gebhart/patrepeval huggingface dataset:
Cloning and Characterization of on 7q21.3 Encoding a Fourth Pyruvate Dehydrogenase Kinase Isoenzyme in Human (1996)

Different isoenzymes of pyruvate dehydrogenase kinase (PDK) inhibit the mitochondrial pyruvate dehydrogenase complex by phosphorylation of the E1alpha subunit, thus contributing to the regulation of glucose metabolism. By positional cloning in the 7q21.3-q22.1 region linked with insulin resistance and non-insulin-dependent diabetes mellitus in the Pima Indians, we identified a gene encoding an additional human PDK isoform, as evidenced by its amino acid sequence identity (>65%) with other mammalian PDKs, and confirmed by biochemical analyses of the recombinant protein. We performed detailed comparative analyses of the gene, termed PDK4, in insulin-resistant and insulin-sensitive Pima Indians, and detected five DNA variants with comparable frequencies in both subject groups. Using quantitative reverse transcription polymerase chain reaction, we found that the variants identified in the promoter and 5'-untranslated region did not correlate with differences in mRNA level in skeletal muscle and adipose tissue. We conclude that alterations in PDK4 are unlikely to be the molecular basis underlying the observed linkage at 7q21.3-q22.1 in the Pima Indians. Information about the genomic organization and promoter sequences of PDK4 will be useful in studies of other members of this family of mitochondrial protein kinases that are important for the regulation of glucose metabolism.
Construction of mammary gland-specific expression vectors for human clotting factor IX and its secretory expression in goat milk. (1997)

Two expression vectors comprised of mouse matrix attachment regions (MARs), bovine beta-casein gene sequence, human factor IX (hFIX) minigene, and cDNA, pMCIXm and pMCIX, were constructed for the purpose of a mammary gland bioreactor. A secretory expression system of hFIX protein in milk was made using stearylamine (SA) liposome to transfect plasmid DNA directly into the mammary gland lobule of a lactating goat. The highest production of hFIX in goat milk was 13.7 ng/ml 3 days after transfection, and the hFIX production in the goat mammary gland transfected with pMCIXm containing hFIX minigene was obviously higher than that transfected with pMCIX containing hFIX cDNA. Activity immuno-analysis and the barium citrate absorption method showed that > 90% hFIX protein in milk appeared to be a gamma-glycosylated and biological activity. This result confirmed the validity of the constructed vectors for further transgenic study, and this assay could also find its success in the evaluation of a foreign gene expression and secretion in the milk as a rapid detection system using liposome to transfect DNA directly into the goat mammary gland.
Landesregierungen als Akteure in der Technologieförderung (1993)

Auch aus staatlicher Sicht ist das strukturpolitische Instrumentarium der Innovations- und Technologieförderung mit einer Reihe gravierender, überdies regional sehr unterschiedlicher Probleme behaftet. Das zentrale Dilemma, vor das sich etwa Technologiepolitik in Berlin gestellt sieht, ist die überaus geringe Resonanz der Wirtschaft. Förderungsmaßnahmen, so die übereinstimmende Erfahrung von Administration und programmimplementierenden Agenturen, rufen lediglich bei einem relativ kleinen, sich auch im Zeitverlauf kaum erweiternden Kreis von Unternehmen Interesse hervor: »Wenn man ein neues Programm macht, dann sagt man, das wird in Anspruch genommen, von sich aus, in einer Größenordnung von 80 Unternehmen [...] und dann bleibt also die große Lücke« (El, S. 35). Neu aufgelegte Programme sprechen einen stabilen Adressatenkreis an, der bereits von früheren Projekten bekannt ist. Infolgedessen findet sich in den Kundenkarteien von Transferstellen und Vermittlungsagenturen ein weitgehend deckungsgleicher Ausschnitt der mittelständischen Wirtschaft: »Die Frage ist, findet eine Neuaufschließung von Unternehmen, die quasi nicht in der Datei sind, statt? Was können wir über diese 350 innovativen Berliner Unternehmendie wir alle kennen — wir sagen, wir haben insgesamt 2 300, dazwischen klafft eine große Zahl — was können wir denn da noch tun für diese Gruppe?« (RTB, S. 20) Rund 15 Prozent des Verarbeitenden Gewerbes in Berlin zeigen sich gegenüber den Förderungsangeboten des Landes aufgeschlossen, weshalb »jeder«, d.h. alle mit Technologiepolitik professionell befaßten Akteure, die betreffenden Unternehmen kennt. Versuche, diesen kleinen, geradezu vertrauten Kreis durch aktives Zugehen auf die Wirtschaft zu vergrößern, waren bisher nicht von durchschlagendem Erfolg gekrönt. Der Wunsch, mit Hilfe staatlicher Mittel »etwas für die Unternehmen zu bewegen« (El), bei der Einführung neuer Produktionsverfahren oder der Produktentwicklung zu helfen, wird meist mit Zurückhaltung oder sogar mit Ablehnung beantwortet: »Aber das Problem ist, daß die Firmen ja nicht mal ernsthaft beraten werden wollen. Der VDI muß die Firmen ja immer noch davon überzeugen« (E2, S. 3).
Antibody to marinobufagenin lowers blood pressure in pregnant rats on a high NaCl intake (2005)

