gebhart/patrepeval huggingface dataset:
MACC1 promotes carcinogenesis of colorectal cancer via β-catenin signaling pathway (2014)

Here we confirmed that metastasis-associated in colon cancer 1 (MACC1) and β-catenin expression were higher in colorectal cancer (CRC) cells and tissues than those in normal colonic epithelial cell line and adjacent non-tumour colorectal mucosa (ANM) tissues, respectively. MACC1 expression was significantly related to histological differentiation (p<0.001), UICC stage (p=0.029), T classification (p=0.017), and N classification (p=0.023). Cox regression analysis demonstrated that high MACC1/abnormal β-catenin expression was the strongest independent prognostic indicator for reduced overall survival in CRC patients. Significant positive correlation between MACC1 expression and abnormal β-catenin expression was found in CRC tissues. MACC1 knockdown dramatically inhibited cellular proliferation, migration, invasion, colony formation, and tumorigenesis, both in vitro and in vivo, but induced apoptosis in CRC cells. Further MACC1 over-expression increased Met, β-catenin, and its downstream genes including c-Myc, cyclin D1, and MMP9 expression, and its upstream gene phos-GSK3β (Ser9) expression. In addition, MACC1 increased vimentin and suppressed E-cadherin in HCT116 cells. Silencing of MACC1 reversed all these changes. Our results firstly suggest that MACC1 plays an important role in carcinogenesis and progression of CRC through β-catenin signaling pathway and mesenchymal-epithelial transition.
The Multicatalytic Proteinase (1989)

The multicatalytic proteinase is a high molecular weight nonlysosomal proteinase which has been isolated from a variety of mammalian tissues and has been suggested to contain several distinct catalytic sites. The enzyme degrades protein and peptide substrates and can cleave bonds on the carboxyl side of basic, hydrophobic, and acidic amino acid residues. The three types of activity have been referred to as trypsin-like, chymotrypsin-like, and peptidyl-glutamyl peptide bond hydrolyzing activities, respectively. All of these proteolytic activities are associated with a single band on native polyacrylamide gels. The pH optimum of the proteinase (pH 7.5-9.5) depends on the substrate. Using synthetic peptide substrates it was possible to demonstrate two distinct activities. Trypsin-like activity is inhibited at concentrations of the peptide aldehyde inhibitors leupeptin and antipain or of N-ethylmaleimide which have little or no effect on chymotrypsin-like activity. Results of mixed-substrate experiments also suggest that there are at least two distinct types of catalytic sites. All proteolytic activity is lost following dissociation by urea or by acid treatment. Polyclonal antibodies raised against the intact multicatalytic proteinase precipitate the complex but have little effect on its proteolytic activities.
Interferon-α and interferon-γ differentially affect pancreatic β-cell phenotype and function (1998)

To better clarify individual roles of interferon (IFN)-alpha and IFN-gamma in beta-cell pathology during the onset of type 1 diabetes mellitus, we compared the effects of these cytokines on insulin production and major histocompatibility complex (MHC) gene expression in pancreatic beta-cell lines. IFN-gamma but not IFN-alpha decreased secreted and intracellular insulin concentrations in betaTC6-F7 and betaTC3 cells. Likewise, IFN-gamma but not IFN-alpha treatment of beta-cells upregulated mRNA expression of MHC class IA antigen-processing genes and surface expression of class IA molecules. Alternatively, class IA MHC expression was upregulated by IFN-gamma and IFN-alpha in the P388D1 macrophage cell line. The observation of constitutive Ifn-alpha6 mRNA expression by a differentiated beta-cell line substantiates previous indications that local expression of IFN-alpha in islets may trigger insulitis. Evidence that IFN-gamma, a product of infiltrating leukocytes, directly decreases beta-cell glucose sensitivity and increases MHC class IA cell surface expression supports the postulate that IFN-gamma magnifies the insulitic process.
Developmental regulation of acidic fibroblast growth factor (aFGF) expression in bovine retina (1993)

