gebhart/patrepeval huggingface dataset:
Exogenous Brain-Derived Neurotrophic Factor Rescues Synaptic Dysfunction inMecp2-Null Mice (2010)

Postnatal deficits in brain-derived neurotrophic factor (BDNF) are thought to contribute to pathogenesis of Rett syndrome (RTT), a progressive neurodevelopmental disorder caused by mutations in the gene encoding methyl-CpG-binding protein 2 (MeCP2). In Mecp2-null mice, a model of RTT, BDNF deficits are most pronounced in structures important for autonomic and respiratory control, functions that are severely affected in RTT patients. However, relatively little is known about how these deficits affect neuronal function or how they may be linked to specific RTT endophenotypes. To approach these issues, we analyzed synaptic function in the brainstem nucleus tractus solitarius (nTS), the principal site for integration of primary visceral afferent inputs to central autonomic pathways and a region in which we found markedly reduced levels of BDNF in Mecp2 mutants. Our results demonstrate that the amplitude of spontaneous miniature and evoked EPSCs in nTS neurons is significantly increased in Mecp2-null mice and, accordingly, that mutant cells are more likely than wild- type cells to fire action potentials in response to primary afferent stimulation. These changes occur without any increase in intrinsic neuronal excitability and are unaffected by blockade of inhibitory GABA currents. However, this synaptopathy is associated with decreased BDNF availability in the primary afferent pathway and can be rescued by application of exogenous BDNF. On the basis of these findings, we hypothesize that altered sensory gating in nTS contributes to cardiorespiratory instability in RTT and that nTS is a site at which restoration of normal BDNF signaling could help reestablish normal homeostatic controls.
Receptor-Dependent Targeting of Lipoproteins to Specific Cell Types of the Liver (2017)

This chapter outlines the strategy to achieve targeting to specific cell types present in one organ, the liver. Very low density lipoproteins (VLDLs) are synthesized by the liver and transport lipids from the liver to extrahepatic sites. Although uptake is exerted by all the different liver cell types, the association of both VLDL and cholesterol-rich VLDL to Kupffer cells is respectively, only 3.5- and 1.2-fold higher. With parenchymal cells no significant difference in uptake between native LDL and methylated LDL was found, whereas it appears that only Kupffer cells internalize LDL in a receptor-dependent way. Chylomicrons are triglyceride-rich lipoproteins, synthesized by the small intestinal epithelium as vehicles to transport absorbed lipids to the plasma compartment. A determination of the in vivo hepatic up-uptake of chylomicrons indicates that 65% of the injected chylomicrons are recovered in the parenchymal cells.
New Calculus for the Treatment of Optical Systems VIII Electromagnetic Theory (1956)

The preceding seven papers of this series present a systematic procedure for computing the effect of an optical system on the state of polarization of the light that passes through it. The M-matrices discussed in the first six papers represent the over-all effect of an optical system; the N-matrices described in Paper VII are essentially path derivatives of the M-matrices and represent the local optical properties at a given point along the light-path.In this paper we suppose that the medium is an anisotropic crystal and note that the description of the local optical properties by the N-matrices must be closely related to the description of the local properties by the dielectric and gyration tensors that are employed in standard crystal optics. We find the exact relation between the N-matrix and the above-mentioned tensors. It is shown how one can compute the dielectric and gyration tensors from a knowledge of the N-matrices for several different directions of the light-path in the crystal. It is also shown how one can compute the N-matrix for any given light direction from a knowledge of the dielectric and gyration tensors; the computation entails finding the square root of a two-by-two complex matrix.Taken together, the eight papers of this series present a compact and systematic procedure for the solution of problems in crystal optics. The N-matrices have the advantage that circular birefringence and circular dichroism are treated in the same framework used for linear birefringence and linear dichroism.
Compartmentalisation of phosphodiesterases and protein kinase A: opposites attract (2005)