These observations provide evidence that MBG contributes to BP elevation in pregnant rats rendered hypertensive by NaCl supplementation.
High-density, high-temperature alkali vapor cell (2008)

We present a vapor cell design that enables resonant optical spectroscopy in high-density, high-temperature alkali metal vapors. Optical access is provided via reflection from the interface between the vapor and a sapphire window. The cell resists corrosion from the highly reactive alkali vapors, in our case, potassium, up to 800 degrees C (number densities up to 10(19) cm(-3)). The cells maintain their integrity for an average of 100 h above 500 degrees C with about 10 heating/cooling cycles.
Molecular cloning of the neu gene: absence of gross structural alteration in oncogenic alleles. (1986)

The neu gene is distantly related to the erbB gene and encodes a cell surface protein that appears to function as a growth factor receptor. To study the mechanisms that caused the conversion of the normal neu gene to an oncogenic allele, we have isolated molecular clones of the neu oncogene as well as a clone of the corresponding protooncogene. The transforming neu oncogene and the proto-neu gene clones exhibit identical restriction enzyme patterns. Amplification of the proto-neu gene in NIH 3T3 cells by means of cotransfection with a dihydrofolate reductase gene resulted in methotrexate-resistant colonies that produce high levels of normal neu-encoded p185 protein. In contrast to cells carrying low levels of the oncogene-encoded protein, these cells appeared normal. The results suggest that the lesion that led to activation of the neu gene is a minor change in DNA sequence and is apparently located in the protein-encoding region of the gene.
Endonuclease Regnase‐1/Monocyte chemotactic protein‐1‐induced protein‐1 (MCPIP1) in controlling immune responses and beyond (2017)

The activation of inflammatory cells is controlled at transcriptional and posttranscriptional levels. Posttranscriptional regulation modifies mRNA stability and translation, allowing for elaborate control of proteins required for inflammation, such as proinflammatory cytokines, prostaglandin synthases, cell surface co-stimulatory molecules, and even transcriptional modifiers. Such regulation is important for coordinating the initiation and resolution of inflammation, and is mediated by a set of RNA-binding proteins (RBPs), including Regnase-1, Roquin, Tristetraprolin (TTP), and AU-rich elements/poly(U)-binding/degradation factor 1 (AUF1). Among these, Regnase-1, also known as Zc3h12a and Monocyte chemotactic protein-1-induced protein-1 (MCPIP1), acts as an endoribonuclease responsible for the degradation of mRNAs involved in inflammatory responses. Conversely, the RBPs Roquin and TTP trigger exonucleolytic degradation of mRNAs by recruiting the CCR4-NOT deadenylase complex. Regnase-1 specifically recognizes stem-loop structures present in 3'-untranslated regions of cytokine mRNAs, and directly degrades the mRNAs in a translation- and ATP-dependent RNA helicase upframeshift 1 (UPF1)-dependent manner that is reminiscent of nonsense-mediated decay. Regnase-1 regulates the activation of innate and acquired immune cells, and is critical for maintaining immune homeostasis as well as preventing over-activation of the immune system under inflammatory conditions. Furthermore, recent studies have revealed that Regnase-1 and its family members are involved not only in immunity but also in various biological processes. In this article, I review molecular mechanisms of Regnase-1-mediated mRNA decay and its physiological roles. WIREs RNA 2018, 9:e1449. doi: 10.1002/wrna.1449 This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications RNA Turnover and Surveillance > Regulation of RNA Stability RNA in Disease and Development > RNA in Disease.
Protein-Reactive, Thermoresponsive Copolymers with High Flexibility and Biodegradability (2008)

