gebhart/patrepeval huggingface dataset:
GABAA receptor modulation by piperine and a non-TRPV1 activating derivative (2013)

The action of piperine (the pungent component of pepper) and its derivative SCT-66 ((2E,4E)-5-(1,3-benzodioxol-5-yl))-N,N-diisobutyl-2,4-pentadienamide) on different gamma-aminobutyric acid (GABA) type A (GABA(A)) receptors, transient-receptor-potential-vanilloid-1 (TRPV1) receptors and behavioural effects were investigated. GABA(A) receptor subtypes and TRPV1 receptors were expressed in Xenopus laevis oocytes. Modulation of GABA-induced chloride currents (I(GABA)) by piperine and SCT-66 and activation of TRPV1 was studied using the two-microelectrode-voltage-clamp technique and fast perfusion. Their effects on explorative behaviour, thermoregulation and seizure threshold were analysed in mice. Piperine acted with similar potency on all GABA(A) receptor subtypes (EC₅₀ range: 42.8±7.6 μM (α₂β₂)-59.6±12.3 μM (α₃β₂). I(GABA) modulation by piperine did not require the presence of a γ(2S)-subunit, suggesting a binding site involving only α and β subunits. I(GABA) activation was slightly more efficacious on receptors formed from β(2/3) subunits (maximal I(GABA) stimulation through α₁β₃ receptors: 332±64% and α₁β₂: 271±36% vs. α₁β₁: 171±22%, p<0.05) and α₃-subunits (α₃β₂: 375±51% vs. α₅β₂:136±22%, p<0.05). Replacing the piperidine ring by a N,N-diisobutyl residue (SCT-66) prevents interactions with TRPV1 and simultaneously increases the potency and efficiency of GABA(A) receptor modulation. SCT-66 displayed greater efficacy on GABA(A) receptors than piperine, with different subunit-dependence. Both compounds induced anxiolytic, anticonvulsant effects and reduced locomotor activity; however, SCT-66 induced stronger anxiolysis without decreasing body temperature and without the proconvulsive effects of TRPV1 activation and thus may serve as a scaffold for the development of novel GABA(A) receptor modulators.
Combining mTOR Inhibitors with Chemotherapy and Other Targeted Therapies in Advanced Breast Cancer: Rationale, Clinical Experience, and Future Directions (2013)

Improvements in survival of patients with breast cancer have been attributed to the development of agents that target key components of dysregulated pathways involved in oncogenesis and progression of breast cancer. Aberrant mammalian target of rapamycin (mTOR) activation has been implicated in oncogenesis, angiogenesis, and the development of estrogen independence and resistance to chemotherapy in breast tumors. Several mTOR inhibitors (sirolimus, everolimus, temsirolimus, and ridaforolimus) have demonstrated antitumor activity in breast cancer cells. Combining mTOR inhibitors with endocrine therapies has demonstrated clinical antitumor activity in patients with metastatic breast cancer. In addition, mTOR inhibitor combinations with various targeted biologic agents or cytotoxic chemotherapeutic agents are being examined in more than 40 clinical trials with some early promising results. Combination therapies targeting multiple components of these central signaling pathways may be an optimal treatment strategy for patients with advanced breast cancer.
Sequential relationships between grey matter and white matter atrophy and brain metabolic abnormalities in early Alzheimer's disease (2010)

Hippocampal atrophy, posterior cingulate and frontal glucose hypometabolism, and white-matter tract disruption are well described early macroscopic events in Alzheimer's disease. The relationships between these three types of alterations have been documented in previous studies, but their chronology still remains to be established. The present study used multi-modal fluorodeoxyglucose-positron emission tomography and magnetic resonance imaging longitudinal data to address this question in patients with amnestic mild cognitive impairment. We found unidirectional, specific sequential relationships between: (i) baseline hippocampal atrophy and both cingulum bundle (r = 0.70; P = 3 × 10⁻³) and uncinate fasciculus (r = 0.75; P = 7 × 10⁻⁴) rate of atrophy; (ii) baseline cingulum bundle atrophy and rate of decline of posterior (r = 0.72; P = 2 × 10⁻³); and anterior (r = 0.74; P = 1 × 10⁻³) cingulate metabolism; and (iii) baseline uncinate white matter atrophy and subgenual metabolism rate of change (r = 0.65; P = 6 × 10⁻³). Baseline local grey matter atrophy was not found to contribute to hypometabolism progression within the posterior and anterior cingulate as well as subgenual cortices. These findings suggest that hippocampal atrophy progressively leads to disruption of the cingulum bundle and uncinate fasciculus, which in turn leads to glucose hypometabolism of the cingulate and subgenual cortices, respectively. This study reinforces the relevance of remote mechanisms above local interactions to account for the pattern of metabolic brain alteration observed in amnestic mild cognitive impairment, and provides new avenues to assess the sequence of events in complex diseases characterized by multiple manifestations.
Differential Expression of Voltage-Gated K + Channel Subunits in Adult Rat Heart (1995)

