gebhart/patrepeval huggingface dataset:
A resolvase-like protein is required for the site-specific integration of the temperate lactococcal bacteriophage TP901-1 (1996)

The integration system of the temperate lactococcal phage TP901-1 was characterized in Lactococcus lactis subsp. cremoris LM0230 and MG1363 with the use of deletion derivatives of the integration vector pBC143 (B. Christiansen, M. G. Johnsen, E. Stenby, F. K. Vogensen, and K. Hammer, J. Bacteriol. 176:1069-1076, 1994). The phage-encoded elements necessary for integration were localized on a 2.8-kb NsiI-EcoRI fragment including the phage attachment site, attP. This fragment was DNA sequenced, and sequence analysis revealed three putatively expressed open reading frames, Orf1, Orf2, and Orf3 By the introduction of mutations within the orf1, orf2, and orf3 genes, it was shown that only Orf1 was necessary for the integration process. Furthermore, it was found that Orf1, attP, and a 425-bp region upstream of the orf1 gene are sufficient for integration. Orf1 contains 485 amino acids and is located just upstream of attP. The N-terminal 150 to 180 amino acids of Orf1 showed 38 to 44% similarity to the resolvase group of site-specific integrases, while no similarity to known proteins was found in the C-terminal end. Bacteriophage TP901-1 therefore contains a unique integration system that does not resemble the Int class of site-specific integrases usually found in temperate bacteriophages. The constructed integration vector, pBC170, integrates into the chromosomal attachment site very efficiently and forms stable transformants with a frequency corresponding to 20% of the transformation efficiency.
Non-damaging Retinal Phototherapy: Dynamic Range of Heat Shock Protein Expression (2010)

Beneficial effects of laser therapy have been previously shown to extend beyond those resulting from destruction of tissue. One hundred millisecond laser exposures at approximately half the threshold power of RPE damage induced transcription of HSP70, an indication of cellular response to sublethal thermal stress. A computational model of retinal hyperthermia can guide further optimization of laser parameters for nondamaging phototherapy.
A Bio-Catalytic Approach to Aliphatic Ketones (2012)

Depleting oil reserves and growing environmental concerns have necessitated the development of sustainable processes to fuels and chemicals. Here we have developed a general metabolic platform in E. coli to biosynthesize carboxylic acids. By engineering selectivity of 2-ketoacid decarboxylases and screening for promiscuous aldehyde dehydrogenases, synthetic pathways were constructed to produce both C5 and C6 acids. In particular, the production of isovaleric acid reached 32 g/L (0.22 g/g glucose yield), which is 58% of the theoretical yield. Furthermore, we have developed solid base catalysts to efficiently ketonize the bio-derived carboxylic acids such as isovaleric acid and isocaproic acid into high volume industrial ketones: methyl isobutyl ketone (MIBK, yield 84%), diisobutyl ketone (DIBK, yield 66%) and methyl isoamyl ketone (MIAK, yield 81%). This hybrid "Bio-Catalytic conversion" approach provides a general strategy to manufacture aliphatic ketones, and represents an alternate route to expanding the repertoire of renewable chemicals.
Phenolic Profiling of Caffeic Acid O-Methyltransferase-Deficient Poplar Reveals Novel Benzodioxane Oligolignols (2004)

Caffeic acid O-methyltransferase (COMT) catalyzes preferentially the methylation of 5-hydroxyconiferaldehyde to sinapaldehyde in monolignol biosynthesis. Here, we have compared HPLC profiles of the methanol-soluble phenolics fraction of xylem tissue from COMT-deficient and control poplars (Populus spp.), using statistical analysis of the peak heights. COMT down-regulation results in significant concentration differences for 25 of the 91 analyzed peaks. Eight peaks were exclusively detected in COMT-deficient poplar, of which four could be purified for further identification using mass spectrometry/mass spectrometry, nuclear magnetic resonance, and spiking of synthesized reference compounds. These new compounds were derived from 5-hydroxyconiferyl alcohol or 5-hydroxyconiferaldehyde and were characterized by benzodioxane moieties, a structural type that is also increased in the lignins of COMT-deficient plants. One of these four benzodioxanes amounted to the most abundant oligolignol in the HPLC profile. Furthermore, all of the differentially accumulating oligolignols involving sinapyl units were either reduced in abundance or undetectable. The concentration levels of all identified oligolignols were in agreement with the relative supply of monolignols and with their chemical coupling propensities, which supports the random coupling hypothesis. Chiral HPLC analysis of the most abundant benzodioxane dimer revealed the presence of both enantiomers in equal amounts, indicating that they were formed by radical coupling reactions under simple chemical control rather than guided by dirigent proteins.
Cyclopropene polymerization and enyne metathesis catalyzed by high oxidation state molybdenum alkylidenes (2008)