Acidic fibroblast growth factor (aFGF) is a signalling molecule implicated in a wide variety of biological processes such as cell growth, differentiation and survival. It has been purified from bovine retina. The present study was carried out to detect which cells in the bovine retina expressed aFGF at the different stages of embryonic and post-natal development. The specific aFGF mRNA and protein were detected by in situ hybridization employing riboprobes and immunocytochemistry using affinity purified polyclonal human recombinant aFGF antibodies respectively. No signal was detected by either technique until 4-5 months and then there was progressive expression of aFGF with terminal morphogenesis of the retina. By 8-9 months of embryonic development, nuclei of the 3 neuronal layers (ganglion cell layer, inner and outer nuclear layers) were all uniformly and intensely labeled. A slight labeling of the pigmented epithelium of the retina was also visible throughout development and maturation. These results showed a good correlation between message and protein expression in these cell types. In contrast, glial cells in the nerve fiber layer and vascular endothelial cells displayed a nuclear immunostaining for the protein in the absence of message. These data suggest that aFGF plays a role in the late steps of retinal differentiation by autocrine and paracrine mechanisms.
Characterization of V642I‐AβPP‐induced cytotoxicity in primary neurons (2004)

Amyloid precursor protein (AbetaPP), a precursor of amyloid beta (Abeta) peptide, is one of the molecules involved in the pathogenesis of Alzheimer's disease (AD). Specific mutations in AbetaPP have been found in patients inheriting familial AD (FAD). These mutant AbetaPP proteins cause cell death in neuronal cell lines in vitro, but the molecular mechanism of cytotoxicity has not yet been clarified completely. We analyzed the cytotoxic mechanisms of the London-type AbetaPP mutant, V642I-AbetaPP, in primary cortical neurons utilizing an adenovirus-mediated gene transfer system. Expression of V642I-AbetaPP protein induced degeneration of the primary neurons. This cytotoxicity was blocked by pertussis toxin, a specific inhibitor for heterotrimeric G proteins, Go/i, and was suppressed by an inhibitor of caspase-3/7 and an antioxidant, glutathione ethyl ester. A specific inhibitor for NADPH oxidase, apocynin, but not a xanthine oxidase inhibitor or a nitric oxide inhibitor, blocked V642I-AbetaPP-induced cytotoxicity. Among mitogen-activated protein kinase (MAPK) family proteins, c-Jun N-terminal kinase (JNK) and p38MAPK, but not extracellular regulated kinase (ERK), were involved in this cytotoxic pathway. The V642I-AbetaPP-induced cytotoxicity was not suppressed by two secretase inhibitors, suggesting that Abeta does not play a major role in this cytotoxicity. Two neuroprotective factors, insulin-like growth factor I (IGF-I) and Humanin, protected these primary neurons from V642I-AbetaPP-induced cytotoxicity. Furthermore, interleukin-6 and -11 also attenuated this cytotoxicity. This study demonstrated that the signaling pathway activated by mutated AbetaPP in the primary neurons is the same as that by the other artificial insults such as antibody binding to AbetaPP and the artificial dimerization of cytoplasmic domain of AbetaPP. The potential of neurotrophic factors and cytokines in AD therapy is also indicated.
Reactions to and antigenicity of two human-rhesus rotavirus reassortant vaccine candidates of serotypes 1 and 2 in Venezuelan infants (1989)

The reactions to and antigenicity of two human-rhesus rotavirus (RRV) reassortants (human rotavirus strain D x RRV and human rotavirus strain DS1 x RRV) with the VP7 neutralization specificity of a serotype 1 or serotype 2 rotavirus were evaluated in a placebo-controlled double-blind trial in 116 1- to 5-month-old infants in Caracas, Venezuela. The children were randomly divided into five groups to receive orally the following inocula: (i) 10(4) PFU of D x RRV reassortant; (ii) 10(4) PFU of DS1 x RRV reassortant; (iii) 10(4) PFU of RRV; (iv) 5 x 10(3) PFU of D x RRV and 5 x 10(3) PFU of RRV; and (v) placebo. The children were examined daily for 7 days following vaccine administration; 8 to 26% of the vaccinated infants developed a mild febrile reaction which in most cases lasted only 1 day. Seroresponses to rotavirus were observed in 39 to 65% of the vaccinees by plaque neutralization assay and in 57 to 88% by an immunoglobulin A enzyme-linked immunosorbent assay. Vaccine shedding was detected in 53 to 86% of the vaccinees. Analysis of neutralization antibody responses indicates that the VP4 protein represents an important component of the response induced by the vaccines.
Biochemical and structural analysis of aminoglycoside acetyltransferase Eis from Anabaena variabilis (2012)

