gebhart/patrepeval huggingface dataset:
Routes and mechanisms of extracellular vesicle uptake (2014)

Extracellular vesicles (EVs) are small vesicles released by donor cells that can be taken up by recipient cells. Despite their discovery decades ago, it has only recently become apparent that EVs play an important role in cell-to-cell communication. EVs can carry a range of nucleic acids and proteins which can have a significant impact on the phenotype of the recipient. For this phenotypic effect to occur, EVs need to fuse with target cell membranes, either directly with the plasma membrane or with the endosomal membrane after endocytic uptake. EVs are of therapeutic interest because they are deregulated in diseases such as cancer and they could be harnessed to deliver drugs to target cells. It is therefore important to understand the molecular mechanisms by which EVs are taken up into cells. This comprehensive review summarizes current knowledge of EV uptake mechanisms. Cells appear to take up EVs by a variety of endocytic pathways, including clathrin-dependent endocytosis, and clathrin-independent pathways such as caveolin-mediated uptake, macropinocytosis, phagocytosis, and lipid raft-mediated internalization. Indeed, it seems likely that a heterogeneous population of EVs may gain entry into a cell via more than one route. The uptake mechanism used by a given EV may depend on proteins and glycoproteins found on the surface of both the vesicle and the target cell. Further research is needed to understand the precise rules that underpin EV entry into cells.
The Ecdysone Response Enhancer of the Fbp1 Gene of Drosophila melanogaster Is a Direct Target for the EcR/USP Nuclear Receptor (1994)

The transcription of the Drosophila melanogaster Fbp1 gene is induced by the steroid hormone 20-hydroxyecdysone and restricted to the late-third-instar fat body tissue. In a previous study we showed that the -68 to -138 region relative to the transcription start site acts as an ecdysone-dependent third-instar fat body-specific enhancer in a transgenic assay. Here we report that seven nucleoprotein complexes are formed in vitro on this enhancer when a nuclear extract from late-third-instar fat body is used in a gel shift assay. Accurate mapping of the binding sites of the complexes revealed a remarkably symmetrical organization. Using specific antibodies, one of the complexes was identified as a heterodimer consisting of the ecdysone receptor (EcR) and Ultraspiracle (USP) proteins. The binding site of the heterodimer as defined by mutagenesis and methylation interference experiments bears strong sequence similarity to the canonical hsp27 ecdysone response element, including an imperfect palindromic structure. The two elements diverge at three positions in both half-sites, indicating that the structure of an active EcR/USP binding site allows considerable sequence variations. In vivo footprinting experiments using ligation-mediated PCR and wild-type or ecdysteroid-deficient larvae show that occupancy of the Fbp1 EcR/USP binding site and adjacent region is dependent on a high concentration of ecdysteroids. These results provide strong evidence for a direct role of the EcR/USP heterodimer in driving gene expression in response to changes of the ecdysteroid titer during Drosophila larval development.
Highly Stable Silver Nanoplates for Surface Plasmon Resonance Biosensing (2012)

An SPR biosensor was developed by employing highly stable Au-protected Ag nanoplates (NP) as enhancers (see picture). Superior performance was achieved by depositing a thin and uniform coating of Au on the Ag surface while minimizing disruptive galvanic replacement and retaining the strong surface plasmon resonance (SPR) of the silver nanoplates.
Screening for fetal trisomies by maternal age and fetal nuchal translucency thickness at 10 to 14 weeks of gestation (1995)

Screening for fetal trisomy 21 can be carried out effectively during the first trimester of pregnancy.
Valganciclovir Results in Improved Oral Absorption of Ganciclovir in Liver Transplant Recipients (2000)

