gebhart/patrepeval huggingface dataset:
Pituitary Corticotroph SOCS-3: Novel Intracellular Regulation of Leukemia-Inhibitory Factor-Mediated Proopiomelanocortin Gene Expression and Adrenocorticotropin Secretion (1998)

As pituitary leukemia-inhibitory factor (LIF) mediates neuroimmune signals to the hypothalamo-pituitary-adrenal axis, we tested the role of intracellular SOCS-3 in corticotroph function. SOCS-3, a cytokine-inducible protein of the suppressor of cytokine signaling (SOCS) family, is expressed in the murine pituitary in vivo. After i.p. injection of LIF (5.0 micrograms/mouse) or interleukin-1 beta (0.1 microgram/mouse) pituitary SOCS-3 mRNA was stimulated 9-fold and 6-fold, respectively. Also, in corticotroph AtT-20 cells LIF and interleukin-1 beta both potently stimulated SOCS-3 mRNA expression. In AtT-20 cells, stable overexpression of SOCS-3 inhibits basal and LIF-stimulated ACTH secretion in comparison to mock-transfected AtT-20 cells (basal: 4426 +/- 118 vs. 4973 +/- 138 pg/ml, P < 0.05; LIF-induced: 5511 +/- 172 vs. 9308 +/- 465 pg/ml, P < 0.001). Stable overexpression of SOCS-3 cDNA in AtT-20 cells also resulted in a significant 50% decrease of LIF-induced POMC mRNA levels (P < 0.05) and POMC promoter activity (P < 0.001), respectively. Western blot analysis revealed an inhibition of LIF-stimulated gp130 and STAT-3 phosphorylation in SOCS-3 overexpressing AtT-20 cells. Thus, SOCS-3 inhibits the Janus kinase (JAK) and signal transducers and activators of transcription (STAT) pathway, which is known to mediate LIF-stimulated ACTH secretion and POMC gene expression. In conclusion, SOCS-3 functions as an intracellular regulator of POMC gene expression and ACTH secretion, acting as a negative feedback mediator of the cytokine-mediated neuro-immuno-endocrine interface.
Ultrasound Enhances Transforming Growth Factor β-Mediated Chondrocyte Differentiation of Human Mesenchymal Stem Cells (2004)

In clinical studies and animal models, low-intensity ultrasound (US) promotes fracture repair and increases mechanical strength. US also promotes cartilage healing by increasing glycosaminoglycan synthesis of chondrocytes. As mesenchymal stem cells (MSCs) have the ability to differentiate into chondrocytes, US may promote their differentiation. Here, we evaluated the effects of US on the differentiation of MSCs toward chondrocytes and cartilage matrix formation. When human MSCs cultured in pellets were treated with transforming growth factor beta (TGF-beta, 10 ng/mL), they differentiated into chondrocytes as assessed by alcian blue staining and immunostaining for aggrecan, but nontreated cell pellets did not. Furthermore, when low-intensity US was applied for 20 min every day to the TGF-beta-treated cell pellets, chondrocyte differentiation was enhanced. Biochemically, aggrecan deposition was increased by 2.9- and 8.7-fold by treatment with TGF-beta alone, and with both TGF-beta and US, respectively. In contrast, cell proliferation and total protein amount appeared unaffected by these treatments. These results indicate that low-intensity US enhances TGF-beta-mediated chondrocyte differentiation of MSCs in pellet culture and that application of US may facilitate larger preparations of chondrocytes and the formation of mature cartilage tissue.
E1-E2 Interactions in Ubiquitin and Nedd8 Ligation Pathways (2011)