Understanding the molecular organisation of intracellular signalling pathways is a topic of considerable research interest. Since many signalling enzymes are widely distributed and have several substrates, a critical component in signal transduction is the control of specificity. This is achieved, in part by the assembly of multiprotein complexes where clusters of signalling enzymes create focal points to disseminate the intracellular action of many hormones. This is particularly true for the cAMP dependent protein kinase (PKA) that is localised throughout the cell via its association with A-kinase anchoring proteins (AKAPs). Recent data suggest that some AKAPs also interact with phosphodiesterases (PDEs). Compartmentalisation of PDEs not only provides an elegant means to control PKA activation by monitoring the local cAMP flux, but also serves to concentrate and segregate the action of these important regulatory enzymes.
Characterization of a human apolipoprotein E gene enhancer element and its associated protein factors. (1990)

An enhancer element in the 5' flanking region of the human apolipoprotein E gene, known as upstream regulatory element 1 (URE1), has previously been implicated in the expression of this gene. The URE1 element, which spans nucleotides -193 to -124 of the 5'-flanking region of the human apolipoprotein E gene, contains two sequences that bind to nuclear proteins, as determined by the DNase I footprinting assay. In the present study of URE1, we have characterized these sequences further. Deletion of one of the footprint sequences, at nucleotides -161 to -141, reduced URE1 enhancer activity substantially. A 30-base pair oligonucleotide that included this protein-binding sequence was able, by itself, to act as an enhancer. This sequence, termed the positive element for transcription (PET), was demonstrated by gel retention analysis to bind at least two protein factors, one of which is the transcription factor Sp1. Sp1 appeared to be the only protein required for the enhancer activity of PET to be manifested. In vitro transcription assays showed that the PET sequence was necessary for efficient transcription directed by the apoE promoter and that the PET sequence was the dominant regulatory element in the apoE promoter. Gel filtration chromatography and PET oligonucleotide-affinity chromatography were used to isolate a second PET-binding factor, a Mr = 55,000 protein, from HeLa cell nuclear extracts. It appeared to compete with Sp1 for a common binding site in the PET sequence, but it was not required for enhancer activity. The second footprint sequence in URE1, at nucleotides -184 to -173, also bound Sp1, but it was not required for enhancer activity. A third Sp1-binding region was located at a proximal GC box element (nucleotides -54 to -45). This region had no enhancer activity, but it was required for maximum transcriptional activity of the apoE promoter. Thus, the regulation of apoE gene expression is influenced by different protein-binding sequences, with transcription factor Sp1 playing major roles in both basal promoter activity and enhancer activity.
Nucleotide sequence and deduced amino add sequence ofEscherichia colipyruvate oxidase, a lipid-activated flavoprotein (1986)

The entire nucleotide sequence of the poxB (pyruvate oxidase) gene of Escherichia coli K-12 has been determined by the dideoxynucleotide (Sanger) sequencing of fragments of the gene cloned into a phage M13 vector. The gene is 1716 nucleotides in length and has an open reading frame which encodes a protein of Mr 62,018. This open reading frame was shown to encode pyruvate oxidase by alignment of the amino acid sequences deduced for the amino and carboxy termini and several internal segments of the mature protein with sequences obtained by amino acid sequence analysis. The deduced amino acid sequence of the oxidase was not unusually rich in hydrophobic sequences despite the peripheral membrane location and lipid binding properties of the protein. The codon usage of the oxidase gene was typical of a moderately expressed protein. The deduced amino acid sequence shares homology with the large subunits of the acetohydroxy acid synthase isozymes I, II, and III, encoded by the ilvB, ilvG, and ilvI genes of E. coli.
X-Linked Hypophosphatemia and FGF23-Related Hypophosphatemic Diseases: Prospect for New Treatment (2018)

Phosphate plays essential roles in many biological processes, and the serum phosphate level is tightly controlled. Chronic hypophosphatemia causes impaired mineralization of the bone matrix and results in rickets and osteomalacia. Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that regulates phosphate metabolism. FGF23 excess induces hypophosphatemia via impaired phosphate reabsorption in the renal proximal tubules and decreased phosphate absorption in the intestines. There are several types of genetic and acquired FGF23-related hypophosphatemic diseases. Among these diseases, X-linked hypophosphatemia (XLH), which is caused by inactivating mutations in the phosphate-regulating endopeptidase homolog, X-linked (PHEX) gene, is the most prevalent form of genetic FGF23-related hypophosphatemic rickets. Another clinically relevant form of FGF23-related hypophosphatemic disease is tumor-induced osteomalacia (TIO), a paraneoplastic syndrome associated with FGF23-producing tumors. A combination of active vitamin D and phosphate salts is the current medical therapy used to treat patients with XLH and inoperative TIO. However, this therapy has certain efficacy- and safety-associated limitations. Several measures to inhibit FGF23 activity have been considered as possible new treatments for FGF23-related hypophosphatemic diseases. In particular, a humanized monoclonal antibody for FGF23 (burosumab) is a promising treatment in patients with XLH and TIO. This review will focus on the phosphate metabolism and the pathogenesis and treatment of FGF23-related hypophosphatemic diseases.
Expression of Genes in Mycobacteria (2003)