The pharmacokinetics of an orally administered valine ester of ganciclovir (GCV), valganciclovir (VGC), were studied. These were compared to the pharmacokinetics of oral and intravenous GCV. Twenty-eight liver transplant recipients received, in an open-label random order with a 3- to 7-day washout, each of the following: 1 g of oral GCV three times a day; 450 mg of VGC per os (p.o.) once a day (q.d.); 900 mg of VGC p.o. q.d.; and 5 mg of intravenous (i.v.) GCV per kg of body weight q.d., given over 1 h. GCV and VGC concentrations were measured in blood over 24 h. One-sided equivalence testing was performed to test for noninferiority of 450 mg of VGC relative to oral GCV (two-sided 90% confidence interval [CI] > 80%) and nonsuperiority of 900 mg of VGC relative to i.v. GCV (two-sided 90% CI < 125%). The exposure of 450 mg of VGC (20.56 microg. h/ml) was found to be noninferior to that of oral GCV (20.15 microg. h/ml; 90% CI for relative bioavailability of 95 to 109%), and the exposure of 900 mg of VGC (42.69 microg. h/ml) was found to be nonsuperior to that of i.v. GCV (47.61 microg. h/ml; 90% CI = 83 to 97%). Oral VGC delivers systemic GCV exposure equivalent to that of standard oral GCV (at 450 mg) or i.v. GCV (at 900 mg of VGC). VGC has promise for effective CMV prophylaxis or treatment with once-daily oral dosing in transplant recipients.
Fusion genes resulting from alternative chromosomal translocations are overexpressed by gene-specific mechanisms in alveolar rhabdomyosarcoma (1997)

Chromosomal translocations identified in hematopoietic and solid tumors result in deregulated expression of protooncogenes or creation of chimeric proteins with tumorigenic potential. In the pediatric solid tumor alveolar rhabdomyosarcoma, a consistent t(2;13)(q35;q14) or variant t(1;13)(p36;q14) translocation generates PAX3-FKHR or PAX7-FKHR fusion proteins, respectively. In this report, we demonstrate that in addition to functional alterations these translocations are associated with fusion product overexpression. Furthermore, PAX3-FKHR and PAX7-FKHR overexpression occurs by distinct mechanisms. Transcription of PAX3-FKHR is increased relative to wild-type PAX3 by a copy number-independent process. In contrast, PAX7-FKHR overexpression results from fusion gene amplification. Thus, gene-specific mechanisms were selected to overexpress PAX3-FKHR and PAX7-FKHR in alveolar rhabdomyosarcoma, presumably due to differences in regulation between the wild-type loci. We postulate that these overexpression mechanisms ensure a critical level of gene product for the oncogenic effects of these fusions.
Evidence for Extensive Resistance Gene Transfer among Bacteroides spp. and among Bacteroides and Other Genera in the Human Colon (2001)

Transfer of antibiotic resistance genes by conjugation is thought to play an important role in the spread of resistance. Yet virtually no information is available about the extent to which such horizontal transfers occur in natural settings. In this paper, we show that conjugal gene transfer has made a major contribution to increased antibiotic resistance in Bacteroides species, a numerically predominant group of human colonic bacteria. Over the past 3 decades, carriage of the tetracycline resistance gene, tetQ, has increased from about 30% to more than 80% of strains. Alleles of tetQ in different Bacteroides species, with one exception, were 96 to 100% identical at the DNA sequence level, as expected if horizontal gene transfer was responsible for their spread. Southern blot analyses showed further that transfer of tetQ was mediated by a conjugative transposon (CTn) of the CTnDOT type. Carriage of two erythromycin resistance genes, ermF and ermG, rose from <2 to 23% and accounted for about 70% of the total erythromycin resistances observed. Carriage of tetQ and the erm genes was the same in isolates taken from healthy people with no recent history of antibiotic use as in isolates obtained from patients with Bacteroides infections. This finding indicates that resistance transfer is occurring in the community and not just in clinical environments. The high percentage of strains that are carrying these resistance genes in people who are not taking antibiotics is consistent with the hypothesis that once acquired, these resistance genes are stably maintained in the absence of antibiotic selection. Six recently isolated strains carried ermB genes. Two were identical to erm(B)-P from Clostridium perfringens, and the other four had only one to three mismatches. The nine strains with ermG genes had DNA sequences that were more than 99% identical to the ermG of Bacillus sphaericus. Evidently, there is a genetic conduit open between gram-positive bacteria, including bacteria that only pass through the human colon, and the gram-negative Bacteroides species. Our results support the hypothesis that extensive gene transfer occurs among bacteria in the human colon, both within the genus Bacteroides and among Bacteroides species and gram-positive bacteria.
Detection and Characterization of Autoagglutination Activity by Campylobacter jejuni (2000)