Initial rates of E1-catalyzed E2 transthiolation have been used as a reporter function to probe the mechanism of 125I-ubiquitin transfer between activation and ligation half-reactions of ubiquitin conjugation. A functional survey of 11 representative human E2 paralogs reveals similar Km for binding to human Uba1 ternary complex (Km(ave)=121±72 nm) and kcat for ubiquitin transfer (kcat(ave)=4.0±1.2 s(-1)), suggesting that they possess a conserved binding site and transition state geometry and that they compete for charging through differences in intracellular concentration. Sequence analysis and mutagenesis localize this binding motif to three basic residues within Helix 1 of the E2 core domain, confirmed by transthiolation kinetics. Partial conservation of the motif among E2 paralogs not recognized by Uba1 suggests that another factor(s) account for the absolute specificity of cognate E2 binding. Truncation of the Uba1 carboxyl-terminal β-grasp domain reduces cognate Ubc2b binding by 31-fold and kcat by 3.5×10(4)-fold, indicating contributions to E2 binding and transition state stabilization. Truncation of the paralogous domain from the Nedd8 activating enzyme has negligible effect on cognate Ubc12 transthiolation but abrogates E2 specificity toward non-cognate carrier proteins. Exchange of the β-grasp domains between ubiquitin and Nedd8 activating enzymes fails to reverse the effect of truncation. Thus, the conserved Helix 1 binding motif and the β-grasp domain direct general E2 binding, whereas the latter additionally serves as a specificity filter to exclude charging of non-cognate E2 paralogs in order to maintain the fidelity of downstream signaling.
On the profile design and optimization of epitaxial Si- and SiGe-base bipolar technology for 77 K applications. I. Transistor DC design considerations (1993)

The DC design considerations associated with optimizing epitaxial Si- and SiGe-base bipolar transistors for the 77-K environment are examined in detail. Transistors and circuits were fabricated using four different vertical profiles, three with a graded-bandgap SiGe base, and one with a Si base for comparison. All four epitaxial-base profiles yield transistors with DC properties suitable for high-speed logic applications in the 77-K environment. The differences between the low-temperature DC characteristics of Si and SiGe transistors are highlighted both theoretically and experimentally. A performance tradeoff associated with the use of an intrinsic spacer layer to reduce parasitic leakage at low temperatures and the consequent base resistance degradation due to enhanced carrier freeze-out is identified. Evidence that a collector-base heterojunction barrier effect severely degrades the current drive and transconductance of SiGe-base transistors operating at low temperatures is provided.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Alternate interactions define the binding of peptides to the MHC molecule IA b (2002)

We have solved the crystal structure of the MHCII molecule, IA(b), containing an antigenic variant of the major IA(b)-binding peptide derived from the MHCII IEalpha chain. The four MHC pockets at p1, p4, p6, and p9 that usually bind peptide side chains are largely empty because of alanines in the peptide at these positions. The complex is nevertheless very stable, apparently because of unique alternate interactions between the IA(b) and peptide. In particular, there are multiple additional hydrogen bonds between the N-terminal end of the peptide and the IA(b) alpha chain and an extensive hydrogen bond network involving an asparagine at p7 position of the peptide and the IA(b) beta chain. By using knowledge of the shape and size of the traditional side chain binding pockets and the additional possible interactions, an IA(b) peptide-binding motif can be deduced that agrees well with the sequences of known IA(b)-binding peptides.
Antitumor Activity of Astaxanthin and Its Mode of Action (2000)

Astaxanthin, a carotenoid without vitamin A activity, may exert antitumor activity through the enhancement of immune responses. Here, we determined the effects of dietary astaxanthin on tumor growth and tumor immunity against transplantable methylcholanthrene-induced fibrosarcoma (Meth-A tumor) cells. These tumor cells express a tumor antigen that induces T cell-mediated immune responses in syngenic mice. BALB/c mice were fed astaxanthin (0.02%, 40 micrograms/kg body wt/day in a beadlet form) mixed in a chemically defined diet starting zero, one, and three weeks before subcutaneous inoculation with tumor cells (3 x 10(5) cells, 2 times the minimal tumorigenic dose). Three weeks after inoculation, tumor size and weight were determined. We also determined cytotoxic T lymphocyte (CTL) activity and interferon-gamma (IFN-gamma) production by tumor-draining lymph node (TDLN) and spleen cells by restimulating cells with Meth-A tumor cells in culture. The astaxanthin-fed mice had significantly lower tumor size and weight than controls when supplementation was started one and three weeks before tumor inoculation. This antitumor activity was paralleled with higher CTL activity and IFN-gamma production by TDLN and spleen cells in the astaxanthin-fed mice. CTL activity by TDLN cells was highest in mice fed astaxanthin for three weeks before inoculation. When the astaxanthin-supplemented diet was started at the same time as tumor inoculation, none of these parameters were altered by dietary astaxanthin, except IFN-gamma production by spleen cells. Total serum astaxanthin concentrations were approximately 1.2 mumol/l when mice were fed astaxanthin (0.02%) for four weeks and appeared to increase in correlation with the length of astaxanthin supplementation. Our results indicate that dietary astaxanthin suppressed Meth-A tumor cell growth and stimulated immunity against Meth-A tumor antigen.
Isolation of Yersinia spp. from bovine feces (1983)

