gebhart/patrepeval huggingface dataset:
Pivotal Advance: HMGB1 expression in active lesions of human and experimental multiple sclerosis (2008)

Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the CNS, most frequently starting with a series of bouts, each followed by complete remission and then a secondary, progressive phase during which the neurological deficit increases steadily. The underlying molecular mechanisms responsible for disease progression are still unclear. Herein, we demonstrate that high mobility group box chromosomal protein 1 (HMGB1), a DNA-binding protein with proinflammatory properties, is evident in active lesions of MS and experimental autoimmune encephalomyelitis (EAE) and that HMGB1 levels correlate with active inflammation. Furthermore, the expression of the innate HMGB1 receptors--receptor for advanced glycation end products, TLR2, and TLR4--was also highly increased in MS and rodent EAE. Additionally, in vitro activation of rodent CNS-derived microglia and bone marrow-derived macrophages demonstrated that microglia were equally as capable as macrophages of translocating HMGB1 following LPS/IFN-gamma stimulation. Significant expression of HMGB1 and its receptors on accumulating activated macrophages and resident microglia may thus provide a positive feedback loop that amplifies the inflammatory response during MS and EAE pathogenesis.
Ultrasonic Dispersions of Single-Walled Carbon Nanotubes (2003)

The nature of single-walled carbon nanotube (SWNT)−solvent interaction that is responsible for the stabilization of ultrasonicated dispersions was investigated using various techniques. It was found that the sonochemical decomposition and polymerization of o-dichlorobenzene (ODCB) is necessary for the stabilization of SWNTs in ODCB. The rate of decomposition of ODCB was shown to be dependent on the shape of the sonication vessel. The decomposition products of sonicated ODCB interact irreversibly with SWNTs. Under similar sonication conditions, N,N-dimethylformamide (DMF) did not induce discernible modification of the near-infrared spectrum of the dispersed SWNTs.
Retroviruses (1988)

First brought to scientific attention as infectious cancer-causing agents nearly 80 years ago, retroviruses are popular in contemporary biology for many reasons. (i) The virus life cycle includes several events--in particular, reverse transcription of the viral RNA genome into DNA, orderly integration of viral DNA into host chromosomes, and utilization of host mechanisms for gene expression in response to viral signals--which are broadly informative about eukaryotic cells and viruses. (ii) Retroviral oncogenesis usually depends on transduction or insertional activation of cellular genes, and isolation of those genes has provided the scientific community with many of the molecular components now implicated in the control of normal growth and in human cancer. (iii) Retroviruses include many important veterinary pathogens and two recently discovered human pathogens, the causative agents of the acquired immunodeficiency syndrome (AIDS) and adult T cell leukemia/lymphoma. (iv) Retroviruses are genetic vectors in nature and can be modified to serve as genetic vectors for both experimental and therapeutic purposes. (v) Insertion of retroviral DNA into host chromosomes can be used to mark cell lineages and to make developmental mutants. Progress in these and other areas of retrovirus-related biology has been enormous during the past two decades, but many practical and theoretical problems remain to be solved.
A comparison of tall fescue and orchardgrass silages for lactating cows (1993)

The feeding value of tall fescue silage (Festuca arundinacea schreb.) harvested at the boot stage of maturity with a crude protein (CP) content of 15.4% was compared to that of orchardgrass silage (Dactylis glomerata) harvested at the same stage of maturity with a CP content of 12.5%. Two feeding trials with lactating cows were used in this comparison. The first trial employed 10 cows in a 2 × 2 Latin- square, with treatment period 35 d in length. In the second experiment five cows were used in a preference trial where individual feed intakes, duration of feeding, and rate of forage consumption were monitored electronically for a period of 9 d.In the first trial, the cows consumed more tall fescue than orchardgrass silage (P &lt; 0.05) (14.08 vs. 12.90 kg d −1 dry matter (DM)) but there were no differences between cows fed the two silages in milk yield (30.4 vs. 29.8 kg d −1 ) or milk compositon. Source of silage did not influence rumen fluid pH, molar percent of volatile fatty acids or plasma glucose; however, plasma urea-N levels were significantly higher (P &lt; 0.05) (17.00 vs. 15.14 mg dL −1 ) when cows were fed tall fescue silage compared with when they were fed orchardgrass silage. In the preference trial employing electronically monitored forage feeding gates, all five cows demonstrated a preference for the tall fescue silage consuming a daily average of 9.83 kg DM for tall fescue compared with 3.73 kg for orchardgrass silage. Cows spent more time (P &lt; 0.05) (68.3 vs. 14.1 min −1 ) and ate faster (69.6 vs. 54.0 g DM min −1 ) from the gates offering tall fescue silage compared with the gates offering orchardgrass silage. From the results of these two trials it was concluded that tall fescue silage was comparable to orchardgrass in supporting milk production and superior to orchardgrass in terms of palatability. Key words: Tall fescue, silage preference, lactating cows
Constitutive tyrosine phosphorylation of the T-cell receptor (TCR) zeta subunit: regulation of TCR-associated protein tyrosine kinase activity by TCR zeta. (1993)

