gebhart/patrepeval huggingface dataset:
Acetylcholine causes rapid nicotinic excitation in the medial habenular nucleus of guinea pig, in vitro (1987)

The actions of ACh in the medial habenular nucleus (MHb) were investigated using extra- and intracellular recording techniques in guinea pig thalamic slice maintained in vitro. Applications of ACh to MHb neurons resulted in rapid excitation followed by inhibition. Neither of these responses was abolished by blockade of synaptic transmission, indicating that they are consequences of ACh action directly on MHb cells. Local applications of the nicotinic agonists nicotine and cytisine caused long-lasting excitation, while applications of another nicotinic agonist, 1,1-dimethyl-4-phenylpiperazinium caused both the excitatory and inhibitory responses. Applications of the muscarinic agonists DL-muscarine and acetyl-beta-methylcholine did not consistently cause either the excitatory or inhibitory response. Adding the nicotinic antagonist hexamethonium to the bathing medium blocked both the excitatory and inhibitory ACh responses, while addition of the muscarinic antagonists atropine or scopolamine had no effect. These results indicate that the effects of ACh on MHb neurons are mediated by nicotinic receptors. Intracellular recordings revealed that ACh or nicotine cause an increase in membrane conductance associated with depolarizations that had an average reversal potential of -16 to -11 mV. These results indicate that the ACh-induced excitation is due to an increase in membrane cation conductance. The inhibitory response that follows ACh-induced depolarization and repetitive firing was associated with a hyperpolarization and an increase in membrane conductance. Similar postexcitatory inhibition could also be elicited by direct depolarization or by applications of glutamate, indicating that the hyperpolarizing response to ACh may be an endogenous postexcitatory potential that is not directly coupled to activation of nicotinic receptors. These results suggest that cholinergic transmission in the MHb may be largely of the nicotinic type. This nucleus may be of one of the major regions of the nervous system through which nicotine mediates its central effects.
Intracellular localization of the 3-hydroxy-3-methylglutaryl coenzme A cycle enzymes in liver. Separate cytoplasmic and mitochondrial 3-hydroxy-3-methylglutaryl coenzyme A generating systems for cholesterogenesis and ketogenesis. (1975)

Acetoacetyl-CoA thiolase and 3-hydroxy-3-methylglutaryl coenzyme synthase which comprise the 3-hydroxy-3-methylglutaryl-CoA-generating system(s) for hepatic cholesterogenesis and ketogenesis exhibit dual mitochondrial and cytoplasmic localization. Twenty to forty per cent of the thiolase and synthase of avian and rat liver are localized in the cytoplasmic compartment, the remainder residing in the mitochondria. In contrast, 3-hydroxy-3 methylglutaryl-CoA lyase, an enzyme unique to the "3-hydroxy-3-methylglutaryl-CoA cycle" of ketogenesis, appears to be localized in the mitochondrion. The small proportion, 4 to 8 percent, of this enzyme found in the cytoplasmic fraction appears to arise via leakage from the mitochondria during cell fractionation in that its properties, pI and stability, are identical to those of the mitochondrial lyase. These results are consistent with the view that ketogenesis which involves all three enzymes, acetoacetyl-CoA thiolase, 3-hydroxy-3-methylglutaryl-CoA synthase and 3-hydroxy-3-methylglutaryl-CoA lyase, occurs exclusively in the mitochondrion, whereas cholesterogenesis, a pathway which involves only the 3-hydroxy-3-methylglutaryl-CoA synthesizing enzymes, is restricted to the cytoplasm. Further fractionation of isolated mitochondria from chicken and rat liver showed that all three of the 3-hydroxy-3-methylglutaryl-CoA cycle enzymes are soluble and are localized within the matrix compartment of the mitochondrion. Likewise, cytoplasmic acetoacetyl-CoA thiolase and 3-hydroxy-3-methylglutaryl-CoA synthase are soluble cytosolic enzymes, no thiolase or synthase activity being detectable in the microsomal fraction. Chicken liver mitochondrial 3-hydroxy-3methylglutaryl-CoA synthase activity consists of a single enzymic species with a pI of 7.2, whereas the cytoplasmic activity is composed of at least two species with pI values of 4.8 and 6.7. Thus it is evident that the mitochondrial and cytoplasmic species are molecularly distinct as has been shown to be the case for the mitochondrial and cytoplasmic acetoacetyl-CoA thiolases from avian liver (Clinkenbeard, K. D., Sugiyama, T., Moss, J., Reed, W. D., and Lane, M. D. (1973) J. Biol. Chem. 248, 2275). Substantial mitochondrial 3-hydroxy-3-methylglutaryl-CoA lyase activity is present in all tissues surveyed, while only liver and kidney possess significant mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase activity. Therefore, it is proposed that tissues other than liver and kidney are unable to generate acetoacetate because they lack the mitochondrial synthase.
Silicon Carbide Whisker-mediated Plant Transformation (2011)