In several gram-negative bacterial pathogens, autoagglutination (AAG) activity is a marker for interaction with host cells and virulence. Campylobacter jejuni strains also show AAG, but this property varies considerably among strains. To examine the characteristics of C. jejuni AAG, we developed a quantitative in vitro assay. For strain 81-176, which shows high AAG, activity was optimal for cells grown for < or = 24 h, was independent of growth temperature, and was best measured for cells suspended in phosphate-buffered saline at 25 degrees C for 24 h. AAG activity was heat labile and was abolished by pronase or acid-glycine (pH 2.2) treatment but not by lipase, DNase, or sodium metaperiodate. Strain 4182 has low AAG activity, but extraction with water increased AAG, suggesting the loss of an inhibitor. Strain 6960 has weak AAG with no effect due to water extraction. Our study with clinical isolates suggests that C. jejuni strains may be grouped into three AAG phenotypes. A variant derived from strain 81116 that is flagellate but immotile showed the strong AAG exhibited by the parent strain, suggesting that motility per se is not necessary for the AAG activity. AAG correlated with both bacterial hydrophobicity and adherence to INT407 cells. Mutants which lack flagella (flaA, flaB, and flbA) or common cell surface antigen (peb1A) were constructed in strain 81-176 by natural transformation-mediated allelic exchange. Both AAG activity and bacterial hydrophobicity were abolished in the aflagellate mutants but not the peb1A mutant. In total, these findings indicate that C. jejuni AAG is highly associated with flagellar expression.
On the mechanism of retrovirus-induced avian lymphoid leukosis: deletion and integration of the proviruses. (1981)

There is considerable evidence that infection by avian lymphoid leukosis viruses can led to tumor development in the target organ of the host. The mechanism by which virus-induced oncogenic transformation occurs, however, is not clearly understood. As a first step toward deciphering this process, we have characterized the proviruses of the lymphoid leukosis viruses in DNAs extracted from the leukotic and metastatic tumors by using restriction enzyme digestion and filter hybridization analysis with radioactive probes specific for the infecting genome. Our results indicate (i) that lymphoid leukosis tumors are clonal in origin; (ii) that there are multiple sites in the cellular genome of the target tissue where the virus DNA can integrate and that, in the majority of the tumors, at least one such site of each tumor is adjacent to a cellular sequence related to the oncogene of MC-29 virus; and (iii) that deletions and other structural alterations in the proviral DNA may facilitate tumorigenesis.
No consistent evidence for association between mtDNA variants and Alzheimer disease (2012)

The current evidence linking common mtDNA variations with AD is not compelling.
Epsilon Amino Caproic Acid Inhibits Streptokinase−Plasminogen Activator Complex Formation and Substrate Binding through Kringle-Dependent Mechanisms (2000)

Lysine side chains induce conformational changes in plasminogen (Pg) that regulate the process of fibrinolysis or blood clot dissolution. A lysine side-chain mimic, epsilon amino caproic acid (EACA), enhances the activation of Pg by urinary-type and tissue-type Pg activators but inhibits Pg activation induced by streptokinase (SK). Our studies of the mechanism of this inhibition revealed that EACA (IC(50) 10 microM) also potently blocked amidolytic activity by SK and Pg at doses nearly 10000-fold lower than that required to inhibit the amidolytic activity of plasmin. Different Pg fragments were used to assess the role of the kringles in mediating the inhibitory effects of EACA: mini-Pg which lacks kringles 1-4 of Glu-Pg and micro-Pg which lacks all kringles and contains only the catalytic domain. SK bound with similar affinities to Glu-Pg (K(A) = 2.3 x 10(9) M(-1)) and to mini-Pg (K(A) = 3.8 x 10(9) M(-)(1)) but with significantly lower affinity to micro-Pg (K(A) = 6 x 10(7) M(-)(1)). EACA potently inhibited the binding of Glu-Pg to SK (K(i) = 5.7 microM), but was less potent (K(i) = 81.1 microM) for inhibiting the binding of mini-Pg to SK and had no significant inhibitory effects on the binding of micro-Pg and SK. In assays simulating substrate binding, EACA also potently inhibited the binding of Glu-Pg to the SK-Glu-Pg activator complex, but had negligible effects on micro-Pg binding. Taken together, these studies indicate that EACA inhibits Pg activation by blocking activator complex formation and substrate binding, through a kringle-dependent mechanism. Thus, in addition to interactions between SK and the protease domain, interactions between SK and the kringle domain(s) play a key role in Pg activation.
Systemic and lung physiological changes in rats after intravascular activation of complement (2001)

