gebhart/patrepeval huggingface dataset:
Staphylococcal β-Toxin Modulates Human Aortic Endothelial Cell and Platelet Function through Sphingomyelinase and Biofilm Ligase Activities (2017)

<i>Staphylococcus aureus</i> causes many infections, such as skin and soft tissue, pneumonia, osteomyelitis, and infective endocarditis (IE). IE is an endovascular infection of native and prosthetic valves and the lining of the heart; it is characterized by the formation of cauliflower-like "vegetations" composed of fibrin, platelets, other host factors, bacteria, and bacterial products. β-Toxin is an <i>S. aureus</i> virulence factor that contributes to the microorganism's ability to cause IE. This cytolysin has two enzymatic activities: sphingomyelinase (SMase) and biofilm ligase. Although both activities have functions in a rabbit model of IE, the mechanism(s) by which β-toxin directly affects human cells and is involved in the infectious process has not been elucidated. Here, we compared the <i>in vitro</i> effects of purified recombinant wild-type β-toxin, SMase-deficient β-toxin (H289N), and biofilm ligase-deficient β-toxin (H162A and/or D163A) on human aortic endothelial cells (HAECs) and platelets. β-Toxin was cytotoxic to HAECs and inhibited the production of interleukin 8 (IL-8) from these cells by both SMase and biofilm ligase activities. β-Toxin altered HAEC surface expression of CD40 and vascular cell adhesion molecule 1 (VCAM-1). HAECs treated with β-toxin displayed granular membrane morphology not seen in treatment with the SMase-deficient mutant. The altered morphology resulted in two possibly separable activities, cell rounding and redistribution of cell membranes into granules, which were not the result of endosome production from the Golgi apparatus or lysosomes. β-Toxin directly aggregated rabbit platelets via SMase activity.<b>IMPORTANCE</b> Each year there are up to 100,000 cases of infective endocarditis (IE) in the United States. <i>S. aureus</i> is the most common pathogen in patients with health care-associated IE and the leading cause of community-associated IE in the developed world. Multiple clonal group strains as defined by the Centers for Disease Control and Prevention, particularly USA200 and other clones encoding β-toxin, are highly associated with IE. Considering the strong association and established contribution of β-toxin in animal models of IE, determining how β-toxin directly affects human cell types, including endothelial cells and platelets, is important. In this study, we demonstrate that β-toxin functions to modulate endothelial cells and platelets by both toxin sphingomyelinase and biofilm ligase activities. Our data suggest that these activities modulate inflammation and increase infection severity.
TAFII250 Is Critical in AML1-ETO Mediated Leukemogenesis (2016)

Abstract Background: Rearrangement between chromosome 8 and 21 is the most frequently observed chromosomal translocation. In AML patients, it leads to the formation of a novel fusion protein AML1-ETO. AML1-ETO functions as a transcriptional regulator to suppress myeloid differentiation and to promote self-renewal of hematopoiesis stem cells, which are of importance in leukemia development. However, AML1-ETO has no enzymatic function, thus targeting AML1-ETO directly is technically difficult. TAFII250, a largest subunit of the transcription factor IID complex (TFIID) serves to bring other components of basal transcription machinery to the preinitiation complex during the transcription initiation. And TAFII250 also plays a crucial role in the expression of genes involved in cell cycle and apoptosis. Yet despite the importance of these processes, there is no direct evidence implicating TAFII250 in cancer development. We have reported that acetylation of AML1-ETO on lysine 43 is critical for AML1-ETO mediated leukemogenesis and used a peptide pulldown strategy to identify proteins that preferring interact with acetylated AML1-ETO and identified TAFII250. Here, we are going to report the functions of TAFII250 in AML1-ETO induced leukemogenesis. Methods: We used Kasumi-1 and SKNO-1 cell lines derived from t(8; 21)AML patients, and a mouse AML1-ETO exon 9a (AE9a) expressing cell line developed from bone marrow cells of mice injected with bone marrow cells infected with AE9a to perform in vitro and in vivo studies. Results: We demonstrate that TAFII250 associates with AML1-ETO in AML cells through its bromodomain recognizing acetylated lysine 43 on AML1-ETO. The knockdown of TAFII250 completely abolished the proliferation of AML1-ETO expressing cells and has little influence on cell growth of non AML1-ETO expressing cells K562 and CD34+ cells. In addition, when we examined cleaved caspase 3 and PARP by western and measured annexin-V through flow cytometry, we found that the deficiency of TAFII250 induces apoptosis in AML1-ETO expressing cells. Further, the co-immunoprecipitation assay revealed that the deficiency of TAFII250 blocks the binding of AML1-ETO to CBFb (core binding factor beta subunit) and the recruitment of AML1-ETO at the promoter regions of a subset of its target genes. Consequently, loss of TAFII250 interferes with the expression of these genes. The depletion of TAFII250 also has negative effect on the self-renewal of leukemic cells, promoting their differentiation. Most importantly, the loss of TAFII250 severely impairs leukemia development in AE9a expressing cells. Conclusions: Together, these results reveal an essential role of TAFII250 in AML1-ETO mediated leukemogenesis and imply that TAFII250 might be a therapeutic target for AML1-ETO expressing AMLs. Disclosures No relevant conflicts of interest to declare.
Definite Integrals Involving Logarithmic Powers, Binomials and Polynomials Expressed in terms of the Lerch Function (2022)