Over the past 10 years, major advances have been made in the field of molecular mycobacterioiogy. These include the generation of shuttle vectors for use in both Escherichia coli and mycobacteria, electroporation protocols to introduce these plasmids into mycobacteria and promoter cassettes, which can be used to drive the expression of cloned genes in the mycobacterial host (, , , , , ). Similar procedures have been instrumental in the study of many aspects of prokaryotic biology but, in their absence, our understanding of basic processes within species of mycobacteria has been limited. Similarly, the ability to overexpress cloned genes in bacteria has been important in revealing the functions of a great diversity of heterologous proteins. Using Mycobacterium vaccae as the host, the available expression technology has allowed the overexpression, purification and crystallization of the Mycobacterium tuberculosis superoxide dismutase (,). The elucidation of the crystal structure of this important enzyme has yielded some very interesting information on protein structure and function in M. tuberculosis. Similarly, the glycosylation of mycobacterial proteins (which cannot be replicated in other bacterial hosts such as E. coli) is being investigated using these expression systems (,). In order to benefit from the wealth of information being presented to the screntitic community in the what has been termed the “post-genomic era of microbiology,” the continued utilization and improvement of such methodology is of paramount importance,
Gram-negative Bacteria-binding Protein, a Pattern Recognition Receptor for Lipopolysaccharide and β-1,3-Glucan That Mediates the Signaling for the Induction of Innate Immune Genes in Drosophila melanogaster Cells (2000)

Pattern recognition receptors, non-clonal immune proteins recognizing common microbial components, are critical for non-self recognition and the subsequent induction of Rel/NF-kappaB-controlled innate immune genes. However, the molecular identities of such receptors are still obscure. Here, we present data showing that Drosophila possesses at least three cDNAs encoding members of the Gram-negative bacteria-binding protein (DGNBP) family, one of which, DGNBP-1, has been characterized. Western blot, flow cytometric, and confocal laser microscopic analyses demonstrate that DGNBP-1 exists in both a soluble and a glycosylphosphatidylinositol-anchored membrane form in culture medium supernatant and on Drosophila immunocompetent cells, respectively. DGNBP-1 has a high affinity to microbial immune elicitors such as lipopolysaccharide (LPS) and beta-1,3-glucan whereas no binding affinity is detected with peptidoglycan, beta-1,4-glucan, or chitin. Importantly, the overexpression of DGNBP-1 in Drosophila immunocompetent cells enhances LPS- and beta-1,3-glucan-induced innate immune gene (NF-kappaB-dependent antimicrobial peptide gene) expression, which can be specifically blocked by pretreatment with anti-DGNBP-1 antibody. These results suggest that DGNBP-1 functions as a pattern recognition receptor for LPS from Gram-negative bacteria and beta-1, 3-glucan from fungi and plays an important role in non-self recognition and the subsequent immune signal transmission for the induction of antimicrobial peptide genes in the Drosophila innate immune system.
Virtual Network Embedding: A Survey (2013)

Network virtualization is recognized as an enabling technology for the future Internet. It aims to overcome the resistance of the current Internet to architectural change. Application of this technology relies on algorithms that can instantiate virtualized networks on a substrate infrastructure, optimizing the layout for service-relevant metrics. This class of algorithms is commonly known as "Virtual Network Embedding (VNE)" algorithms. This paper presents a survey of current research in the VNE area. Based upon a novel classification scheme for VNE algorithms a taxonomy of current approaches to the VNE problem is provided and opportunities for further research are discussed.
Macrophages—proliferation, activation, and cell cycle proteins (1999)