With the advancement in molecular biology, several metabolic and physiological processes have been elucidated at molecular levels discovering the involvement of different genes. Since the advent of plant transformation 33 years ago, use of plant transformation techniques sparked an interest in fundamental and applied research leading to the development of biological and physical methods of foreign DNA delivery into 130 plant species. Modern molecular biology tools have developed rich gene sources which are waiting to be transformed into plant species. But unavailability of efficient transformation methods is a major hurdle to expedite the delivery of these genes into plants. Ever-expanding available gene pools in the era of third generation transgenic plants stressing the delivery of multiple genes for different traits; development and application of new transformation methods is the big need of the time to meet the future challenges for plant improvement. In recent years, silicon-carbide whiskers have proven valuable and effective alternative in which silicon carbide fibers are mixed with plant cells and plasmid DNA, followed by vortexing/oscillation. Cell penetration appears to occur thus whiskers function as numerous fine needles, facilitating DNA entry into cells during the mixing process. This technique is simple, easy and an inexpensive transformation method to deliver the DNA into monocot and dicot plant species. Whiskers, cells and plasmid DNA are combined in a small tube and mixed on a vortex or oscillating mixer. In this chapter we will discuss the use of silicon carbide fibers/whiskers to transform and produce different transgenic plants. This chapter will help the reader to know about emerging applications of silicon carbide and other fibers in the delivery of foreign DNA into plants, and critical parameters affecting DNA delivery efficiency will also be discussed.
Role of mechanical factors in modulating cardiac fibroblast function and extracellular matrix synthesis (2000)

The cardiac fibroblast is the most abundant cell type present in the myocardium and is mainly responsible for the deposition of extracellular matrix (ECM). Important components of cardiac ECM include structural and adhesive proteins such as collagen and fibronectin. Excess deposition of cardiac ECM (fibrosis) has been associated with the pathophysiological mechanical overload of the heart. Therefore, the role of cardiac fibroblasts in "sensing", "integrating" and "responding" to mechanical stimuli is of great interest. The development of in vitro strain apparatuses has allowed scientists to investigate the effects of mechanical stimuli on cardiac fibroblast function. Cardiac fibroblasts express ECM receptors (integrins) which couple mechanical stimuli to functional responses. Mechanical stimulation of cardiac fibroblasts has been shown to result in activation of various signal transduction pathways. The application of defined mechanical stimuli to cultured cardiac fibroblasts has been associated with ECM gene expression, growth factor production, release and/or bioactivity as well as collagenase activity. Ultimately, for fibrosis to develop the overproduction of ECM must overcome any associated increases in collagenase activity. Mechanically induced upregulation of ECM production may follow direct or indirect pathways through the autocrine or paracrine action of growth factors. Given the complex nature of the interstitial milieu of the working heart, additional research is needed to further our understanding of the roles that mechanical stimuli play in excess deposition of myocardial ECM.
Neuronal Death and Blood–Brain Barrier Breakdown after Excitotoxic Injury Are Independent Processes (1999)

