gebhart/patrepeval huggingface dataset:
Functional Interplay between Histone Demethylase and Deacetylase Enzymes (2006)

Histone deacetylase (HDAC) inhibitors are a promising class of anticancer agents for the treatment of solid and hematological malignancies. The precise mechanism by which HDAC inhibitors mediate their effects on tumor cell growth, differentiation, and/or apoptosis is the subject of intense research. Previously we described a family of multiprotein complexes that contain histone deacetylase 1/2 (HDAC1/2) and the histone demethylase BHC110 (LSD1). Here we show that HDAC inhibitors diminish histone H3 lysine 4 (H3K4) demethylation by BHC110 in vitro. In vivo analysis revealed an increased H3K4 methylation concomitant with inhibition of nucleosomal deacetylation by HDAC inhibitors. Reconstitution of recombinant complexes revealed a functional connection between HDAC1 and BHC110 only when nucleosomal substrates were used. Importantly, while the enzymatic activity of BHC110 is required to achieve optimal deacetylation in vitro, in vivo analysis following ectopic expression of an enzymatically dead mutant of BHC110 (K661A) confirmed the functional cross talk between the demethylase and deacetylase enzymes. Our studies not only reveal an intimate link between the histone demethylase and deacetylase enzymes but also identify histone demethylation as a secondary target of HDAC inhibitors.
Hidden Markov Models: Fundamentals and Applications Part 1: Markov Chains and Mixture Models (2000)

The objective of this tutorial is to introduce basic concepts of a Hidden Markov Model (HMM) as a fusion of more simple models such as a Markov chain and a Gaussian mixture model. The tutorial is intended for the practicing engineer, biologist, linguist or programmer who would like to learn more about the above mentioned fascinating mathematical models and include them into one’s repertoire. This lecture presents Markov Chains and Gaussian mixture models, which constitute the preliminary knowledge for understanding Hidden Markov Models.
Syndecan-1 expression has prognostic significance in head and neck carcinoma (1999)

The syndecans are a family of cell-surface heparan sulphate proteoglycans that regulate cell behaviour by binding extracellular matrix molecules such as growth factors. The syndecan family has four members, of which syndecan-1 is the most studied and best characterized. We have studied the prognostic significance of syndecan-1 expression in squamous cell carcinoma (SCC) of the head and neck treated with surgery and post-operative radiotherapy. Paraffin-embedded tissue samples taken from 175 patients with primary SCC, followed up from 2 to 15 years after surgery, were studied for expression of syndecan-1 by immunohistochemistry. A low number (< or =50%, the median value) of syndecan-1-positive tumour cells was associated with low histological grade of differentiation (P<0.0001), a large primary tumour size (T1-2 vs. T3-4, P = 0.02), positive nodal status (NO vs. N1-3, P = 0.0006), and high clinical stage (stage I or II vs. III or IV, P<0.0001). Low syndecan-1 expression was also associated with unfavourable overall survival in a univariate analysis (P = 0.001). In a multivariate survival analysis, the clinical stage and syndecan-1 expression were the only independent prognostic factors. We conclude that syndecan-1 is a novel prognostic factor in SCC of the head and neck treated with surgery and post-operative radiotherapy.
Functional Genomics Evidence Unearths New Moonlighting Roles of Outer Ring Coat Nucleoporins (2014)

There is growing evidence for the involvement of Y-complex nucleoporins (Y-Nups) in cellular processes beyond the inner core of nuclear pores of eukaryotes. To comprehensively assess the range of possible functions of Y-Nups, we delimit their structural and functional properties by high-specificity sequence profiles and tissue-specific expression patterns. Our analysis establishes the presence of Y-Nups across eukaryotes with novel composite domain architectures, supporting new moonlighting functions in DNA repair, RNA processing, signaling and mitotic control. Y-Nups associated with a select subset of the discovered domains are found to be under tight coordinated regulation across diverse human and mouse cell types and tissues, strongly implying that they function in conjunction with the nuclear pore. Collectively, our results unearth an expanded network of Y-Nup interactions, thus supporting the emerging view of the Y-complex as a dynamic protein assembly with diverse functional roles in the cell.
Domain Swapping and Gene Shuffling Identify Sequences Required for Induction of an Avr-Dependent Hypersensitive Response by the Tomato Cf-4 and Cf-9 Proteins (2001)