A family of injectable, biodegradable, and thermosensitive copolymers based on N-isopropylacrylamide, acrylic acid, N-acryloxysuccinimide, and a macromer polylactide-hydroxyethyl methacrylate were synthesized by free radical polymerization. Copolymers were injectable at or below room temperature and formed robust hydrogels at 37 degrees C. The effects of monomer ratio, polylactide length, and AAc content on the chemical and physical properties of the hydrogel were investigated. Copolymers exhibited lower critical solution temperatures (LCSTs) from 18 to 26 degrees C. After complete hydrolysis, hydrogels were soluble in phosphate buffered saline at 37 degrees C with LCSTs above 40.8 degrees C. Incorporation of type I collagen at varying mass fractions by covalent reaction with the copolymer backbone slightly increased LCSTs. Water content was 32-80% without collagen and increased to 230% with collagen at 37 degrees C. Hydrogels were highly flexible and relatively strong at 37 degrees C, with tensile strengths from 0.3 to 1.1 MPa and elongations at break from 344 to 1841% depending on NIPAAm/HEMAPLA ratio, AAc content, and polylactide length. Increasing the collagen content decreased both elongation at break and tensile strength. Hydrogel weight loss at 37 degrees C was 85-96% over 21 days and varied with polylactide content. Hydrogel weight loss at 37 degrees C was 85-96% over 21 days and varied with polylactide content. Degradation products were shown to be noncytotoxic. Cell adhesion on the hydrogels was 30% of that for tissue culture polystyrene but increased to statistically approximate this control surface after collagen incorporation. These newly described thermoresponsive copolymers demonstrated attractive properties to serve as cell or pharmaceutical delivery vehicles for a variety of tissue engineering applications.
Collagen matrix promotes reorganization of pancreatic endocrine cell monolayers into islet-like organoids. (1983)

To evaluate the capacity of pancreatic endocrine cells to reassociate in vitro according to the characteristic topographical pattern observed in the islets of Langerhans in situ, we cultured cells dissociated from neonatal rat pancreas within a three-dimensional collagen matrix. Cell monolayers grown on the surface of collagen gels were covered with a second layer of collagen. This induced the monolayers of endocrine cells to reorganize into smooth-contoured, three-dimensional aggregates, in which non-B cells (identified by electron microscopy and immunofluorescence) had a preferential distribution at the periphery, whereas B cells were concentrated in a central position. These results show that cultured pancreatic endocrine cells have the capacity to reassociate into islet-like organoids in vitro, and that collagen matrices may have a permissive effect on the expression of this potential.
Eosinophilic Esophagitis in Children and Adults (2003)

Children with eosinophilic esophagitis, an isolated, severe esophageal eosinophilia, present with symptoms similar to gastroesophageal reflux but do not experience response to aggressive antireflux therapy. Increasingly, eosinophilic esophagitis is considered to be a separate entity from reflux disease. Current theory suggests that the former may be caused by cell-mediated food hypersensitivity or may be a subset of eosinophilic gastroenteritis. Reports support the efficacy of dietary restriction or corticosteroid therapy. Additional research is needed to determine etiology, allow earlier clinical recognition, and improve treatment.
Inhibition of hedgehog signaling ameliorates hepatic inflammation in mice with nonalcoholic fatty liver disease (2015)

Hepatocyte Hh signaling can promote liver inflammation through osteopontin-mediated macrophage activation; this mechanism importantly contributes to the progression of NAFLD.
Synaptic Modification by Correlated Activity: Hebb's Postulate Revisited (2001)

Correlated spiking of pre- and postsynaptic neurons can result in strengthening or weakening of synapses, depending on the temporal order of spiking. Recent findings indicate that there are narrow and cell type-specific temporal windows for such synaptic modification and that the generally accepted input- (or synapse-) specific rule for modification appears not to be strictly adhered to. Spike timing-dependent modifications, together with selective spread of synaptic changes, provide a set of cellular mechanisms that are likely to be important for the development and functioning of neural networks. When an axon of cell A is near enough to excite cell B or repeatedly or consistently takes part in firing it, some growth or metabolic change takes place in one or both cells such that A's efficiency, as one of the cells firing B, is increased.
Snf1--a Histone Kinase That Works in Concert with the Histone Acetyltransferase Gcn5 to Regulate Transcription (2001)