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2008.
The Catalytic Intermediate Stabilized by a “Down” Active Site Loop for Diaminopimelate Decarboxylase from Helicobacter pylori (2008)

The meso-diaminopimelate decarboxylase (DAPDC, EC 4.1.1.20) catalyzes the final step of L-lysine biosynthesis in bacteria and is regarded as a target for the discovery of antibiotics. Here we report the 2.3A crystal structure of DAPDC from Helicobacter pylori (HpDAPDC). The structure, in which the product L-lysine forms a Schiff base with the cofactor pyridoxal 5'-phosphate, provides structural insight into the substrate specificity and catalytic mechanism of the enzyme, and implies that the carboxyl to be cleaved locates at the si face of the cofactor. To our knowledge, this might be the first reported external aldimine of DAPDC. Moreover, the active site loop of HpDAPDC is in a "down" conformation and shields the ligand from solvent. Mutations of Ile(148) from the loop greatly impaired the catalytic efficiency. Combining the structural analysis of the I148L mutant, we hypothesize that HpDAPDC adopts an induced-fit catalytic mechanism in which this loop cycles through "down" and "up" conformations to stabilize intermediates and release product, respectively. Our work is expected to provide clues for designing specific inhibitors of DAPDC.
Doxorubicin-containing regimen with or without interferon alfa-2b for advanced follicular lymphomas: final analysis of survival and toxicity in the Groupe d'Etude des Lymphomes Folliculaires 86 Trial. (1998)

With long-term follow-up of 6 years, these results confirm that the addition of IFNalpha to a doxorubicin-containing regimen for patients with advanced-stage and clinically aggressive FL not only increased PFS, as in most other similar trials, but also prolonged OS. Toxicity was moderate. The beneficial effects of this combined chemotherapy and IFNalpha regimen on OS probably reflect the selection of FL patients with poor prognostic factors.
A microchanneled ceramic membrane for highly efficient oxygen separation (2013)

A microchanneled ceramic membrane has been developed for oxygen separation. Numerous parallel microchannels traverse the ceramic membrane with one open end and another end terminating with a thin dense layer. Compared with conventional dense membranes, the new membrane substantially increases oxygen permeation flux by a factor of greater than 5.
[Inhibitory effects of nitric oxide and atrial natriuretic peptide on the increase in renal afferent nerve activity induced by intrarenal arterial injection of ET-1 in anesthetized rats]. (2001)

Intrarenal arterial injection of ET-1 can markedly induce the increase in RANA, an effect which is abolished by L-arg or ANP administered by the same route.
Variation in Total and Soluble β-Glucan Content in Hulless Barley:  Effects of Thermal, Physical, and Enzymic Treatments (2000)

Total and soluble beta-glucan content and effects of various treatments of barley grain on extractability and molecular characteristics of soluble beta-glucan were studied. Four types of hulless barley (normal, high amylose, waxy, and zero amylose waxy) from 29 registered and experimental genotypes were analyzed. For each, moisture, protein, amylose, 100 kernel weight, starch, beta-glucan (total and soluble), beta-glucanase activity, and slurry viscosity were determined. Significant differences in total beta-glucan were observed among the groups, with average values of 7. 49%, 6.86%, 6.30%, and 4.38% for high amylose, waxy, zero amylose waxy, and normal barley, respectively. The extractability of beta-glucan in high amylose barley was relatively low (20.6-29.7%) compared to that in normal (29.8-44.3%), zero amylose waxy (34.0-52. 5%), and waxy (36.7-52.7%) barley genotypes. Viscosity of barley flour slurries was affected by the content of soluble beta-glucans, beta-glucanase activity, and molecular weight of beta-glucans. Hydrothermal treatments (autoclaving and steaming) of barley had no effect on extractability of beta-glucans, but prevented enzymic hydrolysis of beta-glucans, and thereby substantially improved their molecular weight. The addition of enzymes (protease and esterase) during extraction and/or physical treatments (sonication) increased extractability of beta-glucans from barley.
Protein-responsive ribozyme switches in eukaryotic cells (2014)