Systemic complement activation has been noted in a variety of shock states, and there is growing evidence that, in addition to being proinflammatory effectors, products of complement activation contribute directly to generalized manifestations of shock, such as hypotension and acidosis. To study the effects of complement activation, we examined responses in rats to systemic activation of complement with cobra venom factor (CVF), including blood pressure, metabolic acidosis, changes in vascular permeability, and lung function. High doses of CVF produced circulatory collapse (mean arterial pressure = 110 +/- 16 and 35 +/- 9 mmHg in control and with CVF, respectively, P < 0.05), metabolic acidosis (HCO concentration = 27.8 +/- 1.7 and 9.6 +/- 3.4 meq/l in control and with CVF, respectively, P < 0.05), extravasation of albumin into the lung and gut, and modest arterial hypoxemia (PO2 = 486 +/- 51 and 201 +/- 36 Torr in control and during 100% O2 breathing, respectively, P < 0.05). Prior depletion of complement protected against these abnormalities. Other interventions, including neutrophil depletion and cyclooxygenase inhibition, prevented lung injury but had much less effect on systemic hemodynamics or gut permeability, suggesting that complement activation products induce injury by neutrophil- and cyclooxygenase-dependent pathways in the lung but not in the gut. These studies underscore the significant systemic abnormalities developing after systemic activation of complement.
Protection against lethal viral infection by vaccination with nonimmunodominant peptides (1996)

CTL response of H-2b mice to influenza PR8 virus is directed against the nucleoprotein (NP)-derived immunodominant 366-374 (NP366PR8) peptide presented by the Db molecule. However, NP has three nonimmunodominant peptides corresponding to the 17-25 (NP17), 55-63 (NP55), and 97-105 (NP97) sequences that have the Db consensus motifs and bind to the Db molecule with an intermediate (NP55) or low (NP17 and NP97) affinity. In a previous report, we have shown that NP55 peptide is naturally processed by infected cells. In the present work, we studied whether nonimmunodominant peptides can protect mice against viral infection. Antiviral protection was evaluated by measuring three parameters: survival after inoculation of a lethal dose of mouse-adapted PR8 virus, percentage of pulmonary lesions in surviving mice, and virus clearance from lungs of infected mice. Our results showed that immunization of B6 mice with nonimmunodominant peptides protected from PR8 virus infection, although less efficiently than immunization with the immunodominant NP366PR8 peptide. Protection was mediated by CD8 T cells. The efficacy of nonimmunodominant peptides correlated with their Db binding affinity; the low affinity binders NP17 and NP97 induced a weaker protection than the intermediate affinity binder NP55. A mixture of NP366PR8 and nonimmunodominant peptides gave a higher protection than NP366PR8 peptide alone. In conclusion, nonimmunodominant peptides protect against a viral infection with an efficacy that is proportional to their affinity for the restricting class I molecule.
Texture classification with tree-structured wavelet transform (2003)

Proposes a multiresolution approach based on a tree-structured wavelet transform for texture classification. The development of tree-structured wavelet transform is motivated by the observation that textures are quasi-periodic signals whose dominant frequencies are located in the middle frequency channels. With the transform, one is able to zoom into desired frequency channels and performs further decomposition. In contrast, the conventional wavelet transform only decomposes subsignals in low frequency channels. A progressive texture classification algorithm which is not only computationally attractive but also has excellent performance is developed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Intraventricular Brain Injection of Adeno-Associated Virus Type 1 (AAV1) in Neonatal Mice Results in Complementary Patterns of Neuronal Transduction to AAV2 and Total Long-Term Correction of Storage Lesions in the Brains of β-Glucuronidase-Deficient Mice (2003)

