gebhart/patrepeval huggingface dataset:
Chemical genetic screen identifies Toxoplasma DJ-1 as a regulator of parasite secretion, attachment, and invasion (2011)

Toxoplasma gondii is a member of the phylum Apicomplexa that includes several important human pathogens, such as Cryptosporidium and Plasmodium falciparum, the causative agent of human malaria. It is an obligate intracellular parasite that can cause severe disease in congenitally infected neonates and immunocompromised individuals. Despite the importance of attachment and invasion to the success of the parasite, little is known about the underlying mechanisms that drive these processes. Here we describe a screen to identify small molecules that block the process of host cell invasion by the T. gondii parasite. We identified a small molecule that specifically and irreversibly blocks parasite attachment and subsequent invasion of host cells. Using tandem orthogonal proteolysis-activity-based protein profiling, we determined that this compound covalently modifies a single cysteine residue in a poorly characterized protein homologous to the human protein DJ-1. Mutation of this key cysteine residue in the native gene sequence resulted in parasites that were resistant to inhibition of host cell attachment and invasion by the compound. Further analysis of the invasion phenotype confirmed that modification of Cys127 on TgDJ-1 resulted in a block of microneme secretion and motility, even in the presence of direct stimulators of calcium release. Together, our results suggest that TgDJ-1 plays an important role that is likely downstream of the calcium flux required for microneme secretion, parasite motility, and subsequent invasion of host cells.
BDNF and Schizophrenia: From Neurodevelopment to Neuronal Plasticity, Learning, and Memory (2013)

Brain-Derived Neurotrophic Factor (BDNF) is a neurotrophin that has been related not only to neurodevelopment and neuroprotection, but also to synapse regulation, learning, and memory. Research focused on the neurobiology of schizophrenia has emphasized the relevance of neurodevelopmental and neurotoxicity-related elements in the pathogenesis of this disease. Research focused on the clinical features of schizophrenia in the past decades has emphasized the relevance of cognitive deficits of this illness, considered a core manifestation and an important predictor for functional outcome. Variations in neurotrophins such as BDNF may have a role as part of the molecular mechanisms underlying these processes, from the neurodevelopmental alterations to the molecular mechanisms of cognitive dysfunction in schizophrenia patients.
Role of Environmental Contamination in the Transmission of Vancomycin-Resistant Enterococci (1997)

David J. Weber, William A. Rutala, Role of Environmental Contamination in the Transmission of Vancomycin-Resistant Enterococci, Infection Control and Hospital Epidemiology, Vol. 18, No. 5 (May, 1997), pp. 306-309
Somatic mtDNA mutations cause aging phenotypes without affecting reactive oxygen species production (2005)

The mitochondrial theory of aging proposes that reactive oxygen species (ROS) generated inside the cell will lead, with time, to increasing amounts of oxidative damage to various cell components. The main site for ROS production is the respiratory chain inside the mitochondria and accumulation of mtDNA mutations, and impaired respiratory chain function have been associated with degenerative diseases and aging. The theory predicts that impaired respiratory chain function will augment ROS production and thereby increase the rate of mtDNA mutation accumulation, which, in turn, will further compromise respiratory chain function. Previously, we reported that mice expressing an error-prone version of the catalytic subunit of mtDNA polymerase accumulate a substantial burden of somatic mtDNA mutations, associated with premature aging phenotypes and reduced lifespan. Here we show that these mtDNA mutator mice accumulate mtDNA mutations in an approximately linear manner. The amount of ROS produced was normal, and no increased sensitivity to oxidative stress-induced cell death was observed in mouse embryonic fibroblasts from mtDNA mutator mice, despite the presence of a severe respiratory chain dysfunction. Expression levels of antioxidant defense enzymes, protein carbonylation levels, and aconitase enzyme activity measurements indicated no or only minor oxidative stress in tissues from mtDNA mutator mice. The premature aging phenotypes in mtDNA mutator mice are thus not generated by a vicious cycle of massively increased oxidative stress accompanied by exponential accumulation of mtDNA mutations. We propose instead that respiratory chain dysfunction per se is the primary inducer of premature aging in mtDNA mutator mice.
Selection of Fluorophore and Quencher Pairs for Fluorescent Nucleic Acid Hybridization Probes (2006)