Genetic devices that directly detect and respond to intracellular concentrations of proteins are important synthetic biology tools, supporting the design of biological systems that target, respond to or alter specific cellular states. Here, we develop ribozyme-based devices that respond to protein ligands in two eukaryotic hosts, yeast and mammalian cells, to regulate the expression of a gene of interest. Our devices allow for both gene-ON and gene-OFF response upon sensing the protein ligand. As part of our design process, we describe an in vitro characterization pipeline for prescreening device designs to identify promising candidates for in vivo testing. The in vivo gene-regulatory activities in the two types of eukaryotic cells correlate with in vitro cleavage activities determined at different physiologically relevant magnesium concentrations. Finally, localization studies with the ligand demonstrate that ribozyme switches respond to ligands present in the nucleus and/or cytoplasm, providing new insight into their mechanism of action. By extending the sensing capabilities of this important class of gene-regulatory device, our work supports the implementation of ribozyme-based devices in applications requiring the detection of protein biomarkers.
Treatment of spinal muscular atrophy by sodium butyrate (2001)

Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by degeneration of the anterior horn cells of the spinal cord, leading to muscular paralysis with muscular atrophy. No effective treatment of this disorder is presently available. Studies of the correlation between disease severity and the amount of survival motor neuron (SMN) protein have shown an inverse relationship. We report that sodium butyrate effectively increases the amount of exon 7-containing SMN protein in SMA lymphoid cell lines by changing the alternative splicing pattern of exon 7 in the SMN2 gene. In vivo, sodium butyrate treatment of SMA-like mice resulted in increased expression of SMN protein in motor neurons of the spinal cord and resulted in significant improvement of SMA clinical symptoms. Oral administration of sodium butyrate to intercrosses of heterozygous pregnant knockout-transgenic SMA-like mice decreased the birth rate of severe types of SMA-like mice, and SMA symptoms were ameliorated for all three types of SMA-like mice. These results suggest that sodium butyrate may be an effective drug for the treatment of human SMA patients.
Quantitation and characterization of glomerular procoagulant activity in experimental glomerulonephritis. (1987)

Glomerular procoagulant activity (PCA) was studied in four different models of experimental glomerulonephritis (GN) in rabbits. These models included 3 macrophage-dependent models: active autologous phase anti-glomerular basement membrane (GBM) antibody induced GN (active anti-GBMGN); passively induced autologous phase anti-GBMGN, and acute serum sickness; and a macrophage independent model of injury, heterologous phase anti-GBMGN was included also. PCA in glomerular lysates was significantly augmented in the three macrophage-dependent models, but not elevated significantly in heterologous anti-GBMGN when compared to glomerular lysates from normal rabbits. The greatest augmentation of PCA was found in glomeruli from rabbits with active anti-GBMGN which also contained the greatest numbers of macrophages. The functional characteristics of the glomerular PCA were similar in each of the models studied. Initiation of coagulation in vitro by these lysates was shown to be dependent on the presence of coagulation Factors VII and V, and largely independent of Factors XII and VIII, suggesting that glomerular PCA activates the extrinsic coagulation pathway. Inhibition studies using concanavalin A and phospholipase C demonstrated that glycoside residues and phospholipids are important chemical moieties for the coagulant activity of PCA. After sonication and ultracentrifugation PCA was found in the cell membrane fraction but not in the cell cytosol of glomerular lysates. These studies provide further evidence that glomerular PCA is markedly augmented in the presence of infiltrating glomerular macrophages and demonstrate that glomerular PCA has the functional characteristics of 'tissue factor', the procoagulant expressed by macrophages on their cell surface membrane. The quantitative association of glomerular PCA with glomerular macrophages, together with the shared functional characteristics of glomerular PCA and macrophage PCA, together suggests that the augmented glomerular PCA in experimental GN is due to tissue factor from infiltrating macrophages (macrophage PCA).
A bacterial platform for fermentative production of plant alkaloids (2011)

