gebhart/patrepeval huggingface dataset:
Identification of the Phr-dependent heat shock regulon in the hyperthermophilic archaeon, Thermococcus kodakaraensis (2009)

The hyperthermophilic archaeon Thermococcus kodakaraensis harbors a putative transcriptional regulator (Tk-Phr) that is orthologous to the Pyrococcus furiosus Phr (Pf-Phr). Pf-Phr, a transcriptional regulator, represses genes encoding the small heat shock protein (sHSP), AAA(+) ATPase and Pf-Phr itself under normal growth temperatures. Here we constructed a gene disruption strain of Tk-Phr (strain KHR1). KHR1 cells showed similar specific growth rates with those of the wild-type strain under various temperatures. A whole genome microarray analysis was performed between KHR1 and wild-type cells grown at 80 degrees C. Transcript levels of more than 20 genes were significantly higher in KHR1 cells. Most genes contained a sequence motif virtually identical to that of Pf-Phr in their 5'-flanking regions. The Tk-Phr regulon included genes encoding sHSP, AAA(+) ATPase, prefoldin, RecA superfamily ATPase and Tip49. On the other hand, more than half of the members in the regulon encoded conserved/hypothetical proteins, raising the possibility that these proteins participate in unidentified processes of the heat shock response. In contrast, Tk-Phr deletion did not lead to dramatic increase in transcript and protein levels of a chaperonin (CpkB) previously shown to respond to heat shock, suggesting the presence of a second, Phr-independent heat shock response mechanism in T. kodakaraensis.
Diffraction data analysis in the presence of radiation damage (2010)

In macromolecular crystallography, the acquisition of a complete set of diffraction intensities typically involves a high cumulative dose of X-ray radiation. In the process of data acquisition, the irradiated crystal lattice undergoes a broad range of chemical and physical changes. These result in the gradual decay of diffraction intensities, accompanied by changes in the macroscopic organization of crystal lattice order and by localized changes in electron density that, owing to complex radiation chemistry, are specific for a particular macromolecule. The decay of diffraction intensities is a well defined physical process that is fully correctable during scaling and merging analysis and therefore, while limiting the amount of diffraction, it has no other impact on phasing procedures. Specific chemical changes, which are variable even between different crystal forms of the same macromolecule, are more difficult to predict, describe and correct in data. Appearing during the process of data collection, they result in gradual changes in structure factors and therefore have profound consequences in phasing procedures. Examples of various combinations of radiation-induced changes are presented and various considerations pertinent to the determination of the best strategies for handling diffraction data analysis in representative situations are discussed.
Immunity to Chlamydia trachomatis is mediated by T helper 1 cells through IFN-gamma-dependent and -independent pathways (1997)

Mucosal immunity to Chlamydia trachomatis in a mouse model of female genital tract infection is mediated predominantly by Th1-type cells, as shown by in vivo neutralization of cytokines involved in the Th1 vs Th2 pathways. Neutralization of IL-12 was associated with an apparent decrease in the infiltration of CD4+ T cells into infected tissues, systemic reductions in the production of IFN-gamma, and prolonged shedding of high levels of bacteria. Neutralization of IL-4 had no detectable effect on host immunity or on bacterial clearance. To dissociate the protective role of IL-12 from that of IL-12-induced IFN-gamma, resistance to C. trachomatis was compared in IL-12-depleted and IFN-gamma-deficient animals. IL-12-depleted mice displayed minimal bacterial clearance for 1 mo post-infection but eventually resolved genital tract infections completely. IFN-gamma-deficient mice, on the other hand, cleared 99.9% of genital Chlamydia within the first 3 wk but then developed systemic disease associated with dissemination of bacteria to multiple organs. Animals surviving this stage often maintained low level persistent infections within the urogenital tract. These results indicate that the bulk of chlamydial clearance from the genital mucosa is mediated by an IL-12-dependent, IFN-gamma-independent mechanism, while prevention of disseminated disease requires the action of IFN-gamma.
Treatment of the Malignant Carcinoid Syndrome (1986)

