor necrosis factor receptor family, is involved in several biological responses. In the sera of systemic lupus erythematosus (SLE) patients, the levels of sCD154 have been shown to be increased, however, few reports have dealt with the biologically active tetramer. Here, we assessed the biological activity of the serum CD154 tetramer using bioassays for BC activation and production nitrite or peroxide. The patients showed a markedly increased total sCD154 serum concentration (12.5 +/- 8.2 vs. 3.9 +/- 1.2 ng/ml; p < 0.001). ba-sCD154 was significantly increased in non-treated patients (7.4 +/- 3.4 ng/ml, n = 22; p < 0.001) and patients with the highest SLE disease activity index (SLEDAI) scores (5.3 +/- 2.9 ng/ml, n = 8), but not in stable patients (1.3 +/- 1.2 ng/ml, n = 30) whose values were similar to normal healthy donors (NHD; 0.8 +/- 0.2 ng/ml). Patients with SLEDAI above 8 that recovered after successful treatment displayed significantly decreased levels of ba-sCD154. We conclude that the bioassay is a useful tool discriminating active and stable SLE, as well as non-treated patients.
Time reversal and object reconstruction with single-cycle pulses (2001)

We demonstrate the reconstruction of one- and two-dimensional objects by numerically backpropagating measured scattered terahertz transients. The spatial resolution determined by the Sparrow criterion is found to correspond to approximately 30% of the peak wavelength and 85% of the mean wavelength of the power spectrum of the single-cycle waveform.
BindingDB Entry 50022503: A novel small molecule met inhibitor induces apoptosis in cells transformed by the oncogenic TPR-MET tyrosine kinase. (2025)

The Met receptor tyrosine kinase has been shown to be overexpressed or mutated in a variety of solid tumors and has, therefore, been identified as a good candidate for molecularly targeted therapy. Activation of the Met tyrosine kinase by the TPR gene was originally described in vitro through carcinogen-induced rearrangement. The TPR-MET fusion protein contains constitutively elevated Met tyrosine kinase activity and constitutes an ideal model to study the transforming activity of the Met kinase. We found, when introduced into an interleukin 3-dependent cell line, TPR-MET induces factor independence and constitutive tyrosine phosphorylation of several cellular proteins. One major tyrosine phosphorylated protein was identified as the TPR-MET oncoprotein itself. Inhibition of the Met kinase activity by the novel small molecule drug SU11274 [(3Z)-N-(3-chlorophenyl)-3-([3,5-dimethyl-4-[(4-methylpiperazin-1-yl)carbonyl]-1H-pyrrol-2-yl]methylene)-N-methyl-2-oxo-2,3-dihydro-1H-indole-5-sulfonamide] led to time- and dose-dependent reduced cell growth. The inhibitor did not affect other tyrosine kinase oncoproteins, including BCR-ABL, TEL-JAK2, TEL-PDGFbetaR, or TEL-ABL. The Met inhibitor induced G(1) cell cycle arrest and apoptosis with increased Annexin V staining and caspase 3 activity. The autophosphorylation of the Met kinase was reduced on sites that have been shown previously to be important for activation of pathways involved in cell growth and survival, especially the phosphatidylinositol-3'-kinase and the Ras pathway. In particular, we found that the inhibitor blocked phosphorylation of AKT, GSK-3beta, and the pro-apoptotic transcription factor FKHR. The characterization of SU11274 as an effective inhibitor of Met tyrosine kinase activity illustrates the potential of targeting for Met therapeutic use in cancers associated with activated forms of this kinase.
Broad-passband-width optical filter for multi/demultiplexer using a diffraction grating and a retroreflector prism (1985)

The letter describes the experimental results of a novel optical filter for a multi/demultiplexer using a diffraction grating and a retroreflector prism. A broader passband width, which is proportional to the difference between the prism base length and the input fibre core diameter, is obtained. The minimum insertion loss is 2.2 dB.
Delivery and Subcellular Targeting of Dendrimer-Based Fluorescent pH Sensors in Living Cells (2010)