The tomato Cf-4 and Cf-9 genes confer resistance to infection by the biotrophic leaf mold pathogen Cladosporium. Their protein products induce a hypersensitive response (HR) upon recognition of the fungus-encoded Avr4 and Avr9 peptides. Cf-4 and Cf-9 share >91% sequence identity and are distinguished by sequences in their N-terminal domains A and B, their N-terminal leucine-rich repeats (LRRs) in domain C1, and their LRR copy number (25 and 27 LRRs, respectively). Analysis of Cf-4/Cf-9 chimeras, using several different bioassays, has identified sequences in Cf-4 and Cf-9 that are required for the Avr-dependent HR in tobacco and tomato. A 10-amino acid deletion within Cf-4 domain B relative to Cf-9 was required for full Avr4-dependent induction of an HR in most chimeras analyzed. Additional sequences required for Cf-4 function are located in LRRs 11 and 12, a region that contains only eight of the 67 amino acids that distinguish it from Cf-9. One chimera, with 25 LRRs that retained LRR 11 of Cf-4, induced an attenuated Avr4-dependent HR. The substitution of Cf-9 N-terminal LRRs 1 to 9 with the corresponding sequences from Cf-4 resulted in attenuation of the Avr9-induced HR, as did substitution of amino acid A433 in LRR 15. The amino acids L457 and K511 in Cf-9 LRRs 16 and 18 are essential for induction of the Avr9-dependent HR. Therefore, important sequence determinants of Cf-9 function are located in LRRs 10 to 18. This region contains 15 of the 67 amino acids that distinguish it from Cf-4, in addition to two extra LRRs. Our results demonstrate that sequence variation within the central LRRs of domain C1 and variation in LRR copy number in Cf-4 and Cf-9 play a major role in determining recognition specificity in these proteins.
Advances in MR imaging of the skin (2006)

MR imaging of the skin is challenging because of the small size of the structures to be visualized. By increasing the gradient amplitude and/or duration, skin layers can be visualized with a voxel size of the order of 20 microm, clearly the smallest obtained for in vivo images in a whole-body imager. Currently, the gradient strength of most commercial systems enables acquisition of such a small voxel size, and the main difficulty has thus become to achieve sufficient detection sensitivity. The signal-to-noise ratio (SNR) can be increased either by increasing the magnetic field strength or by minimizing noise with small coils; cooling copper coils or superconducting coils can enhance the SNR by a factor of 3 or more. MR imaging, because of the large number of parameters it is able to measure, can provide more than the microscopic architecture of the skin: physical parameters such as relaxation times, magnetization transfer or diffusion, and chemical parameters such as the water and fat contents or phosphorus metabolism. In spite of the amount of information they have provided to date, MR imaging and spectroscopy have had limited clinical applications, mainly because cutaneous pathologies are easily accessible to the naked eye and surgery. However, MR technologies indeed represent powerful research tools to study normal and diseased skin.
Glucocorticoid-dependent Wnt signaling by mature osteoblasts is a key regulator of cranial skeletal development in mice (2009)

Glucocorticoids are important regulators of bone cell differentiation and mesenchymal lineage commitment. Using a cell-specific approach of osteoblast-targeted transgenic disruption of intracellular glucocorticoid signaling, we discovered a novel molecular pathway by which glucocorticoids, mainly through the mature osteoblast, regulate the cellular mechanisms that govern cranial skeleton development. Embryonic and neonatal transgenic mice revealed a distinct phenotype characterized by hypoplasia and osteopenia of the cranial skeleton; disorganized frontal, parietal and interparietal bones; increased suture patency; ectopic differentiation of cartilage in the sagittal suture; and disturbed postnatal removal of parietal cartilage. Concurrently, expression of Mmp14, an enzyme essential for calvarial cartilage removal, was markedly reduced in parietal bone and cartilage of transgenic animals. Expression of Wnt9a and Wnt10b was significantly reduced in osteoblasts with disrupted glucocorticoid signaling, and accumulation of beta-catenin, the upstream regulator of Mmp14 expression, was decreased in osteoblasts, chondrocytes and mesenchymal progenitors of transgenic mice. Supracalvarial injection of Wnt3a protein rescued the transgenic cranial phenotype. These results define novel roles for glucocorticoids in skeletal development and delineate how osteoblasts--under steroid hormone control--orchestrate the intricate process of intramembranous bone formation by directing mesenchymal cell commitment towards osteoblastic differentiation while simultaneously initiating and controlling cartilage dissolution in the postnatal mouse.
A structure-function analysis of transcriptional repression mediated by the WT1, Wilms' tumor suppressor protein. (1993)

