gebhart/patrepeval huggingface dataset:
φC31 Integrase Confers Genomic Integration and Long-Term Transgene Expression in Rat Retina (2005)

Subretinal injection of DNA followed by electroporation affords abundant transfer of plasmid DNA in rat RPE. phiC31 integrase confers robust long-term transgene expression by mediating genomic integration of the transgene. These findings suggest that phiC31 integrase may be a simple and effective tool for nonviral long-term gene transfer in the eye.
Amylocyclicin, a Novel Circular Bacteriocin Produced by Bacillus amyloliquefaciens FZB42 (2014)

Bacillus amyloliquefaciens FZB42 is a Gram-positive plant growth-promoting bacterium with an impressive capacity to synthesize nonribosomal secondary metabolites with antimicrobial activity. Here we report on a novel circular bacteriocin which is ribosomally synthesized by FZB42. The compound displayed high antibacterial activity against closely related Gram-positive bacteria. Transposon mutagenesis and subsequent site-specific mutagenesis combined with matrix-assisted laser desorption ionization-time of flight mass spectroscopy revealed that a cluster of six genes covering 4,490 bp was responsible for the production, modification, and export of and immunity to an antibacterial compound, here designated amylocyclicin, with a molecular mass of 6,381 Da. Peptide sequencing of the fragments obtained after tryptic digestion of the purified peptide revealed posttranslational cleavage of an N-terminal extension and head-to-tail circularization of the novel bacteriocin. Homology to other putative circular bacteriocins in related bacteria let us assume that this type of peptide is widespread among the Bacillus/Paenibacillus taxon.
Evaluation and Management of the Patient with Pulmonary Arterial Hypertension (2005)

Increased pressure in the pulmonary circulation, or pulmonary hypertension, is a common disorder that may complicate various cardiopulmonary conditions, including severe obstructive airways disease and left ventricular dysfunction. An increase in pulmonary arterial pressure that is not due to coexistent cardiopulmonary disease, known as pulmonary arterial hypertension, may occur in the absence of a demonstrable cause (idiopathic or familial); as a complication of systemic conditions, such as connective tissue disease, HIV infection, or chronic liver disease; or as a result of the use of fenfluramine anorexigens, amphetamines, or cocaine. The development of disease-specific therapies for pulmonary arterial hypertension over the past decade underscores the importance of diagnosing pulmonary hypertension early in the course of the condition and implementing a treatment strategy that is based on the condition's cause and severity. In this review, the authors present approaches to the diagnosis and management of pulmonary arterial hypertension, using a hypothetical case to highlight the key management points.
Antidepressant Administration Modulates Neural Stem Cell Survival and Serotoninergic Differentiation Through Bcl-2 (2007)

The hippocampus has long been associated with learning, memory, and modulation of emotional responses. Previous studies demonstrated that stress-induced loss of hippocampal neurons may contribute to the pathogenesis of depression. The recent observations supported that antidepressant drugs increase the production of serotoninergic neurotransmitter and they play a critical role in the initiation of neurogenesis in the hippocampus. In order to explore the possible new mechanism of the treatment of depression, we cultured neural stem cells (NSCs) derived from the hippocampus of adult rats as an in vitro model to evaluate the capabilities of neuroprotection and neural differentiation in NSCs by fluoxetine (FL) treatment. Our results showed that 20 microM FL treatment can significantly increase the proliferation rate of NSCs (p<0.05), and up-regulate the mRNA and protein expressions of Bcl-2 in Day-7 FL-treated NSCs (p<0.01). Using Bcl-2 gene silencing with small interfering RNA, our data verified that FL can prevent Fas ligand-induced caspase-dependent apoptosis in NSCs through the activation of Bcl-2. The in vitro observation and immunofluorescent study further demonstrated that FL treatment can stimulate the neurite development and serotoninergic differentiation of NSCs through the activation of Bcl-2. Using microdialysis with high performance liquid chromatography- electrochemical detection, the functional release of serotonin in the differentiating NSCs with FL treatment was increased and simultaneously regulated by the Bcl-2 expressions. In sum, the study results indicate that antidepressant administration can increase NSCs survival, promote the neurite development, and facilitate NSCs differentiating into the functional serotoninergic neurons via the modulation of Bcl-2 expression.
Time‐dependent loss of mitochondrial function precedes progressive histologic cartilage degeneration in a rabbit meniscal destabilization model (2016)

