gebhart/patrepeval huggingface dataset:
Regulation of Telomerase by Telomeric Proteins (2004)

Telomeres are essential for genome stability in all eukaryotes. Changes in telomere functions and the associated chromosomal abnormalities have been implicated in human aging and cancer. Telomeres are composed of repetitive sequences that can be maintained by telomerase, a complex containing a reverse transcriptase (hTERT in humans and Est2 in budding yeast), a template RNA (hTERC in humans and Tlc1 in yeast), and accessory factors (the Est1 proteins and dyskerin in humans and Est1, Est3, and Sm proteins in budding yeast). Telomerase is regulated in cis by proteins that bind to telomeric DNA. This regulation can take place at the telomere terminus, involving single-stranded DNA-binding proteins (POT1 in humans and Cdc13 in budding yeast), which have been proposed to contribute to the recruitment of telomerase and may also regulate the extent or frequency of elongation. In addition, proteins that bind along the length of the telomere (TRF1/TIN2/tankyrase in humans and Rap1/Rif1/Rif2 in budding yeast) are part of a negative feedback loop that regulates telomere length. Here we discuss the details of telomerase and its regulation by the telomere.
The compression of optical pulses using self-phase-modulation and linearly chirped Bragg-gratings in fibers (1995)

We report the first demonstration of pulse compression in optical fiber using linearly chirped Bragg gratings as quadratic compressors for pulses spectrally broadened by self-phase modulation. With the system investigated an initial 2 ps, bandwidth limited pulse is compressed by a factor of >10. The experimental results are found to be in good agreement with analytical and numerical calculations. Such a system allows high quality compression of pulses in optical fiber for the first time.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Localizing transcripts to single cells suggests an important role of uncultured deltaproteobacteria in the termite gut hydrogen economy (2013)

Identifying microbes responsible for particular environmental functions is challenging, given that most environments contain an uncultivated microbial diversity. Here we combined approaches to identify bacteria expressing genes relevant to catabolite flow and to locate these genes within their environment, in this case the gut of a "lower," wood-feeding termite. First, environmental transcriptomics revealed that 2 of the 23 formate dehydrogenase (FDH) genes known in the system accounted for slightly more than one-half of environmental transcripts. FDH is an essential enzyme of H2 metabolism that is ultimately important for the assimilation of lignocellulose-derived energy by the insect. Second, single-cell PCR analysis revealed that two different bacterial types expressed these two transcripts. The most commonly transcribed FDH in situ is encoded by a previously unappreciated deltaproteobacterium, whereas the other FDH is spirochetal. Third, PCR analysis of fractionated gut contents demonstrated that these bacteria reside in different spatial niches; the spirochete is free-swimming, whereas the deltaproteobacterium associates with particulates. Fourth, the deltaproteobacteria expressing FDH were localized to protozoa via hybridization chain reaction-FISH, an approach for multiplexed, spatial mapping of mRNA and rRNA targets. These results underscore the importance of making direct vs. inference-based gene-species associations, and have implications in higher termites, the most successful termite lineage, in which protozoa have been lost from the gut community. Contrary to expectations, in higher termites, FDH genes related to those from the protozoan symbiont dominate, whereas most others were absent, suggesting that a successful gene variant can persist and flourish after a gut perturbation alters a major environmental niche.
Genotyping:The use of single nucleotide polymorphisms in the isolation of common disease genes (2000)

The numerous successes using positional cloning to identify genes mutated in monogenic disorders has galvanised geneticists to start using similar techniques to tackle common complex diseases such as asthma, osteoarthritis, depression and early onset heart disease. The technology is currently at an intermediate stage in which linkage in family studies is being supplemented with locus-specific association studies in populations, enabling accurate localisation of the disease causing or susceptibility gene. These studies are often labour and time intensive unless focus is placed on biological candidate genes. In general, most candidate gene studies for common diseases have been unrewarding. However, single nucleotide polymorphisin (SNP) mapping has accelerated complex disease gene localisation, providing a tool to narrow the linkage region by the detection of multiple SNPs associated with the disease in a relatively small linkage disequilibriuln (LD) region. Identification of susceptibility genes will enable a better understanding of the mechanisms of the disease processes and will facilitate the discovery of new and more efficacious medicines. Whole genome SNP maps will also allow abbreviated SNP profiles to be developed for pharmacogenetic applications, enabling physicians to tailor therapeutic regimens (i.e., identify patients likely to receive therapeutic benefit and not suffer adverse reactions).
In vitro selection of RNA molecules that displace cocaine from the membrane-bound nicotinic acetylcholine receptor (1998)