The chromosome 11p13 Wilms' tumor locus (wt1) encodes a zinc finger-containing transcription factor (WT1). WT1 binds to the consensus sequence (5'-GCGGGGGCG-3') and represses transcription when bound to this site in vivo. The mechanism of repression is not yet defined. To investigate the mechanisms of transcriptional repression and map the domains of WT1 responsible, we constructed hybrid proteins between the yeast GAL4 1-147 DNA binding domain and WT1. Fusion of a 298 amino acid glutamine-proline-rich N-terminal segment of WT1 to the GAL4 DNA binding domain created a potent transcriptional repressor. The use of N- and C-terminal truncations of this segment demonstrated that as few as 96 amino acids were required for active repression by GAL4-WT1 hybrid proteins in NIH3T3 fibroblasts. However, the truncated GAL4-WT1 fusion proteins functioned poorly as repressors in embryonic kidney-derived 293 cells, suggesting cell type-specific requirements for transcriptional repression. Site-directed mutagenesis of the WT1 repression domain revealed that deletion of homopolymeric proline and glycine regions, as well as single amino acid changes, partially inactivated the repression function. Single repressor binding sites placed upstream of the transcription start site conferred WT1-mediated repression to a heterologous promoter, whereas multiple sites resulted in additive (non-synergistic) increases in transcriptional repression. Significant repression of transcription was observed when binding sites were placed 760 base pairs upstream or 1000 base pairs downstream relative to the site of transcription initiation. We conclude that the transcriptional repression function of WT1 is contained in the N-terminal, non-DNA binding domain of the protein and that repression can be functionally transferred to a heterologous DNA binding domain.
Raman Spectroscopy Using a Spatial Heterodyne Spectrometer: Proof of Concept (2011)

The use of a spatial heterodyne interferometer-based spectrometer (SHS) for Raman spectroscopy is described. The motivation for this work is to develop a small, rugged, high-resolution ultraviolet (UV) Raman spectrometer that is compatible with pulsed laser sources and that is suitable for planetary space missions. UV Raman is a particular technical challenge for space applications because dispersive (grating) approaches require large spectrographs and very narrow slits to achieve the spectral resolution required to maximize the potential of Raman spectroscopy. The heterodyne approach of the SHS has only a weak coupling of resolution and throughput, so a high-resolution UV SHS can both be small and employ a wide slit to maximize throughput. The SHS measures all optical path differences in its interferogram simultaneously with a detector array, so the technique is compatible with gated detection using pulsed lasers, important to reject ambient background and mitigate fluorescence (already low in the UV) that might be encountered on a planetary surface where samples are uncontrolled. The SHS has no moving parts, and as the spectrum is heterodyned around the laser wavelength, it is particularly suitable for Raman measurements. In this preliminary report we demonstrate the ability to measure visible wavelength Raman spectra of liquid and solid materials using an SHS Raman spectrometer and a visible laser. Spectral resolution and bandpass are also discussed. Separation of anti-Stokes and Stokes Raman bands is demonstrated using two different approaches. Finally spectral bandpass doubling is demonstrated by forming an interference pattern in both directions on the ICCD detector followed by analysis using a two-dimensional Fourier transform.
Design aspects of poly(alkylcyanoacrylate) nanoparticles for drug delivery (2007)

Poly(alkylcyanoacrylate) (PACA) nanoparticles were first developed 25 years ago taking advantage of the in vivo degradation potential of the polymer and of its good acceptance by living tissues. Since then, various PACA nanoparticles were designed including nanospheres, oil-containing and water-containing nanocapsules. This made possible the in vivo delivery of many types of drugs including those presenting serious challenging delivery problems. PACA nanoparticles were proven to improve treatments of severe diseases like cancer, infections and metabolic disease. For instance, they can transport drugs across barriers allowing delivery of therapeutic doses in difficult tissues to reach including in the brain or in multidrug resistant cells. This review gives an update on the more recent developments and achievements on design aspects of PACA nanoparticles as delivery systems for various drugs to be administered in vivo by different routes of administration.
Cortical Microtubules in Sweet Clover Columella Cells Developed in Microgravity (1995)

