gebhart/patrepeval huggingface dataset:
SCRINSHOT enables spatial mapping of cell states in tissue sections with single-cell resolution (2020)

Changes in cell identities and positions underlie tissue development and disease progression. Although single-cell mRNA sequencing (scRNA-Seq) methods rapidly generate extensive lists of cell states, spatially resolved single-cell mapping presents a challenging task. We developed SCRINSHOT (Single-Cell Resolution IN Situ Hybridization On Tissues), a sensitive, multiplex RNA mapping approach. Direct hybridization of padlock probes on mRNA is followed by circularization with SplintR ligase and rolling circle amplification (RCA) of the hybridized padlock probes. Sequential detection of RCA-products using fluorophore-labeled oligonucleotides profiles thousands of cells in tissue sections. We evaluated SCRINSHOT specificity and sensitivity on murine and human organs. SCRINSHOT quantification of marker gene expression shows high correlation with published scRNA-Seq data over a broad range of gene expression levels. We demonstrate the utility of SCRINSHOT by mapping the locations of abundant and rare cell types along the murine airways. The amenability, multiplexity, and quantitative qualities of SCRINSHOT facilitate single-cell mRNA profiling of cell-state alterations in tissues under a variety of native and experimental conditions.
Integrating heterogeneous local mail systems (1989)

A description is given of the Heterogeneous Mail System. This environment is inexpensive to implement. It is also inexpensive to integrate a new mail system into the environment and to use its services effectively. Diverse classes of mail systems can be integrated into the environment. The system model is examined, with particular attention to the mail semantic managers, the system server, mail submission and delivery, accommodating new systems, security and authentication, and scalability. Experiences with an experimental prototype are reported.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Novel substrates and products of amine oxidase-catalysed reactions (1991)

Conference Article| February 01 1991 Novel substrates and products of amine oxidase-catalysed reactions M. B. H. Youdin; M. B. H. Youdin § *Technion — Faculty of Medicine, Rappaport Family Institute, Department of Pharmacology, Haifa, Israel §To whom correspondence should be addressed Search for other works by this author on: This Site PubMed Google Scholar N. Harshak; N. Harshak *Technion — Faculty of Medicine, Rappaport Family Institute, Department of Pharmacology, Haifa, Israel Search for other works by this author on: This Site PubMed Google Scholar M. Yoshioka; M. Yoshioka †Setusnan University, Department of Pharmaceutical Chemistry, Kyoto, Japan Search for other works by this author on: This Site PubMed Google Scholar H. Araki; H. Araki Search for other works by this author on: This Site PubMed Google Scholar Y. Mukai; Y. Mukai Search for other works by this author on: This Site PubMed Google Scholar G. Gotto G. Gotto ‡Takeda Pharmaceutical Company, Osaka, Japan Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1991) 19 (1): 224–228. https://doi.org/10.1042/bst0190224 Article history Received: September 03 1990 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation M. B. H. Youdin, N. Harshak, M. Yoshioka, H. Araki, Y. Mukai, G. Gotto; Novel substrates and products of amine oxidase-catalysed reactions. Biochem Soc Trans 1 February 1991; 19 (1): 224–228. doi: https://doi.org/10.1042/bst0190224 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search Keywords: MAO, monoamine oxidase, MPTP, N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, GABA, γ-aminobutyric acid, BBB, blood-brain barrier, NMDA, N-methyl-D-aspartate This content is only available as a PDF. © 1991 Biochemical Society1991 Article PDF first page preview Close Modal You do not currently have access to this content.
Effect of prednisolone on the toxicity of Bordetella pertussis for mice (1985)