We studied the effects of a long-acting analogue of somatostatin (SMS 201-995, Sandoz) in 25 patients with histologically proved metastatic carcinoid tumors and the carcinoid syndrome. This drug was self-administered by subcutaneous injection at a dose of 150 micrograms three times daily. Flushing and diarrhea associated with the syndrome were promptly relieved in 22 patients. All 25 patients had an elevated 24-hour urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA) (mean, 265 mg per 24 hours; range, 14 to 1079), which served as an objective indicator of disease activity. Eighteen of the 25 patients (72 percent) had a decrease of 50 percent or more in their urinary 5-HIAA levels, as compared with the pretreatment values. The median duration of this biochemical response was more than 12 months (range, 1 to greater than 18). Since no serious toxicity was observed, we conclude that SMS 201-995 may be appropriate for use as early therapy in patients with symptoms due to the carcinoid syndrome who have not responded to simpler measures.
Floating light-activated microelectrical stimulators tested in the rat spinal cord (2011)

Microelectrodes of neural stimulation utilize fine wires for electrical connections to driving electronics. Breakage of these wires and the neural tissue response due to their tethering forces are major problems encountered with long-term implantation of microelectrodes. The lifetime of an implant for neural stimulation can be substantially improved if the wire interconnects are eliminated. Thus, we proposed a floating light-activated microelectrical stimulator (FLAMES) for wireless neural stimulation. In this paradigm, a laser beam at near infrared (NIR) wavelengths will be used as a means of energy transfer to the device. In this study, microstimulators of various sizes were fabricated, with two cascaded GaAs p-i-n photodiodes, and tested in the rat spinal cord. A train of NIR pulses (0.2 ms, 50 Hz) was sent through the tissue to wirelessly activate the devices and generate the stimulus current. The forces elicited by intraspinal stimulation were measured from the ipsilateral forelimb with a force transducer. The largest forces were around 1.08 N, a significant level of force for the rat forelimb motor function. These in vivo tests suggest that the FLAMES can be used for intraspinal microstimulation even for the deepest implant locations in the rat spinal cord. The power required to generate a threshold arm movement was investigated as the laser source was moved away from the microstimulator. The results indicate that the photon density does not decrease substantially for horizontal displacements of the source that are in the same order as the beam radius. This gives confidence that the stimulation threshold may not be very sensitive to small displacement of the spinal cord relative to the spine-mounted optical power source.
Immune regulation of multiple sclerosis by transdermally applied myelin peptides (2010)

We demonstrate for the first time the immunoregulatory potential of transdermal immunization with myelin peptides in MS patients.
Deletion of the IgH intronic enhancer and associated matrix-attachment regions decreases, but does not abolish, class switching at the mu locus (1998)

The IgH locus intronic enhancer (Emu), located in the intron between the J(H) segments and the Cmu gene, and flanked by two matrix attachment regions (MAR), has been shown to be a major regulator of IgH gene transcription and VDJ recombination. To define the potential role of Emu plus MAR in class switch recombination (CSR), we generated IgG-expressing hybridomas from B cells heterozygous for mutations that delete all of these elements or replace them with a neo(r) gene and analyzed the switch status of the mutated IgH loci. Emu/MAR-deleted IgH loci displayed a highly significant, although not complete, decrease in CSR when compared to unmutated loci in normal hybridomas. Surprisingly, mutant loci with a pgk promoter-driven neo(r) gene replacing the Emu/MAR showed relatively normal switch frequency. These findings indicate that the Emu/MAR region plays a significant, but not necessary role in facilitating class switching at the mu locus. Potential mechanisms for these findings are discussed.
Molecular characterization of the melanocyte lineage-specific antigen gp100. (1994)

The glycoproteins recognized by monoclonal antibody (mAb) NKI-beteb are among the best diagnostic markers for human melanoma because their expression is restricted to melanocytic cells. Recently, we isolated a cDNA clone, termed gp100-c1, which confers immunoreactivity not only to mAb NKI-beteb, but also to two other mAbs used to diagnose malignant melanoma, HMB-50 and HMB-45. In this report, we demonstrate that gp100-c1 cDNA encodes glycoproteins of 100 kDa (gp100) and 10 kDa (gp10) which are recognized by these mAbs in human melanoma cells. The translation product deduced from the open reading frame present in gp100-c1 cDNA is highly homologous to another melanocyte-specific protein, Pmel17. Nucleotide sequence analysis of genomic DNA indicates that the transcripts corresponding to gp100 and Pmel17 cDNAs originate from a single gene via alternative splicing. In all normal and malignant melanocytic cells analyzed, gp100 and Pmel17 RNAs are simultaneously expressed.
Inverse scattering approach based on the field equivalence principle: inversion without a priori information on incident fields (2012)