Synthesis and targeted delivery of dendrimer-based fluorescent biosensors in living HeLa cells are reported. Following electroporation dendrimers are shown to display specific subcellular localization depending on their size and surface charge and this property is preserved when they are functionalized with sensing moieties. We analyze the case of double dendrimer conjugation with pH-sensitive and pH-insensitive molecules leading to the realization of ratiometric pH sensors that are calibrated in vitro and in living cells. By tuning the physicochemical properties of the dendrimer scaffold sensors can be targeted to specific cellular compartments allowing selective pH measurements in different organelles in living cells. In order to demonstrate the modularity of this approach we present three different pH sensors with tuned H(+) affinity by appropriately choosing the pH-sensitive dye. We argue that the present methodology represents a general approach toward the realization of targetable ratiometric sensors suitable to monitor biologically relevant ions or molecules in living cells.
Parathyroid Hormone-Related Protein of Malignancy: Active Synthetic Fragments (1987)

Peptides corresponding to the amino-terminal region of the parathyroid hormone-related protein (PTHrP) of humoral hypercalcemia of malignancy were synthesized. A 34-amino acid peptide, PTHrP(1-34), was two to four times more potent than bovine or human PTH(1-34) in bioassays promoting the formation of adenosine 3',5'-monophosphate (cAMP) and plasminogen activator activity in osteogenic sarcoma cells and adenylate cyclase activity in chick kidney membranes. Like parathyroid hormone itself, in which the activity resides in the first 34 residues, PTHrP peptides of less than 30 residues from the amino terminus showed substantially reduced activity. PTHrP(1-34) had only 6% of the potency of bovine PTH(1-34) in promoting bone resorption in vitro. PTHrP(1-34) strongly promoted the excretion of cAMP and phosphorus and reduced the excretion of calcium in the isolated, perfused rat kidney consistent with the symptoms seen in malignant hypercalcemia.
Medial temporal atrophy on MRI in normal aging and very mild Alzheimer's disease (1997)

Magnetic resonance imaging (MRI)-based volumetric measurements of medial temporal lobe (MTL) structures can discriminate between normal elderly control subjects and patients with Alzheimer's disease (AD) of moderate to advanced severity. In terms of clinical utility, however, a more important issue concerns the ability of the technique to differentiate between normal elderly control subjects and AD patients with the very mildest form of the disease. We performed MRI-based volumetric measurements of the hippocampus, parahippocampal gyrus, and amygdala in 126 cognitively normal elderly control subjects and 94 patients with probable AD. The diagnosis of AD was made according to NINDS/ADRDA criteria, and disease severity was categorized by Clinical Dementia Rating (CDR) scores. Patients with CDR 0.5 were classified as very mild, CDR 1 as mild, and CDR 2 as moderate disease severity. Volumes of each structure declined with increasing age in control subjects and did so in parallel for men and women. The volume of each measured MTL structure also declined with age in patients with AD. The volume of each MTL structure was significantly smaller in AD patients than control subjects (p < 0.001). Of the several MTL measures, the total hippocampal volumetric measurements were best at discriminating control subjects from AD patients. The mean hippocampal volumes for AD patients relative to control subjects by severity of disease were as follows: very mild AD (CDR 0.5) -1.75 SD below the control mean, mild AD (CDR 1) -1.99 SD, and moderate AD (CDR 2) -2.22 SD. Age- and gender-adjusted, normalized MRI-based hippocampal volumetric measurements provide a sensitive marker of the MTL neuroanatomic degeneration in AD early in the disease process.
Mammalian microRNAs: experimental evaluation of novel and previously annotated genes (2010)

