gebhart/patrepeval huggingface dataset:
Adjacent Sequences Influence DNA Repair Accompanying Transposon Excision in Maize (1996)

Mobile elements transposing via DNA intermediates often leave small rearrangements, or "transposon footprints," at sites where they excise. Each excision event leaves its own footprint and, at any given site, these vary in size and sequence. Footprint formation involves DNA repair of sequences flanking the element. We have analyzed the footprints formed by a 2-kb Ds element excising from six different sites in exons of the maize waxy (Wx) gene. We find that groups of footprints left at individual sites are surprisingly nonrandom; different excision products predominate consistently at each site. Less frequent footprints left by each insertion appear related to the predominant type. The data suggest that flanking sequences affect the DNA repair processes associated with element excision. Two models have been proposed to explain footprint formation, one featuring a 5' exonuclease and the other featuring hairpin loop formation and an endonuclease. Our data have interesting implications for both these models. Evidence is also presented to support the presence of a separate excision mechanism that can remove Ac/Ds elements without leaving any footprint and that operates in parallel with the footprint-forming mechanism.
Peroxisome proliferator–activated receptor α mediates the adaptive response to fasting (1999)

Prolonged deprivation of food induces dramatic changes in mammalian metabolism, including the release of large amounts of fatty acids from the adipose tissue, followed by their oxidation in the liver. The nuclear receptor known as peroxisome proliferator-activated receptor alpha (PPARalpha) was found to play a role in regulating mitochondrial and peroxisomal fatty acid oxidation, suggesting that PPARalpha may be involved in the transcriptional response to fasting. To investigate this possibility, PPARalpha-null mice were subjected to a high fat diet or to fasting, and their responses were compared with those of wild-type mice. PPARalpha-null mice chronically fed a high fat diet showed a massive accumulation of lipid in their livers. A similar phenotype was noted in PPARalpha-null mice fasted for 24 hours, who also displayed severe hypoglycemia, hypoketonemia, hypothermia, and elevated plasma free fatty acid levels, indicating a dramatic inhibition of fatty acid uptake and oxidation. It is shown that to accommodate the increased requirement for hepatic fatty acid oxidation, PPARalpha mRNA is induced during fasting in wild-type mice. The data indicate that PPARalpha plays a pivotal role in the management of energy stores during fasting. By modulating gene expression, PPARalpha stimulates hepatic fatty acid oxidation to supply substrates that can be metabolized by other tissues.
Defective IL-10 production in severe phenotypes of Crohn’s disease (2009)

Loss of tolerance toward commensal bacteria has been invoked as a mechanism for Crohn's disease. IL-10 is a key anti-inflammatory cytokine that plays a role in induction and maintenance of tolerance. The aim of this study is to determine IL-10 production in response to bacterial components in Crohn's disease patients, who were classified according to their phenotypes as stricturing, penetrating, or inflammatory. Peripheral blood was obtained from Crohn's disease patients and healthy controls. Cytokine production was measured in whole blood cultures, isolated CD4(+) cells, and monocyte-derived dendritic cells (MDDCs). Under unstimulated conditions, IL-10, but not IL-12, was down-regulated significantly in blood cultures of patients with severe phenotypes, compared with inflammatory, nonpenetrating, nonstricturing Crohn's disease patients. In response to LPS, IL-10 was up-regulated more significantly in patients with no fistulae or fibrosis. Study of IL-10 production by isolated cell subsets showed that DCs, but not CD4(+) T cells, from penetrating Crohn's disease produced significantly less IL-10 in response to LPS. Differences were not associated with the 1082A/G polymorphism in the IL-10 gene promoter. We show a defect in IL-10 production in whole blood cell cultures and MDDCs in patients with severe forms of Crohn's disease. This defect in IL-10 production by a group of Crohn's disease patients may represent a mechanism mediating more severe manifestations of the disease. We propose that treatment with IL-10 or IL-10-inducing therapies could be of particular benefit to these group of patients.
Expression and Functions of P‐glycoprotein (mdr 1 gene product) in Normal and Malignant Tissues (1990)