An inverse scattering approach based on the field equivalence principle is developed for reconstructing the parameters of the medium of a scattering object. A problem equivalent to the original scattering problem but internal to the measurement surface is set up. The equivalent surface currents determined by the measured total-field data rigorously yield the incident fields in the region under test, so the approach does not require explicit knowledge of the incident fields. Taking into account the fact that the equivalent surface currents produce a null field external to the surface, a functional of the medium's parameters is introduced, and a genetic algorithm is applied to minimization of the functional. Numerical simulations for imaging defects in a known dielectric cylinder from only total-field data measured on an observation surface are performed to illustrate the efficacy of the proposed inversion method.
In vitro modeling of central nervous system myelination and remyelination (2011)

This review aims to summarize the current techniques to study myelination and remyelination in culture systems. We attempt to put these into historical context, and to identify the strengths and weaknesses of each approach, which vary depending on the experimental question to be tested. We discuss the difficulty and importance of quantification of myelination and in particular remyelination. Finally, we provide our predictions of how these techniques will and should develop in the future.
Third-Generation Biosensor for Lactose Based on Newly Discovered Cellobiose Dehydrogenase (2005)

The present paper describes the principle and characteristics of a biosensor for lactose based on a third-generation design involving cellobiose dehydrogenase. As resulted from a previous comparative study (submitted manuscript), the novelty of this lactose biosensor is based on highly efficient direct electron transfer between two newly discovered cellobiose dehydrogenases (CDH), from the white rot fungi Trametes villosa and Phanerochaete sordida, and a solid spectrographic graphite electrode. CDH was immobilized on the electrode surface (0.073 cm2) by simple physical adsorption, and the CDH-modified electrode was next inserted into a wall-jet amperometric cell connected on-line to a flow injection setup (0.5 mL x min(-1)). The P. sordida CDH-based lactose biosensor, proved to be the better one, has a detection limit for lactose of 1 microM, a sensitivity of 1100 microA x mM(-1) x cm(-2), a response time of 4 s (the time required to obtain the maximum peak current), and a linear range from 1 to 100 microM lactose (correlation coefficient 0.998). The simplicity of construction and analytical characteristics make this CDH-based lactose biosensor an excellent alternative to previous lactose biosensors reported in the literature or commercially available. The CDH-lactose sensor was used to quantify the content of lactose in pasteurized milk, buttermilk, and low-lactose milk, using the standard addition method. No effects of the samples matrixes were observed. The operational stability of the sensor was tested for 11 h by continuous injection of 100 microM lactose (290 injections). The final signal of the sensor was maintained at 98% of its initial signal, with a low standard deviation of 1.72 (RSD 2.41%).
The simian virus 40 large T antigen. A lot packed into a little. (1987)

Simian virus 40 (SV40) large T antigen is an 81,000 Mr, multifunctional viral phosphoprotein. Certain of its functions are essential to the viral replication process in monkey cells. Others, as yet undefined in biochemical terms, contribute to its neoplastic transforming activity. This review focuses on the known structure-function relationships of this protein and reflects upon the potential significance of its transforming properties in the natural host species of this virus.
Glucagon-like peptide-1 and the exenatide analogue AC3174 improve cardiac function, cardiac remodeling, and survival in rats with chronic heart failure (2010)

Chronic treatment with either GLP-1 or AC3174 showed promising cardioprotective effects in a rat model of CHF. Hence, GLP-1 receptor agonists may represent a novel approach for the treatment of patients with CHF or cardiovascular disease associated with type 2 diabetes.
Light-Induced Translation of Motorized Molecules on a Surface (2016)