MicroRNAs (miRNAs) are small regulatory RNAs that derive from distinctive hairpin transcripts. To learn more about the miRNAs of mammals, we sequenced 60 million small RNAs from mouse brain, ovary, testes, embryonic stem cells, three embryonic stages, and whole newborns. Analysis of these sequences confirmed 398 annotated miRNA genes and identified 108 novel miRNA genes. More than 150 previously annotated miRNAs and hundreds of candidates failed to yield sequenced RNAs with miRNA-like features. Ectopically expressing these previously proposed miRNA hairpins also did not yield small RNAs, whereas ectopically expressing the confirmed and newly identified hairpins usually did yield small RNAs with the classical miRNA features, including dependence on the Drosha endonuclease for processing. These experiments, which suggest that previous estimates of conserved mammalian miRNAs were inflated, provide a substantially revised list of confidently identified murine miRNAs from which to infer the general features of mammalian miRNAs. Our analyses also revealed new aspects of miRNA biogenesis and modification, including tissue-specific strand preferences, sequential Dicer cleavage of a metazoan precursor miRNA (pre-miRNA), consequential 5' heterogeneity, newly identified instances of miRNA editing, and evidence for widespread pre-miRNA uridylation reminiscent of miRNA regulation by Lin28.
Fibroblast migration in fibrin gel matrices. (1993)

In healing wounds and many solid tumors, locally increased microvascular permeability results in extravasation of fibrinogen and its extravascular coagulation to form a fibrin gel, with concomitant covalent cross-linking of fibrin by factor XIIIa. Subsequently, inflammatory cells, fibroblasts, and endothelial cells migrate into the gel and organize it into granulation tissue and later into mature collagenous connective tissue. To gain insight into some of the cell migration events associated with these processes, we developed a quantitative in vitro assay that permits the study of fibroblast migration in fibrin gels. Early passage human or rat fibroblasts were allowed to attach to tissue culture dishes and then were overlaid with a thin layer of fibrinogen that was clotted with thrombin. Fibroblasts began to migrate upwards into the fibrin within 24 hours and their numbers and the distance migrated were quantified over several days. The extent of fibroblast migration was affected importantly by the nature of the fibrin clot. Fibroblasts migrated optimally into gels prepared from fibrinogen at concentrations of -3 mg/ml; ie, near normal plasma fibrinogen levels. Migration was greatly enhanced by extensive cross-linking of the fibrin alpha-chains by factor XIIIa, as occurs when clotting takes place in vivo. When fibrinogen was clotted in Dulbecco's modified Eagle's medium, gamma-chains were cross-linked, but alpha-chain cross-linking was strikingly inhibited, and fibroblasts migrated poorly. Gels prepared from factor XIII-depleted fibrinogen exhibited neither alpha-nor gamma-chain cross-linking and did not support fibroblast migration. Further purification of fibrinogen by anion exchange high pressure liquid chromatography depleted fibrinogen of fibronectin, plasminogen, and other impurities; this purified fibrinogen clotted to form fibrin gels that supported reproducible fibroblast migration.
Identification and characterization of the ARP1 gene, a target for the human acute leukemia ALL1 gene (1998)

ALL1, the human homologue of Drosophila trithorax, is directly involved in human acute leukemias associated with abnormalities at 11q23. Using the differential display method, we isolated a gene that is down-regulated in All1 double-knockout mouse embryonic stem (ES) cells. The gene, designated ARP1 (also termed RIEG, Ptx2, or Otlx2), is a member of a family of homeotic genes containing a short motif shared with several homeobox genes. Using a bacterially synthesized All1 polypeptide encompassing the AT-hook motifs, we identified a 0.5-kb ARP1 DNA fragment that preferentially bound to the polypeptide. Within this DNA, a region of approximately 100 bp was protected by the polypeptide from digestion with ExoIII and DNase I. Whole-mount in situ hybridization to early mouse embryos of 9.5-10.5 days indicated a complex pattern of Arp1 expression spatially overlapping with the expression of All1. Although the ARP1 gene is expressed strongly in bone marrow cells, no transcripts were detected in six leukemia cell lines with 11q23 translocations. These results suggest that ARP1 is up-regulated by the All1 protein, possibly through direct interaction with an upstream DNA sequence of the former. The results are also consistent with the suggestion that ALL1 chimeric proteins resulting from 11q23 abnormalities act in a dominant negative fashion.
Characterization of Cyanobacteriochrome TePixJ from a Thermophilic Cyanobacterium Thermosynechococcus elongatus Strain BP-1 (2006)