Electron micrographs of columella cells from sweet clover seedlings grown and fixed in microgravity revealed longitudinal and cross sectioned cortical microtubules. This is the first report demonstrating the presence and stability of this network in plants in microgravity.
Gold Nanoshells on Polystyrene Cores for Control of Surface Plasmon Resonance (2005)

A method is presented for synthesizing core-shell structures consisting of monodisperse polystyrene latex nanospheres as cores and gold nanoparticles as shells. Use of polystyrene spheres as the core in these structures is advantageous because they are readily available commercially in a wide range of sizes, and with dyes or other molecules doped into them. Gold nanoparticles, ranging in size from 1 to 20 nm, are prepared by reduction of a gold precursor with sodium citrate or tetrakis(hydroxymethyl)phosphonium chloride (THPC). Carboxylate-terminated polystyrene spheres are functionalized with 2-aminoethanethiol hydrochloride (AET), which forms a peptide bond with carboxylic acid groups on their surface, resulting in a thiol-terminated surface. Gold nanoparticles then bind to the thiol groups to provide up to about 50% coverage of the surface. These nanoparticles serve as seeds for growth of a continuous gold shell by reduction of additional gold precursor. The shell thickness and roughness can be controlled by the size of the nanoparticle seeds as well as by the process of their growth into a continuous shell. By variation of the relative sizes of the latex core and the thickness of the gold overlayer, the plasmon resonance of the nanoshell can be tuned to specific wavelengths across the visible and infrared range of the electromagnetic spectrum, for applications ranging from the construction of photonic crystals to biophotonics. The position and width of the plasmon resonance extinction peak are well-predicted by extended Mie scattering theory.
Antithrombotic properties of L-cysteine, N-(mercaptoacetyl)-D-Tyr-Arg- Gly-Asp-sulfoxide (G4120) in a hamster platelet-rich femoral vein thrombosis model (1992)

Platelet aggregation plays an important role in the pathogenesis in arterial thrombotic disorders. The binding of fibrinogen via the Arg- Gly-Asp (RGD) recognition sequence to the platelet glycoprotein IIb/IIIa (GPIIb/IIIa) receptor is an essential step of platelet aggregation induced by various physiologic agonists, and RGD-containing peptides that bind to the GPIIb/IIIa receptor inhibit thrombus formation in vivo. L-cysteine, N-(mercaptoacetyl)D-tyrosyl-L- arginylglycyl-L alpha-aspartyl-cyclic (1----5)-sulfide, 5-oxide (G4120), a cyclic RGD-containing synthetic pentapeptide, inhibits adenosine diphosphate (ADP)-induced platelet aggregation with 50% inhibition (IC50) at a concentration of 0.05 microgram/mL in human plasma, 0.12 microgram/mL in hamster plasma, and 11 micrograms/mL in rat plasma. Corresponding values for the linear tetrapeptide Arg-Gly- Asp-Phe (RGDF) were 7 and 100 micrograms/mL in human and hamster plasma. The antithrombotic effects of G4120 and RGDF were evaluated in a hamster model consisting of a mural platelet-rich femoral vein thrombus induced by standardized endothelial cell damage. Bolus intravenous injection of G4120 was followed by a biphasic disappearance of G4120 from plasma with t1/2 alpha of 3.7 minutes and t1/2 beta of 63 minutes, corresponding to a plasma clearance of 5.2 +/- 0.68 mL/min. Bolus intravenous injection of G4120 inhibited ex vivo platelet aggregation with 0.5 mumol/L ADP and in vivo thrombus formation in a dose-dependent manner, with ID50 of 11 and 11 micrograms/kg, respectively. Bolus injection of RGDF inhibited in vivo thrombus formation; 43% inhibition was obtained at a dose of 30 mg/kg. Thus, this hamster platelet-rich femoral vein thrombosis model may be useful for the investigation of the antithrombotic properties of platelet GPIIb/IIIa antagonistic peptides. The cyclic synthetic peptide G4120 appears to have a very potent antithrombotic activity in vivo.
Immunomodulation of fucosyl-lactose and lacto-N-fucopentaose on mononuclear cells from multiple sclerosis and healthy subjects. (2006)