With the introduction of simple and relatively inexpensive methods for labeling nucleic acids with nonradioactive labels, doors have been opened that enable nucleic acid hybridization probes to be used for research and development, as well as for clinical diagnostic applications. The use of fluorescent hybridization probes that generate a fluorescence signal only when they bind to their target enables real-time monitoring of nucleic acid amplification assays. The use of hybridization probes that bind to the amplification products in real-time markedly improves the ability to obtain quantitative results. Furthermore, real-time nucleic acid amplification assays can be carried out in sealed tubes, eliminating carryover contamination. Because fluorescent hybridization probes are available in a wide range of colors, multiple hybridization probes, each designed for the detection of a different nucleic acid sequence and each labeled with a differently colored fluorophore, can be added to the same nucleic acid amplification reaction, enabling the development of high-throughput multiplex assays. It is therefore important to carefully select the labels of hybridization probes, based on the type of hybridization probe used in the assay, the number of targets to be detected, and the type of apparatus available to perform the assay. This chapter outlines different aspects of choosing appropriate labels for the different types of fluorescent hybridization probes used with different types of spectrofluorometric thermal cyclers.
Cellular cholesterol substrate pools for adenosine-triphosphate cassette transporter A1-dependent high-density lipoprotein formation (2008)

Current evidence suggests that ABCA1-mediated cholesterol efflux to apoA-I involves mobilization of cholesterol from plasma membrane, endoplasmic reticulum, trans-Golgi network, late endocytic and lysosomal compartments, and cholesteryl ester droplets. Apart from lipidating apoA-I directly, ABCA1 has also been found to efflux cholesterol indirectly to apoA-I in plasma membranes.
Nanomaterials Based on DNA (2010)

The combination of synthetic stable branched DNA and sticky-ended cohesion has led to the development of structural DNA nanotechnology over the past 30 years. The basis of this enterprise is that it is possible to construct novel DNA-based materials by combining these features in a self-assembly protocol. Thus, simple branched molecules lead directly to the construction of polyhedrons, whose edges consist of double helical DNA and whose vertices correspond to the branch points. Stiffer branched motifs can be used to produce self-assembled two-dimensional and three-dimensional periodic lattices of DNA (crystals). DNA has also been used to make a variety of nanomechanical devices, including molecules that change their shapes and molecules that can walk along a DNA sidewalk. Devices have been incorporated into two-dimensional DNA arrangements; sequence-dependent devices are driven by increases in nucleotide pairing at each step in their machine cycles.
A Synthetic Module for the metH Gene Permits Facile Mutagenesis of the Cobalamin-Binding Region of Escherichia coli Methionine Synthase:  Initial Characterization of Seven Mutant Proteins (1996)

Cobalamin-dependent methionine synthase from Escherichia coli is a monomeric 136 kDa protein composed of multiple functional regions. The X-ray structure of the cobalamin-binding region of methionine synthase reveals that the cofactor is sandwiched between an alpha-helical domain that contacts the upper face of the cobalamin and an alpha/beta (Rossmann) domain that interacts with the lower face. An unexpected conformational change accompanies binding of the methylcobalamin cofactor. The dimethylbenzimidazole ligand to the lower axial position of the cobalt in the free cofactor is displaced by histidine 759 from the Rossmann domain [Drennan, C. L., Huang, S., Drummond, J. T., Matthews, R. G., & Ludwig, M. L. (1994) Science 266, 1669]. In order to facilitate studies of the roles of amino acid residues in the cobalamin-binding region of methionine synthase, we have constructed a synthetic module corresponding to nucleotides (nt) 1741-2668 in the metH gene and incorporated it into the wild-type metH gene. This module contains unique restriction sites at approximately 80 base pair intervals and was synthesized by overlap extension of 22 synthetic oligonucleotides ranging in length from 70 to 105 nt and subsequent amplification using two sets of primers. Expression of methionine synthase from a plasmid containing the modified gene was shown to be unaffected by the introduction of the synthetic module. E. coli does not synthesize cobalamin, and overexpression of MetH holoenzyme requires accelerated cobalamin transport. Growth conditions are described that enable the production of holoenzyme rather than apoenzyme. We describe the construction and initial characterization of seven mutants. Four mutations (His759Gly, Asp757Glu, Asp757Asn, and Ser810Ala) alter residues in the hydrogen-bonded network His-Asp-Ser that connects the histidine ligand of the cobalt to solvent. Three mutations (Phe708Ala, Phe714Ala, and Leu715Ala) alter residues in the cap region that covers the upper face of the cobalamin. The His759Gly mutation has profound effects, essentially abolishing steady-state activity, while the Asp757, Ser810, Phe708, and Leu715 mutations lead to decreases in activity. These mutations asses the importance of individual residues in modulating cobalamin reactivity.
Ab Initio Study of the Reaction between N_2O_5 and H_2O (2000)