Prednisolone, given orally or intraperitoneally before challenge, protected mice against the lethal effect of a crude cell extract of Bordetella pertussis containing heat-labile toxin (HLT) as the major toxic component. Prednisolone did not diminish the lethal toxicity of heated B. pertussis cell suspensions containing pertussis toxin and endotoxin but devoid of HLT. This suggests that the protective effect of the steroid was directed against the HLT. When live bacteria were injected intraperitoneally, prednisolone showed a protective effect against the initial toxaemia. By day 7, however, the protection was no longer evident and the steroid promoted the survival of the organisms within the peritoneal cavity. These findings are discussed in the light of reports of the beneficial effects of corticosteroids in the treatment of whooping cough and in relation to a possible role for HLT in the pathogenesis of the disease.
Interleukin 2 induces tyrosine phosphorylation and activation of p72-74 Raf-1 kinase in a T-cell line. (1991)

Interleukin 2 (IL-2) is a lymphokine, produced by T cells upon antigenic or mitogenic stimulation, that is a critical regulator of T-cell proliferation. Although the binding of IL-2 to its receptor has been well characterized, the molecular mechanisms by which IL-2 transmits its signal from the membrane to the interior of the cell are poorly understood. Like most other growth factors, IL-2 causes rapid phosphorylation of proteins within its target cells. Unlike many other growth factors, however, the known subunits of the IL-2 receptor lack tyrosine-specific kinase activity, and little is known about the kinases whose activities are regulated by IL-2. Here we show that IL-2 (but not IL-4) induces rapid phosphorylation of the p72-74 serine/threonine-specific kinase encoded by the c-Raf-1 protooncogene in an IL-2-dependent murine T-cell line, CTLL-2, and that this phosphorylation is associated with increased kinase activity in p72-74 Raf-1-containing immune complexes. The concentration dependence of IL-2-mediated elevations in Raf-1 kinase activity correlated well with IL-2-stimulated proliferation of CTLL-2 cells. Furthermore, much of the IL-2-stimulated phosphorylation of p72-74 Raf-1 occurred on tyrosines. To our knowledge, the Raf-1 kinase represents the first endogenous substrate of an IL-2-regulated tyrosine kinase to be identified.
Extracellular Signal-Regulated Kinase 7 (ERK7), a Novel ERK with a C-Terminal Domain That Regulates Its Activity, Its Cellular Localization, and Cell Growth (1999)

Mitogen-activated protein (MAP) kinases play distinct roles in a variety of cellular signaling pathways and are regulated through multiple mechanisms. In this study, a novel 61-kDa member of the MAP kinase family, termed extracellular signal-regulated kinase 7 (ERK7), has been cloned and characterized. Although it has the signature TEY activation motif of ERK1 and ERK2, ERK7 is not activated by extracellular stimuli that typically activate ERK1 and ERK2 or by common activators of c-Jun N-terminal kinase (JNK) and p38 kinase. Instead, ERK7 has appreciable constitutive activity in serum-starved cells that is dependent on the presence of its C-terminal domain. Interestingly, the C-terminal tail, not the kinase domain, of ERK7 regulates its nuclear localization and inhibition of growth. Taken together, these results elucidate a novel type of MAP kinase whereby interactions via its C-terminal tail, rather than extracellular signal-mediated activation cascades, regulate its activity, localization, and function.
Laminin-5γ-2 (LAMC2) Is Highly Expressed in Anaplastic Thyroid Carcinoma and Is Associated With Tumor Progression, Migration, and Invasion by Modulating Signaling of EGFR (2013)

To our knowledge, this is the first report investigating the effect of LAMC2 on cell growth, cell cycle, migration, invasion, and EGFR signaling in ATC cells, suggesting that LAMC2 may be a potential therapeutic target for the treatment of ATC.
Oxidative Responses of Human and Murine Macrophages During Phagocytosis of Leishmania chagasi (2001)