Modification of histones is an important element in the regulation of gene expression. Previous work suggested a link between acetylation and phosphorylation, but questioned its mechanistic basis. We have purified a histone H3 serine-10 kinase complex from Saccharomyces cerevisiae and have identified its catalytic subunit as Snf1. The Snf1/AMPK family of kinases function in conserved signal transduction pathways. Our results show that Snf1 and the acetyltransferase Gcn5 function in an obligate sequence to enhance INO1 transcription by modifying histone H3 serine-10 and lysine-14. Thus, phosphorylation and acetylation are targeted to the same histone by promoter-specific regulation by a kinase/acetyltransferase pair, supporting models of gene regulation wherein transcription is controlled by coordinated patterns of histone modification.
Engineering the Substrate Specificity of the Abl Tyrosine Kinase (1999)

c-Abl is a non-receptor tyrosine kinase that is involved in a variety of signaling pathways. Activated forms of c-Abl are associated with some forms of human leukemia. Presently, no high resolution structure of the tyrosine kinase domain of Abl is available. We have developed a structural homology model of the catalytic domain of Abl based on the crystal structure of the insulin receptor tyrosine kinase. Using this model as a guide, we selected residues near the active site predicted to play a role in peptide/protein substrate recognition. We expressed and purified 15 mutant forms of Abl with single amino acid substitutions at these positions and tested their peptide substrate specificity. We report here the identification of seven residues involved in recognition of the P-1, P+1, and P+3 positions of bound peptide substrate. Mutations in these residues cause distinct changes in substrate specificity. The results suggest features of Abl substrate recognition that may be relevant to related tyrosine kinases.
CGA-362622 Antagonizes Annual Grass Control with Clethodim1 (2002)

Field and greenhouse experiments were conducted to evaluate clethodim, CGA-362622, mixtures thereof, and sequential treatments for control of broadleaf signalgrass, fall panicum, goosegrass, and large crabgrass. In greenhouse experiments, clethodim alone provided 93 and 100% control of three- to four-leaf goosegrass at the low (105 g ai/ha) and high (140 g/ha) rates, respectively, whereas CGA-362622 did not control grasses in greenhouse or field experiments. Control of six- to eight-leaf goosegrass in the greenhouse with clethodim was 75% for the low rate and 89% for the high rate. Control of goosegrass in greenhouse studies was reduced at least 43 percentage points with CGA-362622 and clethodim at the high rate in mixture compared with control provided by clethodim at the high rate alone. When CGA-362622 and clethodim were applied in mixture in field studies, the effectiveness of the graminicide was decreased from > 97 to < 57% control for all annual grasses. Antagonism of clethodim activity was greater than that of the tank mixture when clethodim was applied 1 d after CGA-362622 on large crabgrass, goosegrass, and fall panicum. Clethodim applied 7 d before or after CGA-362622 controlled the four grass species as well as did clethodim applied alone. When CGA-362622 was applied to goosegrass alone, fresh weight accumulation stopped for a period of 4 d compared with untreated plants. Normal growth resumed after 4 d.Nomenclature: CGA-362622, N-[(4,6-dimethoxy-2-pyrimidinyl)carbamoyl]-3-(2,2,2-trifluoroethoxy)-pyridin-2-sulfonamide sodium salt; clethodim; broadleaf signalgrass, Brachiaria platyphylla (Griseb.) Nash #3 BRAPP; fall panicum, Panicum dichotomiflorum (L.) # PANDI; goosegrass, Eleusine indica (L.) Gaertn. # ELEIN; large crabgrass, Digitaria sanguinalis (L.) Scop. # DIGSA.Additional index words: Antagonism, growth analysis, orthogonal contrasts.Abbreviations: ALS, acetolactase synthase (EC 4.1.3.18); DAT, days after treatment; POST, postemergence.
Alteration of Adenosine Receptors in Patients with Chronic Obstructive Pulmonary Disease (2005)

This is the first report showing the presence of adenosine receptors in lung parenchyma in subjects with COPD compared with control smokers. These novel findings strengthen the hypothesis of a potential role played by adenosine receptors in the pathogenesis of COPD.
Gene silencing in chick embryos with a vector‐based small interfering RNA system (2003)

In this paper, the use of vector-based RNA interference (RNAi) to specifically interfere with gene expression in chick embryos is reported. In ovo electroporation was carried out to transfer a small interfering RNA (siRNA) expression vector into chick embryos. En2 was chosen for the target gene because the family gene, En1, is expressed in a similar pattern. Four sets of 19-mer sequences were designed with the En2 open reading frame region connected to a sequence of short hairpin RNA (shRNA), which exerts siRNA effects after being transcribed, and inserted into pSilencer U6-1.0 vector. En2 and En1 expression were suppressed by the siRNA whose sequence completely matched En2 and En1. Suppression occurred when the siRNA sequence differed by up to two nucleotides from the target sequence. The sequence that differed by four nucleotides from the target gene did not show siRNA effects. One set that completely matched the En2 target did not show siRNA effects, which may be due to location of the siRNA in the target gene. Thus, multiple sets of shRNA must be prepared if we are to consider. This system will greatly contribute to the analysis of function of genes of interest, because the target gene can be silenced in a locally and temporally desired manner.
Encasing Mattresses in Black Plastic Will Not Provide Thermal Control of Bed Bugs, Cimex spp. (Hemiptera: Cimicidae) (2006)