Yersinia spp. were sought in 618 fecal samples from cows. Four strains of Yersinia enterocolitica, serotype O:12,26 (one), O:13,7 (two), and O:18 (one); seven strains of Yersinia kristensenii, serotype O:11,24 (five) and O:12,26 (two); and one strain of Yersinia pseudotuberculosis serotype IIB, were isolated. This is the first time that Y. pseudotuberculosis has been isolated from cows in Japan, and the isolation of serotype IIB of this organism from cows seems to be the first in the world.
[Effect of siRNA targeting PML-RARa fusion gene on activity of the acute promyelocytic leukemia cell line NB4]. (2014)

This study aims to investigate the effects of small interference RNA (siRNA) targeting PML-RARa mRNA on the activity of the acute promyelocytic leukemia cell line NB4. The proliferation inhibition was evaluated by MTT assay and colony-formation inhibiting test. Apoptosis was determined by flow cytometry after siRNA treatment. The results showed that the cell growth of siRNA treated group was inhibited, and the apoptosis of NB4 could be induced. The siRNA targeting PML-RARα mRNA might be a valid therapy of acute promyelocytic leukemia.
Hybrid HIV/MSCV LTR Enhances Transgene Expression of Lentiviral Vectors in Human CD34+Hematopoietic Cells (2001)

HIV-based lentiviral vectors can transduce nondividing cells, an important advantage over murine leukemia virus (MLV)-based vectors when transducing slowly dividing hematopoietic stem cells. However, we find that in human CD34(+) hematopoietic cells, the HIV-based vectors with an internal cytomegalovirus (CMV) promoter express transgenes 100- to 1,000-fold less than the MLV-based retroviral vector murine stem cell virus (MSCV). To increase the expression of the integrated lentivirus, we replaced CMV promoter with that of the Rous sarcoma virus or MSCV and obtained a modest augmentation in expression. A more dramatic effect was seen when the CMV enhancer/promoter was removed and the HIV long-terminal repeat (LTR) was replaced by a novel HIV/MSCV hybrid LTR. This vector retains the ability to transduce nondividing cells but now expresses its transgene (enhanced green fluorescent protein) 10- to 100-fold greater than the original HIV-based vector. When compared under identical conditions, the HIV vector with the hybrid LTR transduced a higher percentage of CD34(+) cells than the MSCV-based retroviral vector (19.4% versus 2.4%). The number of transduced cells and level of transgene expression remain constant over 5-8 weeks as determined by long-term culture-initiating cells, fluoresence-activated cell sorting, and nonobese diabetic/severe combined immunodeficiency repopulation assay.
LXXXVI.—A method for preparing the formyl derivatives of the aromatic amines (1895)

H. R. Hirst and J. B. Cohen, J. Chem. Soc., Trans., 1895, 67, 829 DOI: 10.1039/CT8956700829
The onconeural antigen Nova-1 is a neuron-specific RNA-binding protein, the activity of which is inhibited by paraneoplastic antibodies (1996)

