gebhart/patrepeval huggingface dataset:
Restriction of Secretory Granule Motion near the Plasma Membrane of Chromaffin Cells (2001)

We used total internal reflection fluorescence microscopy to study quantitatively the motion and distribution of secretory granules near the plasma membrane (PM) of living bovine chromaffin cells. Within the approximately 300-nm region measurably illuminated by the evanescent field resulting from total internal reflection, granules are preferentially concentrated close to the PM. Granule motion normal to the substrate (the z direction) is much slower than would be expected from free Brownian motion, is strongly restricted over tens of nanometer distances, and tends to reverse directions within 0.5 s. The z-direction diffusion coefficients of granules decrease continuously by two orders of magnitude within less than a granule diameter of the PM as granules approach the PM. These analyses suggest that a system of tethers or a heterogeneous matrix severely limits granule motion in the immediate vicinity of the PM. Transient expression of the light chains of tetanus toxin and botulinum toxin A did not disrupt the restricted motion of granules near the PM, indicating that SNARE proteins SNAP-25 and VAMP are not necessary for the decreased mobility. However, the lack of functional SNAREs on the plasma or granule membranes in such cells reduces the time that some granules spend immediately adjacent to the PM.
Prebiotic Synthesis of Methionine (1972)

Methionine has been shown to be a product of the action of a spark discharge on a simulated primitive earth atmosphere containing CH(4), N(2), NH(3), H(2)O, and H(2)S or CH(3)SH. Acrolein has also been shown to be a product of the discharge and is proposed as an intermediate in the prebiotic synthesis of methionine and of glutamic acid, homocysteine, homoserine, and alpha,gamma-diaminobutyric acid.
Extracellular matrix (ECM) microstructural composition regulates local cell-ECM biomechanics and fundamental fibroblast behavior: a multidimensional perspective (2004)

The extracellular matrix (ECM) provides the principal means by which mechanical information is communicated between tissue and cellular levels of function. These mechanical signals play a central role in controlling cell fate and establishing tissue structure and function. However, little is known regarding the mechanisms by which specific structural and mechanical properties of the ECM influence its interaction with cells, especially within a tissuelike context. This lack of knowledge precludes formulation of biomimetic microenvironments for effective tissue repair and replacement. The present study determined the role of collagen fibril density in regulating local cell-ECM biomechanics and fundamental fibroblast behavior. The model system consisted of fibroblasts seeded within collagen ECMs with controlled microstructure. Confocal microscopy was used to collect multidimensional images of both ECM microstructure and specific cellular characteristics. From these images temporal changes in three-dimensional cell morphology, time- and space-dependent changes in the three-dimensional local strain state of a cell and its ECM, and spatial distribution of beta1-integrin were quantified. Results showed that fibroblasts grown within high-fibril-density ECMs had decreased length-to-height ratios, increased surface areas, and a greater number of projections. Furthermore, fibroblasts within low-fibril-density ECMs reorganized their ECM to a greater extent, and it appeared that beta1-integrin localization was related to local strain and ECM remodeling events. Finally, fibroblast proliferation was enhanced in low-fibril-density ECMs. Collectively, these results are significant because they provide new insight into how specific physical properties of a cell's ECM microenvironment contribute to tissue remodeling events in vivo and to the design and engineering of functional tissue replacements.
Nitric oxide pathways in Alzheimer's disease and other neurodegenerative dementias (2004)

