gebhart/patrepeval huggingface dataset:
Identification of a Matrix-Degrading Phenotype in Human Tuberculosis In Vitro and In Vivo (2001)

Tuberculous meningitis is characterized by cerebral tissue destruction. Monocytes, pivotal in immune responses to Mycobacterium tuberculosis, secrete matrix metalloproteinase-9 (MMP-9), which facilitates leukocyte migration across the blood-brain barrier, but may cause cerebral injury. In vitro, human monocytic (THP-1) cells infected by live, virulent M. tuberculosis secreted MMP-9 in a dose-dependent manner. At 24 h, MMP-9 concentrations increased 10-fold to 239 +/- 75 ng/ml (p = 0.001 vs controls). MMP-9 mRNA became detectable at 24--48 h. In contrast, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) gene expression and secretion were similar to constitutive levels from controls at 24 h and increased just 5-fold by 48 h. In vivo investigation revealed MMP-9 concentration per leukocyte in cerebrospinal fluid (CSF) from tuberculous meningitis patients (n = 23; median (range), 3.19 (0.19--31.00) ng/ml/cell) to be higher than that in bacterial (n = 12; 0.23 (0.01--18.37) ng/ml/cell) or viral meningitis (n = 20; 0.20 (0.04--31.00) ng/ml/cell; p < 0.01). TIMP-1, which was constitutively secreted into CSF, was not elevated in tuberculous compared with bacterial meningitis or controls. Thus, a phenotype in which MMP-9 activity is relatively unrestricted by TIMP-1 developed both in vitro and in vivo. This is functionally significant, since MMP-9 concentrations per CSF leukocyte (but not TIMP-1 concentrations) were elevated in fatal tuberculous meningitis and in patients with signs of cerebral tissue damage (unconsciousness, confusion, or neurological deficit; p < 0.05). However, MMP-9 activity was unrelated to the severity of systemic illness. In summary, M. tuberculosis-infected monocytic cells develop a matrix-degrading phenotype, which was observed in vivo and relates to clinical signs reflecting cerebral injury in tuberculous meningitis.
Stage-Specific Regulation ofSolanum lycopersicumLeaf Maturation by Class 1 KNOTTED1-LIKE HOMEOBOX Proteins (2009)

Class 1 KNOTTED1-LIKE HOMEOBOX (KNOXI) genes encode transcription factors that are expressed in the shoot apical meristem (SAM) and are essential for SAM maintenance. In some species with compound leaves, including tomato (Solanum lycopersicum), KNOXI genes are also expressed during leaf development and affect leaf morphology. To dissect the role of KNOXI proteins in leaf patterning, we expressed in tomato leaves a fusion of the tomato KNOXI gene Tkn2 with a sequence encoding a repressor domain, expected to repress common targets of tomato KNOXI proteins. This resulted in the formation of small, narrow, and simple leaves due to accelerated differentiation. Overexpression of the wild-type form of Tkn1 or Tkn2 in young leaves also resulted in narrow and simple leaves, but in this case, leaf development was blocked at the initiation stage. Expression of Tkn1 or Tkn2 during a series of spatial and temporal windows in leaf development identified leaf initiation and primary morphogenesis as specific developmental contexts at which the tomato leaf is responsive to KNOXI activity. Arabidopsis thaliana leaves responded to overexpression of Arabidopsis or tomato KNOXI genes during the morphogenetic stage but were largely insensitive to their overexpression during leaf initiation. These results imply that KNOXI proteins act at specific stages within the compound-leaf development program to delay maturation and enable leaflet formation, rather than set the compound leaf route.
Growth differentiation factor 15 induces growth and metastasis of human liver cancer stem-like cells via AKT/GSK-3β/β-catenin signaling (2017)

Our studies suggest that CD13+CD44+ SCs may represent a subset of LCSCs. GDF15 promotes the growth and metastasis of SCs by activating AKT/GSK-3β/β-catenin signaling pathway. Promisingly, GDF15 could be considered as a potential therapeutic target in liver cancer.
Collagen Fibril Diameter and Leather Strength (2013)