The nicotinic acetylcholine receptor (AChR) controls signal transmission between cells in the nervous system. Abused drugs such as cocaine inhibit this receptor. Transient kinetic investigations indicate that inhibitors decrease the channel-opening equilibrium constant [Hess, G. P. & Grewer, C. (1998) Methods Enzymol. 291, 443-473]. Can compounds be found that compete with inhibitors for their binding site but do not change the channel-opening equilibrium? The systematic evolution of RNA ligands by exponential enrichment methodology and the AChR in Torpedo californica electroplax membranes were used to find RNAs that can displace inhibitors from the receptor. The selection of RNA ligands was carried out in two consecutive steps: (i) a gel-shift selection of high-affinity ligands bound to the AChR in the electroplax membrane, and (ii) subsequent use of nitrocellulose filters to which both the membrane-bound receptor and RNAs bind strongly, but from which the desired RNA can be displaced from the receptor by a high-affinity AChR inhibitor, phencyclidine. After nine selection rounds, two classes of RNA molecules that bind to the AChR with nanomolar affinities were isolated and sequenced. Both classes of RNA molecules are displaced by phencyclidine and cocaine from their binding site on the AChR. Class I molecules are potent inhibitors of AChR activity in BC3H1 muscle cells, as determined by using the whole-cell current-recording technique. Class II molecules, although competing with AChR inhibitors, do not affect receptor activity in this assay; such compounds or derivatives may be useful for alleviating the toxicity experienced by millions of addicts.
A Novel Plant Leucine-Rich Repeat Receptor Kinase Regulates the Response ofMedicago truncatulaRoots to Salt Stress (2009)

In plants, a diverse group of cell surface receptor-like protein kinases (RLKs) plays a fundamental role in sensing external signals to regulate gene expression. Roots explore the soil environment to optimize their growth via complex signaling cascades, mainly analyzed in Arabidopsis thaliana. However, legume roots have significant physiological differences, notably their capacity to establish symbiotic interactions. These major agricultural crops are affected by environmental stresses such as salinity. Here, we report the identification of a leucine-rich repeat RLK gene, Srlk, from the legume Medicago truncatula. Srlk is rapidly induced by salt stress in roots, and RNA interference (RNAi) assays specifically targeting Srlk yielded transgenic roots whose growth was less inhibited by the presence of salt in the medium. Promoter-beta-glucuronidase fusions indicate that this gene is expressed in epidermal root tissues in response to salt stress. Two Srlk-TILLING mutants also failed to limit root growth in response to salt stress and accumulated fewer sodium ions than controls. Furthermore, early salt-regulated genes are downregulated in Srlk-RNAi roots and in the TILLING mutant lines when submitted to salt stress. We propose a role for Srlk in the regulation of the adaptation of M. truncatula roots to salt stress.
On Bayesian Analysis of Mixtures with an Unknown Number of Components (1997)

This article is a contribution to the methodology of fully Bayesian mixture modelling. We stress the word &amp;quot;fully&amp;quot; in two senses. First, we model the number of components and the mixture component parameters jointly and base inference about these quantities on their posterior probabilities. This is in contrast to most previous Bayesian treatments of mixture estimation, which consider models for different numbers of components separately, and use significance tests or other non-Bayesian criteria to infer the number of components. Secondly, we aim to present posterior distributions of our objects of inference (model parameters and predictive densities), and not just &amp;quot;best estimates&amp;quot;. There are three key ideas in our treatment. First, we demonstrate that novel MCMC methods, the &amp;quot;reversible jump&amp;quot; samplers introduced by Green (1994, 1995), can be used to sample mixture representations with an unknown and hence varying number of components. We believe these methods are preferable on grounds of convenience,
Aldosterone synthase inhibition improves cardiovascular function and structure in rats with heart failure: a comparison with spironolactone (2008)