Leishmania chagasi, the cause of South American visceral leishmaniasis, must survive antimicrobial responses of host macrophages to establish infection. Macrophage oxidative responses have been shown to diminish in the presence of intracellular leishmania. However, using electron spin resonance we demonstrated that murine and human macrophages produce O2-during phagocytosis of opsonized promastigotes. Addition of the O2- scavenger 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl to cultures resulted in increased infection, suggesting that O2- enhances macrophage leishmanicidal activity. The importance of NO. produced by inducible NO synthase (iNOS) in controlling murine leishmaniasis is established, but its role in human macrophages has been debated. We detected NO. in supernatants from murine, but not human, macrophages infected with L. chagasi. Nonetheless, the iNOS inhibitor N(G)-monomethyl-L-arginine inhibited IFN-gamma-mediated intracellular killing by both murine and human macrophages. According to RNase protection assay and immunohistochemistry, iNOS mRNA and protein were expressed at higher levels in bone marrow of patients with visceral leishmaniasis than in controls. The iNOS protein also increased upon infection of human macrophages with L. chagasi promastigotes in vitro in the presence of IFN-gamma. These data suggest that O2- and NO. each contribute to intracellular killing of L. chagasi in human and murine macrophages.
Polysurgery of cell sheet grafts overcomes diffusion limits to produce thick, vascularized myocardial tissues (2006)

Recently, the field of tissue engineering has progressed rapidly, but poor vascularization remains a major obstacle in bioengineering cell-dense tissues, limiting the viable size of constructs due to hypoxia, nutrient insufficiency, and waste accumulation. Therefore, new technologies for fabricating functional tissues with a well-organized vasculature are required. In the present study, neonatal rat cardiomyocytes were harvested as intact sheets from temperature-responsive culture dishes and stacked into cell-dense myocardial tissues. However, the thickness limit for layered cell sheets in subcutaneous tissue was approximately 80 microm (3 layers). To overcome this limitation, repeated transplantation of triple-layer grafts was performed at 1, 2, or 3 day intervals. The two overlaid grafts completely synchronized and the whole tissues survived without necrosis in the 1 or 2 day interval cases. Multistep transplantation also created approximately 1 mm thick myocardium with a well-organized microvascular network. Furthermore, functional multilayer grafts fabricated over a surgically connectable artery and vein revealed complete graft perfusion via the vessels and ectopic transplantation of the grafts was successfully performed using direct vessel anastomoses. These cultured cell sheet integration methods overcome long-standing barriers to producing thick, vascularized tissues, revealing a possible solution for the clinical repair of various damaged organs, including the impaired myocardium.
Local Inhibition of Sebaceous Gland Growth by Topically Applied RU 58841 (1995)

The biological activity of a series of nonsteroidal, pure androgen receptor inhibitors was compared using the Syrian hamster ear skin sebaceous gland model. RU 58841, RU 56187, RU 38882 and cyproterone acetate were applied topically for 4 weeks on the ventral ear pinna of sexually mature male Syrian hamsters. Their order of efficacy was as follows: RU 58841 > RU 56187 > RU 38882 > cyproterone acetate. Maximal reduction of 60% in the size of the sebaceous glands was observed in hamsters treated with RU 58841 at a dose of 10 micrograms per day. This degree of inhibition occurred without any systemic side effects as shown by the absence of inhibition on the contralateral untreated ear pinna. Longer treatment did not produce greater inhibition since extending the treatment period from 4 weeks to 12 weeks showed similar data. The effect of RU 58841 was reversible since the inhibited sebaceous glands returned to normal size within 4 weeks after the cessation of the topical applications. The potent localized inhibition of sebaceous glands by RU 58841 demonstrates the excellent potential of this compound as a topical drug for the treatment of acne and other androgen-mediated disorders.
Production and characterization of neutralizing monoclonal antibodies that recognize an epitope in domain 2 ofBacillus anthracisprotective antigen (2006)

Antibodies against the protective antigen (PA) of Bacillus anthracis play a key role in response to infection by this important pathogen. The aim of this study was to produce and characterize monoclonal antibodies (mAbs) specific for PA and to identify novel neutralizing epitopes. Three murine mAbs with high specificity and nanomolar affinity for B. anthracis recombinant protective antigen (rPA) were produced and characterized. Western immunoblot analysis, coupled with epitope mapping using overlapping synthetic peptides, revealed that these mAbs recognize a linear epitope within domain 2 of rPA. Neutralization assays demonstrate that these mAbs effectively neutralize lethal toxin in vitro.
Task‐Oriented Learning on the Web (1999)