Polyclonal antibodies against each of the K+ channel subunits (Kv1.2, Kv1.4, Kv1.5, Kv2.1, and Kv4.2) shown previously to be expressed in adult rat heart at the mRNA level were used to examine the distributions of these K+ channel subunits in adult rat atrial and ventricular membranes. Immunohistochemistry on isolated adult rat ventricular myocytes revealed strong labeling with the anti-Kv4.2 and anti-Kv1.2 antibodies. Although somewhat weaker (than with anti-Kv1.2 or anti-Kv4.2), positive staining was also observed with the anti-Kv1.5 and anti-Kv2.1 antibodies. Ventricular myocytes exposed to the anti-Kv1.4 antibody, in contrast, did not appear significantly different from background. Qualitatively similar results were obtained on isolated adult rat atrial myocytes. Western blots of atrial and ventricular membrane proteins confirmed the presence of Kv1.2, Kv1.5, Kv2.1, and Kv4.2 and revealed differences in the relative abundances of these subunits in the two membrane preparations. Kv4.2, for example, is more abundant in ventricular than in atrial membranes, whereas Kv1.2 and Kv2.1 are higher in atrial membranes; Kv1.5 levels are comparable in the two preparations. In contrast to these results, nothing was detected in Western blots of atrial or ventricular membrane proteins with the anti-Kv1.4 antibody at concentrations that revealed intense labeling of a 97-kD protein in adult rat brain membranes. A very faint band was detected at 97 kD in the atrial and ventricular preparations when the anti-Kv1.4 antibody was used at a 5- to 10-fold higher concentration. The simplest interpretation of these results is that Kv1.4 is not an abundant protein in adult rat atrial or ventricular myocytes. Therefore, it seems unlikely that Kv1.4 plays an important role in the formation of functional depolarization-activated K+ channels in these cells. The relation(s) between the (other four) K+ channel subunits and the depolarization-activated K+ channels identified electrophysiologically in adult rat atrial and ventricular myocytes is discussed in the present study.
Monocarboxylate Transporter 4 Regulates Maturation and Trafficking of CD147 to the Plasma Membrane in the Metastatic Breast Cancer Cell Line MDA-MB-231 (2007)

Metastatic cancer cells increase glucose consumption and metabolism via glycolysis, producing large quantities of lactate. Recent work has shown that lactate efflux is mediated by monocarboxylate transporters (MCT), which are composed of a catalytic unit (MCT) and an accessory subunit (CD147), comprising the functional lactate transporter. CD147, an extracellular matrix metalloproteinase (MMP) inducer, is highly expressed in metastatic cancer cells. Because aerobic glycolysis is a hallmark of metastatic cancer, we examined whether increases in CD147 expression were linked to MCT expression in MDA-MB-231, a highly metastatic breast cancer cell line. MCT4 mRNA and protein expression were increased in MDA-MB-231 cells compared with cells derived from normal mammary tissue. MCT4 colocalized with CD147 in the plasma membrane and in membrane blebs shed from the cell surface. Small interfering RNA-mediated silencing of MCT4 impaired the maturation and trafficking of CD147 to the cell surface, resulting in accumulation of CD147 in the endoplasmic reticulum. Silencing MCT4 also resulted in fewer membrane blebs and decreased migration of MDA-MB-231 cells in vitro. Knockdown of CD147 resulted in loss of MCT4 in the plasma membrane and accumulation of the transporter in endolysosomes. These studies establish for the first time that increased expression of CD147 in metastatic cancer cells is coupled to the up-regulation of MCT4. The synergistic activities of the MCT/CD147 complex could facilitate migration of tumor cells by CD147-mediated MMP induction and lactate-stimulated angiogenesis and hyaluronan production. These data provide a molecular link between two hallmarks of metastatic cancer: the glycolytic switch and increased expression of CD147.
TDP-43-Mediated Neuron Loss In Vivo Requires RNA-Binding Activity (2010)