The secondary metabolites of higher plants include diverse chemicals, such as alkaloids, isoprenoids and phenolic compounds (phenylpropanoids and flavonoids). Although these compounds are widely used in human health and nutrition, at present they are mainly obtained by extraction from plants and extraction yields are low because most of these metabolites accumulate at low levels in plant cells. Recent advances in synthetic biology and metabolic engineering have enabled tailored production of plant secondary metabolites in microorganisms, but these methods often require the addition of expensive substrates. Here we develop an Escherichia coli fermentation system that yields plant alkaloids from simple carbon sources, using selected enzymes to construct a tailor-made biosynthetic pathway. In this system, engineered cells cultured in growth medium without additional substrates produce the plant benzylisoquinoline alkaloid, (S)-reticuline (yield, 46.0 mg l(-1) culture medium). The fermentation platform described here offers opportunities for low-cost production of many diverse alkaloids.
The Effect of Externally Applied Subatmospheric Pressure on Serum Myoglobin Levels after a Prolonged Crush/Ischemia Injury (2002)

This study shows that application of subatmospheric pressure to an affected body part is associated with lower serum myoglobin levels.
Troponin-tropomyosin interactions. Fluorescence studies of the binding of troponin, troponin T and chymotryptic troponin T fragments to specifically labeled tropomyosin (1984)

We have studied the interaction between troponin and tropomyosin by means of a fluorescent probe, N-(1- anilinonaphth -4-yl)maleimide (ANM), attached to the cysteine-190 residues of tropomyosin. The binding of troponin and troponin T to ANM-tropomyosin produces substantial increases in the label fluorescence. Analysis of the binding profiles indicates that both troponin and troponin T bind with a 1:1 stoichiometry. We have obtained and characterized several chymotryptic fragments of troponin T by digestion of isolated troponin T or whole troponin. An N-terminal fragment from troponin T which is slightly less than two-thirds of the whole molecule binds to tropomyosin without affecting the label fluorescence; a C-terminal fragment composed of the rest of the troponin T molecule causes a substantial enhancement of the label fluorescence. We have also isolated a complex containing the C-terminal troponin T fragment together with troponin I and troponin C from whole troponin, which also enhanced the label fluorescence. These observations indicate an elongated region of attachment between troponin T and tropomyosin.
Expression of the Interleukin-7 Receptor Alpha Chain (CD127) on Virus-Specific CD8 + T Cells Identifies Functionally and Phenotypically Defined Memory T Cells during Acute Resolving Hepatitis B Virus Infection (2006)

Virus-specific CD8+ T cells play a central role in the outcome of several viral infections, including hepatitis B virus (HBV) infection. A key feature of virus-specific CD8+ T cells is the development of memory. The mechanisms resulting in the establishment of T-cell memory are still only poorly understood. It has been suggested that T-cell memory may depend on the survival of virus-specific CD8+ T cells in the contraction phase. Indeed, a population of effector cells that express high levels of the interleukin-7 receptor alpha chain (CD127) as the precursors of memory CD8+ T cells has recently been identified in mice. However, very little information is currently available about the kinetics of CD127 expression in an acute resolving viral infection in humans and its association with disease pathogenesis, viral load, and functional and phenotypical T-cell characteristics. To address these important issues, we analyzed the HBV-specific CD8+ T-cell response longitudinally in a cohort of six patients with acute HBV infection who spontaneously cleared the virus. We observed the emergence of CD127 expression on antigen-specific CD8+ memory T cells during the course of infection. Importantly, the up-regulation of CD127 correlated phenotypically with a loss of CD38 and PD-1 expression and acquisition of CCR7 expression: functionally with an enhanced proliferative capacity and clinically with the decline in serum alanine aminotransferase levels and viral clearance. These results suggest that the expression of CD127 is a marker for the development of functionally and phenotypically defined antigen-specific CD8+ memory T cells in cleared human viral infections.
Preclinical assessment of potential interactions between botulinum toxin and neuromodulation for bladder micturition reflex (2015)