Nitric oxide (NO) is an enzymatic product of nitric oxide synthase (NOS). NO has significant physiological functions and an increasing body of evidence suggests that NO pathways are implicated in a number of neurological disorders, including Alzheimer's disease (AD) and other neurodegenerative dementias. NO is continuously released by endothelial cells in the vascular system, whereas advanced age in the presence of vascular risk factor causes a decrease in cerebral blood flow, involving microvasculopathy with impaired NO release, which in turn results in regional metabolic dysfunction. This finding suggests that vascular pathology plays a crucial role in the pathogenesis of so-called neurodegenerative dementias. Inflammatory responses are commonly found in the brain under a variety of neurodegenerative dementias, including AD and dementia with Lewy bodies, in which up-regulation of NOS expression, suggesting overproduction of NO, is found in neurons and glia. NO is thought to be involved in such neuroinflammation due to its free radical properties, which compromise cellular integrity and viability via mitochondrial damage. Further studies to elucidate NO pathways in neurodegenerative dementias could lead to a better understanding of their pathogenesis and improved therapeutic strategies, and therefore are certainly warranted.
Influence of Amla (Emblica officinalis Gaertn.) on Hypercholesterolemia and Lipid Peroxidation in Cholesterol-Fed Rats (2005)

The effects of amla on low-density lipoprotein (LDL) oxidation and cholesterol levels were investigated in vitro and in vivo using Cu(2+)-induced LDL oxidation and cholesterol-fed rats. SunAmla and ethyl acetate (EtOAc) extract of amla significantly inhibited thiobarbituric acid (TBA)-reactive substance level in the Cu(2+)-induced LDL oxidation and the effects were stronger than those of probucol. In addition, the administration of SunAmla (at a dose of 20 or 40 mg/kg body weight/d) or EtOAc extract of amla (at a dose of 10 or 20 mg/kg body weight/d) for 20 d to rats fed 1% cholesterol diet significantly reduced total, free and LDL-cholesterol levels in a dose-dependent manner, and EtOAc extract of amla exhibited more potent serum cholesterol-lowering effect than SunAmla in the same amount. Furthermore, the oxidized LDL level in serum was markedly elevated in cholesterol-fed control rats as compared with normal rats, while it was significantly decreased by the administration of SunAmla or EtOAc extract of amla. Moreover, the serum TBA-reactive substance level was also significantly decreased after oral administration of SunAmla or EtOAc extract of amla. These results suggest that amla may be effective for hypercholesterolemia and prevention of atherosclerosis.
Methylation profiling of the DNA repair genes in glioblastoma multiforme and its clinical relevance (2004)

1572 Background: Alterations of DNA repair protein have been associated with sensitivity to anticancer drugs, and transcriptional repression by promoter hypermethylation is an essential role in the protein inactivation. Recently methylation of the O6-methylguanine-DNA methyltransferase (MGMT) promoter is an expected predictor not only of responsiveness to chemotherapy but also of prognosis of patient with glioma. The aim of this study was to investigate the methylation profile in DNA repair genes, MGMT, FANCF and hMLH1, of glioblastoma multiforme and correlation between the methylation status and outcome of the patients. Methods: In 40 adult patients with glioblastoma multiforme treated with surgery, irradiation, and/or chemotherapy (ACNU: n=19, cisplatin: n=11), median age at diagnosis was 55 years old, and median overall survival time was 14 months. Promoter hypermethylation of MGMT, hMLH1 and FANCF genes in tumor DNA was examined using the methylation-specific PCR assay and COBRA (combined bisulfite restriction analysis) method. We analyzed relation between methylation status of the MGMT promoter and survival in these patients. Results: The hypermethylation in MGMT, FANCF and hMLH1 promoter were detected 24 of 40 (60%), 1 of 40 (2.5%), and 0 of 40, respectively. Kaplan-Meier analysis and log-rank test revealed no significant difference in overall survival between patient subgroups divided by methylation status of MGMT promoter. Cox proportional hazard regression analysis adjusted for age of onset and extent of surgical resection showed the MGMT promoter hypermethylation had no significant association with overall survival time. Conclusions: In our series, promoter hypermethylation of MGMT was not a predictive factor for outcome, however, more controlled study would be required to validate this result. And it is still suggested epigenetic alteration of MGMT might influence nature of glioblastoma compared with other DNA repair genes. No significant financial relationships to disclose.
A metal-free cathode for organic semiconductor devices (1998)