Closed expressions using the Lerch function for a definite integral are derived and evaluated. Some of these closed expressions are given in Gradshteyn and Ryzhik. Some special cases of the integral are derived and discussed. The majority of the results in this work are new.
MicroRNAs Control Macrophage Formation and Activation: The Inflammatory Link between Obesity and Cardiovascular Diseases (2014)

Activation and recruitment of resident macrophages in tissues in response to physiological stress are crucial regulatory processes in promoting the development of obesity-associated metabolic disorders and cardiovascular diseases. Recent studies have provided compelling evidence that microRNAs play important roles in modulating monocyte formation, macrophage maturation, infiltration into tissues and activation. Macrophage-dependent systemic physiological and tissue-specific responses also involve cell-cell interactions between macrophages and host tissue niche cell components, including other tissue-resident immune cell lineages, adipocytes, vascular smooth muscle and others. In this review, we highlight the roles of microRNAs in regulating the development and function of macrophages in the context of obesity, which could provide insights into the pathogenesis of obesity-related metabolic syndrome and cardiovascular diseases.
Sirolimus pharmacokinetics in pediatric renal transplant recipients receiving calcineurin inhibitor co‐therapy (2006)

We have previously reported sirolimus (SRL) pharmacokinetics (PK) in pediatric renal transplant recipients on a calcineurin inhibitor (CNI)-free protocol. We now report pediatric SRL PK in pediatric renal transplant patients receiving SRL + CNI. SRL was dosed to achieve target trough levels between 10 and 20 ng/mL. We performed 49 SRL PK profiles in pediatric renal transplant recipients receiving SRL in combination with either cyclosporine (CsA; 25 profiles), or tacrolimus (TCL; 24 profiles). Ten of the SRL + TCL profiles were obtained from children receiving SRL on a b.i.d. dosing regimen. All other SRL profiles were q.d. regimens. We calculated, the maximum concentration (C(max)), AUC, apparent clearance (aCL; dose/AUC) for dose in mg/m(2), and mean residence time (MRT). SRL levels were measured at 6 and 7 time points for b.i.d. and q.d. dosing, respectively. Regression analysis of SRL trough values vs. AUC showed good correlation in the SRL q.d. + CsA, SRL q.d. + TCL, and SRL b.i.d. + TCL groups (r(2) = 0.95, 0.68, and 0.44, respectively). SRL aCL corrected for body surface area was higher in children aged 0-5 yr receiving SRL with either CsA or TCL. SRL dosing schedule should be tailored to each patient. Higher SRL aCL may be present in younger children when administered with CNI.
Matching commercial thrips predating phytoseids with the highly diversified climatic conditions of different strawberry production systems (2017)