Inhibition of aldosterone synthase, the key enzyme in aldosterone formation, could be an alternative strategy for mineralocorticoid-receptor antagonists in congestive heart failure (CHF), but its effect in CHF is unknown.We compared, in rats with CHF, the effects of a 7 day and a 12 week treatment with the aldosterone synthase inhibitor FAD286 (4 mg kg(-1) day(-1)) with those induced by spironolactone (80 mg kg(-1) day(-1)). FAD286/spironolactone increased cardiac output without modifying arterial pressure. Long-term FAD286 and spironolactone reduced left ventricular (LV) end-diastolic pressure, LV relaxation constant, and LV dilatation, and these effects were more marked with FAD286, whereas both drugs reduced LV hypertrophy and collagen accumulation to the same extent. Long-term FAD286/spironolactone prevented CHF-related enhancement in LV ACE and reduction in LV ACE-2, but only FAD286 prevented the reduction in LV AT(2) receptors. FAD286, but not long-term spironolactone, reduced the CHF-related enhancements in LV reactive oxygen species, reduced-oxidized glutathione ratio, and aortic nicotinamide adenine dinucleotide phosphate oxidase activity. FAD286 normalized the CHF-induced impairment of endothelium-dependent vasodilatation.In experimental CHF, FAD286 and spironolactone improve LV haemodynamics, remodelling, and function, but only FAD286 persistently normalizes LV 'redox status'. These results suggest that aldosterone synthase inhibition is a potential therapeutic strategy for the treatment of CHF.
A(2A) adenosine receptor deficiency attenuates brain injury induced by transient focal ischemia in mice. (1999)

Extracellular adenosine critically modulates ischemic brain injury, at least in part through activation of the A(1) adenosine receptor. However, the role played by the A(2A) receptor has been obscured by intrinsic limitations of A(2A) adenosinergic agents. To overcome these pharmacological limitations, we explored the consequences of deleting the A(2A) adenosine receptor on brain damage after transient focal ischemia. Cerebral morphology, as well as vascular and physiological measures (before, during, and after ischemia) did not differ between A(2A) receptor knock-out and wild-type littermates. The volume of cerebral infarction, as well as the associated neurological deficit induced by transient filament occlusion of the middle cerebral artery, were significantly attenuated in A(2A) receptor knock-out mice. This neuroprotective phenotype of A(2A) receptor-deficient mice was observed in different genetic backgrounds, confirming A(2A) receptor disruption as its cause. Together with complimentary pharmacological studies, these data suggest that A(2A) receptors play a prominent role in the development of ischemic injury within brain and demonstrate the potential for anatomical and functional neuroprotection against stroke by A(2A) receptor antagonists.
Nitro‐fatty Acids Occur in Human Plasma in the Picomolar Range: a Targeted Nitro‐lipidomics GC–MS/MS Study (2009)

First studies on the occurrence of nitrated fatty acids in plasma of healthy subjects revealed basal concentrations of 600 nM for free/nonesterified nitro-oleic acid (NO(2)-OA) as measured by liquid chromatography tandem mass spectrometry (LC-MS/MS). We recently showed by a gas chromatography tandem mass spectrometry (GC-MS/MS) method the physiological occurrence of two isomers, i.e., 9-NO(2)-OA and 10-NO(2)-OA, at mean basal plasma concentrations of 880 and 940 pM, respectively. In consideration of this large discrepancy we modified our originally reported method by replacing solid-phase extraction (SPE) by solvent extraction with ethyl acetate and by omitting the high-performance liquid chromatography (HPLC) step for a more direct detection and with the potential for lipidomics studies. Intra-assay imprecision and accuracy of the modified method in human plasma were 1-34% and 91-221%, respectively, for added NO(2)-OA concentrations in the range 0-3,000 pM. This method provided basal plasma concentrations of 306 +/- 44 pM for 9-NO(2)-OA and 316 +/- 33 pM for 10-NO(2)-OA in 15 healthy subjects. Nitro-arachidonic acid and nitro-linolenic acid were not detectable in the plasma samples. In summary, our studies show 9-NO(2)-OA and 10-NO(2)-OA as endogenous nitrated fatty acids in human plasma in the pM range; HPLC is recommendable as a sample clean-up step for reliable quantification of nitro-oleic acids by GC-MS/MS.
Therapy of superficial bladder cancer. (1996)