Nova-1, a protein expressed in tumors and neurons, is a target antigen in a human paraneoplastic motor disorder [paraneoplastic opsoclonus-myoclonus ataxia (POMA)]. We evaluated the relationship between the function of Nova-1 and its role as a disease antigen. We show that Nova-1 is a neuron-specific RNA-binding protein with sequence and functional similarities to FMR-1. Nova-1 mRNA is restricted to the subcortical nervous system, and the protein binds to RNA with high affinity. Nova-1 KH domains mediate this RNA binding, and point mutations within them abrogate binding. POMA disease antisera (6/6) recognize the third KH domain but not an inactive point mutant, and affinity-purified antibody blocks Nova-1 RNA binding. Thus, a cardinal feature of POMA is the production of antibodies that inhibit Nova-1-RNA interactions, suggesting such inhibition may cause the neurological disease.
Human amiloride-sensitive epithelial Na+ channel γ subunit promoter: functional analysis and identification of a polypurine-polypyrimidine tract with the potential for triplex DNA formation (2000)

The mRNA for the epithelial Na(+) channel gamma subunit (gammaENaC) is regulated developmentally in the lung, colon and distal nephron and in response to Na(+) deprivation and systemic corticosteroids in the distal colon. Because such regulation is likely to be at the level of gene transcription, we examined the function of the promoter and other 5' flanking elements of the human gammaENaC gene. The proximal 5' flanking region contains two GC boxes but does not contain a TATA box. A 450 bp human gammaENaC fragment (-459 to +40) directed the expression of luciferase in H441 cells and primer extension analysis in transfected cells confirmed the correct initiation of human gammaENaC-luciferase chimaeric transcripts. By deletional analysis, GC boxes at -21 and -52 were found to be critical for this promoter activity. To begin to identify transcription factors that bind to the core promoter, a double-stranded oligonucleotide that corresponded to this region was synthesized and tested in a gel mobility-shift assay. Incubation of this radiolabelled oligonucleotide with nuclear extracts from H441 and FRTL5 cells resulted in the formation of four specific and distinct DNA-protein complexes. On the basis of antibody 'supershift' assays, one of these factors corresponds to Sp1, whereas the other three correspond to Sp3. Further upstream, an approx. 300 nt (-1143 to -839) polypurine-polypyrimidine tract (PPy tract) containing internal mirror repeats was identified. When contained in a supercoiled plasmid, the approx. 1200 nt 5' flanking region was sensitive to S1 endonuclease, which was consistent with the formation of an intramolecular triplex DNA ('H-DNA') structure with an unpaired single strand. High-resolution mapping with S1 endonuclease and sequencing of S1-generated clones confirmed that all S1-sensitive sites were within the PPy tract. Finally, a negative regulatory element was identified between -1525 and -1296 that functioned in lung, colon and collecting duct cell lines.
The Different Mechanisms of Habit and Past Behavior on Evaluations and IS Continuance Intention: An Empirical Investigation (2007)

Although much research has examined conscious use, which involves deliberate evaluation and decision making, we know less about automatic use, which occurs spontaneously with little conscious effort. The purpose of this study is to investigate the different underlying mechanisms of habitual usage and past usage in IS context. We tested the proposed hypotheses using 232 cross-sectional responses from actual users of Google search engine. Our results show that as individuals get into the habit of continuously using a system, the predictive power of evaluations on intention will be diluted. Consequently, the more usage is performed out of habit, the less cognitive planning is involved and the relationship between evaluations and intention weakens. In contrast, past behavior, though considered as an indicator or a proxy of habit, demonstrates a dissimilar mechanism from habit. We then discuss important findings that emerged from the study and suggest practical implications.
The effect of carbon nanotubes on the fracture toughness and fatigue performance of a thermosetting epoxy polymer (2011)