Alteration and/or mutations of the ribonucleoprotein TDP-43 have been firmly linked to human neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). The relative impacts of TDP-43 alteration, mutation, or inherent protein function on neural integrity, however, remain less clear--a situation confounded by conflicting reports based on transient and/or random-insertion transgenic expression. We therefore performed a stringent comparative investigation of impacts of these TDP-43 modifications on neural integrity in vivo. To achieve this, we systematically screened ALS/FTLD-associated and synthetic TDP-43 isoforms via same-site gene insertion and neural expression in Drosophila; followed by transposon-based motor neuron-specific transgenesis in a chick vertebrate system. Using this bi-systemic approach we uncovered a requirement of inherent TDP-43 RNA-binding function--but not ALS/FTLD-linked mutation, mislocalization, or truncation--for TDP-43-mediated neurotoxicity in vivo.
Transcriptional regulation by iron of a Vibrio cholerae virulence gene and homology of the gene to the Escherichia coli fur system (1990)

We have previously described an iron-regulated virulence determinant in Vibrio cholerae. Strain MBG40, which contains a TnphoA insertion mutation in the iron-regulated gene irgA, has reduced virulence in a newborn mouse model and has lost the major 77-kDa iron-regulated outer membrane protein. We report here the cloning of the irgA'-'phoA gene fusion, the sequencing of the 5'-proximal portion of irgA, and the definition of its promoter region by primer extension. The deduced amino acid sequence of the amino-terminal portion of IrgA is homologous to the ferrienterochelin receptor of Escherichia coli (FepA), suggesting that IrgA may be the iron-vibriobactin outer membrane receptor. Iron regulation of irgA in an E. coli background and that of the E. coli gene slt-IA in a V. cholerae background are reciprocal, suggesting a common mechanism of iron regulation. Regulation of irgA by iron in V. cholerae occurs at the transcriptional level, and there is an interrupted dyad symmetric sequence in the vicinity of the promoter that is homologous to Fur binding sites of E. coli. Unlike iron-regulated genes in E. coli, however, transcription of irgA requires an additional 900 bp of upstream DNA that contains an open reading frame in inverse orientation to irgA.
Skeletal muscle growth in lean and obese Zucker rats. (1983)

Obese Zucker rats exhibit marked hyperphagia when compared to lean littermates but deposit a smaller percentage of total dietary energy as body protein. This study was designed to determine the roles of skeletal muscle protein synthesis, protein degradation, RNA, or DNA in producing the lower muscle mass of obese rats. At 44 days, 3 hindlimb muscles, the extensor digitorum longus (EDL), the gastrocnemius and the plantaris were significantly smaller in the obese animals. At 72 days, the differences in weights of these muscles were more pronounced. Protein synthesis and degradation were determined in the soleus at 44 days of age using an in vitro whole muscle incubation technique. Protein synthesis rate was significantly decreased in the obese animals. These changes were accompanied by reductions in both RNA and DNA levels. Significant changes in nucleic acid levels were observed in both the red and white portions of the gastrocnemius muscle. These changes in the anabolic process of protein accretion appear to be sufficient to account for the reduced muscle mass in the obese Zucker rat.
Volatile constituents of essential oils isolated from different parts of cinnamon (Cinnamomum zeylanicum Blume) (2002)

Abstract Cinnamon ( Cinnamomum zeylanicum Blume, syn C verum JS Presl, family Lauraceae) is an important spice and aromatic tree cultivated in Sri Lanka and India. On steam distillation, different parts of cinnamon yield volatile oils of varying composition. In the present investigation the profiles of essential oils isolated from tender twigs bearing reproductive parts, from pedicels of buds and flowers, from buds and flowers, from pedicels of fruits and from fruits were analysed by gas chromatography (GC) and GC/mass spectrometry (GC/MS). The essential oil yields of the different plant parts were: tender twigs, 0.40%; pedicels of buds and flowers, 0.36%; buds and flowers, 0.04%; pedicels of fruits, 0.33%; fruits, 0.32%. The tender twig oil was richer in α‐phellandrene (3.4%), limonene (1.6%) and ( E )‐cinnamaldehyde (4.0%). The volatile oils from pedicels were richer in neryl acetate (1.4–2.0%), ( E )‐cinnamyl acetate (58.1–64.5%) and β‐caryophyllene (9.6–11.1%). Higher amounts of ( Z )‐cinnamyl acetate (6.1%), α‐humulene (2.2%), δ‐cadinene (2.2%), humulene epoxide I (5.0%), α‐muurolol (4.9%) and α‐cadinol (2.4%) were observed in the oil of buds and flowers. The fruit oil showed greater concentrations of α‐pinene (4.2%), β‐pinene (1.9%) and linalool (27.4%). However, all the oils contained linalool (3.6–27.4%), ( E )‐cinnamyl acetate (22.0–64.5%) and β‐caryophyllene (6.9–11.1%) as their major compounds. This is the first report on the oil profiles of pedicels and of buds and flowers of cinnamon. © 2002 Society of Chemical Industry
Relatos breves publicados en revistas, otras mediaciones literarias entre Esapaña y Francia en la primera mitad del siglo XX (2012)