Our understanding of mammalian cell proliferation has increased enormously over the past decade. A major advance has been identification and characterization of cyclins and their catalytic partners, cyclin-dependent kinases (cdks). The following brief review highlights the role of macrophages as a cell model for many of the major advances in this field. Macrophages were central to the identification of D-type cyclins and cdk4. In addition, it appears the first work showing that cell cycle proteins are the targets for anti-proliferative agents was performed in macrophages. In these latter studies, and a number of subsequent studies in other cell types, it was shown that many antimitogenic agents repressed cyclin and/or cdk expression. However, recent work in this laboratory suggests macrophage D-type cyclins may also be involved in processes other than proliferation. We have unexpectedly found that macrophages treated with lipopolysaccharide (LPS) express high levels of cyclin D2, even though LPS simultaneously represses cyclin D1 levels and potently blocks proliferation. These data, and those showing the yeast extract Zymosan A also raises cyclin D2 levels, suggest cyclin D2 plays a role in macrophage activation.
Distinct subpopulations of enteric neuronal progenitors defined by time of development, sympathoadrenal lineage markers and Mash-1-dependence (1996)

Enteric and sympathetic neurons have previously been proposed to be lineally related. We present independent lines of evidence that suggest that enteric neurons arise from at least two lineages, only one of which expresses markers in common with sympathoadrenal cells. In the rat, sympathoadrenal markers are expressed, in the same order as in sympathetic neurons, by a subset of enteric neuronal precursors, which also transiently express tyrosine hydroxylase. If this precursor pool is eliminated in vitro by complement-mediated lysis, enteric neurons continue to develop; however, none of these are serotonergic. In the mouse, the Mash-1-/- mutation, which eliminates sympathetic neurons, also prevents the development of enteric serotonergic neurons. Other enteric neuronal populations, however, including those that contain calcitonin gene related peptide are present. Enteric tyrosine hydroxylase-containing cells co-express Mash-1 and are eliminated by the Mash-1-/- mutation, consistent with the idea that in the mouse, as in the rat, these precursors generate serotonergic neurons. Serotonergic neurons are generated early in development, while calcitonin gene related peptide-containing enteric neurons are generated much later. These data suggest that enteric neurons are derived from at least two progenitor lineages. One transiently expresses sympathoadrenal markers, is Mash-1-dependent, and generates early-born enteric neurons, some of which are serotonergic. The other is Mash-1-independent, does not express sympathoadrenal markers, and generates late-born enteric neurons, some of which contain calcitonin gene related peptide.
Graph-Based Message-Passing Schedules for Decoding LDPC Codes (2004)

We study a wide range of graph-based message-passing schedules for iterative decoding of low-density parity-check (LDPC) codes. Using the Tanner graph (TG) of the code and for different nodes and edges of the graph, we relate the first iteration in which the corresponding messages deviate from their optimal value (corresponding to a cycle-free graph) to the girths and the lengths of the shortest closed walks in the graph. Using this result, we propose schedules, which are designed based on the distribution of girths and closed walks in the TG of the code, and categorize them as node based versus edge based, unidirectional versus bidirectional, and deterministic versus probabilistic. These schedules, in some cases, outperform the previously known schedules, and in other cases, provide less complex alternatives with more or less the same performance. The performance/complexity tradeoff and the best choice of schedule appear to depend not only on the girth and closed-walk distributions of the TG, but also on the iterative decoding algorithm and channel characteristics. We examine the application of schedules to belief propagation (sum-product) over additive white Gaussian noise (AWGN) and Rayleigh fading channels, min-sum (max-sum) over an AWGN channel, and Gallager's algorithm A over a binary symmetric channel.
Gene expression analysis reveals matrilysin as a key regulator of pulmonary fibrosis in mice and humans (2002)