The main structural component of leather and skin is type I collagen in the form of strong fibrils. Strength is an important property of leather, and the way in which collagen contributes to the strength is not fully understood. Synchrotron-based small angle X-ray scattering (SAXS) is used to measure the collagen fibril diameter of leather from a range of animals, including sheep and cattle, that had a range of tear strengths. SAXS data were fit to a cylinder model. The collagen fibril diameter and tear strength were found to be correlated in bovine leather (r(2) = 0.59; P = 0.009), with stronger leather having thicker fibrils. There was no correlation between orientation index, i.e., fibril alignment, and fibril diameter for this data set. Ovine leather showed no correlation between tear strength and fibril diameter, nor was there a correlation across a selection of other animal leathers. The findings presented here suggest that there may be a different structural motif in skin compared with tendon, particularly ovine skin or leather, in which the diameter of the individual fibrils contributes less to strength than fibril alignment does.
Membrane Translocation Mechanism of the Antimicrobial Peptide Buforin 2 (2004)

The antimicrobial peptide magainin 2 isolated from the skin of the African clawed frog Xenopus laevis crosses lipid bilayers by transiently forming a peptide-lipid supramolecular complex pore inducing membrane permeabilization and flip-flop of membrane lipids [Matsuzaki, K., Murase, O., Fujii, N., and Miyajima, K. (1996) Biochemistry 35, 11361-11368]. In contrast, the antimicrobial peptide buforin 2 discovered in the stomach tissue of the Asian toad Bufo bufo gargarizans efficiently crosses lipid bilayers without inducing severe membrane permeabilization or lipid flip-flop, and the Pro(11) residue plays a key role in this unique property [Kobayashi, S, Takeshima, K., Park, C. B., Kim, S. C., and Matsuzaki, K. (2000) Biochemistry 39, 8648-8654]. To elucidate the translocation mechanism, the secondary structure and the orientation of the peptide in lipid bilayers as well as the effects of the peptide concentration, the lipid composition, and the cis-trans isomerization of the Pro peptide bond on translocation efficiency were investigated. The translocation efficiencies of F10W-buforin 2 (BF2), P11A-BF2, and F5W-magainin 2 (MG2) across egg yolk L-alpha-phosphatidyl-DL-glycerol (EYPG)/egg yolk L-alpha-phosphatidylcholine (1/1) bilayers were dependent supralinearly on the peptide concentration, suggesting that the translocation mechanisms of these peptides are similar. The incorporation of the negative curvature-inducing lipid egg yolk L-alpha -phosphatidylethanolamine completely suppressed the translocation of BF2, indicating the induction of the positive curvature by BF2 on the membrane is related to the translocation process, similarly to MG2. In pure EYPG, where the repulsion between polycationic BF2 molecules is reduced, membrane permeabilization and coupling lipid flip-flop were clearly observed. Structural studies by use of Fourier transform infrared-polarized attenuated total reflection spectroscopy indicated that BF2 assumed distorted helical structures in EYPG/EYPC bilayers. A BF2 analogue with an alpha-methylproline, which fixed the peptide bond to the trans configuration, translocated similarly to the parent peptide, suggesting the cis-trans isomerization of the Pro peptide bond is not involved in the translocation process. These results indicate that BF2 crosses lipid bilayers via a mechanism similar to that of MG2. The presence of Pro(11) distorts the helix, concentrating basic amino acid residues in a limited amphipathic region, thus destabilizing the pore by enhanced electrostatic repulsion, enabling efficient translocation.
Bacterial Nanobioreactors–Directing Enzyme Packaging into Bacterial Outer Membrane Vesicles (2015)

All bacteria shed outer membrane vesicles (OMVs) loaded with a diverse array of small molecules, proteins, and genetic cargo. In this study we sought to hijack the bacterial cell export pathway to simultaneously produce, package, and release an active enzyme, phosphotriesterase (PTE). To accomplish this goal the SpyCatcher/SpyTag (SC/ST) bioconjugation system was utilized to produce a PTE-SpyCatcher (PTE-SC) fusion protein and a SpyTagged transmembrane porin protein (OmpA-ST), known to be abundant in OMVs. Under a range of physiological conditions the SpyTag and SpyCatcher domains interact with one another and form a covalent isopeptide bond driving packaging of PTE into forming OMVs. The PTE-SC loaded OMVs are characterized for size distribution, number of vesicles produced, cell viability, packaged PTE enzyme kinetics, OMV loading efficiency, and enzyme stability following iterative cycles of freezing and thawing. The PTE-loaded OMVs exhibit native-like enzyme kinetics when assayed with paraoxon as a substrate. PTE is often toxic to expression cultures and has a tendency to lose activity with improper handling. The coexpression of OmpA-ST with PTE-SC, however, greatly improved the overall PTE production levels by mitigating toxicity through exporting of the PTE-SC and greatly enhanced packaged enzyme stability against iterative cycles of freezing and thawing.
Optically Stimulated Luminescence Dosimetry (1983)