The goals of this work were to characterize progression of osteoarthritic cartilage degeneration in a rabbit medial meniscus destabilization (MMD) model and then to use the model to identify pre-histologic disruptions in chondrocyte metabolism under chronically elevated joint contact stresses in vivo. To characterize PTOA progression, 24 rabbits received either MMD or sham surgery. Limb loading was analyzed preoperatively and at regular postoperative intervals using a Tekscan pressure-sensitive walkway. Animals were euthanized 8 (n = 8 MMD; n = 8 sham) or 26 weeks (n = 8 MMD) postoperatively for histological cartilage evaluation by an objective, semi-automated Mankin scoring routine. To examine pre-histologic pathology, MMD was performed on an additional 20 rabbits, euthanized 1 (n = 9) or 4 weeks (n = 10) postoperatively. Chondrocytes were harvested fresh for measurement of mitochondrial function, an intracellular indicator of pathology after mechanical injury. Both MMD and sham surgery caused slight decreases in limb loading which returned to preoperative levels after 2 weeks. Histologically apparent cartilage damage progressed from 8 to 26 weeks after MMD. Changes in chondrocyte respiration were variable at 1 week, but by 4 weeks postoperatively chondrocyte mitochondrial function was significantly reduced. Many human injuries that lead to PTOA are relatively mild, and the cell-level mechanisms leading to disease remain unclear. We have documented PTOA progression in an animal model of subtle joint injury under continued use, and demonstrated that this model provides a realistic environment for investigation of multi-stage cellular pathology that develops prior to overt tissue degeneration and which could be targeted for disease modifying treatments. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:590-599, 2017.
Electrophysiological Study of a Novel Large Pore Formed by Bax and the Voltage-dependent Anion Channel That Is Permeable to Cytochrome c (2000)

The Bcl-2 family of proteins, consisting of anti-apoptotic and pro-apoptotic members, regulates cell death by controlling mitochondrial membrane permeability that is crucial for apoptotic signal transduction. We have recently shown that some of these proteins, such as Bcl-x(L), Bax, and Bak, directly modulate the mitochondrial voltage-dependent anion channel (VDAC) and thus regulate apoptogenic cytochrome c release and potential loss. To elucidate the molecular mechanisms of VDAC regulation by Bcl-2 family proteins, an electrophysiological study was carried out. It was found that VDAC and pro-apoptotic Bax created a large pore, with conductance levels 4- and 10-fold greater than those of the VDAC and Bax channels, respectively. Although the VDAC and Bax channels both show ion selectivity and voltage-dependent modulation of their activity, the VDAC-Bax channel had neither of their properties. Anti-apoptotic Bcl-x(L) and its BH4 oligopeptide completely closed the VDAC, in contrast to the Bax. Cytochrome c passed through a single VDAC-Bax channel but not through the VDAC or Bax channel in a planar lipid bilayer. These data provide direct evidence that VDAC forms a novel large pore together with Bax.
Recent advances in catalytic hydrogenation of carbon dioxide (2011)

Owing to the increasing emissions of carbon dioxide (CO(2)), human life and the ecological environment have been affected by global warming and climate changes. To mitigate the concentration of CO(2) in the atmosphere various strategies have been implemented such as separation, storage, and utilization of CO(2). Although it has been explored for many years, hydrogenation reaction, an important representative among chemical conversions of CO(2), offers challenging opportunities for sustainable development in energy and the environment. Indeed, the hydrogenation of CO(2) not only reduces the increasing CO(2) buildup but also produces fuels and chemicals. In this critical review we discuss recent developments in this area, with emphases on catalytic reactivity, reactor innovation, and reaction mechanism. We also provide an overview regarding the challenges and opportunities for future research in the field (319 references).
Adeno-Associated Viral Vectors at the Frontier between Tolerance and Immunity (2015)

International audience
Targeted Replacement of Mouse Apolipoprotein A-I with Human ApoA-I or the Mutant ApoA-IMilano (2003)