Pulmonary fibrosis is a progressive and largely untreatable group of disorders that affects up to 100,000 people on any given day in the United States. To elucidate the molecular mechanisms that lead to end-stage human pulmonary fibrosis we analyzed samples from patients with histologically proven pulmonary fibrosis (usual interstitial pneumonia) by using oligonucleotide microarrays. Gene expression patterns clearly distinguished normal from fibrotic lungs. Many of the genes that were significantly increased in fibrotic lungs encoded proteins associated with extracellular matrix formation and degradation and proteins expressed in smooth muscle. Using a combined set of scoring systems we determined that matrilysin (matrix metalloproteinase 7), a metalloprotease not previously associated with pulmonary fibrosis, was the most informative increased gene in our data set. Immunohistochemisry demonstrated increased expression of matrilysin protein in fibrotic lungs. Furthermore, matrilysin knockout mice were dramatically protected from pulmonary fibrosis in response to intratracheal bleomycin. Our results identify matrilysin as a mediator of pulmonary fibrosis and a potential therapeutic target. They also illustrate the power of global gene expression analysis of human tissue samples to identify molecular pathways involved in clinical disease.
MicroRNA-340 Inhibits Tumor Cell Proliferation and Induces Apoptosis in Endometrial Carcinoma Cell Line RL 95-2 (2016)

BACKGROUND The purpose of our study was to investigate the functional role of microRNA-340 (miR-340) in endometrial carcinoma (EC). MATERIAL AND METHODS Human EC cell line RL 95-2 was transfected with miR-340 mimics, inhibitors, or controls. After 48 h of transfection, the cell viability was determined by 3-(4, 5-dimethyl-2- thiazolyl)-2, 5-diphenyl -2-H-tetrazolium bromide (MTT) assay. The BrdU assay and apoptosis assay were performed to determine the effects of miR-340 mimics or inhibitors on cell proliferation and apoptosis, respectively. The underlying mechanisms involved in cell proliferation and apoptosis were explored by measuring the protein levels of cell cycle regulators (p27 kinase inhibition protein (KIP) 1 and p21) and apoptosis-related factors (B-cell lymphoma-2 (Bcl-2), Bax, pro-Caspase 3, and active-Caspase-3). RESULTS Overexpression of miR-340 significantly inhibited the cell viability (P<0.05) and cell proliferation (P<0.01) of RL 95-2 cells compared with the control group, but increased the apoptosis (P<0.01). However, suppression of miR-340 had opposite results. Moreover, the protein levels of p27 KIP1, Bax, pro-Caspase 3, and active-Caspase-3 were significantly increased by overexpression of miR-340 but were statistically decreased by suppression of miR-340. Contrary results were found in the protein levels of Bcl-2. However, no significant differences were found in p21 expression. CONCLUSIONS MiRNA-340 acts as an anti-oncogene in EC cell line RL 95-2 by inhibition of tumor cell proliferation and induction of apoptosis.
Significance of the Dissociation of Dna2 by Flap Endonuclease 1 to Okazaki Fragment Processing in Saccharomyces cerevisiae (2009)

Okazaki fragments are initiated by short RNA/DNA primers, which are displaced into flap intermediates for processing. Flap endonuclease 1 (FEN1) and Dna2 are responsible for flap cleavage. Replication protein A (RPA)-bound flaps inhibit cleavage by FEN1 but stimulate Dna2, requiring that Dna2 cleaves prior to FEN1. Upon cleavage, Dna2 leaves a short flap, which is then cut by FEN1 forming a nick for ligation. Both enzymes require a flap with a free 5'-end for tracking to the cleavage sites. Previously, we demonstrated that FEN1 disengages the tracking mechanism of Dna2 to remove it from the flap. To determine why the disengagement mechanism evolved, we measured FEN1 dissociation of Dna2 on short RNA and DNA flaps, which occur during flap processing. Dna2 tracked onto these flaps but could not cleave, presenting a block to FEN1 entry. However, FEN1 disengaged these nonproductively bound Dna2 molecules, proceeding on to conduct proper cleavage. These results clarify the importance of disengagement. Additional results showed that flap substrate recognition and tracking by FEN1, as occur during fragment processing, are required for effective displacement of the flap-bound Dna2. Dna2 was recently shown to dissociate flap-bound RPA, independent of cleavage. Using a nuclease-defective Dna2 mutant, we reconstituted the sequential dissociation reactions in the proposed RPA/Dna2/FEN1 pathway showing that, even without cutting, Dna2 enables FEN1 to cleave RPA-coated flaps. In summary, RPA, Dna2, and FEN1 have evolved highly coordinated binding properties enabling one protein to succeed the next for proper and efficient Okazaki flap processing.