This paper describes the cellular and tissue distribution of P-glycoprotein (P-GP) (mdr1 gene product), the role of P-GP in vivo and immunodiagnosis of multi-drug-resistant cancers. We mainly used MRK 16 monoclonal antibody (MAb) reactive with P-GP. P-GP was found to be expressed very strongly in the adrenal cortex of adults and strongly in the renal tubules of the kidney, capillary blood vessels of the brain, and also in placenta. Interestingly, P-GP was not distributed in fetal and neonatal adrenals, and thus may be closely related to adrenal maturation. A high level of P-GP expression was also seen in all cases of functional hormone-producing adrenal tumor, one case of insulinoma, two cases of untreated colonic cancer, one case each of untreated lung cancer, gastric cancer and breast cancer, six cases of renal cell carcinoma and 17 cases of bladder cancer. Using flow cytometry and immunocytochemistry, we investigated the reactivity of MRK 16 MAb with peripheral human mononuclear cells (mainly blastic cells and lymphocytes) from 31 patients with leukemia or malignant lymphoma. Reactivity with MRK 16 MAb was observed in five cases. Some cases reflected the prior administration of adriamycin, vincristine and VP-16, which are known to induce P-GP expression. P-GP-MRK 16-protein A-Sepharose complex derived from human adrenal possessed marked ATPase activity. These data suggest that P-GP may play a physiological role in the human adrenal. Finally, diagnostic criteria of multi-drug-resistant cancers are presented.
Behavior, Biochemistry, and Hibernation in Black, Grizzly, and Polar Bears (1983)

Ralph A. Nelson, G. Edgar Folk, Jr., Egbert W. Pfeiffer, John J. Craighead, Charles J. Jonkel, Dianne L. Steiger, Behavior, Biochemistry, and Hibernation in Black, Grizzly, and Polar Bears, Bears: Their Biology and Management, Vol. 5, A Selection of Papers from the Fifth International Conference on Bear Research and Management, Madison, Wisconsin, USA, February 1980 (1983), pp. 284-290
Stress Pathways in the Rat Cochlea and Potential for Protection from Acquired Deafness (2002)

Noise overstimulation will induce or influence intracellular molecular pathways in the cochlea. One of these is the 'classical' stress response pathway involving heat shock proteins. Hsp70 is induced in the cochlea by a wide variety of stresses including noise, hyperthermia and ototoxic drugs. When a stress that induces Hsp70 is applied to the cochlea, there is protection from a subsequent noise that would normally cause a permanent hearing loss. An upstream regulator of heat shock protein transcription, heat shock factor 1, is expressed in the cochlea and activated by stress. Mice lacking this heat shock factor have reduced recovery from noise-induced hearing loss. The same noise exposure that induces Hsp70 also increases the level of glial cell line-derived neurotrophic factor in the cochlea. Moreover, when this neurotrophic factor is applied into the perilymph of scala tympani prior to a noise exposure there is a significant reduction in hair cell loss and hearing loss. With the potential for activation of multiple pathways in the response to noise, gene microarrays can be useful to examine global gene expression. Initial studies examined differential gene expression immediately following a mild noise exposure (from which there is complete recovery) versus an intense noise (giving profound permanent deafness). Differential expression of several immediate early genes was found following the intense but not the mild noise exposure.
Prophylaxis of migraine headache (2010)

A 40-year-old woman presented with an eight-year history of migraine headaches. The headaches occurred once or twice per week, but usually responded well to a triptan taken soon after onset. Sometimes the headache returned the next day, necessitating a second dose. Occasionally the headaches did not
Small molecule and protein-based neurotrophic ligands: agonists and antagonists as therapeutic agents (1999)