The T-cell receptor (TCR) zeta subunit is an important component of the TCR complex, involved in signal transduction events following TCR engagement. In this study, we showed that the TCR zeta chain is constitutively tyrosine phosphorylated to similar extents in thymocytes and lymph node T cells. Approximately 35% of the tyrosine-phosphorylated TCR zeta (phospho zeta) precipitated from total cell lysates appeared to be surface associated. Furthermore, constitutive phosphorylation of TCR zeta in T cells occurred independently of antigen stimulation and did not require CD4 or CD8 coreceptor expression. In lymph node T cells that constitutively express tyrosine-phosphorylated TCR zeta, there was a direct correlation between surface TCR-associated protein tyrosine kinase (PTK) activity and expression of phospho zeta. TCR stimulation of these cells resulted in an increase in PTK activity that coprecipitated with the surface TCR complex and a corresponding increase in the levels of phospho zeta. TCR ligations also contributed to the detection of several additional phosphoproteins that coprecipitated with surface TCR complexes, including a 72-kDa tyrosine-phosphorylated protein. The presence of TCR-associated PTK activity also correlated with the binding of a 72-kDa protein, which became tyrosine phosphorylated in vitro kinase assays, to tyrosine phosphorylated TCR zeta. The cytoplasmic region of the TCR zeta chain was synthesized, tyrosine phosphorylated, and conjugated to Sepharose beads. Only tyrosine-phosphorylated, not nonphosphorylated, TCR zeta beads were capable of immunoprecipitating the 72-kDa protein from total cell lysates. This 72-kDa protein is likely the murine equivalent of human PTK ZAP-70, which has been shown to associate specifically with phospho zeta. These results suggest that TCR-associated PTK activity is regulated, at least in part, by the tyrosine phosphorylation status of TCR zeta.
Genetic definition of the Escherichia coli zwf "soxbox," the DNA binding site for SoxS-mediated induction of glucose 6-phosphate dehydrogenase in response to superoxide (1995)

In Escherichia coli K-12, transcription of zwf, the gene for glucose 6-phosphate dehydrogenase, is subject to growth rate-dependent regulation and is activated by SoxS in response to superoxide stress. To define genetically the site of SoxS activation, we undertook a detailed deletion analysis of the zwf promoter region. Using specifically targeted 5' and 3' deletions of zwf sequences, we localized the SoxS activation site to a 21-bp region upstream of the zwf promoter. This minimal "soxbox" was able to confer paraquat inducibility when placed upstream of a normally unresponsive gnd-lacZ protein fusion. In addition, we used these findings as the basis for resecting unnecessary sequences from the region upstream of the promoters of two other SoxS-regulated genes, sodA and nfo. Like the zwf soxbox, the regions required for SoxS activation of sodA and nfo appear to lie just upstream or overlap the -35 hexamers of the corresponding promoters. Importantly, the sequence boundaries established here by deletion analysis agree with the primary SoxS recognition sites of zwf, sodA, and nfo that we previously identified in vitro by gel mobility shift and DNase I protection assays with a purified MalE-SoxS fusion protein.
HDL Apolipoprotein-Related Peptides in the Treatment of Atherosclerosis and other Inflammatory Disorders (2010)