Molecular machines are a key component in the vision of molecular nanotechnology and have the potential to transport molecular species and cargo on surfaces. The motion of such machines should be triggered remotely, ultimately allowing a large number of molecules to be propelled by a single source, with light being an attractive stimulus. Here, we report upon the photoinduced translation of molecular machines across a surface by characterizing single molecules before and after illumination. Illumination of molecules containing a motor unit results in an enhancement in the diffusion of the molecules. The effect vanishes if an incompatible photon energy is used or if the motor unit is removed from the molecule, revealing that the enhanced motion is due to the presence of the wavelength-sensitive motor in each molecule.
Antiapoptotic Effects of Estrogen in Normal and Cancer Human Cervical Epithelial Cells (2004)

The present study investigated the antiapoptotic effects of estrogen in normal and cancer human cervical cells and the mechanisms involved. Baseline apoptosis in human cervical epithelial cells is mediated predominantly by P2X7-receptor-induced, Ca(2+)-dependent activation of the mitochondrial (caspase-9) pathway. Treatment with 10 nM 17beta-estradiol blocked apoptosis induced by the P2X7-receptor ligands ATP and 2',3'-0-(4-benzoylbenzoyl)-ATP in normal human cervical epithelial cells (hECEs) and attenuated the effect in hECEs immortalized with human papillomavirus-16 (ECE16-1) and the cancer cervical cells HT3 and CaSki. Diethylstilbestrol and to a lesser degree estrone could mimic the effects of 17beta-estradiol, whereas actinomycin-D and cycloheximide attenuated the response. The antiapoptotic effect of estrogen did not depend on cell cycle phase, and in both normal and cancer cervical cells, it involved attenuation of activation of caspase-9 and the terminal caspase-3. However, involvement of cascades upstream to the caspase-9 differed in normal vs. cancer cervical cells. In the normal hECEs estrogen blocked P2X7-receptor-induced calcium influx. In contrast, in the cancer CaSki cells, estrogen up-regulated expression of Bcl-2 and attenuated Ca(2+)-induced mitochondrial swelling (i.e. formation of mitochondrial permeability transition pores). Estrogen had no effect on P2X7-receptor-induced apoptosis in the anaplastic SiHa and Hela cells. These results point to a novel antiapoptotic effect of estrogen in the cervix that is independent of its mitogenic function. The results also suggest that cancer cervical cells evolved antiapoptotic mechanisms that enable the cells to evade apoptosis and could therefore promote tumor progression.
Divalent cations promote TALE DNA-binding specificity (2019)

Recent advances in gene editing have been enabled by programmable nucleases such as transcription activator-like effector nucleases (TALENs) and CRISPR-Cas9. However, several open questions remain regarding the molecular machinery in these systems, including fundamental search and binding behavior as well as role of off-target binding and specificity. In order to achieve efficient and specific cleavage at target sites, a high degree of target site discrimination must be demonstrated for gene editing applications. In this work, we studied the binding affinity and specificity for a series of TALE proteins under a variety of solution conditions using in vitro fluorescence methods and molecular dynamics (MD) simulations. Remarkably, we identified that TALEs demonstrate high sequence specificity only upon addition of small amounts of certain divalent cations (Mg2+, Ca2+). However, under purely monovalent salt conditions (K+, Na+), TALEs bind to specific and non-specific DNA with nearly equal affinity. Divalent cations preferentially bind to DNA over monovalent cations, which attenuates non-specific interactions between TALEs and DNA and further stabilizes specific interactions. Overall, these results uncover new mechanistic insights into the binding action of TALEs and further provide potential avenues for engineering and application of TALE- or TALEN-based systems for genome editing and regulation.
Cyp1 Inhibition Prevents Doxorubicin‐Induced Cardiomyopathy in a Zebrafish Heart‐Failure Model (2020)

Doxorubicin is a highly effective chemotherapy agent used to treat many common malignancies. However, its use is limited by cardiotoxicity, and cumulative doses exponentially increase the risk of heart failure. To identify novel heart failure treatment targets, a zebrafish model of doxorubicin-induced cardiomyopathy was previously established for small-molecule screening. Using this model, several small molecules that prevent doxorubicin-induced cardiotoxicity both in zebrafish and in mouse models have previously been identified. In this study, exploration of doxorubicin cardiotoxicity is expanded by screening 2271 small molecules from a proprietary, target-annotated tool compound collection. It is found that 120 small molecules can prevent doxorubicin-induced cardiotoxicity, including 7 highly effective compounds. Of these, all seven exhibited inhibitory activity towards cytochrome P450 family 1 (CYP1). These results are consistent with previous findings, in which visnagin, a CYP1 inhibitor, also prevents doxorubicin-induced cardiotoxicity. Importantly, genetic mutation of cyp1a protected zebrafish against doxorubicin-induced cardiotoxicity phenotypes. Together, these results provide strong evidence that CYP1 is an important contributor to doxorubicin-induced cardiotoxicity and highlight the CYP1 pathway as a candidate therapeutic target for clinical cardioprotection.
Elevated MMP-12 protein levels in induced sputum from patients with COPD (2005)