The suggestion that bed bug (Cimex spp.; Hemiptera: Cimicidae)-infested mattresses wrapped in black plastic and exposed to sunlight will be heated sufficiently to kill the bed bugs was tested. Two types of mattresses were tested: a thin mattress of solid foam rubber and a thick multilayered inner spring mattress. Temperature probes were placed on both upper and lower sides of the mattresses, which were wrapped in black plastic and placed outside on a summer day for >9 h wherein the ambient temperature peaked at 36.5°C. The maximum recorded temperature on the upper (sun-exposed) sides was 85°C for both mattresses, whereas lower side temperatures for the thick mattress never exceeded 35°C, and some areas of the thin mattress failed to exceed 36.5°C. Therefore, with published thermal death points of 40–45°C depending on exposure time, and opportunities for bed bugs to avoid lethal temperatures by retreating from hot zones, this technique seems to be not suitable for bed bug management.
Pivotal role of ABCA1 in reverse cholesterol transport influencing HDL levels and susceptibility to atherosclerosis (2001)

The identification of mutations in ABCA1 in patients with Tangier disease and familial HDL deficiency demonstrated that inadequate transport of phospholipid and cholesterol to the extracellular space results in the hypercatabolism of lipid-poor nascent HDL particles. However, the relationship between changes in ABCA1 activity and HDL levels is not clear. To address this question directly in vivo, we have used bacterial artificial chromosome transgenic approaches, which allow for appropriate developmental and cellular localization of human ABCA1 in mouse tissues. Increased expression of ABCA1 is directly associated with an increase in HDL levels, and the relationship between the increase in efflux and HDL is completely linear (r2 = 0.87). Preliminary data have suggested that coronary artery disease (CAD) is increased in heterozygotes for ABCA1 deficiency. These results may have been biased by clinical sampling, and CAD end points are insensitive markers. We have now used surrogate end points of intima-media complex thickness (IMT) and have shown that mean IMT in ABCA1 heterozygotes is indeed increased. A strong correlation between adjusted IMT and HDL cholesterol values and apolipoprotein A-I-driven efflux has been established. These studies suggest that compromised ABCA1 activity leads to accelerated and early atherogenesis and provides a link between the cholesterol deposition in macrophages within the arterial wall and cholesterol efflux in humans.
Twenty-five years of shared life with vancomycin-resistant enterococci: is it time to divorce? (2012)

Twenty-five years ago, isolation of vancomycin-resistant Enterococcus faecium (VREm) was reported both in the UK and in France. Since then, VREm has spread worldwide in hospitals. Hospital outbreaks appeared to be related to the evolution since the end of 1980s of a subpopulation of E. faecium highly resistant to ampicillin and fluoroquinolones (the so-called clonal complex CC17) that later acquired resistance to vancomycin. CC17 isolates are presumably better adapted than other E. faecium isolates to the constraints of the hospital environment and most contain mobile genetic elements, phage genes, genes encoding membrane proteins, regulatory genes, a putative pathogenicity island and megaplasmids. Colonization and persistence are major features of VREm. Inherent characteristics of E. faecium including a remarkable genome plasticity, in part due to acquisition of IS elements, in particular IS16, have facilitated niche adaptation of this distinct E. faecium subpopulation that is multiply resistant to antibiotics. Quinupristin/dalfopristin and linezolid are licensed for the treatment of VREm infections, with linezolid often used as a first-line treatment. However, the emergence of plasmid-mediated resistance to linezolid by production of a Cfr methyltransferase in Enterococcus faecalis is worrying. Daptomycin has not been extensively evaluated for the treatment of VREm infections and resistant mutants have been selected under daptomycin therapy. Although control of VRE is challenging, a laissez-faire policy would result in an increased number of infections and would create an irreversible situation. Although so far unsuccessful, dissemination of glycopeptide-resistant Staphylococcus aureus with van genes acquired from resistant enterococci cannot be ruled out.