Elevations of HDL levels or modifying the inflammatory properties of HDL are being evaluated as possible treatment of atherosclerosis, the underlying mechanism responsible for most cardiovascular diseases. A promising approach is the use of small HDL apoprotein-related mimetic peptides. A number of peptides mimicking the repeating amphipathic α-helical structure in apoA-I, the major apoprotein in HDL, have been examined in vitro and in animal models. Several peptides have been shown to reduce early atherosclerotic lesions, but not more mature lesions unless coadministered with statins. These peptides also influence the vascular biology of the vessel wall and protect against other acute and chronic inflammatory diseases. The biologically active peptides are capable of reducing the pro-inflammatory properties of LDL and HDL, likely due to their high affinity for oxidized lipids. They are also capable of influencing other processes, including ABCA1 mediated activation of JAK-2 in macrophages, which may contribute to their anti-atherogenic function. The initial studies involved monomeric 18 amino acid peptides, but tandem peptides are being investigated for their anti-atherogenic and anti-inflammatory properties as they more closely resemble the repeating structure of apoA-I. Peptides based on other HDL associated proteins such as apoE, apoJ and SAA have also been studied. Their mechanism of action appears to be distinct from the apoA-I based mimetics.
Carbonic anhydrase IX, an endogenous hypoxia marker, expression in head and neck squamous cell carcinoma and its relationship to hypoxia, necrosis, and microvessel density. (2001)

Carbonic anhydrase IX (CA IX) is a transmembrane glycoprotein with an active extracellular enzyme site. We have shown previously that it was hypoxia inducible and may therefore be an endogenous marker of hypoxia. It is overexpressed in some tumors, particularly renal cell carcinoma. The aim of this study was to examine the expression and localization of CA IX in head and neck squamous cell carcinoma (HNSCC) and relate this to the location of tumor microvessels, angiogenesis, necrosis, and stage. Expression of CA IX was determined by immunoblotting in three HNSCC cell lines grown in normoxia and hypoxia (pO(2) 0.1%) and three paired tumor and normal tissue samples of HNSCC. Archived paraffin sections (79) of HNSCC were immunostained with antibodies to CA IX and CD34 to determine microvessel density (MVD). By double staining sections with CA IX and CD34, the distance between blood vessels and the start of CA IX expression and necrosis was calculated. CA IX was induced by hypoxia in all three HNSCC cell lines and overexpressed in HNSCC tumor tissue. Overexpression was localized to the perinecrotic area of the tumor on immunostaining, and the percentage area of the tumor expressing CA IX was significantly higher with more tumor necrosis (P = 0.001), a high MVD (P = 0.02), and advanced stage (P = 0.033) on univariate analysis and necrosis (P = 0.0003) and MVD (P = 0.0019) on multivariate analysis. The median distance between a blood vessel and the start of CA IX expression was 80 microm (range, 40-140 microm). CA IX is overexpressed in HNSCC because of hypoxia and is a potential biomarker for hypoxia in this tumor. Overexpression may help to maintain the intracellular pH, giving tumor cells a survival advantage and enhancing resistance to radiotherapy and chemotherapy. CA IX is a potential target for future therapy in HNSCC.
Congenital Cytomegalovirus Infection in an Urban Canadian Community (1980)

congenital cytomegalovirus (CMV) infection was diagnosed in 64 (0.42%) of 15,212 infants born in Hamilton, Ontario, Canada, during a period of 44 consecutive months. Urine specimens collected within 48 hr of birth were screened for CMV by inoculation into cell cultures. Only four infants had clinical or laboratory findings in the first week of life that suggested cytomegalic inclusion disease; CMV infection was mild or inapparent in the remainder. Fourteen CMV-positive infants (21.9%) had birth weights of less than or equal to 2,500 g, including eight of 11 premature infants (less than or equal to 37 weeks of gestation). Only five CMV-positive infants were small for gestational age. Overall, there were no significant differences between CMV-positive and CMV-negative infants in mean gestational age or mean measurements of weight and head circumference at birth. Mothers of CMV-positive infants were predominantly younger, primiparous women of lower educational and economic status, and the number who were unmarried was about threefold greater than among mothers of uninfected infants.
Investigation of the Actinobacillus actinomycetemcomitans genome by pulsed field gel electrophoresis (1997)