SUMMARY This paper describes three examples of learning environments that have been created for the Web to enable task‐oriented learning. The environments described in this paper allow students to develop and apply their skills and knowledge in a simulated environment. Three different environments are described; each taken from a different discipline. They are supported by the technical infrastructure provided by the Clyde Virtual University which is an initiative sponsored by the Scottish Higher Education Funding Council and has served universities in the West of Scotland since 1995.
Hodgkin‘s Lymphoma: Molecular Targets and Novel Treatment Strategies (2006)

The WHO classification of Hodgkin's lymphoma (HL) distinguishes between two major subtypes, classical and nodular lymphocyte predominant HL. Approximately 95% of patients with HL will have the classical HL histology, which is characterized by the presence of rare malignant Hodgkin's and Reed-Sternberg cells among an overwhelming number of benign reactive cells. In recent years, new studies have shed more light on the biological and molecular features of Hodgkin's and Reed-Sternberg cells, providing hope that new targeted therapy may be developed to enhance the cure rate and to reduce treatment-related toxicity. In this review, the current understanding of the pathology and biology of HL will be discussed, as well as the current treatment approaches for patients with classical HL. Future treatment strategies will also be discussed based on our understanding of HL biology.
Antinociceptive profiles of non-peptidergic neurokinin1 and neurokinin2 receptor antagonists: a comparison to other classes of antinociceptive agent (1995)

This study compared the antinociceptive properties of systemic administration of selective, non-peptidergic antagonists at neurokinin (NK1 and NK2) receptors to those of other classes of antinociceptive agent. (All doses are in mg/kg.) In mice, the NK1 antagonist, CP 99,994, preferentially (inhibitory dose50 (ID50) = 4.4) inhibited the late phase (LP) as compared to the early phase (EP) (16.1) of formalin-induced licking (FIL). A high dose (17.6) elicited ataxia in the rotarod test. Acetic acid-induced writhing was reduced at intermediate doses (10.0) whereas the tail-flick (TF) response to thermal and mechanical stimuli was inhibited only at high doses (22.7 and 17.7, respectively). Modulation of stimulus intensity did not modify the influence of CP 99,994 upon the response to heat. A similar pattern of data was acquired with RP 67,580, although this NK1 antagonist more potently inhibited writhing (2.8). In contrast, RP 68,651, the inactive isomer of RP 67,580, neither reduced the LP of FIL nor modified writhing indicating that these actions of RP 67,580 were stereospecific. Three further NK1 antagonists, SR 140,333, WIN 51,708 and WIN 62,577, likewise inhibited the LP of FIL and failed to modify the TF response at non-ataxic doses. Further, SR 140,333 (0.5) and WIN 51,708 (1.4) were potent ligands in the writhing procedure. The NK2 antagonist, SR 48,966, mimicked NK1 antagonists in preferentially inhibiting the LP (7.7) as compared to the EP (26.9) of FIL. Further, only at doses higher than those evoking ataxia (20.9) did SR 48,968 modify the TF response (36.5 and 32.0 for heat and pressure, respectively). However, it differed to NK1 antagonists in being inactive in the writhing test (> 40.0). In comparison to these NK1 and NK2 antagonists, the mu-opioid agonists (morphine and fentanyl) and kappa-opioid agonists (enadoline and U 69,593) equipotently inhibited all nociceptive responses at doses not provoking ataxia. While the glycine B receptor partial agonist, (+)-HA 966, selectively blocked the LP of FIL and did not evoke ataxia, the NMDA receptor channel blocker, (+)-MK 801, elicited antinociception only at doses close to those provoking ataxia. Finally, the NSAIDs, indomethacin and ibuprofen, the BK2 antagonist, Hoe 140 and the nitric oxide synthase (NOS) inhibitors, L-NAME and 7 nitroindazole, inhibited the LP (but not the EP) of FIL and (except for L-NAME) also reduced writhing: in contrast, they did not evoke ataxia and were inactive in the TF procedures.(ABSTRACT TRUNCATED AT 400 WORDS)
ErgoWELL - An Integrative Strategy (2012)