Journal Article Optically Stimulated Luminescence Dosimetry Get access R.P. Rao, R.P. Rao Search for other works by this author on: Oxford Academic PubMed Google Scholar M. deMurcia, M. deMurcia Search for other works by this author on: Oxford Academic PubMed Google Scholar J. Gasiot J. Gasiot Search for other works by this author on: Oxford Academic PubMed Google Scholar Radiation Protection Dosimetry, Volume 6, Issue 1-4, 1 December 1983, Pages 64–66, https://doi.org/10.1093/oxfordjournals.rpd.a082868 Published: 01 December 1983
IL-17 Enhances the Net Angiogenic Activity and In Vivo Growth of Human Non-Small Cell Lung Cancer in SCID Mice through Promoting CXCR-2-Dependent Angiogenesis (2005)

In this study, we examined the biological action of IL-17 on human non-small cell lung cancer (NSCLC). Although IL-17 had no direct effect on the in vitro growth rate of NSCLC, IL-17 selectively augmented the secretion of an array of angiogenic CXC chemokines, including CXCL1, CXCL5, CXCL6, and CXCL8 but not angiostatic chemokines, by three different NSCLC lines. Endothelial cell chemotactic activity (as a measure of net angiogenic potential) was increased in response to conditioned medium from NSCLC stimulated with IL-17 compared with those from unstimulated NSCLC. Enhanced chemotactic activity was suppressed by neutralizing mAb(s) to CXCL1, CXCL5, and CXCL8 or to CXCR-2 but not to vascular endothelial growth factor-A. Transfection with IL-17 into NSCLC had no effect on the in vitro growth, whereas IL-17 transfectants grew more rapidly compared with controls when transplanted in SCID mice. This IL-17-elicited enhancement of NSCLC growth was associated with increased tumor vascularity. Moreover, treatment with anti-mouse CXCR-2-neutralizing Ab significantly attenuated the growth of both neomycin phosphotransferase gene-transfected and IL-17-transfected NSCLC tumors in SCID mice. A potential role for IL-17 in modulation of the human NSCLC phenotype was supported by the findings that, in primary NSCLC tissues, IL-17 expression was frequently detected in accumulating and infiltrating inflammatory cells and that high levels of IL-17 expression were associated with increased tumor vascularity. These results demonstrate that IL-17 increases the net angiogenic activity and in vivo growth of NSCLC via promoting CXCR-2-dependent angiogenesis and suggest that targeting CXCR-2 signaling may be a novel promising strategy to treat patients with NSCLC.
Sites of [3H]taurine Uptake in the Rat Substantia Nigra in Relation to the Release of Taurine from the Striatonigral Pathway (1990)

The autoradiographic localization of radiolabelled taurine taken up in the rat substantia nigra in vivo together with conditions of release of the [3H]taurine taken up into brain slices were studied to determine whether they are consistent with the hypothesis that taurine may act as a neurotransmitter in the striatonigral pathway. At the light microscopic level the main cellular elements that became radiolabelled following the injection of [3H]taurine into the substantia nigra could be identified as glial cells. Electron microscope autoradiography confirmed that a subpopulation of glial cells including astrocytes, pericytes, and oligodendrocytes were radiolabelled and that neuronal perikarya were not radiolabelled. In addition, axonal elements including both terminal and preterminal boutons were found to have silver grains overlying them and were thus considered to be radiolabelled. This was supported by a quantitative analysis of the distribution of the silver grains; whereas glial elements had a significantly higher number of grains associated with them than with any other structure, axonal elements had a significantly greater number of grains than dendritic structures. Release of the preloaded [3H]taurine from superfused slices of substantia nigra occurred in response to veratridine, was calcium-dependent and was sensitive to inhibition by high magnesium concentrations or tetrodotoxin. Following the destruction of neurons in the striatum by ibotenic acid injections, although the weight of the ipsilateral substantia nigra was reduced, the uptake of [3H]taurine was not altered. In contrast to this, the veratridine-stimulated release was markedly attenuated, implying that the destruction of striatal neurons causes the loss of sites in the substantia nigra from which exogenous taurine is released. These results add further support to previous suggestions that taurine might act as a neurotransmitter or neuromodulator in the striatonigral pathway.
Comparison of clinical signs, diagnostic findings, organisms isolated, and clinical outcome in dogs with bacterial pneumonia: 93 cases (1986-1991) (1995)