Flower inhabiting thrips (Order: Thysanoptera) are a major threat to fruit quality in strawberry production around the world. As chemical control is often inefficient, alternative control measures are of broad and current interest. Their fast reproduction makes predatory mites highly suitable for thrips control in a crop with a relatively short cropping season like strawberry. However, climatic conditions of strawberry production can differ strongly depending on the production system (glasshouse, plastic tunnel, open field, ) and the time span of cultivation (depending mostly on planting date and the type of cultivar: summer-or everbearing). As predatory mites typically display a temperature-dependent life history and the current commercially available thrips predating phytoseids vary in geographic origin , one can assume that under certain climatic conditions some species will be more applicable than others. The goal of this study is to determine which species are suitable for which climatic conditions. Therefore all (Belgian) production systems and time spans are categorized into three climate types, simulated in the laboratory. The population build-up of seven predatory mite species (A. degenerans, A. montdorensis, A. andersoni, A. limonicus, A. swirskii, N. cucumeris and E. gallicus) were assessed for each of these climatic conditions. Under the coldest condition (A), the in West-Europe indigenous E. gallicus was the only species with a significant population build up. When moderate conditions (B) were simulated E. gallicus, N. cucumeris and A. limonicus were most successful. The warmest regime (C) was most adequate for E. gallicus and A. swirskii.
Cellular interactions of<i>Candida albicans</i>with human oral epithelial cells and enterocytes (2009)

The human pathogenic fungus Candida albicans can cause systemic infections by invading epithelial barriers to gain access to the bloodstream. One of the main reservoirs of C. albicans is the gastrointestinal tract and systemic infections predominantly originate from this niche. In this study, we used scanning electron and fluorescence microscopy, adhesion, invasion and damage assays, fungal mutants and a set of fungal and host cell inhibitors to investigate the interactions of C. albicans with oral epithelial cells and enterocytes. Our data demonstrate that adhesion, invasion and damage by C. albicans depend not only on fungal morphology and activity, but also on the epithelial cell type and the differentiation stage of the epithelial cells, indicating that epithelial cells differ in their susceptibility to the fungus. C. albicans can invade epithelial cells by induced endocytosis and/or active penetration. However, depending on the host cell faced by the fungus, these routes are exploited to a different extent. While invasion into oral cells occurs via both routes, invasion into intestinal cells occurs only via active penetration.
p53Ψ is a transcriptionally inactive p53 isoform able to reprogram cells toward a metastatic-like state (2014)

Although much is known about the underlying mechanisms of p53 activity and regulation, the factors that influence the diversity and duration of p53 responses are not well understood. Here we describe a unique mode of p53 regulation involving alternative splicing of the TP53 gene. We found that the use of an alternative 3' splice site in intron 6 generates a unique p53 isoform, dubbed p53Ψ. At the molecular level, p53Ψ is unable to bind to DNA and does not transactivate canonical p53 target genes. However, like certain p53 gain-of-function mutants, p53Ψ attenuates the expression of E-cadherin, induces expression of markers of the epithelial-mesenchymal transition, and enhances the motility and invasive capacity of cells through a unique mechanism involving the regulation of cyclophilin D activity, a component of the mitochondrial inner pore permeability. Hence, we propose that p53Ψ encodes a separation-of-function isoform that, although lacking canonical p53 tumor suppressor/transcriptional activities, is able to induce a prometastatic program in a transcriptionally independent manner.
Efficacy of Vitamin A-containing Lubricant in Dry Eye Syndrome Evaluated by Impression Cytology (2008)

: vitamin A
Supplemental Table 1 from ATM Regulates 3-Methylpurine-DNA Glycosylase and Promotes Therapeutic Resistance to Alkylating Agents (2023)

&lt;p&gt;PDF file - 96KB, Supplemental Table 1: Predicted phosphorylation sites for human MPG.&lt;/p&gt;
Growth of Mesenchymal Stem Cells at the Surface of Silicone, Mineral and Plant-Based Oils (2022)

Abstract Bioemulsions are attractive platforms for the expansion of adherent cells in bioreactors. Their design relies on the self-assembly of protein nanosheets at liquid-liquid interfaces, displaying strong interfacial mechanical properties and promoting integrin-mediated cell adhesion. However, most systems developed to date have focused on fluorinated oils, which are unlikely to be accepted for direct implantation of resulting cell products for regenerative medicine, and protein nanosheets self-assembly at other interfaces has not been investigated. In this report, the composition of aliphatic pro-surfactants palmitoyl chloride and sebacoyl chloride, on the assembly kinetics of poly(L-lysine) at silicone oil interfaces and characterisation of ultimate interfacial shear mechanics and viscoelasticity is presented. The impact of the resulting nanosheets on the adhesion of mesenchymal stem cells (MSCs) is investigated via immunostaining and fluorescence microscopy, demonstrating the engagement of the classic focal adhesion-actin cytoskeleton machinery. The ability of MSCs to proliferate at the corresponding interfaces is quantified. In addition, expansion of MSCs at other non-fluorinated oil interfaces, based on mineral and plant-based oils is investigated. Finally, the proof-of-concept of such non-fluorinated oil systems for the formulation of bioemulsions supporting stem cell adhesion and expansion is demonstrated.
Polarization-dependent fluorescence correlation spectroscopy for studying structural properties of proteins in living cell (2016)