The Mycobacterium tuberculosis enhanced intracellular survival (Eis_Mtb) protein is a clinically important aminoglycoside (AG) multi-acetylating enzyme. Eis homologues are found in a variety of mycobacterial and non-mycobacterial species. Variation of the residues lining the AG-binding pocket and positions of the loops bearing these residues in the Eis homologues dictates the substrate specificity and, thus, Eis homologues are Nature-made tools for elucidating principles of AG recognition by Eis. Here, we demonstrate that the Eis from Anabaena variabilis (Eis_Ava), the first non-mycobacterial Eis homologue reported, is a multi-acetylating AG-acetyltransferase. Eis_Ava, Eis from Mycobacterium tuberculosis (Eis_Mtb), and Eis from Mycobacterium smegmatis (Eis_Msm) have different structures of their AG-binding pockets. We perform comparative analysis of these differences and investigate how they dictate the substrate and cosubstrate recognition and acetylation of AGs by Eis.
Genome Alteration Print (GAP): a tool to visualize and mine complex cancer genomic profiles obtained by SNP arrays (2009)

We describe a method for automatic detection of absolute segmental copy numbers and genotype status in complex cancer genome profiles measured with single-nucleotide polymorphism (SNP) arrays. The method is based on pattern recognition of segmented and smoothed copy number and allelic imbalance profiles. Assignments were verified by DNA indexes of primary tumors and karyotypes of cell lines. The method performs well even for poor-quality data, low tumor content, and highly rearranged tumor genomes.
Cellular uptake and dynamics of unlabeled freestanding silicon nanowires (2016)

The ability to seamlessly merge electronic devices with biological systems at the cellular length scale is an exciting prospect for exploring new fundamental cell biology and in designing next-generation therapeutic devices. Semiconductor nanowires are well suited for achieving this goal because of their intrinsic size and wide range of possible configurations. However, current studies have focused primarily on delivering substrate-bound nanowire devices through mechanical abrasion or electroporation, with these bulkier substrates negating many of the inherent benefits of using nanoscale materials. To improve on this, an important next step is learning how to distribute these devices in a drug-like fashion, where cells can naturally uptake and incorporate these electronic components, allowing for truly noninvasive device integration. We show that silicon nanowires (SiNWs) can potentially be used as such a system, demonstrating that label-free SiNWs can be internalized in multiple cell lines (96% uptake rate), undergoing an active "burst-like" transport process. Our results show that, rather than through exogenous manipulation, SiNWs are internalized primarily through an endogenous phagocytosis pathway, allowing cellular integration of these materials. To study this behavior, we have developed a robust set of methodologies for quantitatively examining high-aspect ratio nanowire-cell interactions in a time-dependent manner on both single-cell and ensemble levels. This approach represents one of the first dynamic studies of semiconductor nanowire internalization and offers valuable insight into designing devices for biomolecule delivery, intracellular sensing, and photoresponsive therapies.
Extracellular Chloride and the Maintenance of Spontaneous Epileptiform Activity in Rat Hippocampal Slices (1999)

Previous studies showed that furosemide blocks spontaneous epileptiform activity without diminishing synaptic transmission or reducing hyperexcited field responses to electrical stimuli. We now test the hypothesis that the antiepileptic effects of furosemide are mediated through its blockade of the Na+,K+,2Cl- cotransporter and thus should be mimicked by a reduction of extracellular chloride ([Cl-]o). In the first set of experiments, field recordings from the CA1 cell body layer of hippocampal slices showed that spontaneous bursting developed within 10-20 min in slices perfused with low-[Cl-]o (7 mM) medium but that this spontaneous epileptiform activity ceased after a further 10-20 min. Intracellular recordings from CA1 pyramidal cells showed that normal action potential discharge could be elicited by membrane depolarization, even after the tissue was perfused with low-[Cl-]o medium for >2 h. In a second set of experiments, spontaneous bursting activity was induced in slices by perfusion with high-[K+]o (10 mM), bicuculline (100 microM), or 4-aminopyridine (100 microM). In each case, recordings from the CA1 region showed that reduction of [Cl-]o to 21 mM reversibly blocked the bursting within 1 h. Similar to previous observations with furosemide treatment, low-[Cl-]o medium blocked spontaneous hypersynchronous discharges without reducing synaptic hyperexcitability (i.e., hyperexcitable field responses evoked by electrical stimulation). In a third set of experiments, prolonged exposure (>1 h after spontaneous bursting ceased) of slices to systematically varied [Cl-]o and [K+]o resulted in one of three types of events: 1) spontaneous, long-lasting, and repetitive negative field potential shifts (7 mM [Cl-]o; 3 mM [K+]o); 2) oscillations consisting of 5- to 10-mV negative shifts in the field potential, with a period of approximately 1 cycle/40 s (16 mM [Cl-]o; 12 mM [K+]o); and 3) shorter, infrequently occurring negative field shifts lasting 20-40 s (21 mM [Cl-]o; 3 mM [K+]o). Our observations indicate that the effects of low [Cl-]o on neuronal synchronization and spontaneous discharge are time dependent. Similar effects were seen with furosemide and low [Cl-]o, consistent with the hypothesis that the antiepileptic effect of furosemide is mediated by the drug's effect on chloride transporters. Finally, the results of altering extracellular potassium along with chloride suggest that blockade of the Na+, K+,2Cl- cotransporter, which normally transports chloride from the extracellular space into glial cells, is key to these antiepileptic effects.
Expression of oestrogen receptor and oestrogen-inducible genes ps2 and erd5 in large bowel mucosa and cancer (1998)