Intravesical therapy has been used in the management of superficial transitional cell carcinoma (TCC) of the urinary bladder (Ie, Ta, Tl, and carcinoma in situ [CIS]) with specific objectives that include treating existing/residual tumor, preventing recurrence of tumor, preventing disease progression, and prolonging survival. The initial clinical stage and grade remain the main determinant factors in survival irrespective of the treatment. Intravesical chemotherapy has shown a decrease in short-term tumor recurrence rates, but has had no positive impact on disease progression or prolongation of survival. Presently, bacillus Calmette-Guèrin vaccine (BCG) immunotherapy remains the most effective treatment and prophylaxis for TCC (Ta, Tl, CIS) and has positive outcome on tumor recurrence rate, disease progression, and prolongation of survival. Prostatic urethral mucosal involvement with bladder cancer can also be effectively treated with BCG intravesical immunotherapy. Interferons, keyhole limpet hemocyanin and photofrin-photodynamic therapy are under investigation in the management of TCC and early results are encouraging. This review highlights and summarizes the recent advances in intravesical therapy and prophylaxis of superficial TCC.
Evidence that estrogens modulate activity and increase the number of 1,25-dihydroxyvitamin D receptors in osteoblast-like cells (ROS 17/2.8) (1992)

A detailed understanding of the mechanism of action of estrogen on bones is still lacking. The present study was designed to examine possible modulation by 17 beta-estradiol (E2) on the effects of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] and on vitamin D receptors (VDR) in the ROS 17/2.8 osteoblast-like cell line. Cells were grown in phenol-red free medium supplemented with charcoal-stripped fetal calf serum (FCS). Total cellular VDR were measured in cell homogenates after extraction with a KCl hypertonic buffer. VDR-binding capacity doubled in the presence of 10 nM E2 (16.2 +/- 2.3 vs. 7.0 +/- 1.3 fmol/mg protein, respectively; P less than 0.01), while the Kd for 1,25-(OH)2D3 did not change (approximately 0.1 nM). Tamoxifen alone had no effect on VDR, while it completely abolished the E2-induced increase in VDR, indicating that the effect was specific for E2 and estrogen receptor mediated. 1,25-(OH)2D3 inhibited cell proliferation, determined by [3H] thymidine incorporation to DNA, in a dose-dependent fashion between 0.01-100 nM. The inhibitory effect of 1,25-(OH)2D3 on cell proliferation was significantly augmented in the presence of E2 (10 nM). 1,25-(OH)2D3 increased osteocalcin secretion to the medium by the cells in a dose-dependent fashion between 0.01-100 nM. In the presence of E2 (10 nM), maximal osteocalcin secretion in response to 1,25-(OH)2D3 was 3.5-fold higher than that in response to 1,25-(OH)2D3 alone. These results indicate that E2 modulates 1,25-(OH)2D3 activity in osteoblast-like cells, and that this effect can be attributed to an increase in VDR.
Manganese doped zinc sulphide nanoparticles by aqueous method (1995)

Zinc sulphide nanoparticles in the size range ∼10–40 Å diameter have been synthesized using the aqueous chemical method. Scanning tunneling microscopy showed that particles are indeed nanosize particles. The size dependent band gap could be varied from a bulk value of 3.68 to 4.5 eV. X-ray diffraction indicated that nanoparticles are crystalline except for those with band gap ∼4.5±0.1 eV. Nanoparticles with particle size ∼21×2 Å diameter or energy gap 4.1×0.1 eV were doped with manganese. The photoluminescence peak at ∼600 nm corresponding to yellow light emission was observed. Atomic absorption studies show that maximum luminescence intensity is achievable with 0.12 at. wt % of Mn doping.
Effects of Mixing Conditions on Pasta Dough Development and Biochemical Changes (1999)