Rotational diffusion measurement is predicted as an important method in cell biology because the rotational properties directly reflect molecular interactions and environment in the cell. To prove this concept, polarization-dependent fluorescence correlation spectroscopy (pol-FCS) measurements of purified fluorescent proteins were conducted in viscous solution. With the comparison between the translational and rotational diffusion coefficients obtained from pol-FCS measurements, the hydrodynamic radius of an enhanced green fluorescent protein (EGFP) was estimated as a control measurement. The orientation of oligomer EGFP in living cells was also estimated by pol-FCS and compared with Monte Carlo simulations. The results of this pol-FCS experiment indicate that this method allows an estimation of the molecular orientation using the characteristics of rotational diffusion. Further, it can be applied to analyze the degree of molecular orientation and multimerization or detection of tiny aggregation of aggregate-prone proteins.
A nanomonitor compared to ELISA for C-reactive protein detection in patient blood (2011)

The nanomonitors are multi scale “point-of care” devices comprised of high density nanopores formed from the integration of nanoporous alumina membranes onto metallic microscale platforms. The nanomonitors have approximately 250,000 nanowells per sensing site and use antibody binding reactions for detection of proteins. The antigen explored was C-reactive protein (CRP), an inflammatory biomarker associated with cardiovascular disease. Protein detection on the nanomonitor was achieved through electrical impedance spectroscopy. We performed a prospective cohort study of patients undergoing vascular surgery and compared the nanomonitor results to the industry standard ELISA (enzyme-linked immuno-sorbant assay) for the measurement of CRP in patient blood using Bland-Altman and mixed effects model statistical techniques. No statistical difference was found between the nanomonitor, ELISA, and CRP results, p = 0.994. In addition, the mean inter-assay coefficient of variation (CV) for the nanomonitor was 1.3%, and mean intra-assay CV 1.8%. The mean inter-assay CV for ELISA was 6.1%, and mean intra-assay CV was 5.2%. The nanomonitor time-to-result was 15 minutes and the ELISA was 3 hours, a critical time saving for patient care. In conclusion, we validated the use of the nanomonitor in clinical patient blood samples for the detection of CRP.
RodZ modulates geometric localization of the bacterial actin MreB to regulate cell shape (2018)

In the rod-shaped bacterium Escherichia coli, the actin-like protein MreB localizes in a curvature-dependent manner and spatially coordinates cell-wall insertion to maintain cell shape, although the molecular mechanism by which cell width is regulated remains unknown. Here we demonstrate that the membrane protein RodZ regulates the biophysical properties of MreB and alters the spatial organization of E. coli cell-wall growth. The relative expression levels of MreB and RodZ change in a manner commensurate with variations in growth rate and cell width, and RodZ systematically alters the curvature-based localization of MreB and cell width in a concentration-dependent manner. We identify MreB mutants that alter the bending properties of MreB filaments in molecular dynamics simulations similar to RodZ binding, and show that these mutants rescue rod-like shape in the absence of RodZ alone or in combination with wild-type MreB. Thus, E. coli can control its shape and dimensions by differentially regulating RodZ and MreB to alter the patterning of cell-wall insertion, highlighting the rich regulatory landscape of cytoskeletal molecular biophysics.
Probing Tumor Microenvironment with In Vivo Phage Display (2013)

Abstract : The purpose of this study is to develop specific probes that target various cells populations in the tumor microenvironment. Tumor stroma contains many cell populations, such as vascular endothelial cells, immune cells, mesenchymal cells, and extracellular matrix, which are critical to tumor development and progression. Although various probes have been developed for tumor vasculature, there is a scarcity of markers for tumor macrophages, fibroblasts, nerve cells and the matrix. The goal of our group is to make technical improvements in our phage display system, and find peptides that target carcinoma-associated fibroblasts (CAFs) in breast tumors. To reach the goal, we have improved our phage display technology by involving in the screens iRGD, a tumor-specific tissue-penetrating peptide. iRGD enhanced the penetration of co-applied phage libraries into breast tumor tissue by two fold, allowing the libraries to reach and probe the stromal compartments within the tumors. We have also optimized high throughput sequencing for phage DNA, and methods to isolate CAFs from breast tumor tissue. Multiple phage library screens are underway. In parallel, we have made an unexpected discovery that iRGD itself is an efficient CAF-targeting peptide, and that the iRGD receptor neuropilin-1 is a potential CAF marker in breast tumors. iRGD in combination with novel CAF-targeting peptides may result in an efficient probe for breast tumor imaging and therapy.
Heteronuclear dipolar recoupling in solid-state nuclear magnetic resonance by amplitude-, phase-, and frequency-modulated Lee–Goldburg cross-polarization (2005)