Multi-walled carbon nanotubes, with a typical length of 140 μm and a diameter of 120 nm, have been used to modify an anhydride-cured epoxy polymer. The modulus, fracture energy and the fatigue performance of the modified polymers have been investigated. Microscopy showed that these long nanotubes were agglomerated, and that increasing the nanotube content increased the severity of the agglomeration. The addition of nanotubes increased the modulus of the epoxy, but the glass transition temperature was unaffected. The measured fracture energy was also increased, from 133 to 223 J/m2 with the addition of 0.5 wt% of nanotubes. The addition of the carbon nanotubes also resulted in an increase in the fatigue performance. The threshold strain-energy release-rate, G th, increased from 24 J/m2 for the unmodified material to 73 J/m2 for the epoxy with 0.5 wt% of nanotubes. Electron microscopy of the fracture surfaces showed clear evidence of nanotube debonding and pull-out, plus void growth around the nanotubes, in both the fracture and fatigue tests. The modelling study showed that the modified Halpin–Tsai equation can fit very well with the measured values of the Young’s modulus, when the orientation and agglomeration of the nanotubes are considered. The fracture energy of the nanotube-modified epoxies was predicted, by considering the contributions of the toughening mechanisms of nanotube debonding, nanotube pull-out and plastic void growth of the epoxy. This indicated that debonding and pull-out contribute to the toughening effect, but the contribution of void growth is not significant. There was excellent agreement between the predictions and the experimental results.
Dendritic cell maturation is required for initiation of the immune response (1997)

Abstract Dendritic cells (DC) are professional antigen-presenting cells (APC) whose primary function is to capture, process, and present antigens to unprimed T cells [1, 2]. They comprise a system of leukocytes widely distributed in all tissues, especially in those that provide an environmental interface (skin and mucosal surfaces) and in lymphoid organs [1].
Nerve growth factor modulates keratinocyte proliferation in murine skin organ culture (1994)

Despite the fact that several cell types residing in or travelling through the skin are targets and/or sources of nerve growth factor (NGF), little is known about the role of NGF in skin development, physiology and disease. Employing a previously defined skin organ culture assay for studying the proliferation of murine keratinocytes in their natural tissue environment, we have assessed the effect of murine NGF (7S) on keratinocyte proliferation in intact skin derived from two defined stages of the murine hair cycle. We found that 10-200 ng/ml NGF stimulated epidermal keratinocyte proliferation in organ-cultured C57 BL-6 mouse skin in the telogen phase of the hair cycle. Follicle keratinocyte proliferation was stimulated by 100 ng/ml NGF in telogen skin organ culture, but this concentration of NGF inhibited both epidermal and follicle keratinocyte proliferation in organ culture of anagen skin. The latter inhibitory effect of NGF was abrogated by co-incubation with neutralizing anti-NGF antibodies or with the protein kinase C inhibitor staurosporine. The proliferation-modulatory effects of NGF were associated with the induction of significant mast cell degranulation, and were inhibited by cromoglycate co-administration. This is the first report of a modulatory, hair cycle-dependent effect of NGF on keratinocyte proliferation in situ, which may require the presence of mast cells. Our study supports the notion of auto- and paracrine functions of NGF in murine skin physiology, which can be further assessed in the physiologically relevant mouse model delineated here.
[Primary and secondary hypocholesterolemia]. (2010)

Hypocholesterolemia is characterized by serum total cholesterol that is lower than the 5th percentile for age and sex, or the cut-off value which predicts the adverse prognosis by epidemiological study. Unlike hypercholesterolemia, physicians pay less attention to the morbidity, causes and consequences of hypocholesterolemia in clinical practice. In fact, hypocholesterolemia is a common dislipidemia, and mainly results from secondary factors. The causes of primary hypocholesterolemia are some disorders owing to genetic mutation in the pathway of cholesterol absorption, biosynthesis or metabolism, including abetalipoproteinemia, hypobetalipoproteinemia, Tangier disease, chylomicron retention disease and inherited disorders of cholesterol biosynthesis. The causes of secondary hypocholesterolemia comprise anemia, hyperthyroidism, malignancy, live disease, critical illness, serious stress, malabsorption or malnutrition, acute or chronic infection, chronic inflammation, and use of some drugs. In addition, what's more important is that hypocholesterolemia can result in some adverse events, such as increased mortality, intracerebral hemorrhage, cancer, infection, adrenal failure, suicide and mental disorder. Therefore, with the practice of intensive lipid-lowering treatment and the tendency to the increased indications of statins, it's high time that physicians attached more importance to hypocholesterolemia.
A botanical macroscope (2009)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.