MMP-12 is markedly increased in induced sputum from patients with stable COPD compared with controls, suggesting a role for MMP-12 in the development of COPD in smokers.
Protection and Labelling of Thymidine by a Fluorescent Photolabile Group (2001)

A fluorescent photolabile group including coumarin and MeNPOC moieties was synthesized to protect 5′-OH terminal function of thymidine (T). Its photochemical and photophysical properties were studied, in particular the photocleavage (photodeprotection under a 365-nm irradiation) is only lowered by a factor of two by addition of the fluorophore. Fluorescence properties of the coumarin probe are not changed upon irradiation, which is satisfactory for the application required, i.e., in situ synthesis of DNA microarrays.
Human Enhancer of Filamentation 1, a Novel p130cas-Like Docking Protein, Associates with Focal Adhesion Kinase and Induces Pseudohyphal Growth in Saccharomyces cerevisiae (1996)

Budding in Saccharomyces cerevisiae follows a genetically programmed pattern of cell division which can be regulated by external signals. On the basis of the known functional conservation between a number of mammalian oncogenes and antioncogenes with genes in the yeast budding pathway, we used enhancement of pseudohyphal budding in S. cerevisiae by human proteins expressed from a HeLa cDNA library as a morphological screen to identify candidate genes that coordinate cellular signaling and morphology. In this report, we describe the isolation and characterization of human enhancer of filamentation 1 (HEF1), an SH3-domain-containing protein that is similar in structure to pl30cas, a recently identified docking protein that is a substrate for phosphorylation by a number of oncogenic tyrosine kinases. In contrast to p130cas, the expression of HEF1 appears to be tissue specific. Further, whereas p130cas is localized predominantly at focal adhesions, immunofluorescence indicates that HEF1 localizes to both the cell periphery and the cell nucleus and is differently localized in fibroblasts and epithelial cells, suggesting a more complex role in cell signalling. Through immunoprecipitation and two-hybrid analysis, we demonstrate a direct physical interaction between HEF1 and p130cas, as well as an interaction of the SH3 domain of HEF1 with two discrete proline-rich regions of focal adhesion kinase. Finally, we demonstrate that as with p130cas, transformation with the oncogene v-abl results in an increase in tyrosine phosphorylation on HEF1, mediated by a direct association between HEF1 and v-Abl. We anticipate that HEF1 may prove to be an important linking element between extracellular signalling and regulation of the cytoskeleton.
Successful immunization against gastric infection with Helicobacter species: use of a cholera toxin B-subunit-whole-cell vaccine (1994)

In previous studies we found that immunizing mice with a sonicate of Helicobacter felis and adjuvant cholera toxin (CT; 10 micrograms) protected the animals against challenge with viable H. felis. The aim of this study was to determine whether a low dose of CT or its nontoxic B subunit (CTB) was effective as an adjuvant in Helicobacter oral vaccines. Significant protection against viable H. felis challenge was achieved in the animals immunized with H. felis antigen plus the combination of 0.5 microgram of CT and 10 micrograms of CTB (96%), with H. felis antigen plus 0.5 microgram of CT (95%), and with H. felis antigen plus 10 micrograms of CTB (83%). No protective effect was found in the mice immunized with either H. felis antigen alone or adjuvant CTB and CT alone. Twenty-six percent of mice immunized with Helicobacter pylori antigen plus CT (10 micrograms) were protected against H. felis challenge, confirming the value of the model in predicting effects of immunization in humans. The observation that immunity can be induced with a nontoxic adjuvant CTB opens the way for human studies with H. pylori vaccines and is a further step along the road to effective strategies of prevention of gastroduodenal diseases of major world significance.