Since there is a preponderance of large bowel cancer in males, both in humans and in experimental models, and hormone replacement therapy is protective, a role for sex steroid hormones in the pathogenesis of this neoplasm seems likely. Evidence of functional oestrogen receptor has been looked for in large bowel mucosa and cancer. Expression of oestrogen receptor, and of the oestrogen-inducible receptor-associated genes pS2 and ERD5, was sought. Oestrogen receptor mRNA was detected in cancers and paired normal mucosae in equal amounts. In situ hybridization identified stromal cells above the muscularis mucosae that were positive for oestrogen receptor mRNA. pS2 mRNA was also detected, with a signal intensity significantly higher in normal mucosa compared with cancers, whereas the reverse was seen with ERD5 mRNA levels. pS2 and ERD5 were expressed in epithelium, with the former in a greater amount in distal colon and rectum than proximal colon. Although oestrogen-inducible and receptor-associated genes are expressed in large bowel mucosa, their expression does not correlate with oestrogen receptor.
Reducing the complexity of the register file in dynamic superscalar processors (2001)

Dynamic superscalar processors execute multiple instructions out-of-order by looking for independent operations within a large window. The number of physical registers within the processor has a direct impact on the size of this window as most in-flight instructions require a new physical register at dispatch. A large multi-ported register file helps improve the instruction-level parallelism (ILP), but may have a detrimental effect on clock speed, especially in future wire-limited technologies. In this paper, we propose a register file organization that reduces register file size and port requirements for a given amount of ILP. We use a two-level register file organization to reduce register file size requirements, and a banked organization to reduce port requirements. We demonstrate empirically that the resulting register file organizations have reduced latency and (in the case of the banked organization) energy requirements for similar instructions per cycle (IPC) performance and improved instructions per second (IPS) performance in comparison to a conventional monolithic register file. The choice of organization is dependent on design goals.
CTLA4Ig Inhibits Airway Eosinophilia and Hyperresponsiveness by Regulating the Development of Th1/Th2 Subsets in a Murine Model of Asthma (1998)

Complete T-cell activation requires two distinct signals, one delivered via the T-cell receptor, and the second "co-stimulatory" signal through CD28/B7 ligation. Previous studies showed that the blockade of CD28/B7 ligation alters differentiation of Th1/Th2 lymphocyte subsets in vitro and in vivo. The present study was designed to determine the effect of a CD28/B7 antagonist (CTLA4Ig) on Th1/Th2 development in Schistosoma mansoni-sensitized and airway-challenged mice. Treatment of mice with CTLA4Ig beginning 1 wk after sensitization abolished airway responsiveness to intravenous methacholine determined 96 h following antigen challenge. We also found a significant reduction in bronchoalveolar lavage (BAL) eosinophilia, and reduced peribronchial eosinophilic infiltration and mucoid-cell hyperplasia. Furthermore, CTLA4Ig treatment significantly decreased interleukin (IL)-4 and IL-5 content in BAL fluid in vivo, and the production of IL-5 by lung lymphocytes stimulated with soluble egg antigen (SEA) in vitro. In contrast, the content of interferon-gamma in BAL fluid and supernatant from SEA-stimulated lung lymphocytes from CTLA4Ig-treated mice was increased significantly compared with untreated animals. Thus, CTLA4Ig inhibits eosinophilic airway inflammation and airway hyperresponsiveness in S. mansoni-sensitized and airway-challenged mice, most likely due to attenuated secretion of Th2-type cytokines and increased secretion of Th1-type cytokines.
Formation of calcium phosphate/collagen composites through mineralization of collagen matrix (2000)