Pulsed field gel electrophoresis was used to investigate nineteen strains of Actinobacillus actinomycetemcomitans. The genome was found to contain a single chromosome whose size we estimate to be 2300 kb from the sum of restriction fragments generated with rare cutting endonucleases. We detected the presence of large plasmids with sizes ranging from 35 to 300 kb. In some strains, extrachromosomal elements constitute over 20% of the total genome. Comparison of the profiles of ApaI digests of the 19 strains showed a high degree of polymorphism with 13 different profiles, providing a new tool for epidemiological studies.
Chimeric picornavirus polyproteins demonstrate a common 3C proteinase substrate specificity (1989)

Cross-species proteolytic processing was demonstrated by the 3C proteinases of human rhinovirus 14 and coxsackievirus B3 on poliovirus-specific polypeptide precursors. Chimeric picornavirus cDNA genomes were constructed in a T7 transcription vector in which the poliovirus 3C coding region was substituted with the corresponding allele from human rhinovirus 14 or coxsackievirus B3. In vitro translation and processing of the polypeptides encoded by the chimeric genomes demonstrated that the proteolytic processing of poliovirus P2 region (nonstructural) proteins could be functionally substituted by the heterologous proteinases. In contrast, the 3C proteinase activities expressed from the chimeric genomes were incapable of recognizing the poliovirus-specific processing sites within the capsid precursor. Since the amino acid sequences flanking and inclusive of the P2 region cleavage sites of the three viruses are not stringently conserved, these results provide evidence for the existence of common conformational determinants necessary for 3C-mediated processing.
Editorial Vol.5(3) (2015)

DOI: http://dx.doi.org/10.3329/bioethics.v5i3.21537Bangladesh Journal of Bioethics 2014; vol 5 issue 3
A Novel PNA-Monomer for Recognition of Thymine in Triple-Helix Structures (2003)

To expand the triplex recognition repertoire of Nucleic Acids, novel nucleobases that recognize thymine in a T-A base pair are still required. A novel conformationally constrained PNA-monomer (II) capable of binding T in a triplex motif was designed and synthesized in 7 steps starting from commercially available dimethyl 2-oxoglutarate.
The Affinity of Elongation Factor Tu for an Aminoacyl-tRNA Is Modulated by the Esterified Amino Acid (2004)

When different mutations were introduced into the anticodon loop and at position 73 of YFA2, a derivative of yeast tRNA(Phe), a single tRNA body was misacylated with 13 different amino acids. The affinities of these misacylated tRNAs for Thermus thermophilus elongation factor Tu (EF-Tu).GTP were determined using a ribonuclease protection assay. A range of 2.5 kcal/mol in the binding energies was observed, clearly demonstrating that EF-Tu specifically recognizes the side chain of the esterified amino acid. Furthermore, this specificity can be altered by introducing a mutation in the amino acid binding pocket on the surface of EF-Tu. Also, when discussed in conjunction with the previously determined specificity of EF-Tu for the tRNA body, these experiments further demonstrate that EF-Tu uses thermodynamic compensation to bind cognate aminoacyl-tRNAs similarly.
Antihypertensive effects of chronic anti-TGF-β antibody therapy in Dahl S rats (2002)