La literatura francesa y la espanola no han dejado de contagiarse de manera reciproca mediante corrientes y traducciones literarias, intermediarios a los que se pueden sumar, entre otros, las revistas y las colecciones donde tuvieron salida tantos relatos breves y semibreves en diversos formatos. Intermediarios contagiados entre ellos mismos, contribuyen tambien al contagio entre las literaturas: las mismas colecciones y revistas, huespedes de traducciones y de tendencias literarias, impulsan las relaciones literarias supranacionales y son impulsadas a su vez por la prensa y su masificacion desde el siglo XIX en Francia y Espana, como en el resto de la cultura escrita. Sin embargo, por su vinculacion con ese medio periodistico, que tan excelente alojamiento y servicio presta a lo literario breve, las narrativas breves varias asi como las colecciones y las revistas literarias se han visto asociadas con lo paraliterario
Structural Analysis of Arabidopsis thaliana Chromosome 5. IV. Sequence Features of the Regions of 1,456,315 bp Covered by Nineteen Physically Assigned P1 and TAC Clones (1998)

Nineteen P1 and TAC clones, which have been precisely localized to the fine physical map of Arabidopsis thaliana chromosome 5, were newly sequenced, and their sequence features were analysed. The total length of the clones sequenced was 1,456,315 bp. Together with the previously reported sequences, the regions of chromosome 5 that have been sequenced to date is now 5,310,105 bp. When the sequences determined in this study were subjected to similarity search against protein and expressed sequence tag (EST) databases and analysis with computer programs for gene modeling, a total of 354 potential protein-coding genes and/or gene segments were identified. The average density of the assigned genes and/or gene segments was one gene per 4,114 bp. Introns were identified in 75% of the potential protein genes, and the average number per gene and the average length of the introns were 3.7 and 194 bp, respectively. These sequence features are essentially identical to those in the previously reported sequences. The numbers of the Arabidopsis ESTs matched to each of the predicted genes have been counted to monitor the transcription level. The sequence data and gene information are available on the World Wide Web database KAOS (the Kazusa Arabidopsis data Opening Site) at http://www.kazusa.or.jp/arabi/.
DNA Damage Produced by Enediynes in the Human Phosphoglycerate Kinase Gene in Vivo:  Esperamicin A1 as a Nucleosome Footprinting Agent (1998)

We have used both conventional and a modified version of ligation-mediated polymerase chain reaction (LMPCR) to study the role of chromatin structure in the selection of DNA targets by three DNA-cleaving enediynes in whole cells. On the basis of previous studies of enediyne target selection in nucleosomes, we focused on nucleosomes present in the human X-linked phosphoglycerate kinase (PGK1) gene. Damage produced by esperamicin A1 in cells containing a transcriptionally inactive copy of the X-chromosome is reduced compared to that in naked DNA in two regions that encompass approximately 130 and approximately 150 base pairs upstream of the PGK1 gene. These sizes are consistent with nucleosome core DNA. Damage produced by esperamicin A1 in the transcriptionally active form of the gene, in which nucleosomes are not apparent, did not show such a pattern. Esperamicin C, an analogue of esperamicin A1 lacking an intercalating anthranilate moiety, and calicheamicin, both groove binders, were found to cleave DNA throughout the nucleosome core and linker. These results confirm hypotheses generated from studies in isolated chromatin and reconstituted nucleosomes and suggest that enediynes may prove useful as chromatin footprinting agents.
Synergy between glycated human serum albumin and tumor necrosis factor-alpha for interleukin-8 gene expression and protein secretion in human retinal pigment epithelial cells. (1998)