In the process of ozone hole formation, polar stratospheric clouds (PSCs) play an essential role. To understand the formation and the character of PSCs, we have carried out quantum chemical calculations on the N2O5 + H2O reaction system, using different calculation methods. At the QCISD(T)//MP2/6 - 311 G(d,p)level, it is found that for the gas- phase reaction △H0 = - 39.5kJ·mol-1, △G0 = - 36. 1kJ·mol-1, Ea=88.2kJ·mol-1 at 298K, respectively. These results are consistent with the facile hydrolysis of N2O5 by moisture.
Assessment of Catheter Tip Contact Force Resulting in Cardiac Perforation in Swine Atria Using Force Sensing Technology (2011)

Perforation of the atrial wall in a swine model can occur over a wide range of CF values. Perforation can occur with a CF as low as 77 g. Ablation reduces the perforating force by 23%.
The U1 snRNP-associated factor Luc7p affects 5' splice site selection in yeast and human (2007)

yLuc7p is an essential subunit of the yeast U1 snRNP and contains two putative zinc fingers. Using RNA-protein cross-linking and directed site-specific proteolysis (DSSP), we have established that the N-terminal zinc finger of yLuc7p contacts the pre-mRNA in the 5' exon in a region close to the cap. Modifying the pre-mRNA sequence in the region contacted by yLuc7p affects splicing in a yLuc7p-dependent manner indicating that yLuc7p stabilizes U1 snRNP-pre-mRNA interaction, thus reminding of the mode of action of another U1 snRNP component, Nam8p. Database searches identified three putative human yLuc7p homologs (hLuc7A, hLuc7B1 and hLuc7B2). These proteins have an extended C-terminal tail rich in RS and RE residues, a feature characteristic of splicing factors. Consistent with a role in pre-mRNA splicing, hLuc7A localizes in the nucleus and antibodies raised against hLuc7A specifically co-precipitate U1 snRNA from human cell extracts. Interestingly, hLuc7A overexpression affects splicing of a reporter in vivo. Taken together, our data suggest that the formation of a wide network of protein-RNA interactions around the 5' splice site by U1 snRNP-associated factors contributes to alternative splicing regulation.
Computer assisted planning and custom-made surgical guide for malunited pronation deformity after first metatarsophalangeal joint arthrodesis in rheumatoid arthritis: A case report (2014)

Arthrodesis of the first metatarsophalangeal (MTP-1) joint is a widely used procedure for the treatment of hallux valgus in patients with MTP-1 degeneration, severe or recurrent deformity, or inflammatory arthritis. In this case, ten years earlier, the patient's MTP-1 joint had been fused in a severe pronation deformity position. Subsequently, a laterally shifted tibial sesamoid and osseous rising of the phalanx base caused painful callosities. To correct the pronated deformity accurately, a custom-made surgical guide based on a three-dimensional computer tomography (3D-CT) simulation system was used. After correction of the deformity, the MTP-1 joint was again fused. Adequate correction was achieved, and the patient no longer complains of pain and can perform full weight-bearing on the forefoot. The difficulty and importance of placing the MTP-1 joint in an adequate rotational position in MTP-1 joint arthrodesis surgery were confirmed, as was the utility of 3D evaluation and a custom-made surgical guide for rotational adjustment between the metatarsal and the proximal phalanx. We believe that this system should be one of the indicators for adjusting the rotation, especially in revision MTP-1 joint fusion surgery.
Molecular and enzymatic characterization of two stilbene synthases from Eastern white pine (Pinus strobus) A single Arg/His difference determines the activity and the pH dependence of the enzymes (1995)