Several types of calcium phosphate/collagen composites, including noncrystalline calcium phosphate/collagen, poorly crystalline carbonate-apatite (PCCA)/collagen, and PCCA + tetracalcium phosphate/collagen composites, were prepared through the mineralization of collagen matrix. The type I collagen was presoaked with a PO(3-)(4) containing solution and then immersed in a Ca(2+) containing solution to allow mineral deposition. The solution of 0.56 M sodium dibasic phosphate (Na(2)HPO(4)) with a pH of nearly 14 was metastable and its crystallization produced Na(2)HPO(4) and sodium tripolyphosphate hexahydrate (Na(5)P(3)O(10)). 6H(2)O), leading to a controlled release of orthophosphate ions during the subsequent mineral precipitation. The development of the composites was investigated in detail. The mineral contributed up to 60-70% of the weight of the final composites. The strength and Young's modulus of the composites in tensile tests overlapped the lower range of values reported for bone. When implanted in muscle tissue, the composite showed biodegradability that was partly through a multinucleated giant cell mediated process. In a bone explant culture model it was observed that bone-derived cells deposited mineralizing collagenous matrix on the composite.
Facile Synthesis toward the Optimal Structure-Conductivity Characteristics of the Argyrodite Li6PS5Cl Solid-State Electrolyte (2018)

The high Li-ion conductivity of the argyrodite Li<sub>6</sub>PS<sub>5</sub>Cl makes it a promising solid electrolyte candidate for all-solid-state Li-ion batteries. For future application, it is essential to identify facile synthesis procedures and to relate the synthesis conditions to the solid electrolyte material performance. Here, a simple optimized synthesis route is investigated that avoids intensive ball milling by direct annealing of the mixed precursors at 550 °C for 10 h, resulting in argyrodite Li<sub>6</sub>PS<sub>5</sub>Cl with a high Li-ion conductivity of up to 4.96 × 10<sup>-3</sup> S cm<sup>-1</sup> at 26.2 °C. Both the temperature-dependent alternating current impedance conductivities and solid-state NMR spin-lattice relaxation rates demonstrate that the Li<sub>6</sub>PS<sub>5</sub>Cl prepared under these conditions results in a higher conductivity and Li-ion mobility compared to materials prepared by the traditional mechanical milling route. The origin of the improved conductivity appears to be a combination of the optimal local Cl structure and its homogeneous distribution in the material. All-solid-state cells consisting of an 80Li<sub>2</sub>S-20LiI cathode, the optimized Li<sub>6</sub>PS<sub>5</sub>Cl electrolyte, and an In anode showed a relatively good electrochemical performance with an initial discharge capacity of 662.6 mAh g<sup>-1</sup> when a current density of 0.13 mA cm<sup>-2</sup> was used, corresponding to a C-rate of approximately C/20. On direct comparison with a solid-state battery using a solid electrolyte prepared by the mechanical milling route, the battery made with the new material exhibits a higher initial discharge capacity and Coulombic efficiency at a higher current density with better cycling stability. Nevertheless, the cycling stability is limited by the electrolyte stability, which is a major concern for these types of solid-state batteries.
Rapid and flexible biochemical assays for evaluating 4′-phosphopantetheinyl transferase activity (2011)

PPTases (phosphopantetheinyl transferases) are of great interest owing to their essential roles in activating fatty acid, polyketide and non-ribosomal peptide synthetase enzymes for both primary and secondary metabolism, as well as an increasing number of biotechnological applications. However, existing techniques for PPTase characterization and development are cumbersome and technically challenging. To address this, we have developed the indigoidine-synthesizing non-ribosomal peptide synthetase BpsA as a reporter for PPTase activity. Simple co-transformation allows rapid assessment of the ability of a PPTase candidate to activate BpsA in vivo. Kinetic parameters with respect to either CoA or BpsA as variable substrate can then be derived in vitro by continuously measuring the rate of indigoidine synthesis as the PPTase progressively converts BpsA from its apo into holo form. Subsequently, a competition assay, in which BpsA and purified carrier proteins compete for a limited pool of CoA, enables elucidation of kinetic parameters for a PPTase with those carrier proteins. We used this system to conduct a rapid characterization of three different PPTase enzymes: Sfp of Bacillus subtilis A.T.C.C.6633, PcpS of Pseudomonas aeruginosa PAO1, and the putative PPTase PP1183 of Ps. putida KT2440. We also demonstrate the utility of this system for discovery and characterization of PPTase inhibitors.