Medical records were reviewed for 93 dogs with bacterial pneumonia from which transtracheal aspiration samples were obtained for culturing of Mycoplasma spp and aerobic bacteria. On the basis of culture results, there were 65 Mycoplasma-positive dogs, including 7 dogs for which only Mycoplasma spp were isolated, and 28 Mycoplasma-negative dogs. Most dogs were > 5 years old, and differences in breed or gender distribution among the 3 groups of dogs were not detected. Hematologic and serum biochemical analysis results did not differ significantly between Mycoplasma-positive and Mycoplasma-negative dogs. Fifty-three of 93 (57%) dogs had a concurrent medical problem that may have predisposed them to developing bacterial pneumonia as a sequelae to aspiration or immunosuppression. Mycoplasma-positive dogs were significantly (P < 0.005) more likely to have > 1 species of bacteria isolated from their transtracheal aspiration samples. Clinical outcome was favorable when antimicrobials were selected on the basis of antimicrobial susceptibility results for the other bacterial isolates and not on results of the antimicrobial activity against Mycoplasma spp. It could not be determined whether Mycoplasma spp were primary pathogens or only opportunists.
Frequencies of Memory T Cells Specific for Varicella‐Zoster Virus, Herpes Simplex Virus, and Cytomegalovirus by Intracellular Detection of Cytokine Expression (2000)

Memory T cells specific for varicella-zoster virus (VZV), herpes simplex virus (HSV), and human cytomegalovirus (HCMV) were compared in immune adults by intracellular cytokine (ICC) detection. The mean percentages of CD4+ T cells were 0.11% for VZV and 0.22% for HSV by interferon (IFN)-gamma production; the frequency for HCMV was significantly higher at 1.21%. Percentages of VZV-, HSV-, and HCMV-specific CD4+ T cells were similar by use of tumor necrosis factor (TNF)-alpha. HCMV-stimulated CD8+ T cells produced IFN-gamma (1.11%) and TNF-alpha (1.71%); VZV- and HSV-specific CD8+ T cells were not detectable. VZV CD4+ T cell numbers were similar in young adults with natural or vaccine-induced immunity. VZV CD4+ T cells were significantly less frequent in older adults. Secondary varicella immunization did not increase VZV-specific CD4+ T cell frequencies by ICC assay. Numbers of memory T cells specific for herpesviruses may vary with sites of viral latency and with host age.
Measuring facial expressions by computer image analysis (1999)

Facial expressions provide an important behavioral measure for the study of emotion, cognitive processes, and social interaction. The Facial Action Coding System (Ekman & Friesen, 1978) is an objective method for quantifying facial movement in terms of component actions. We applied computer image analysis to the problem of automatically detecting facial actions in sequences of images. Three approaches were compared: holistic spatial analysis, explicit measurement of features such as wrinkles, and estimation of motion flow fields. The three methods were combined in a hybrid system that classified six upper facial actions with 91% accuracy. The hybrid system outperformed human nonexperts on this task and performed as well as highly trained experts. An automated system would make facial expression measurement more widely accessible as a research tool in behavioral science and investigations of the neural substrates of emotion.
Hepatic acyl-coenzyme A:cholesterol acyltransferase activity is decreased in patients with cholesterol gallstones. (1990)

Altered hepatic cholesterol metabolism has been implicated in the etiology of cholesterol gallstones. This hypothesis has been examined by determining acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity in liver biopsies from 31 cholesterol gallstone patients and 12 control subjects. Hepatic ACAT activity in gallstone patients was decreased to one-third that in controls (P less than 0.001). No differences in hepatic homogenate or microsomal free and total cholesterol concentrations were observed between the two groups. However, marked increases in free (107%) and total (98%) cholesterol concentrations were found in the cytosolic fraction of liver biopsies from gallstone patients. The total phospholipid concentration of the liver homogenate fraction was unchanged in both groups; however, the microsomal total phospholipid concentration was reduced by 17% (P less than 0.01) in gallstone samples compared with controls. This difference did not result in a significantly increased microsomal cholesterol/phospholipid ratio for the gallstone group (0.180 +/- 0.030) compared with the control group (0.169 +/- 0.042). These results show that hepatic ACAT activity is significantly decreased in cholesterol gallstone patients. These changes in ACAT activity in livers of patients with cholesterol gallstones are consistent with the known increase in the amount of free cholesterol secreted in the bile of these patients. Thus, the changes in ACAT activity may contribute to the pathogenesis of cholesterol gallstones.
Airway neutrophils and interleukin-17 (2000)