Abstract The global workforce are faced with challenges of the digitalized age; the nature of work has changed. Employees are becoming knowledge workers that are more sedentary using static loaded postures and positions throughout the day. Both technology and the nature of work has changed over the last decade, however the human anatomy has remained the same. Due to this mismatch there is an increasing incidence of low back pain, neck pain, shoulder syndromes, and carpal tunnel, etc. Therefore ergonomics is an essential science that must be considered in the reduction of these injuries in the workplace. Adopting a systematic approach assesses the dynamic relationships between the end user, the work task, equipment, workspace, environment and the organization at large. A participatory wellness approach ensures that all stakeholders gain ownership and are accountable for effective change in the development, implementation and evaluation stages of injury and disease prevention. Using both of these methodologies ensures that there is a significant impact at operational, tactical and strategic levels of the organization. Ultimately this will assist in using the current organization infrastructure to support and cascade ergonomic principles throughout the company. At a corporate level an emerging trend is to integrate ergonomics with corporate wellness programs. Therefore this paper demonstrates the successful integration between wellness and ergonomics. This success is showcased through a study sample of 160 employees over a year long cohort. The results indicate a significant reduction in work related musculoskeletal injuries, reduction in absenteeism for work related musculoskeletal injuries and successful behavior change in adopting practices in injury prevention. This partnership in science is referred by the author as ErgoWELL - the integration between ergonomics and wellness.
Treatment Effect of Rifampicin on Cholestasis (2005)

Rifampicin, a semisynthetic antibiotic, has been discovered serendipitously to have beneficial effect on cholestasis. The mechanism, as recently demonstrated, is its induction of pregnane X receptor to regulate the genes involved in bile acids biosynthesis, detoxification and transportation. Thus, toxic bile acids like lithocholic acid are hydrolysed by increased CYP3A4 into a less toxic form. Activation of efflux pumps also facilitates excretion of bile acids from hepatic cells. Furthermore, rifampicin inhibits CYP7A1, a rate-limiting enzyme in the conversion of cholesterol into bile acids, and so reducing bile acids synthesis. However, rifampicin also causes hepatotoxicity in some cases. This limits its use in the treatment of cholestasis. The prospective approaches to overcome the problems could be to find modification of rifampicin chemical structure or find other inducers.
A Novel Listeria monocytogenes -Based DNA Delivery System for Cancer Gene Therapy (2010)

Bacteria-mediated transfer of plasmid DNA to mammalian cells (bactofection) has been shown to have significant potential as an approach to express heterologous proteins in various cell types. This is achieved through entry of the entire bacterium into cells, followed by release of plasmid DNA. In a murine model, we show that Listeria monocytogenes can invade and spread in tumors, and establish the use of Listeria to deliver genes to tumors in vivo. A novel approach to vector lysis and release of plasmid DNA through antibiotic administration was developed. Ampicillin administration facilitated both plasmid transfer and safety control of vector. To further improve on the gene delivery system, we selected a Listeria monocytogenes derivative that is more sensitive to ampicillin, and less pathogenic than the wild-type strain. Incorporation of a eukaryotic-transcribed lysin cassette in the plasmid further increased bacterial lysis. Successful gene delivery of firefly luciferase to growing tumors in murine models and to patient breast tumor samples ex vivo was achieved. The model described encompasses a three-phase treatment regimen, involving (1) intratumoral administration of vector followed by a period of vector spread, (2) systemic ampicillin administration to induce vector lysis and plasmid transfer, and (3) systemic administration of combined moxifloxacin and ampicillin to eliminate systemic vector. For the first time, our results reveal the potential of Listeria monocytogenes for in vivo gene delivery.