BoNT-A increased the bladder capacity, but compensating for additional saline infusion to the enlarged urinary bladder in BoNT-A pretreated rats, the bladder contractions induced by bladder filling were attenuated by SNS. BoNT-A did not alter the ability of SNS to inhibit bladder contraction following intradetrusor injection of BoNT-A for 2 days, 1-2 weeks or 1 month. These results support further pre-clinical and clinical studies to evaluate potential interactions or combination therapy with neuromodulation and intradetrusor BoNT-A therapeutic approaches.
Stem Cells: New Excitement, Persistent Questions (2000)

On pages 1775 and 1779, independent research teams describe experiments in which bone marrow cells became neuronlike cells in the brain, providing new evidence for the versatility of adult stem cells. But ample uncertainties must be resolved before such results can be translated into therapeutics. The most important next step, say several stem cell researchers, is to identify the molecular processes that underlie the impressive feats of stem cells, as many of the purported breakthroughs are simply observations.
Structural flexibility in the Burkholderia mallei genome (2004)

The complete genome sequence of Burkholderia mallei ATCC 23344 provides insight into this highly infectious bacterium's pathogenicity and evolutionary history. B. mallei, the etiologic agent of glanders, has come under renewed scientific investigation as a result of recent concerns about its past and potential future use as a biological weapon. Genome analysis identified a number of putative virulence factors whose function was supported by comparative genome hybridization and expression profiling of the bacterium in hamster liver in vivo. The genome contains numerous insertion sequence elements that have mediated extensive deletions and rearrangements of the genome relative to Burkholderia pseudomallei. The genome also contains a vast number (>12,000) of simple sequence repeats. Variation in simple sequence repeats in key genes can provide a mechanism for generating antigenic variation that may account for the mammalian host's inability to mount a durable adaptive immune response to a B. mallei infection.
Correction of the Intermetatarsal Angle Component of Hallux Valgus Using Fiberwire-Attached Endo-buttons (2012)

The 1st-2nd intermetatarsal angular component of the hallux valgus deformity can be corrected by an osteotomysparing
technique using ultra high molecular weight polyethylene (UHMWPE) braided suture (Fiberwire, Arthrex,
Naples, FL) attached endo-buttons to reduce and maintain the correction. This paper will outline the surgical approach,
advantages and post-operative care necessary to implement this technique.
Aberrant expression of the Th2 cytokine IL-21 in Hodgkin lymphoma cells regulates STAT3 signaling and attracts Treg cells via regulation of MIP-3α (2008)

The malignant Hodgkin/Reed-Sternberg (HRS) cells of classical Hodgkin lymphoma (HL) are derived from mature B cells, but have lost a considerable part of the B cell-specific gene expression pattern. Consequences of such a lineage infidelity for lymphoma pathogenesis are currently not defined. Here, we report that HRS cells aberrantly express the common cytokine-receptor gamma-chain (gamma(c)) cytokine IL-21, which is usually restricted to a subset of CD4(+) T cells, and the corresponding IL-21 receptor. We demonstrate that IL-21 activates STAT3 in HRS cells, up-regulates STAT3 target genes, and protects HRS cells from CD95 death receptor-induced apoptosis. Furthermore, IL-21 is involved in up-regulation of the CC chemokine macrophage-inflammatory protein-3alpha (MIP-3alpha) in HRS cells. MIP-3alpha in turn attracts CCR6(+)CD4(+)CD25(+)FoxP3(+)CD127(lo) regulatory T cells toward HRS cells, which might favor their immune escape. Together, these data support the concept that aberrant expression of B lineage-inappropriate genes plays an important role for the biology of HL tumor cells.
Recent advances in DNA microarrays. (2001)

The structure of the human genome is almost completely elucidated and the life sciences will now aim for a general and integrated study of gene expressions and the functional elucidation of proteins. In such a study, various new techniques have been developed, and DNA microarray technology is the most representative one. As for the DNA microarray techniques, several thousands to tens of thousands of gene segments are immobilized on a glass slide at high density, and cDNA probes prepared from specific cells or tissues are hybridized on the slides from which gene expression profiles are obtained at one sweep in a short time. The present development of this technique and its possible application to medicine-related fields are described.