Pinus strobus (Eastern white pine) contains stilbenes biosynthetically derived from cinnamoyl-CoA (pinosylvin) or dihydrocinnamoyl-CoA (dihydropinosylvin). We screened a P. strobus cDNA library with a stilbene synthase (STS) probe from Pinus sylvestris. The eight isolated cDNAs represented two closely related STS genes with five amino acid differences in the proteins. The enzyme properties were investigated after heterologous expression in Escherichia coli. Both proteins preferred cinnamoyl-CoA against dihydrocinnamoyl-CoA and thus represented pinosylvin synthases. Otherwise they revealed large differences. STS1 had only 3-5% of the activity of STS2, its pH optimum was shifted to lower values (pH 6), and it synthesized with cinnamoyl-CoA a second unknown product. Site-directed mutagenesis demonstrated that a single Arg-to-His exchange in STS1 was responsible for all of the differences. The proton acceptor properties of His are discussed as the reason for the properties of STS1.
Translating embeddings for modeling multi-relational data (2015)

We consider the problem of embedding entities and relationships of multi-relational data in low-dimensional vector spaces. Our objective is to propose a canonical model which is easy to train, contains a reduced number of parameters and can scale up to very large databases. Hence, we propose TransE, a method which models relationships by interpreting them as translations operating on the low-dimensional embeddings of the entities. Despite its simplicity, this assump-tion proves to be powerful since extensive experiments show that TransE signif-icantly outperforms state-of-the-art methods in link prediction on two knowledge bases. Besides, it can be successfully trained on a large scale data set with 1M entities, 25k relationships and more than 17M training samples. 1
LoGPG: Modeling network contention in message-passing programs (2001)

In many real applications, for example, those with frequent and irregular communication patterns or those using large messages, network contention and contention for message processing resources can be a significant part of the total execution time. This paper presents a new cost model, called LoGPC, that extends the LogP and LogGP models to account for the impact of network contention and network interface DMA behavior on the performance of message passing programs. We validate LoGPC by analyzing three applications implemented with Active Messages on the MIT Alewife multiprocessor. Our analysis shows that network contention accounts for up to 50 percent of the total execution time. In addition, we show that the impact of communication locality on the communication costs is at most a factor of two on Alewife. Finally, we use the model to identify trade-offs between synchronous and asynchronous message passing styles.
Protection from pulmonary hypertension with an orally active endothelin receptor antagonist in hypoxic rats (1995)

The aim of this study was to investigate the potential role of endothelin (ET) in the development of chronic hypoxic pulmonary hypertension. Pulmonary vascular reactivity to ET-1 was first examined in isolated perfused lungs from normoxic and chronically hypoxic rats in the presence of bosentan, a new nonpeptide mixed antagonist of ETA and ETB receptors. The effect of chronic treatment with bosentan was then examined in rats that were exposed to chronic hypoxia and developed pulmonary hypertension. In lungs from normoxic rats, bosentan (10(-5) M) abolished the vasodilator responses to ET-1 (10(-10) M) or to the ETB-selective agonist IRL-1620 (10(-10) M) and attenuated the vasoconstrictor responses to 10(-9) M ET-1 (from 8.7 +/- 0.7 to 1.8 +/- 0.3 mmHg, P < 0.01) or 10(-9) M IRL-1620 (from 1.5 +/- 0.4 to 0.4 +/- 0.1 mmHg, P < 0.05). In lungs from chronically hypoxic rats, the pressor response to 3 x 10(-10) M ET-1 was abolished by bosentan and partially reduced by the selective ETA antagonist BQ-123. In conscious rats previously exposed to hypoxia for 15 days, pretreatment with bosentan (100 mg.kg-1.day-1 by gavage) for 3 days attenuated the increase in systemic arterial pressures and the concomitant decrease of cardiac output in response to an intravenous bolus of ET-1 (3 x 10(-10) M). In rats exposed to hypoxia for 15 days and simultaneously treated with bosentan, pulmonary arterial pressure was lower (P < 0.05) and right ventricular hypertrophy was less severe (P < 0.01) than in control hypoxic rats treated with vehicle.(ABSTRACT TRUNCATED AT 250 WORDS)
Gentle cell trapping and release on a microfluidic chip by in situ alginate hydrogel formation (2005)