Chemokine production by human retinal pigment epithelium (HRPE) cells is believed to play an important role in ocular inflammation and immune responses. In our previous studies, we demonstrated that glycated human serum albumin (GHSA) strongly stimulates HRPE cells and human corneal keratocytes to produce chemokines. In the present study, we further examined the effects of GHSA on TNF-alpha- and IL-1 beta-induced HRPE IL-8 and monocyte chemoattractant protein (MCP)-1 gene expression and protein secretion in HRPE. At maximally effective concentrations, GHSA (2000 micrograms/ml) potentiated TNF-alpha (20 ng/ml)-stimulated HRPE IL-8 secretion approximately 7-fold. Consistent with the above observations were the time- and dose-dependent increases in the steady-state IL-8 mRNA after coadministration with these two factors, although the half-life of IL-8 mRNA (30 minutes) was not altered by GHSA. In contrast to IL-8, the TNF-alpha-induced HRPE MCP-1 gene expression was only slightly enhanced by GHSA. Moreover, potentiation of HRPE IL-8 generation by GHSA appeared to be selective for TNF-alpha because, under similar conditions, GHSA was unable to enhance the IL-1 beta-stimulated IL-8 gene expression and protein secretion. The IL-1 beta-stimulated HRPE MCP-1 production was also unchanged by GHSA. Collectively, these results suggest specific potentiation of TNF-alpha-induced HRPE IL-8 by human serum albumin that has been glycated either during circulation or locally within tissue. This interaction may be relevant to a variety of ocular diseases involving breakdown of the blood-retinal barrier.
An evaluation of confocal versus conventional imaging of biological structures by fluorescence light microscopy. (1987)

Scanning confocal microscopes offer improved rejection of out-of-focus noise and greater resolution than conventional imaging. In such a microscope, the imaging and condenser lenses are identical and confocal. These two lenses are replaced by a single lens when epi-illumination is used, making confocal imaging particularly applicable to incident light microscopy. We describe the results we have obtained with a confocal system in which scanning is performed by moving the light beam, rather than the stage. This system is considerably faster than the scanned stage microscope and is easy to use. We have found that confocal imaging gives greatly enhanced images of biological structures viewed with epifluorescence. The improvements are such that it is possible to optically section thick specimens with little degradation in the image quality of interior sections.
Association of Fcγ receptor IIb polymorphism with susceptibility to systemic lupus erythematosus in Chinese: a common susceptibility gene in the Asian populations (2003)

The association of Fcgamma receptor (FcgammaR) polymorphisms with systemic lupus erythematosus (SLE) has been demonstrated in various populations; however, the results have been inconsistent. We recently identified a single-nucleotide polymorphism encoding a non-synonymous substitution, Ile232Thr (I232T), of FCGR2B and its association with SLE in Japanese and in Thais. Multiple functional FcgammaR genes with polymorphisms (FCGR2A, FCGR2B, FCGR3A, and FCGR3B) cluster in 1q23, and some of them are in linkage disequilibrium (LD). To differentiate contributions from multiple-linked loci, comparison of different populations may provide useful information. In this study, we analyzed the above four FCGR polymorphisms of the Chinese patients and controls for the association with SLE. FCGR2A-H131R, FCGR2B-I232T, FCGR3A-F176V, and FCGR3B genotypes were determined in 167 Chinese patients with SLE and 129 healthy controls. Association was examined using case-control analysis. Allele frequencies of FCGR2B-232T and FCGR3A-176F were significantly increased in SLE [odds ratio (OR) = 1.67 and OR = 1.41, respectively]. Interestingly, while these alleles had a tendency of positive LD in the controls, FCGR2B-232T was in positive association with FCGR3A-176V in SLE, suggesting that these two alleles were associated with SLE in an independent manner. Comparison between SLE with and without nephritis indicated significant association of FCGR2B-232T with nephritis (OR = 2.65). When the present results were combined with our previous data on the Japanese and the Thais using meta-analytic methods, highly significant and independent association was observed for FCGR2B and FCGR3A genotypes. These results strongly suggested that FCGR2B is a common susceptibility factor to SLE in the Asians.
[Rational surgery of early gastric cancer]. (1988)

Reduced operation for gastric cancer (R1 operation) is indicated for early gastric cancer without lymph node metastasis. We examined which cases can be regarded as early gastric cancer. Mucosal cancer of macroscopically I, IIa, and IIb type that is 2 cm or less in diameter and located at C and macroscopically IIa type submucosal cancer 1 cm or less in diameter appeared to be indicated for this operation. However, preoperative selection of these cases is difficult, and at present, reduction surgery cannot be performed with confidence. Therefore, we have proposed rational surgery for early gastric cancer consisting of removal of the tumor and dissection of group 1 lymph nodes, the lymph node along the left gastric artery, that along the common hepatic artery, and that around the celiac artery. This procedure seems to be appropriate in terms of antitumor immune response of regional lymph nodes and surgical results.