ABSTRACT Mixing of commercial durum wheat semolina with water was performed under different conditions in a Brabender micromixer equipped with pastamaking shafts. Semolina filling of the mixing chamber was 30.4–42.9% (v/v), shaft speed was 10–110 rpm, temperature was 10–40°C, and hydration level was 47–52.5% (db). The blend of water and semolina evolved from individualized hydrated particles (HP) to a dough product (DP) as a function of these conditions. Torque values ( T ) and the specific mechanical energies (SME) were recorded during mixing as a function of time. Terms from these curves were defined to characterize the mixing process: t o (starting time of dough development), t d (time to reach the maximum dough consistency), T m (mean torque value after dough development), and SME f (total energy applied to the dough during mixing). Transformation of HP into DP and the mixing temperature were the main parameters affecting t o , t d , T m , and SME f . Protein aggregate distribution was measured by size‐exclusion HPLC, protein solubility in 0.01 N acetic acid, free ‐SH content, soluble arabinoxylans, reducing sugars, ferulic acid, carotenoid content, and oxidase activities to characterize the biochemical changes that occurred during pasta dough formation. DP was characterized by lower amounts of insoluble glutenin aggregates, lower protein solubility in dilute acetic acid, lower free ‐SH content, ferulic acid, carotenoid content, and lower oxidoreductase activities as compared to HP. Once the dough was developed, the effects of mixing speed, temperature, or hydration level on the biochemical composition of the blend were null or low compared to the modifications that were observed when the blends changed from HP to DP. The t o and SME f were the most significant parameters in characterizing the pasta dough mixing process in relation to biochemical changes.
Species specificity of anti-acetylcholine receptor antibodies elicited by synthetic peptides (1987)

Two peptides corresponding to amino acid residues 351-368 of the alpha-subunits of Torpedo and human acetylcholine receptor (AChR) were synthesized. These peptides contain a segment (residues 355-364) which displays the greatest variability in amino acid sequence between the two species. Antibodies elicited against the two peptides cross-reacted with the respective native AChRs and were shown to be species specific by radioimmunoassay, immunoblotting, and immunofluorescence microscopy. Thus, antibodies against the Torpedo peptide cross-reacted with Torpedo AChR but did not bind to mammalian or chicken AChR. Antibodies against the human peptide proved to be specific probes for mammalian muscle AChR. They cross-reacted with mammalian AChR (human, calf, mouse, and rat) but not with Torpedo or chicken AChR. These antibodies were also shown to react preferentially with the extrajunctional form of muscle AChR, as compared to their reactivity with junctional muscle AChR. In immunofluorescence experiments, the anti-human peptide antibody stained AChR aggregates in sectioned or ethanol-permeabilized rat and mouse myotubes grown in culture but did not stain living myotubes. This indicates that the sequence 351-368 of the alpha-subunit of mammalian AChR is on the cytoplasmic face of muscle cell membranes, as predicted theoretically.
The mechanism of cell death in Listeria monocytogenes-infected murine macrophages is distinct from apoptosis (1997)

Various pathogenic bacteria with the capacity to live within eukaryotic cells activate an apoptotic program in infected host cells. Induction of apoptosis by Listeria monocytogenes in murine dendritic cells and hepatocytes has been described. Here we address the questions of whether and how the pathogen kills macrophages, its most important habitat. Employing several complementary techniques aimed at discriminating between apoptosis and necrosis, we show that murine bone marrow-derived macrophages (BMM) undergo delayed necrosis but not apoptosis when infected with listeriolysin (Hly)-producing L. monocytogenes. This pathogen failed to elicit apoptotic morphology, DNA fragmentation, and surface annexin V binding of macrophages, in contrast to Shigella flexneri infection or gliotoxin treatment, which were used as positive controls. Furthermore, macrophages infected with L. monocytogenes released lower quantities of interleukin-1beta (IL-1beta) than did Shigella flexneri-infected ones, indicating diminished or even absent activation of IL-1-converting enzyme in macrophages harboring L. monocytogenes. We conclude that murine BMM die by necrosis after several hours of cytoplasmic replication of L. monocytogenes. The pathogen may benefit from this feature by the possibility of taking advantage of cells of "pseudo-healthy" appearance, thus avoiding rapid elimination by other phagocytes.
Haptic feedback in robot-assisted minimally invasive surgery (2008)

The designs of existing commercial RMIS systems are not conducive for force feedback, and creative solutions are needed to create compelling tactile feedback systems. Surgeons, engineers, and neuroscientists should work together to develop effective solutions for haptic feedback in RMIS.