Despite a pro-atherogenic profile, individuals carrying the molecular variant (R173C) of apolipoprotein (apo)A-I, named apoA-I(Milano) (apoA-I(M)), appear to be at reduced risk for cardiovascular disease. To develop an in vivo system to explore, in a controlled manner, the effects of apoA-I(M) on lipid metabolism, we have used the gene targeting technology, or "gene knock-in" (gene k-in), to replace the murine apoA-I gene with either human apoA-I or apoA-I(M) genes in embryonic stem cells. As in human carriers, mice expressing apoA-I(M) (A-I(M) k-in) are characterized by low concentrations of the human apolipoprotein and reduced high density lipoprotein cholesterol levels, compared with A-I k-in animals. The aim of the present study was to investigate the basic mechanisms of hypoalphalipoproteinemia associated with the apoA-I(M) mutation. ApoA-I and apoA-I(M) mRNA expression, as assessed by Northern blot analysis and quantitative real time reverse transcription-PCR, did not exhibit significant differences in either liver or intestine. Moreover, human apolipoprotein synthesis rates were similar in the k-in lines. When the secretion rate of the human apolipoproteins was assessed in cultured hepatocytes from the mouse lines, secretion from apoA-I(M)-expressing cells was markedly reduced (42% for A-I(M) k-in and 36% for A-I/A-I(M) k-in mice) as compared with that of A-I k-in hepatocytes. These results provide the first evidence that the hypoalphalipoproteinemia in apoA-I(M) human carriers may be partially explained by impaired apoA-I(M) secretion.
Hibernation-associated gene regulation of plasma proteins with a collagen-like domain in mammalian hibernators. (1993)

In mammals, hibernation is expressed by only a limited number of species, and the molecular mechanisms underlying hibernation are not well understood. Recently, we have found plasma proteins which disappear from blood specifically during hibernation in a mammalian hibernator, the chipmunk. Here, we report the cDNA cloning of these chipmunk hibernation-related proteins, HP-20, -25, and -27, and analyses of their expression. All three proteins contain a collagen-like domain near the N terminus and are highly homologous to each other. Their mRNAs were detected only in liver in nonhibernating chipmunks, and in hibernating chipmunks, the amounts were reduced to less than 1/10 of those in nonhibernating chipmunks, indicating that HP-20, -25, and -27 mRNA expression is regulated similarly in association with hibernation. Southern blot analyses of the squirrel family with each of chipmunk HP-20, -25, and -27 cDNA revealed that a nonhibernating species (tree squirrel) as well as another hibernating species (ground squirrel) retained the corresponding genes. However, their transcripts were detected only with the hibernating species, and in hibernating ground squirrels, their levels were greatly reduced compared with those in nonhibernating animals, as were the cases with the chipmunk. These observations are the first line of evidence for occurrence of hibernation-associated gene regulation. The results would indicate the commitment of HP-20, -25, and -27 to hibernation and support the idea that genetic controls are involved in mammalian hibernation.
Yeast CAL1 is a structural and functional homologue to the DPR1 (RAM) gene involved in ras processing (1991)

A 2.3-kilobase pair DNA fragment of the yeast CAL1 gene was cloned by complementation of the cal1-1 mutation, which causes a defect in nuclear division and bud formation (Ohya, Y., Ohsumi, Y., and Anraku, Y. (1984) Mol. & Gen. Genet. 193, 389-394). Nucleotide sequencing of this fragment revealed a single open reading frame (ORF) encoding a polypeptide of 376 amino acids. Comparative analysis of the predicted amino acid sequence has shown that the CAL1 product has similarity to two yeast proteins: the DPR1 (RAM) gene product that is involved in processing of ras protein at the farnesylation step, and the essential ORF2 protein whose structural gene has a head-to-head arrangement with PRP4, which is involved in mRNA processing. Functional homology between CAL1 and DPR1 has also been suggested from genetic evidence that multiple copies of the CAL1 gene suppress the growth defects of a dpr1 null mutant at high temperature. This suppression is Ca(2+)-dependent, since it was not observed in complete medium containing 200 microM CaCl2 but was apparent in medium containing 100 mM CaCl2. From sequence analysis of the cal1-1 mutation, together with the alignment of the three gene products, we have concluded that the conserved Gly328 in the C terminus is important for activity. We suggest that the CAL1 protein participates in a ras-like C-terminal modification of proteins involved in nuclear division and bud growth.
The biphasic nature and temperature dependence of the activation of human plasminogen by urokinase. A simple urokinase assay based on this phenomenon. (1979)