We introduce a class of low-reflectivity, high-transparency, nonmetallic cathodes useful for a wide range of electrically active, transparent organic devices. The metal-free cathode employs a thin film of copper phthalocyanine (CuPc) capped with a film of low-power, radio-frequency sputtered indium tin oxide (ITO). The CuPc prevents damage to the underlying organic layers during the ITO sputtering process. We present a model suggesting that damage-induced states at the cathode/organic film interface are responsible for the electron injection properties of the contact. Due to the low contact reflectivity, a non-antireflection-coated, metal-free transparent organic light-emitting device (MF-TOLED) is demonstrated with 85% transmission in the visible, emitting nearly identical amounts of light in the forward and backscattered directions. The MF-TOLED performance is found to be comparable to that of conventional TOLEDs employing a more reflective and absorptive cathode consisting of a semitransparent thin film of Mg:Ag capped with ITO.
Activated Platelets Release Two Types of Membrane Vesicles: Microvesicles by Surface Shedding and Exosomes Derived From Exocytosis of Multivesicular Bodies and -Granules (1999)

Platelet activation leads to secretion of granule contents and to the formation of microvesicles by shedding of membranes from the cell surface. Recently, we have described small internal vesicles in multivesicular bodies (MVBs) and alpha-granules, and suggested that these vesicles are secreted during platelet activation, analogous to the secretion of vesicles termed exosomes by other cell types. In the present study we report that two different types of membrane vesicles are released after stimulation of platelets with thrombin receptor agonist peptide SFLLRN (TRAP) or alpha-thrombin: microvesicles of 100 nm to 1 microm, and exosomes measuring 40 to 100 nm in diameter, similar in size as the internal vesicles in MVBs and alpha-granules. Microvesicles could be detected by flow cytometry but not the exosomes, probably because of the small size of the latter. Western blot analysis showed that isolated exosomes were selectively enriched in the tetraspan protein CD63. Whole-mount immuno-electron microscopy (IEM) confirmed this observation. Membrane proteins such as the integrin chains alpha(IIb)-beta(3) and beta(1), GPIbalpha, and P-selectin were predominantly present on the microvesicles. IEM of platelet aggregates showed CD63(+) internal vesicles in fusion profiles of MVBs, and in the extracellular space between platelet extensions. Annexin-V binding was mainly restricted to the microvesicles and to a low extent to exosomes. Binding of factor X and prothrombin was observed to the microvesicles but not to exosomes. These observations and the selective presence of CD63 suggest that released platelet exosomes may have an extracellular function other than the procoagulant activity, attributed to platelet microvesicles.
Rapid Histochemistry Using Slow Off-rate Modified Aptamers With Anionic Competition (2011)

Immunohistochemistry is used in both research and clinical settings to identify proteins in tissue samples. Despite the power and versatility of immunohistochemistry, limitations are imposed by the slow diffusion of antibodies through tissue and the need for secondary staining or signal amplification. Aptamers can circumvent these limitations, but their application has been hindered by nonspecific binding to cellular components, particularly in the nucleus. Here we describe unique slow off-rate modified aptamers that facilitate rapid and selective binding to target proteins in tissue. Specifically, we have developed a fluorescent aptamer that binds to the human epidermal growth factor receptor 2 (HER2) in breast carcinomas quickly and specifically, and we have shown that the slow off-rate of the aptamer from the HER2 protein contributes to its selectivity. These findings open the door to aptamer histochemistry applications in both research and clinical settings, including intraoperative diagnostics in which speed and accuracy are paramount.
Cross-linking of streptomycin to the 16S ribosomal RNA of Escherichia coli (1987)

[3H]Dihydrostreptomycin was cross-linked to the 30S ribosomal subunit from Escherichia coli with the bifunctional reagent nitrogen mustard. The cross-linking primarily involved the 16S RNA. To localize the site of cross-linking of streptomycin to the 16S RNA, we hybridized RNA labeled with streptomycin to restriction fragments of the 16S RNA gene. Labeled RNA hybridized to DNA fragments corresponding to bases 892-917 and bases 1394-1415. These two segments of the ribosomal RNA must be juxtaposed in the ribosome, since there is a single binding site for streptomycin. This region has been implicated both in the decoding site and in the binding of initiation factor IF-3, indicating its functional importance.
Abortions, fetal death, and stillbirths in pregnant pygmy goats inoculated with tachyzoites of Neospora caninum (1995)