AbstractThe neurotrophins are proteins of a growth factor family that affect the survival, growth and/or differentiation of neurones and several other populations derived from the neuroectoderm. Neurotrophins and their receptors are important targets for therapy of human disease, with potential applications ranging from treatment of chronic or acute neurodegeneration, to pain or cancer. Several neurotrophins have been used clinically. However, they are poor pharmacological agents because of drawbacks inherent to proteins when used as drugs. Consequently, several pharmacological agents and approaches have been patented to exploit these important targets. Amongst the pharmacological agents that do not act directly via neurotrophin receptors we include those that modulate or induce local expression of neurotrophins, immunophilins and other agents with neurotrophic-like activity. These are usually agonistic agents. Amongst compounds that bind to and act via neurotrophin receptors we include peptide analogues and peptidomimetics of neurotrophins of anti-neurotrophin receptor antibodies. These agents can be agonistic or antagonistic. Other approaches involve antagonists of the neurotrophins themselves, usually large receptor-derived peptides as decoy docking sites. Small molecule, non-peptide synthetic agonists and antagonists of either neurotrophins or neurotrophin receptors will be valuable therapeutic agents for diseases that have markets worth billions of US dollars. Consequently, it is not surprising that some patents have made similar claims both in compositions of matter and in indications.KeywordsAlzheimer's diseasedrugsligandnerve growth factorneurodegenerationneuroectodermneurotrophinimmunophilinspainParkinson's diseasepeptidomimeticsreceptorstroketherapytumour
Detection of gene amplification by genomic hybridization to cDNA microarrays. (2000)

Gene amplification is one of the major mechanisms of oncogene activation in tumorigenesis. To facilitate the identification of genes mapping to amplified regions, we have used a technique based on the hybridization of total genomic DNA to cDNA microarrays. To aid detection of the weak signals generated in this complex hybridization, we have used a tyramide-based technique that allows amplification of a fluorescent signal up to 1000-fold. Dilution experiment suggests that amplifications of 5-fold and higher can be detected by this approach. The technique was validated using cancer cell lines with several known gene amplifications, such as those affecting MYC, MYCN, ERBB2, and CDK4. In addition to the detection of the known amplifications, we identified a novel amplified gene, ZNF133, in the neuroblastoma cell line NGP. Hybridization of NGP cDNA on an identical array also revealed over expression of ZNF133. Parallel analysis of genomic DNA for copy number and cDNA for expression now provides rapid approach to the identification of amplified genes and chromosomal regions in tumor cells.
Underground tuning: quantitative regulation of root growth (2015)

Plants display a high degree of phenotypic plasticity that allows them to tune their form and function to changing environments. The plant root system has evolved mechanisms to anchor the plant and to efficiently explore soils to forage for soil resources. Key to this is an enormous capacity for plasticity of multiple traits that shape the distribution of roots in the soil. Such root system architecture-related traits are determined by root growth rates, root growth direction, and root branching. In this review, we describe how the root system is constituted, and which mechanisms, pathways, and genes mainly regulate plasticity of the root system in response to environmental variation.
Greater Number of Capillary Endothelial Cell Mitochondria in Brain Than in Muscle (1975)

The selective permeability of the brain mircrocirculatory bed (the blood-brain barrier-BBB) is widely believed to have its locus at the brain capillary endothelial cell. Whereas capillaries in other tissue are nonspecifically permeable to all small molecules by virtue of open clefts between endothelial cells, cellular fenestrae and pino-cytosis, these nonspecific routes of exchange are virtually absent in brain, and transcapil-lary exchange probably takes place through the membranous walls and the cytoplasm of endothelial cells. Although most organic molecular exchange is probably bidirectional and net flux is determined by concentration gradients, recent studies have suggested a unidirectional flux out of the brain for potassium, iodide and organic anions (1-3). Such uphill unidirectional transport would require a source of energy in the brain capillary endothelial cell.If the brain capillary wall performs an energy-dependent excretory function as a substantial part of its total metabolic work, it might be expected that brain capillary endothelial cells would contain more mitochondria than a tissue with nonspecifically permeable capillaries, such as skeletal muscle.Materials and Methods. To test this hypothesis, rat brain and skeletal muscle capillaries were examined by electron microscopy and counts made of the number of mitochondria encountered in random sections. A 175-g male Wistar rat on routine diet and in apparently good health, was sacrificed, routinely perfused with glutaral-dehyde, embedded, and sectioned for electron microscopy. Anesthesia was induced with 35% chloral hydrate and respiration supported with 95% O2 and 5% CO2. Two tenths milliliter heparin and 0.8 ml 1 % NaNO2 were injected intracardiac, and a cannula was placed in the ascending aorta. The right atrium was cut, and the rat perfused with 500 ml 1.25% glutaraldehyde and 1% paraformaldehyde in 0.135 M phosphate buffer at pH 7.2. The animal was cooled for 4 hr in a plastic bag at 4°. Six blocks were taken from cerebellar vermis and six blocks from the vastus medialis muscle; washed in dextrose buffer, secondarily fixed with 1 % buffered osmium tetroxide, dehydrated, and embedded in epon resin 812. Thick sections were used to select capillaries; thin sections were stained with both uranium and lead.
Fibulin-4 and -5, but not Fibulin-2, are Associated with Tropoelastin Deposition in Elastin-Producing Cell Culture (2010)