Neuronal damage in the CNS after excitotoxic injury is correlated with blood-brain barrier (BBB) breakdown. We have used a glutamate analog injection model and genetically altered mice to investigate the relationship between these two processes in the hippocampus. Our results show that BBB dysfunction occurs too late to initiate neurodegeneration. In addition, plasma infused directly into the hippocampus is not toxic and does not affect excitotoxin-induced neuronal death. To test plasma protein recruitment in neuronal degeneration, we used plasminogen-deficient (plg(-/-)) mice, which are resistant to excitotoxin-induced degeneration. Plasminogen is produced in the hippocampus and is also present at high levels in plasma, allowing us to determine the contribution of each source to cell death. Intrahippocampal delivery of plasminogen to plg(-/-) mice restored degeneration to wild-type levels, but intravenous delivery of plasminogen did not. Finally, although the neurons in plg(-/-) mice do not die after excitotoxin injection, BBB breakdown occurs to a similar extent as in wild-type mice, indicating that neuronal death is not necessary for BBB breakdown. These results indicate that excitotoxin-induced neuronal death and BBB breakdown are separable events in the hippocampus.
L-Myc Overexpression and Detection of Auto-Antibodies against L-Myc in Both the Serum and Pleural Effusion from a Patient with Non-Small Cell Lung Cancer. (1997)

Non-small cell lung cancer patient was found to have auto-antibodies against L-Myc in both the serum and pleural effusion. The titer of anti-L-Myc antibodies was higher in the pleural effusion than in the serum. Overexpression of L-Myc without DNA amplification was observed in the tumor cells. L-Myc antigen was not detected in either the serum or the pleural effusion. Anti-nuclear antibodies were also detected in both the serum and pleural effusion, although this patient did not have collagen-vascular disease.(Internal Medicine 36: 724-727, 1997)
Biosynthesis of Novel Aromatic Copolyesters from Insoluble 11-Phenoxyundecanoic Acid by Pseudomonas putida BM01 (1996)

Two types of novel aromatic copolyesters were synthesized from 11-phenoxyundecanoic acid (11-POU) as the sole carbon source and the cosubstrates 11-POU and octanoate, respectively, by isolated Pseudomonas putida BM01 that is known to accumulate high concentrations of medium-chain-length polyesters. Insoluble 11-POU was recrystallized in situ in buffer by alkaline treatment and pH adjustment, followed by autoclaving. The resulting microcrystals, whose structure was different from that of the commercially available crystalline powder, suspended in media were rapidly consumed by the bacterium. Synthesized polymers were characterized by gas chromatography, nuclear magnetic resonance spectroscopy, and differential scanning calorimetry. The aromatic copolyesters synthesized from 11-POU were composed of two monomer units consisting of 3-hydroxy-5-phenoxyvalerate (5POHV) as the major component (72 to 85 mol%) and 3-hydroxy-7-phenoxyheptanoate (7POHH) as the minor component (15 to 28 mol%). The aromatic copolyesters showed a crystalline melting transition at 70(deg)C. When the bacterium was grown on the cosubstrates 11-POU and octanoate, the bacterium synthesized the copolyesters composed of aromatic and aliphatic monomers poly(5POHV-co-7POHH-co-3-hydroxy-9-phenoxynonanoate-co-3-hydroxyalkanoates) . The addition of octanoate in the feed shifted the major monomer unit in the polymer from 5POHV to 7POHH. A further-fragmented metabolite, 3-phenoxypropionate, whose concentration reached a steady state at the time of greatest polyester accumulation, was detected in the medium. The metabolic pathway of 11-POU is suggested.
Granulocyte-Macrophage Colony-Stimulating Factor Expressed by Recombinant Respiratory Syncytial Virus Attenuates Viral Replication and Increases the Level of Pulmonary Antigen-Presenting Cells (2001)