A putative photoreceptor gene, TepixJ, of a thermophilic cyanobacterium is homologous to SypixJ1 that mediates positive phototaxis in the unicellular motile cyanobacterium Synechocystis sp. PCC 6803. The putative chromophore-binding GAF domain of TePixJ protein was overexpressed as a fusion with a polyhistidine tag (His-TePixJ_GAF) in Synechocystis cells and isolated to homogeneity. The photoreversible conversion of His-TePixJ_GAF showed peaks at 531, 341 and 266 nm for the green light-absorbing form (Pg form), and peaks at 433 and 287 nm for the blue light-absorbing form (Pb form). At 77K, the Pg form fluoresced at 580 nm, while the Pb form did not emit any fluorescence. Mass spectrometry of the tryptic chromopeptide demonstrated that a phycocyanobilin isomer binds to the conserved cysteine at ring A via a thioether bond. It is established that TePixJ and SyPixJ1 are novel photoreceptors in cyanobacteria ('cyanobacteriochromes') that are similar, but distinct from the phytochromes and bacteriophytochromes.
Crystallisation in polymer films: control of morphology and kinetics of an organic dye in a polysilicone matrix (1997)

The successful selection, design and synthesis of additives for the control of nucleation and crystallisation of a red anthraquinone based dye is described. This procedure is based on the crystal structure and morphology of solution grown crystals and in this study the possibility of using the same approach to control crystallisation within an amorphous polymeric matrix is explored. The work has been motivated by the desire to prepare stable dye sheets for thermal transfer printing applications, yet the parallel with natural biomineralisation processes is clear.
p38 Mitogen-activated Protein Kinase Mediates the Transcriptional Induction of the Atrial Natriuretic Factor Gene through a Serum Response Element (1998)

In various cell types certain stresses can stimulate p38 mitogen-activated protein kinase (p38 MAPK), leading to the transcriptional activation of genes that contribute to appropriate compensatory responses. In this report the mechanism of p38-activated transcription was studied in cardiac myocytes where this MAPK is a key regulator of the cell growth and the cardiac-specific gene induction that occurs in response to potentially stressful stimuli. In the cardiac atrial natriuretic factor (ANF) gene, a promoter-proximal serum response element (SRE), which binds serum response factor (SRF), was shown to be critical for ANF induction in primary cardiac myocytes transfected with the selective p38 MAPK activator, MKK6 (Glu). This ANF SRE does not possess sequences typically required for the binding of the Ets-related ternary complex factors (TCFs), such as Elk-1, indicating that p38-mediated induction through this element may take place independently of such TCFs. Although p38 did not phosphorylate SRF in vitro, it efficiently phosphorylated ATF6, a newly discovered SRF-binding protein that is believed to serve as a co-activator of SRF-inducible transcription at SREs. Expression of an ATF6 antisense RNA blocked p38-mediated ANF induction through the ANF SRE. Moreover, when fused to the Gal4 DNA-binding domain, an N-terminal 273-amino acid fragment of ATF6 was sufficient to support trans-activation of Gal4/luciferase expression in response to p38 but not the other stress kinase, N-terminal Jun kinase (JNK); p38-activating cardiac growth promoters also stimulated ATF6 trans-activation. These results indicate that through ATF6, p38 can augment SRE-mediated transcription independently of Ets-related TCFs, representing a novel mechanism of SRF-dependent transcription by MAP kinases.