Elastic system fibers consist of microfibrils and tropoelastin. During development, microfibrils act as a template on which tropoelastin is deposited. Fibrillin-1 is the major component of microfibrils. It is not clear whether elastic fiber-associated molecules, such as fibulins, contribute to tropoelastin deposition. Among the fibulin family, fibulin-2, -4 and -5 are capable of binding to tropoelastin and fibrillin-1. In the present study, we used the RNA interference (RNAi) technique to establish individual gene-specific knockdown of fibulin-2, -4 and -5 in elastin-producing cells (human gingival fibroblasts; HGF). We then examined the extracellular deposition of tropoelastin using immunofluorescence. RNAi-mediated down-regulation of fibulin-4 and -5 was responsible for the diminution of tropoelastin deposition. Suppression of fibulin-5 appeared to inhibit the formation of fibrillin-1 microfibrils, while that of fibulin-4 did not. Similar results to those for HGF were obtained with human dermal fibroblasts. These results suggest that fibulin-4 and -5 may be associated in different ways with the extracellular deposition of tropoelastin during elastic fiber formation in elastin-producing cells in culture.
Glycated Hemoglobin and Risk of Stroke in People Without Known Diabetes in the European Prospective Investigation Into Cancer (EPIC)–Norfolk Prospective Population Study (2007)

In contrast to the continuous linear relationship observed between blood glucose level and coronary heart disease risk, the association between blood glucose level and stroke risk appears to be more consistent with a threshold relationship. These observations may give insights into the differing pathogenesis of different vascular diseases.
Angiotensin II as a pro-inflammatory mediator. (2002)

Angiotensin II (Ang II), the most important component of the renin-angiotensin system, is usually associated with hypertension and renal failure. Through its pro-inflammatory actions, it also plays an important role in each step of the development of atherosclerotic plaques and plaque rupture. Ang II stimulates the expression of nuclear factor-kappaB (NFkappaB), a transcription factor which regulates gene expression of inflammatory cytokines such as interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1). Ang II type 1 receptors (AT1) and angiotensin converting enzyme (ACE) are dramatically increased in atherosclerotic plaques, particularly in monocytes at the fibrous cap. Thus, in multiple ways, Ang II is a critical factor in atherosclerotic plaque formation, inflammation and plaque stability. ACE inhibitors and AT1R inhibitors could therefore be appropriate therapeutic agents in the treatment of atherosclerosis.
Fecal microbiota transplantation: current status and future directions (2011)

The etiology of ulcerative colitis (UC) is unknown. However, evidence suggests that host–microbial interactions play an important role in the pathogenesis of colitis, contributing to longstanding i...
Carotenoid Distribution in Certain Naturally Occurring Algae and in some Artificially Induced Mutants of Chlorella pyrenoidosa (1960)

SUMMARY: The carotenoids of pure cultures of two members of the Class Chrysophyceae were examined; the main pigments in Ochromonas danica and Prymnesium parvum are fucoxanthin and β-carotene. The main carotenoids of Cyanidium caldarium are β-carotene and zeaxanthin; these observations support the view that this alga represents a transitional form between the cryptomonads and the green algae. The distribution of polyenes and carotenoids in a number of ultra-violet induced mutants of Chlorella pyrenoidosa is described.
Microwave-Assisted Polyol Synthesis of CuInTe2 and CuInSe2 Nanoparticles (2003)