Activation of plasminogen is a biphasic process, the first phase is temperature independent, the second phase is not. The first phase of activation is completed immediately when urokinase (UK) is combined with plasminogen. At 4 degrees C the fibrinolytic activity generated in the first phase is directly proportional to the concentration of UK used for activation. This linear relationship permits the construction of a standard curve for the quantitative measurement of UK in samples with unknown concentrations of UK. The second, slower phase of activation follows the first only at higher temperatures (e.g. 28 degrees C), is limited by the plasminogen concentration, and is completed within 30 minutes of incubations. Activation of plasminogen by streptokinase under the same conditions follows a different pattern.
Cycling Versus Continuous Mode In Neuromodulator Programming: A Crossover, Randomized, Controlled Trial (2016)

This is a randomized, controlled, blind, crossover trial comparing cycling versus continuous programming of a sacral neuromodulator in women diagnosed with overactive bladder (OAB). At 6 months, treatment order significantly affected Overactive Bladder Questionnaire - Short Form (OABq-SF) symptom scores. The cycling followed by continuous stimulation group had superior OABq-SF scores (p > 0.02).
Novel germline variants identified in the inner mitochondrial membrane transporter TIMM44 and their role in predisposition to oncocytic thyroid carcinomas (2006)

Familial Non-Medullary Thyroid Carcinoma (fNMTC) represents 3-7% of all thyroid tumours and is associated with some of the highest familial risks among all cancers, with an inheritance pattern compatible with an autosomal dominant model with reduced penetrance. We previously mapped a predisposing locus, TCO (Thyroid tumour with Cell Oxyphilia) on chromosome 19p13.2, for a particular form of thyroid tumour characterised by cells with an abnormal proliferation of mitochondria (oxyphilic or oncocytic cells). In the present work, we report the systematic screening of 14 candidate genes mapping to the region of linkage in affected TCO members, that led us to identify two novel variants respectively in exon 9 and exon 13 of TIMM44, a mitochondrial inner membrane translocase for the import in the mitochondria of nuclear-encoded proteins. These variants were co-segregating with the TCO phenotype, were not present in a large group of controls and were predicted to negatively affect the protein (exon 9 change) or the transcript (exon 13 change). Functional analysis was performed in vitro for both changes and although no dramatic loss of function effects were identified for the mutant alleles, subtler effects might still be present that could alter Timm44 function and thus promote oncocytic tumour development. Thus we suggest that TIMM44 should be considered for further studies in independent samples of affected individuals with TCO.
A Convenient Synthesis of 5-Fluoropyrimidines Using 1-(Chloromethyl)-4-fluoro-1,4-diazabicyclo[2.cntdot.2.cntdot.2]octane Bis(tetrafluoroborate)-SELECTFLUOR Reagent (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA Convenient Synthesis of 5-Fluoropyrimidines Using 1-(Chloromethyl)-4-fluoro-1,4-diazabicyclo[2.cntdot.2.cntdot.2]octane Bis(tetrafluoroborate)-SELECTFLUOR ReagentG. Sankar Lal, W. Pastore, and R. PesaresiCite this: J. Org. Chem. 1995, 60, 22, 7340–7342Publication Date (Print):November 1, 1995Publication History Published online1 May 2002Published inissue 1 November 1995https://pubs.acs.org/doi/10.1021/jo00127a046https://doi.org/10.1021/jo00127a046research-articleACS PublicationsRequest reuse permissionsArticle Views756Altmetric-Citations29LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (3)»Supporting Information Supporting Information Get e-Alerts
Restoration of impulse noise corrupted images using long-range correlation (1998)