An obstacle to developing a vaccine against human respiratory syncytial virus (RSV) is that natural infection typically does not confer solid immunity to reinfection. To investigate methods to augment the immune response, recombinant RSV (rRSV) was constructed that expresses murine granulocyte-macrophage colony-stimulating factor (mGM-CSF) from a transcription cassette inserted into the G-F intergenic region. Replication of rRSV/mGM-CSF in the upper and lower respiratory tracts of BALB/c mice was reduced 23- to 74- and 5- to 588-fold, respectively, compared to that of the parental rRSV. Despite this strong attenuation of replication, the level of RSV-specific serum antibodies induced by rRSV/mGM-CSF was comparable to, or marginally higher than, that of the parental rRSV. The induction of RSV-specific CD8(+) cytotoxic T cells was moderately reduced during the initial infection, which might be a consequence of reduced antigen expression. Mice infected with rRSV/mGM-CSF had elevated levels of pulmonary mRNA for gamma interferon (IFN-gamma) and interleukin 12 (IL-12) p40 compared to animals infected by wild-type rRSV. Elevated synthesis of IFN-gamma could account for the restriction of RSV replication, as was observed previously with an IFN-gamma-expressing rRSV. The accumulation of total pulmonary mononuclear cells and total CD4(+) T lymphocytes was accelerated in animals infected with rRSV/mGM-CSF compared to that in animals infected with the control virus, and the level of IFN-gamma-positive or IL-4-positive pulmonary CD4(+) cells was elevated approximately twofold. The number of pulmonary lymphoid and myeloid dendritic cells and macrophages was increased up to fourfold in mice infected with rRSV/mGM-CSF compared to those infected with the parental rRSV, and the mean expression of major histocompatibility complex class II molecules, a marker of activation, was significantly increased in the two subsets of dendritic cells. Enhanced antigen presentation likely accounts for the maintenance of a strong antibody response despite reduced viral replication and would be a desirable property for a live attenuated rRSV vaccine.
Isoflurane prevents acquired epilepsy in rat models of temporal lobe epilepsy (2016)

Given that isoflurane is a widely used volatile anesthetic, and is used for inhalational long-term sedation in critically ill patients at risk to develop epilepsy, our findings hold a promising potential to be successfully translated into the clinic. Ann Neurol 2016;80:896-908.
Mutations in the kinesin-like protein Eg5 disrupting localization to the mitotic spindle. (1995)

Eg5, a member of the bimC subfamily of kinesin-like microtubule motor proteins, localizes to spindle microtubules in mitosis but not to interphase microtubules. We investigated the molecular basis for spindle localization by transient transfection of Xenopus A6 cells with myc-tagged derivatives of Eg5. Expressed at constitutively high levels from a cytomegalovirus promoter, mycEg5 protein is cytoplasmic throughout interphase, begins to bind microtubules in early prophase, and remains localized to spindle and/or midbody microtubules through mitosis to the end of telophase. Both N- and C-terminal regions of Eg5 are required for this cell-cycle-regulated targeting. Eg5 also contains within its C-terminal domain a sequence conserved among bimC subfamily proteins that includes a potential p34cdc2 phosphorylation site. We show that mutation of a single threonine (T937) within this site to nonphosphorylatable alanine abolishes localization of the mutant protein to the spindle, whereas mutation of T937 to serine preserves spindle localization. We hypothesize that phosphorylation of Eg5 may regulate its localization to the spindle in the cell cycle.
Characterization and Purification of Polydisperse Reconstituted Lipoproteins and Nanolipoprotein Particles (2009)

Heterogeneity is a fact that plagues the characterization and application of many self-assembled biological constructs. The importance of obtaining particle homogeneity in biological assemblies is a critical goal, as bulk analysis tools often require identical species for reliable interpretation of the results-indeed, important tools of analysis such as x-ray diffraction typically require over 90% purity for effectiveness. This issue bears particular importance in the case of lipoproteins. Lipid-binding proteins known as apolipoproteins can self assemble with liposomes to form reconstituted high density lipoproteins (rHDLs) or nanolipoprotein particles (NLPs) when used for biotechnology applications such as the solubilization of membrane proteins. Typically, the apolipoprotein and phospholipids reactants are self assembled and even with careful assembly protocols the product often contains heterogeneous particles. In fact, size polydispersity in rHDLs and NLPs published in the literature are frequently observed, which may confound the accurate use of analytical methods. In this article, we demonstrate a procedure for producing a pure, monodisperse NLP subpopulation from a polydisperse self-assembly using size exclusion chromatography (SEC) coupled with high resolution particle imaging by atomic force microscopy (AFM). In addition, NLPs have been shown to self assemble both in the presence and absence of detergents such as cholate, yet the effects of cholate on NLP polydispersity and separation has not been systematically examined. Therefore, we examined the separation properties of NLPs assembled in both the absence and presence of cholate using SEC and native gel electrophoresis. From this analysis, NLPs prepared with and without cholate showed particles with well defined diameters spanning a similar size range. However, cholate was shown to have a dramatic affect on NLP separation by SEC and native gel electrophoresis. Furthermore, under conditions where different sized NLPs were not sufficiently separated or purified by SEC, AFM was used to deconvolute the elution pattern of different sized NLPs. From this analysis we were able to purify an NLP subpopulation to 90% size homogeneity by taking extremely fine elutions from the SEC. With this purity, we generate high quality NLP crystals that were over 100 microm in size with little precipitate, which could not be obtained utilizing the traditional size exclusion techniques. This purification procedure and the methods for validation are broadly applicable to other lipoprotein particles.
Plasma Cannabinoid Pharmacokinetics following Controlled Oral Δ9-Tetrahydrocannabinol and Oromucosal Cannabis Extract Administration (2010)