This study examined the role of transforming growth factor-beta (TGF-beta) in the development of hypertension and renal disease in 9-wk-old male Dahl salt-sensitive (Dahl S) rats fed an 8% NaCl diet for 3 wk. The rats received an intraperitoneal injection of a control or an anti-TGF-beta antibody (anti-TGF-beta Ab) every other day for 2 wk. Mean arterial pressure was significantly lower in Dahl S rats treated with anti-TGF-beta Ab (177 +/- 3 mmHg, n = 12) than in control rats (190 +/- 4 mmHg, n = 17). Anti-TGF-beta Ab therapy also reduced proteinuria from 226 +/- 20 to 154 +/- 16 mg/day. Renal blood flow, cortical blood flow, and creatinine clearance were not significantly different in control and treated rats; however, medullary blood flow was threefold higher in the treated rats than in the controls. Despite the reduction in proteinuria, the degree of glomerulosclerosis and renal hypertrophy was similar in control and anti-TGF-beta Ab-treated rats. Renal levels of TGF-beta1 and -beta2, alpha-actin, type III collagen, and fibronectin mRNA decreased in rats treated with anti-TGF-beta Ab. To examine whether an earlier intervention with anti-TGF-beta Ab would confer additional renoprotection, these studies were repeated in a group of 6-wk-old Dahl S rats. Anti-TGF-beta Ab therapy significantly reduced blood pressure, proteinuria, and the degree of glomerulosclerosis and renal medullary fibrosis in this group of rats. The results indicate that anti-TGF-beta Ab therapy reduces blood pressure, proteinuria, and the renal injury associated with hypertension.
Functional interactions of HPK1 with adaptor proteins (2005)

Hematopoietic progenitor kinase 1 (HPK1 or MAP4K1) is a hematopoietic-specific mammalian STE20-like protein serine/threonine kinase, comprised of a STE20-like kinase domain in its N-terminus, four proline-rich motifs, a caspase cleavage site, and a distal C-terminal Citron homology domain. HPK1 is involved in many cellular signaling cascades that include MAPK signaling, antigen receptor signaling, apoptosis, growth factor signaling, and cytokine signaling. HPK1 binds many adaptor proteins including members of the Grb2 family, Nck family, Crk family, SLP-76 family, and actin-binding adaptors like HIP-55. HPK1 tyrosine phosphorylation and kinase activation depend on the presence of adaptor proteins. Adaptor proteins are required not only for linking HPK1 to cell surface receptors like the EGFR, but also for downstream gene transcription like NFAT, AP-1 and IL-2. The HPK1 association with Crk, CrkL, and HIP-55 mediate HPK1-dependent c-Jun N-terminal kinase (JNK) activation, while the association of HPK1 with SLP-76, Gads, CrkL, Grb2, and Grap affect T- and B-cell dependent gene transcription. Interestingly, HPK1 has been implicated in both increasing and decreasing NFAT, AP-1, and IL-2 gene transcription in T-cells where adaptor proteins play a key role. Lastly, HPK1 will phosphorylate Crk and CrkL, in vitro, which presents a novel possibility for the regulation of adaptor proteins and downstream signaling events.
Structural Basis for the Exceptional in vivo Efficacy of Bisphosphonate Drugs (2006)

To understand the structural basis for bisphosphonate therapy of bone diseases, we solved the crystal structures of human farnesyl pyrophosphate synthase (FPPS) in its unliganded state, in complex with the nitrogen-containing bisphosphonate (N-BP) drugs zoledronate, pamidronate, alendronate, and ibandronate, and in the ternary complex with zoledronate and the substrate isopentenyl pyrophosphate (IPP). By revealing three structural snapshots of the enzyme catalytic cycle, each associated with a distinct conformational state, and details about the interactions with N-BPs, these structures provide a novel understanding of the mechanism of FPPS catalysis and inhibition. In particular, the accumulating substrate, IPP, was found to bind to and stabilize the FPPS-N-BP complexes rather than to compete with and displace the N-BP inhibitor. Stabilization of the FPPS-N-BP complex through IPP binding is supported by differential scanning calorimetry analyses of a set of representative N-BPs. Among other factors such as high binding affinity for bone mineral, this particular mode of FPPS inhibition contributes to the exceptional in vivo efficacy of N-BP drugs. Moreover, our data form the basis for structure-guided design of optimized N-BPs with improved pharmacological properties.
Antiallergic substance from Asarum sagittarioides and synthesis of some analogues. (1987)

The MeOH extract of Asarum sagittarioides (Aristolochiaceae) showed antihistaminic activity. N-Isobutyl-3, 4-methylenedioxybenzamide (1) was isolated as the active principle, and this compound was proved to be an antiallergic substance by pharmacological studies. Furthermore, in order to investigate the structure-activity relationships, some analogues of 1 were synthesized, and compounds 4 and 5 were found to show more potent activity than 1.