We present a new algorithm that can remove impulse noise from corrupted images while preserving details. The algorithm is fundamentally different from the traditional methods in that it can utilize information not just of a local window centered about the corrupted pixel, but also of some remote regions in the image. Computer simulations indicate that our algorithm outperforms many existing techniques.
The Tetraspanin Protein CD37 Regulates IgA Responses and Anti-Fungal Immunity (2009)

Immunoglobulin A (IgA) secretion by plasma cells in the immune system is critical for protecting the host from environmental and microbial infections. However, the molecular mechanisms underlying the generation of IgA(+) plasma cells remain poorly understood. Here, we report that the B cell-expressed tetraspanin CD37 inhibits IgA immune responses in vivo. CD37-deficient (CD37-/-) mice exhibit a 15-fold increased level of IgA in serum and significantly elevated numbers of IgA(+) plasma cells in spleen, mucosal-associated lymphoid tissue, as well as bone marrow. Analyses of bone marrow chimeric mice revealed that CD37-deficiency on B cells was directly responsible for the increased IgA production. We identified high local interleukin-6 (IL-6) production in germinal centers of CD37-/- mice after immunization. Notably, neutralizing IL-6 in vivo reversed the increased IgA response in CD37-/- mice. To demonstrate the importance of CD37-which can associate with the pattern-recognition receptor dectin-1-in immunity to infection, CD37-/- mice were exposed to Candida albicans. We report that CD37-/- mice are evidently better protected from infection than wild-type (WT) mice, which was accompanied by increased IL-6 levels and C. albicans-specific IgA antibodies. Importantly, adoptive transfer of CD37-/- serum mediated protection in WT mice and the underlying mechanism involved direct neutralization of fungal cells by IgA. Taken together, tetraspanin protein CD37 inhibits IgA responses and regulates the anti-fungal immune response.
Platelet-Activating Factor in Brain Regions After Transient Ischemia in Gerbils (1996)

PAF is increased in gerbil brain in response to ischemia at early stages of reperfusion. PAF increases could contribute to the onset and progress of ischemic neuropathology.
The metamorphosis of a molecule: from soluble enzyme to the leukocyte receptor CD38 (1999)

Human CD38 is a 45-kDa type II membrane glycoprotein with an intricate pattern of expression in leukocytes, although evidence is accumulating of its quite widespread expression in cells of nonvascular origin. CD38 is a member of a nascent eukaryotic gene family encoding cytosolic and membrane-bound enzymes whose substrate is NAD, a coenzyme ubiquitously distributed in nature. Functionally, CD38 is an eclectic molecule with the ability not only to catalyze but also to signal, to mobilize calcium, and to adhere to itself, to hyaluronan, and to other ligands. Interaction with CD38 on various leukocyte subpopulations has profound though diverse consequences on their life-span, but these effects seem to be independent of the enzymatic activity of the molecule. CD38 challenges our expectations of a surface molecule and we must sift through its many guises to unmask its true nature.
A practical manual on the Monte Carlo method for random walk problems (1959)

This report is written to serve as a guide to those persons who, having no previous experience with Monte Carlo methods, wish to apply these methods to their own problems. Particular emphasis is given to techniques which are useful in dealing with probIems concerned with the diffusion of particles (and gamma rays) in material media of some complexity, both from a geometrical and a nuclear standpoint. Included as an appendix are brief summaries of a variety of problems of the above-mentioned type to which the methods described have been applied successfully. (auth)
Molecular mechanisms of NF-κB activation induced by bacterial lipopolysaccharide through Toll-like receptors (2000)

Septic shock, caused by exaggerated host responses to various microbial products typified by lipopolysaccharide (LPS), remains the leading cause of death in trauma patients. Gaining insight into the nature of host interactions with LPS will certainly facilitate attempts to develop effective anti-sepsis drugs. Tremendous progress has been made during the past few years in understanding the mechanisms of pathogen-induced host responses. Toll-like receptor (TLR) 4 and 2 have been implicated as major receptors for signaling initiated by LPS and many other microbial products following their binding to CD14. In addition, many signaling intermediates involved in LPS-induced cell activation, particularly activation of the transcription factor NF-kappaB, have been identified and characterized. Further investigations with these molecules will certainly reward us with more effective therapeutic drugs to treat septic shock as well as many other inflammatory and infectious disorders.