Neospora caninum-induced abortion is a major production problem in the dairy cattle industry in the United States and worldwide. Abortions attributable to naturally acquired N caninum infection also have been observed in pygmy goats. We studied experimentally induced infections with N caninum in pregnant pygmy does to determine whether abortions attributable to N caninum infection would occur after inoculation. Seven pregnant pygmy does (1 control doe and 6 inoculated with N caninum) were studied. The control doe remained clinically normal throughout the study and delivered 2 healthy kids. Abortion, fetal death, and stillbirths were observed in some pregnant does inoculated with N caninum. Two pregnant pygmy does inoculated with N caninum early in gestation (day 51) had fetuses that died and were aborted, or died and were reabsorbed. Neospora caninum tachyzoites and lesions were observed in the brain, spinal cord, and heart of aborted fetuses; parasites also were isolated from the placenta. Four additional pregnant pygmy does (2 inoculated at mid-gestation [day 85], and 2 at late gestation [day 127]) did not abort after inoculation. However, 1 doe inoculated during mid-gestation delivered a stillborn fetus that had died about 1 week prior to parturition. This kid was congenitally infected with N caninum. Neospora caninum was isolated from the placentas of all inoculated does examined. Neonatal neosporosis was not observed in live-born kids, nor were stages of N caninum isolated from any live-born kid. Does did not undergo abortion or have congenitally infected kids when they were rebred and evaluated for neosporosis.
Web Usage Mining Data Preparation (2005)

Web usage mining refers to the automatic discovery and analysis of patterns in clickstream and associated data collected or generated as a result of user interactions with Web resources on one or more Web sites. The goal of Web usage mining is to capture, model, and analyze the behavioral patterns and profiles of users interacting with a Web site. Analyzing such data can help these organizations determine the lifetime value of clients, design cross marketing strategies across products and services, evaluate the effectiveness of promotional campaigns, optimize the functionality of Web-based applications, provide more personalized content to visitors, and find the most effective logical structure for their Web space.
Characterization and chromosomal localization of the human proto-oncogene BMI-1 (1993)

The proto-oncogene bmi-1 is frequently activated by Moloney murine leukemia proviral insertions in E mu-myc transgenic mice1,2. Using a mouse bmi-1 cDNA probe a transcript of 3.3 kb was detected on Northern blots of human Burkitt's lymphoma cell lines. We have isolated and sequenced cDNA clones from a human erythroleukemia cell line (K562) derived cDNA library, using different mouse bmi-1 cDNA fragments as a probe. Analysis of genomic BMI-1 sequences reveals a gene structure which is very similar to that of the mouse, consisting of at least 10 exons. The human cDNA is 3203 bp in length and shows 86% identity to the mouse nucleotide sequence. The open reading frame encodes a protein of 326 amino acids which shares 98% identity to the amino acid sequence of mouse bmi-1 protein. In vitro translation experiments show that human cDNA derived RNA translates into a protein with a mobility of 44-46 kD on SDS polyacrylamide gels. Fluorescence in situ hybridization (FISH) on metaphase chromosome spreads located the human BMI-1 gene to the short arm of chromosome 10 (10p13), a region known to be involved in translocations in various leukemias.
Parallel microparticle manipulation using an imaging fiber-bundle-based optical tweezer array and a digital micromirror device (2006)