The 1,2-fucosyl-oligosaccharides, and among these the 2'-fucosyl-lactose (2'-FL) and lacto-N-fucopentaose (LNFP)-I, are quantitatively the most represented oligosaccharides of human milk. They are also seen to represent an important immune device to prevent nursing infants from severe infectious diarrhoea. Recent evidences show that the appearance of 2'-FL and LNFP-I in human colostrums is synchronised with the macrophage inhibition and that LNFP-III induces a Th2 response from the mouse peripheral immune system. Since mannosyl-fucosyl receptors are described on the macrophage surface, all these evidences allow us to investigate on the possible immune function of human 2'-FL and LNFP-I in vitro on LPS-activated mononuclear cells (MNC) from 12 patients with multiple sclerosis (MS) and 20 matched health controls (HC). We found that 2'-FL and LNFP-I significantly decrease, to a different extent, the MNC proliferation from both HC and MS patients, in a linear and dose-dependent manner. 2'-FL and LNFP-I also reduce the production of IL-12 and IFN-γ, particularly in MS patients as compared to HC (p=0.01 and p<0.001, respectively), while increasing that of IL-10. The overall immunomodulatory effect of 2'-FL and LNFP I here presented may represent a future therapeutic option for the abnormal immune response found in some monocyte-mediated diseases.
Synthesis, cloning, and identification of DNA sequences complementary to mRNAs for alpha and beta subunits of thyrotropin. (1980)

Double-stranded cDNA sequences were synthesized, by using as templates mRNA for alpha and beta subunits of thyrotropin purified from mouse thyrotrophic pituitary tumours and cloned in Escherichia coli RR1 by insertion in the Pst I site of the bacterial plasmid pBR322 by use of poly(dA) x poly(dT) homopolymeric extensions. Plasmids containing inserted cDNA sequences were selected by resistance to tetracycline and sensitivity to ampicillin; those containing thyrotropin cDNA sequences were identified by colony hybridization with an 125I-labeled mixture of alpha and beta thyrotropin mRNAs. Plasmids carrying either alpha or beta thyrotropin cDNA sequences were further identified by hybridization to highly purified 125I-labeled alpha or beta thyrotropin mRNA, respectively. Two plasmids, one containing a 400-nucleotide alpha thyrotropin cDNA insert and the other containing a 710-nucleotide beta thyrotropin cDNA insert, were purified and characterized by restriction endonuclease digestions. Plasmid [32P]DNA containing either alpha or beta thyrotropin cDNA was then used as a hybridization probe for further characterization of alpha and beta thyrotropin mRNA from the mouse thyrotropic tumor. RNA was fractionated by agarose gel electrophoresis under denaturing and nondenaturing conditions and transferred to diazobenzyloxymethyl-paper. alpha thyrotropin mRNA of two sizes, 650 and approximately equal to 1500 nucleotides long, were identified. The larger alpha thyrotropin mRNA appeared to have marked secondary structure in its native form in contrast to the 650-nucleotide alpha thyrotropin mRNA. However, only one form of beta thyrotropin mRNA was detected with an apparent size of 710 nucleotides. We have successfully cloned and identified alpha and beta thyrotropin cDNA sequences in bacterial plasmids and used them to identify a second form of alpha thyrotropin mRNA.
Reactive and non-reactive lymphocytes in experimental allergic encephalomyelitis. (1977)

Myelin basic protein (BP),induces an increased in vitro proliferative response of peritoneal exudate cells (PEC), compared with that given by pheripheral blood lymphocytes (PBL), in guinea-pigs with experimental allergic encephaloMYELITIS (EAE). This response is determined by the nature of the lymphocytes in such exudates. We have also found that: (a) the majority of peritoneal lymphocytes from non-sensitized animals are E-rosetting (T cells) (59 percent) or null cells (greater than 40 percent) with EAC-rosetting (B cells) comprising 1 percent or less of cells; (b) both T cells and null cells respond equally to BP as determined by a technique combining rosette-formation and autoradiography; (c) the increased in vitro peritoneal lymphocyte response in animals with EAE cannot be explained solely by the number of null cells since peripheral blood and lymph nodes also contain appreciable numbers of null cells.