Microfluidic devices are increasingly used to perform biological experiments on a single-cell basis. However, long-term stability of cell positions is still an issue. A novel biocompatible method for cell entrapment and release on a microchip is presented. It is based on the controlled formation of an alginate hydrogel by bringing two laminar flows of alginate and calcium ions in the range of 2 mM to 40 mM into contact. The resulting growth of a gel bar is used to enclose and immobilize yeast cells. Adding ethylenediaminetetraacetic acid (EDTA) to the alginate solution allows for control of the hydrogel growth, and by varying the ratio of Ca(2+) to EDTA concentrations gel growth or gel shrinkage can be induced at will. Trapped cells are released during shrinkage of the gel. The trapping efficiency for different cell speeds is investigated and the properties of gel growth are discussed using a diffusion model. Precise positioning of a single cell is demonstrated. The technique presented allows not only the reversible immobilization of cells under gentle conditions but also offers the potential of long-term cell cultures as shown by on-chip incubation of yeast cells. The procedure may provide a simple and fully biocompatible technique for a multitude of innovative experiments on cells in microsystems.
Protective effect and mechanism of phosphatidylserine in UVB‐induced human dermal fibroblasts (2013)

Phosphatidylserine (PS), a highly enriched membrane phospholipid component, is known to have several physiological roles, such as activating signaling enzymes and antioxidant activity. However, the protective biological mechanisms of PS in human skin have not been clearly investigated. In this study, we investigated the anti‐photoaging effects of PS and its possible mechanisms in UVB‐induced human dermal fibroblasts (HDFs). After 24 h incubation, PS significantly increased type I procollagen synthesis with or without UVB exposure. The expressions of MMP‐1 and pro‐MMP‐1 were inhibited, and activities of total MMPs were decreased in a dose‐dependent manner by treatment of PS in UVB‐induced HDFs. The MAPKs/AP‐1 signaling pathway was downregulated by PS in a dose‐dependent manner. PS increases procollagen synthesis and inhibits MMP‐1 expression and activity by downregulating MAPKS/AP‐1 signaling pathways. This study suggests that PS can be used as a therapeutic agent to prevent UVB‐induced skin photoaging and perhaps even natural skin aging. Practical applications: In this study, we evaluated the protective effects and mechanism of PS on UV induced photoaging in human dermal fibroplasts. PS increases type I procollagen synthesis and decreases MMP‐1 activity by downregulating the MAPK/AP‐1 signaling pathway in UVB‐induced HDFs. These results suggest that PS can be used as a therapeutic agent for the treatment and prevention of photoaging and possibly even natural aging in human skin. For medicinal and cosmetic application, further studies on in vivo clinical applications are necessary to fully elucidate the function and mechanism of PS on human skin photoaging.
Effects of 5'-terminal modifications on the biological activity of defective interfering RNAs of Sindbis virus (1988)

We have been studying defective interfering (DI) genomes of the RNA enveloped virus Sindbis virus. Deletion mapping of a DI cDNA demonstrated that only sequences at the 3' and 5' termini of the genome are required for the DI RNA to be biologically active. We constructed a series of cDNAs that transcribe DI RNAs differing only in 5'-terminal sequences. Two of the 5' termini identical to ones found in naturally occurring DI RNAs are the 5' terminus of the virion RNA (DI-549) and the first 142 nucleotides from the 5' terminus of the subgenomic 26S mRNA attached to the 5' terminus of the virion RNA (DI-15). The latter has a 42-nucleotide deletion from nucleotides 25 to 66 in the 26S RNA sequence. These DI RNA transcripts were biologically active, but one (DI-526) which did not have the 42-nucleotide deletion of DI-15 was not replicated. The DI RNA isolated after the presumed amplification of the DI-526 transcript had deleted the first 54 nucleotides of the 26S RNA sequences. The 5' terminus of Sindbis virion RNA contains a stem and loop region that is conserved among alphaviruses. An 11-nucleotide deletion in DI-549 that disrupted this stem and loop rendered this DI RNA inactive. In contrast, this same deletion in DI-15 and one that removed an additional 100 nucleotides of the virion 5' terminus did not prevent its amplification. We did not detect by computer analysis any common secondary structures among the biologically active DI RNAs that distinguished them from those RNAs that were not amplified. Our results support the conclusion that tertiary structure or the ability of the RNA to adapt its structure upon interaction with protein is important in the recognition process.