This paper presents a theoretical, numerical, and experimental study of phase- and frequency-switched Lee-Goldburg cross-polarization (FSLG-CP) under magic-angle spinning conditions. It is shown that a well-defined amplitude modulation of one of the two radio-frequency (rf) fields in the FSLG-CP sequence results in highly efficient heteronuclear dipolar recoupling. The recoupled dipolar interaction is gamma-encoded and, under ideal conditions, the effective spin Hamiltonian is equivalent to that in continuous-wave Lee-Goldburg CP. In practice, however, FSLG-CP is less susceptible to rf field mismatch and inhomogeneity, and provides better suppression of (1)H spin diffusion. The performance of FSLG-CP is experimentally demonstrated on liquid-crystalline samples exhibiting motionally averaged dipolar couplings.
Structure and morphology of low mechanical loss TiO<sub>2</sub>-doped Ta<sub>2</sub>O<sub>5</sub> (2020)

The exceptional stability required from high finesse optical cavities and high precision interferometers is fundamentally limited by Brownian motion noise in the interference coatings of the cavity mirrors. In amorphous oxide coatings these thermally driven fluctuations are dominant in the high index layer compared to those in the low index SiO 2 layer in the stack. We present a systematic study of the evolution of the structural and optical properties of ion beam sputtered TiO 2 -doped Ta 2 O 5 films with annealing temperature. We show that low mechanical loss in TiO 2 -doped Ta 2 O 5 with a Ti cation ratio = 0.27 is associated with a material that consists of a homogeneous titanium-tantalum-oxygen mixture containing a low density of nanometer sized Ar-filled voids. When the Ti cation ratio is 0.53, phase separation occurs leading to increased mechanical loss. These results suggest that amorphous mixed oxides with low mechanical loss could be identified by considering the thermodynamics of ternary phase formation.
Technique for the preparation of Streptomyces peptidases and N-acetylmuramyl-L-alanine amidase active on bacterial wall peptidoglycans (1969)

peer reviewed
Induction of Type I Interferon Secretion through Recombinant Newcastle Disease Virus Expressing Measles Virus Hemagglutinin Stimulates Antibody Secretion in the Presence of Maternal Antibodies (2010)

Measles virus (MV) vaccine effectively protects seronegative individuals against infection. However, inhibition of vaccine-induced seroconversion by maternal antibodies after vaccination remains a problem, as it leaves infants susceptible to MV infection. In cotton rats, passive transfer of MV-specific IgG mimics maternal antibodies and inhibits vaccine-induced seroconversion. Here, we report that immunization in the presence of passively transferred IgG inhibits the secretion of neutralizing antibodies but not the generation of MV-specific B cells. This finding suggested that MV-specific B cells require an additional stimulus to mature into antibody-secreting plasma cells. In order to provide such a stimulus, we generated a recombinant Newcastle disease virus (NDV) expressing the MV hemagglutinin (NDV-H). In contrast to MV, NDV-H induced high levels of type I interferon in plasmacytoid dendritic cells and in lung tissue. In cotton rats immunized with NDV-H, neutralizing antibodies were also generated in the presence of passively transferred antibodies. In the latter case, however, the level and kinetics of antibody generation were reduced. In vitro, alpha interferon stimulated the activation of MV-specific B cells from MV-immune spleen cells. NDV infection (which induces alpha interferon) had the same effect, and stimulation could be abrogated by antibodies neutralizing alpha interferon, but not interleukin 6 (IL-6). In vivo, coapplication of UV-inactivated MV with NDV led to increased MV-specific antibody production in the presence and absence of passively transferred antibodies. These data indicate that MV-specific B cells are being generated after immunization in the presence of maternal antibodies and that the provision of alpha interferon as an additional signal leads to antibody secretion.