Nanoparticles of the CuInTe(2) (CIT) and CuInSe(2) (CIS) alloys have been prepared using the microwave-assisted polyol method. In this simple and quick reaction the polyol is both the solvent and the reducing agent. XRD studies show that nanoparticles of CIT and CIS are formed in the body-centered tetragonal structure and their average diameters are approximately 94 and approximately 83 nm, respectively. Electron microscopy studies show that these formed particles are poorly aggregated with a mean diameter of 100 and 85 nm, respectively. The products have been characterized by different analytical techniques, and the electronic properties have been measured using photoacoustic spectroscopy (PAS).
Host resistance directed selectively against H-2-deficient lymphoma variants. Analysis of the mechanism. (1985)

Three independent variants with a profound reduction of cell surface H-2 have been selected from the C57BL/6 mouse-derived RBL-5 and EL-4 T lymphomas. After subcutaneous inoculation of low cell doses in syngeneic mice, the H-2- variants failed to grow out, whereas the H-2+ control lines showed progressive growth. No difference in growth rate or cloning efficiency was detectable in tissue culture. The in vivo difference in tumor outgrowth was analyzed in detail for one of the H-2-low lines. The outgrowth difference remained after the H-2-low variant and the control line had been injected subcutaneously in opposite flanks of the same mouse, and it was not dependent upon activity of mature T cells, since the same result was seen in athymic nude mice. The difference was partially sensitive to irradiation of the hosts. When mice were pretreated with anti-asialo GM1 antiserum, known to depress natural killer (NK) cell activity, the difference in outgrowth was abolished, and both the control line and the H-2- variant showed progressive growth in vivo. Experiments comparing the distribution and survival of isotope-prelabeled variant and wild type cells indicated that a rapid elimination of the former took place within 24 h after intravenous injection. These differences in tumor elimination were not seen in mice treated with anti-asialo GM1 antiserum. We conclude that the reduced tumorigenicity of sublines with impaired H-2 expression is largely, if not exclusively due to rapid elimination by NK cells. These findings may reflect an inverse, indirect relation between factors controlling H-2 expression and NK sensitivity. Another possible explanation is that major histocompatibility complex (MHC)-encoded gene products are directly involved in a regulatory signal in the NK cell system. According to this interpretation, immunological selectivity in the NK cell system would be achieved by the failure to recognize self-MHC, irrespective of the presence of foreign antigens, i.e. by detection of no-self rather than of nonself. This may also explain previous observations on H-2-linked hybrid resistance against lymphoid grafts and changes in H-2 phenotypes associated with tumor progression.
The Effect of Angiotensin-Converting-Enzyme Inhibition on Diabetic Nephropathy (1993)

Captopril protects against deterioration in renal function in insulin-dependent diabetic nephropathy and is significantly more effective than blood-pressure control alone.
Accurate spatial and temporal transgene expression driven by a 3.8‐kilobase promoter of the bovine β‐casein gene in the lactating mouse mammary gland (1998)

The spatial, temporal, and hormonal pattern of expression of the β-casein gene is highly regulated and confined to the epithelial cells of the lactating mammary gland. Previous studies have shown that 1.7 kb of the bovine β-casein promoter were able to drive cell-specific and hormone-dependent expression to a mouse mammary cell line but failed to induce accurate expression to the mammary gland of transgenic mice. We investigated here the ability of 3.8 kb of the bovine β-casein gene promoter to drive the expression of the human growth hormone (hGH) gene in transgenic mice. A Northern blot analysis using total RNA obtained from different tissues of lactating and nonlactating females revealed the presence of hGH mRNA only in the mammary gland of lactating females. hGH mRNA was not detectable in the mammary gland of virgin females or males. A developmental analysis showed that hGH mRNA only peaked on parturition, resembling more closely the bovine β-casein temporal expression pattern rather than the murine. In situ hibridization studies performed on mammary gland sections showed that the cellular pattern of hGH expression was homogeneous in all lobules from heterozygous and homozygous transgenic mice. Silver grain counts on the tissue sections highly correlated with the hGH contents in the milk determined by radioimmunoassay (r = 0.996). Thus 3.8 kb of the bovine β-casein promoter direct a high-level expression of a reporter gene to the lactating mammary gland of transgenic mice in a tissue-specific and developmentally regulated manner. Mol. Reprod. Dev. 49:236–245, 1998. © 1998 Wiley-Liss, Inc.