Inherited metabolic disorders that affect the central nervous system typically result in pathology throughout the brain; thus, gene therapy strategies need to achieve widespread delivery. We previously found that although intraventricular injection of the neonatal mouse brain with adeno-associated virus serotype 2 (AAV2) results in dispersed gene delivery, many brain structures were poorly transduced. This limitation may be overcome by using different AAV serotypes because the capsid proteins use different cellular receptors for entry, which may allow enhanced global targeting of the brain. We tested this with AAV1 and AAV5 vectors. AAV5 showed very limited brain transduction after neonatal injection, even though it has different transduction patterns than AAV2 in adult brain injections. In contrast, AAV1 vectors, which have not been tested in the brain, showed robust widespread transduction. Complementary patterns of transduction between AAV1 and AAV2 were established and maintained in the adult brain after neonatal injection. In the majority of structures, AAV1 transduced many more cells than AAV2. Both vectors transduced mostly neurons, indicating that differential expression of receptors on the surfaces of neurons occurs in the developing brain. The number of cells positive for a vector-encoded secreted enzyme (beta-glucuronidase) was notably greater and more widespread in AAV1-injected brains. A comprehensive analysis of AAV1-treated brains from beta-glucuronidase-deficient mice (mucopolysaccharidosis type VII) showed complete reversal of pathology in all areas of the brain for at least 1 year, demonstrating that the combination of this serotype and experimental strategy is therapeutically effective for treating global neurometabolic disorders.
Do maternal and intrauterine factors influence blood pressure in childhood? (1992)

It has been proposed that maternal health and nutrition may be important in the development of adult cardiovascular risk, and that blood pressure may be an important intermediate step in this process. To examine the relevance of this hypothesis in contemporary British children, the relationships of several maternal factors to blood pressure were studied in 3360 children of European origin aged 5-7 years. Maternal age, height, and body mass index were all positively related to blood pressure in childhood but these relationships were abolished once the child's body build was taken into account. Maternal social class, educational attainment, and history of smoking in pregnancy showed no relationship with blood pressure in childhood. Parity showed an inverse association with blood pressure, but this appeared to be due to an association between total sibship size and blood pressure, suggesting a postnatal rather than a prenatal origin. Blood pressure was higher in children whose mothers had a history of high blood pressure but this association was no stronger than that for paternal history. Both birth weight and gestational age were inversely related to blood pressure at 5-7 years. The association between birth weight and blood pressure was attenuated by standardisation for gestational age, and the relationships between birth weight and blood pressure were similar in preterm and full term infants. No specific association between blood pressure and the maternal factors studied have been observed in this population. Hypotheses relating maternal factors to cardiovascular risk need to specify the timing and nature of their effects more precisely. Although the relationship between birth weight and blood pressure is not fully understood, it appears to reflect size at birth rather than fetal growth rate.
Snapshot imaging spectropolarimetry in the visible and infrared (2008)

Two imaging systems have been designed and built to function as snapshot imaging spectropolarimeters; one system made to operate in the visible part of the spectrum, the other for the long wavelength infrared, 8 to 12 microns. The devices are based on computed tomographic imaging channeled spectropolarimetry (CTICS), a unique technology that allows both the spectra and the polarization state for all of the wavelength bands in the spectra to be simultaneously recorded from every spatial position in an image with a single integration period of the imaging system. The devices contain no moving parts and require no scanning, allowing them to acquire data without the artifacts normally associated with scanning spectropolarimeters. Details of the two imaging systems will be presented.
Comprehensive serological profiling of human populations using a synthetic human virome (2015)

The human virome plays important roles in health and immunity. However, current methods for detecting viral infections and antiviral responses have limited throughput and coverage. Here, we present VirScan, a high-throughput method to comprehensively analyze antiviral antibodies using immunoprecipitation and massively parallel DNA sequencing of a bacteriophage library displaying proteome-wide peptides from all human viruses. We assayed over 10(8) antibody-peptide interactions in 569 humans across four continents, nearly doubling the number of previously established viral epitopes. We detected antibodies to an average of 10 viral species per person and 84 species in at least two individuals. Although rates of specific virus exposure were heterogeneous across populations, antibody responses targeted strongly conserved "public epitopes" for each virus, suggesting that they may elicit highly similar antibodies. VirScan is a powerful approach for studying interactions between the virome and the immune system.