In this letter, the authors present a method to selectively capture and release microparticles using an imaging fiber-bundle-based optical tweezer array system. By integrating a digital micromirror device into a tweezer array system, patterns of optical traps can be generated on the distal face of a fiber bundle. A 2×2 array of traps was created to capture, release, and recapture microparticles in solution. This straightforward process enables individual control of the size, shape, and position of each trap in the array.
Rapid Construction of a Squalamine Mimic (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRapid Construction of a Squalamine MimicAndrzej Sadownik, Gang Deng, Vaclav Janout, Steven L. Regen, Edward M. Bernard, Ken Kikuchi, and Donald ArmstrongCite this: J. Am. Chem. Soc. 1995, 117, 22, 6138–6139Publication Date (Print):June 1, 1995Publication History Published online1 May 2002Published inissue 1 June 1995https://pubs.acs.org/doi/10.1021/ja00127a034https://doi.org/10.1021/ja00127a034research-articleACS PublicationsRequest reuse permissionsArticle Views298Altmetric-Citations60LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Genetic Variability among Group A and Group B Respiratory Syncytial Viruses in a Children’s Hospital (1998)

Respiratory syncytial (RS) viruses isolated over three epidemic periods in a children's hospital in the United States were analyzed. The viruses (n = 174) were characterized as to major antigenic group (group A or B) by a PCR-based assay. Group A RS viruses were dominant the first 2 years, followed by a year with group B dominance (ratios of group A to group B viruses for epidemic periods, 56/4 for 1993-1994, 42/3 for 1994-1995, and 19/50 for 1995-1996). Genetic variability within the groups was assessed by restriction fragment analysis of PCR products; 79 isolates were also analyzed by nucleotide sequence determination of a variable region of the glycoprotein G gene. Among the group A RS virus isolates, this G-protein variable region had amino acid differences of as great as 38%. The G-protein amino acids of the group A viruses differed by up to 31% from the G-protein amino acids of a prototype (A2) group A virus. Among the group B RS virus G proteins, amino acid differences were as great as 14%. The G-protein amino acids of the group B viruses differed by up to 27% from the G-protein amino acids of a prototype (18537) group B virus. The group A and group B RS viruses demonstrated genetic variability between years and within individual years. Phylogenetic analysis revealed that there were multiple evolutionary lineages among both the group A and group B viruses. Among the recent group B isolates, variability was less than that seen for the group A viruses. However, comparisons to prototype strains revealed that the group B RS viruses may vary more extensively than was observed over the 3 years studied in the present investigation.
Regulation of tumor necrosis factor alpha transcription in macrophages: involvement of four kappa B-like motifs and of constitutive and inducible forms of NF-kappa B. (1990)

This study characterizes the interaction of murine macrophage nuclear proteins with the tumor necrosis factor alpha (TNF-alpha) promoter. Gel retardation and methylation interference assays showed that stimulation of TNF-alpha gene transcription in peritoneal exudate macrophages was accompanied by induction of DNA-binding proteins that recognized with different affinities four elements related to the kappa B consensus motif and a Y-box motif. We suggest that the basal level of TNF-alpha expression in macrophages is due to the binding of a constitutive form of NF-kappa B, present at low levels in nuclei from resting thioglycolate exudate peritoneal macrophages, to some if not all of the kappa B motifs; we postulate that this constitutive form contains only the 50-kilodalton (kDa) DNA-binding protein subunits of NF-kappa B, not the 65-kDa protein subunits (P. Baeuerle and D. Baltimore, Genes Dev. 3:1689-1698, 1989). Agents such as glucocorticoids, which decrease TNF-alpha transcription, diminished the basal level of nuclear NF-kappa B. Stimulation of Stimulation of TNF-alpha transcription in macrophages by lipopolysaccharide, gamma interferon, or cycloheximide led to an increased content of nuclear NF-kappa B. This induced factor represents a different form of NF-kappa B, since it generated protein-DNA complexes of slower mobility; we propose that this induced form of NF-kappa B contains both the 50- and 65-kDa protein subunits, the latter ones being necessary to bind NF-kappa B to its cytoplasmic inhibitor in uninduced cells (Baeuerle and Baltimore, Genes Dev., 1989). In resting cells, this inducible form of NF-kappa B was indeed detectable in the cytosol after deoxycholate treatment. UV cross-linking experiments and gel retardation assays indicated that the inducible form of NF-kappa B is in a higher-order complex with other proteins.