It is well known that exacerbations of obstructive airways disease such as asthma and chronic obstructive pulmonary disease are associated with an increased number of neutrophils in the airways. However, the mechanisms behind this phenomenon are poorly understood. There is in vivo experimental evidence that the number of airway neutrophils is controlled by certain T-lymphocytes, but the mediators responsible for this lymphocyte-related neutrophilia have not yet been identified. In this review, novel evidence that the T-lymphocyte-related cytokine interleukin (IL)-17 can link the activation of certain T-lymphocytes to the recruitment and activation of airway neutrophils is described. The IL-17-induced neutrophil recruitment is mediated via induced CXC chemokine release through steroid-sensitive mechanisms and is modulated by release of endogenous tachykinins. These effects of IL-17 are potentiated by other pro-inflammatory cytokines such as (IL-1beta) and tumour necrosis factor-alpha. Clinical studies are needed to evaluate whether or not targeting these mechanisms can provide a useful pharmacotherapeutical approach against exaggerated mobilization of neutrophils in obstructive airways disease.
Phospholipase D in cell proliferation and cancer. (2003)

Phospholipase D (PLD) has emerged as a regulator of several critical aspects of cell physiology. PLD, which catalyzes the hydrolysis of phosphatidylcholine (PC) to phosphatidic acid (PA) and choline, is activated in response to stimulators of vesicle transport, endocytosis, exocytosis, cell migration, and mitosis. Dysregulation of these cell biological processes occurs in the development of a variety of human tumors. It has now been observed that there are abnormalities in PLD expression and activity in many human cancers. In this review, evidence is summarized implicating PLD as a critical regulator of cell proliferation, survival signaling, cell transformation, and tumor progression.
NewDrosophilaintrons originate by duplication (1998)

We have analyzed the phylogenetic distribution of introns in the gene coding for xanthine dehydrogenase in 37 species, including 31 dipterans sequenced by us. We have discovered three narrowly distributed novel introns, one in the medfly Ceratitis capitata, the second in the willistoni and saltans groups of Drosophila, and the third in two sibling species of the willistoni group. The phylogenetic distribution of these introns favors the "introns-late" theory of the origin of genes. Analysis of the nucleotide sequences indicates that all three introns have arisen by duplication of a preexisting intron, which is pervasive in Drosophila and other dipterans (and has a homologous position as an intron found in humans and other diverse organisms).
Informal information gathering techniques for active reading (2012)

GatherReader is a prototype e-reader with both pen and multi-touch input that illustrates several interesting design trade-offs to fluidly interleave content consumption behaviors (reading and flipping through pages) with information gathering and informal organization activities geared to active reading tasks. These choices include (1) relaxed precision for casual specification of scope; (2) multiple object collection via a visual clipboard; (3) flexible workflow via deferred action; and (4) complementary use of pen+touch. Our design affords active reading by limiting the transaction costs for secondary subtasks, while keeping users in the flow of the primary task of reading itself.
Mushrooms and the Mycology of Consciousness (2016)

Mycologist Paul Stamets examines how mushrooms can help the health of people and the planet.
Post‐ischemic brain damage: targeting PARP‐1 within the ischemic neurovascular units as a realistic avenue to stroke treatment (2008)

Stroke is the third leading cause of death in industrialized countries but efficacious stroke treatment is still an unmet need. Preclinical research indicates that different molecules afford protection from ischemic neurodegeneration, but all clinical trials conducted so far have inexorably failed. Critical re-evaluation of experimental data shows that all the components of the neurovascular unit, such as neurons, glia, endothelia and basal membranes, must be protected during the ischemic insult to obtain substantial and long-lasting neuroprotection. Here, we propose the nuclear enzyme poly(ADP-ribose) polymerase (PARP-1) as a key effector of cell death in the various elements of the neurovascular units, and assert that drugs inhibiting PARP-1 may therefore represent valuable tools for pharmacological treatment of stroke patients.
Peptide length-based prediction of peptide–MHC class II binding (2006)

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