These data suggest that CBD modulation of THC's effects is not due to a pharmacokinetic interaction at these therapeutic doses.
E-cadherin expression is silenced by DNA hypermethylation in human breast and prostate carcinomas. (1995)

Expression of the Ca(2+)-dependent, homotypic cell:cell adhesion molecule, E-cadherin (E-cad), suppresses tumor cell invasion and metastasis in experimental tumor models. Decreased E-cad expression is common in poorly differentiated, advanced-stage carcinomas. These data implicate E-cad as an "invasion suppressor" gene. The mechanism by which E-cad is silenced in advanced stage carcinomas is unclear. In this report, we show that: (a) the 5' CpG island of E-cad is densely methylated in E-cad-negative breast and prostate carcinoma cell lines and primary breast carcinoma tissue but is unmethylated in normal breast tissue; (b) treatment with the demethylating agent, 5-aza-2'-deoxycytidine, partially restores E-cad RNA and protein levels in E-cad-negative breast and prostate carcinoma cell lines; and (c) and E-cad promoter/CAT construct is expressed in both E-cad-positive and -negative breast and prostate carcinoma cell lines, indicating that these cells have the active transcriptional machinery necessary for E-cad expression. Our data demonstrate that frequent loss of E-cad expression in human breast and prostate carcinomas results from hypermethylation of the E-cad promoter region.
The effect of prebonding heat treatment on the separability of Au wire from Ag-plated Cu alloy substrate (2002)

The wire bonding technology that relies on subsequent wire separation of a connection has a possibility of becoming a key packaging technology in the environmentally friendly aspects of the recycling of mounting materials, such as the reworking of chip on board (COB) mounting and the application of the inter-poserless chip size package (CSP) in the manufacturing process. This study investigated how heat treatment before bonding affects separability at the ball bonding area. For the investigation, we used bonding pairs of Ag-plated Cu alloy substrate and An wire. Heating a board to 150/spl deg/C before wire bonding degraded wire bondability but improved separability. An analysis of Ag plating by Auger electron spectroscopy (AES) and x-ray photoelectron spectroscopy (XPS) revealed that the heat treatment caused the Cu on the board to diffuse into the Ag plating and to deposit concentrations of Cu in the form of Cu(OH)/sub 2/ and CuCl/sub 2/ on the Ag surface.
Tetracycline and minocycline treatment (1982)

The effect of 1,000 mg of tetracycline hydrochloride and 200 mg of minocycline hydrochloride on Propionibacterium acnes levels and skin-surface lipid levels was measured in 15 patients with acne. Minocycline produced a significantly greater reduction in the P acnes counts that persisted even up to three weeks after discontinuation of the minocycline therapy, in contrast to the return of P acnes to baseline counts within three weeks after discontinuation of tetracycline therapy. A similar persistence of effect for reduction of skin-surface free fatty acid levels and clinical lesions was also seen with minocycline therapy.
A New Method for Carrier-Phase-Based Precise Point Positioning (2002)

ABSTRACT: This paper describes a carrier-phase–based precise point positioning (PPP) method based a new observation model. Unlike the traditional PPP processing method, the new method allows for exploitation of the integer characteristics of carrier-phase ambiguities. The new method also opens the door for the development of new algorithms for ambiguity resolution to support real-time PPP applications in the future. Numerical results indicate that the new method is superior to the traditional PPP processing method in terms of positional accuracy, convergence speed, and filter stability.