gebhart/patrepeval huggingface dataset:
Intrastriatal implantation of fibroblasts genetically engineered to produce brain-derived neurotrophic factor prevents degeneration of dopaminergic neurons in a rat model of Parkinson's disease (1995)

Parkinson's disease (PD) is a neurodegenerative disorder characterized by a progressive loss of the dopaminergic neurons of the substantia nigra pars compacta (SNpc). Although various treatments are successfully used to alleviate the symptoms of PD, none of them prevents or halts the neurodegenerative process of the disease. Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family of proteins, supports the survival and the differentiation of dopaminergic neurons. BDNF also prevents the death of dopaminergic neurons in vitro, which suggests that it may be of possible use in the development of neuroprotective therapies for PD. To determine whether BDNF is neuroprotective for SNpc dopaminergic neurons in the adult brain, we used a rat model of PD in which degeneration of 60-70% of these neurons was induced by an intrastriatal injection of 6-hydroxydopamine (6-OHDA). We report here that intrastriatal grafts of fibroblasts genetically engineered to produce BDNF partially prevent the loss of nerve terminals and completely prevent the loss of cell bodies of the nigrostriatal dopaminergic pathway that is induced by the intrastriatal injection of 6-OHDA. In contrast, the implantation of control fibroblasts that did not produce BDNF failed to protect nerve terminals and cell bodies against 6-OHDA-induced damage. Our observation that grafts of BDNF-producing fibroblasts protect against 6-OHDA-induced degeneration of SNpc dopaminergic neurons in the adult rat brain opens new perspectives for treatments aimed at the prevention of neurodegeneration in PD, using gene therapy and neurotrophic factors such as BDNF.
Binding of Basic Fibroblast Growth Factor to Fibrinogen and Fibrin (1998)

Fibrin is formed at sites of tissue injury and provides the temporary matrix needed to support the initial endothelial cell responses needed for vessel repair. Basic fibroblast growth factor (bFGF) also acts at sites of injury and stimulates similar vascular cell responses. We have, therefore, investigated whether there are specific interactions between bFGF and fibrinogen and fibrin that could play a role in coordinating these actions. Binding studies were performed using bFGF immobilized on Sepharose beads and soluble 125I-labeled fibrinogen and also using Sepharose-immobilized fibrinogen and soluble 125I-bFGF. Both systems demonstrated specific and saturable binding. Scatchard analysis indicated two classes of binding sites for each with Kd values of 1.3 and 260 nM using immobilized bFGF; and Kd values of 0.9 and 70 nM using immobilized fibrinogen. After conversion of Sepharose-immobilized fibrinogen to fibrin by treatment with thrombin, bFGF also demonstrated specific and saturable binding with two classes of binding sites having Kd values of 0.13 and 83 nM. Fibrin binding was also investigated by clotting a solution of bFGF and fibrinogen, and two classes of binding sites were demonstrated using this system with Kd values of 0.8 and 261 nM. The maximum molar binding ratios of bFGF to fibrinogen were between 2.0 and 4.0 with the four binding systems. We conclude that bFGF binds specifically and saturably to fibrinogen and fibrin with high affinity, and this may have implications regarding the localization of its effect at sites of tissue injury.
One-step isolation and characterization of nuclear membranes (1974)

Abstract Purified fractions of nuclei from rat liver and isolated calf thymocytes are treated with 0.5 M MgCl2 or with an alkaline buffer, pH 8.5. Such procedures dissociate nuclear membranes from the chromatin. The membranes are simply floated in a gradient. The recovery in the membrane band obtained by the Mg2+ technique is 55 to 60 %. Freeze-etching studies of the membrane pellets provide a good way to check their purity, pores being very conspicuous. A 5'-nucleotidase and an ATPase are detected on the nuclear membranes of thymocytes, as well as a still undescribed 3'-nucleotidase. However, no marker enzymes for the nuclear membrane have been found. The topology of sugar residues on the nuclear membranes is studied by means of lectins. Concanavalin A binds in large amounts to nuclear envelopes, both on the inner and outer leaflets, but not to pores.
Effects of protein charge heterogeneity in protein-polyelectrolyte complexation (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEffects of protein charge heterogeneity in protein-polyelectrolyte complexationJeongsook M. Park, Barry B. Muhoberac, Paul L. Dubin, and Jiulin XiaCite this: Macromolecules 1992, 25, 1, 290–295Publication Date (Print):January 1, 1992Publication History Published online1 May 2002Published inissue 1 January 1992https://doi.org/10.1021/ma00027a047Request reuse permissionsArticle Views1414Altmetric-Citations287LEARN 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 InReddit PDF (839 KB) Get e-Alertsclose Get e-Alerts
A TCR Targeting the HLA-A*0201–Restricted Epitope of MAGE-A3 Recognizes Multiple Epitopes of the MAGE-A Antigen Superfamily in Several Types of Cancer (2010)

Adoptive immunotherapy using TCR-engineered PBLs against melanocyte differentiation Ags mediates objective tumor regression but is associated with on-target toxicity. To avoid toxicity to normal tissues, we targeted cancer testis Ag (CTA) MAGE-A3, which is widely expressed in a range of epithelial malignancies but is not expressed in most normal tissues. To generate high-avidity TCRs against MAGE-A3, we employed a transgenic mouse model that expresses the human HLA-A*0201 molecule. Mice were immunized with two HLA-A*0201-restricted peptides of MAGE-A3: 112-120 (KVAELVHFL) or MAGE-A3: 271-279 (FLWGPRALV), and T cell clones were generated. MAGE-A3-specific TCR α- and β-chains were isolated and cloned into a retroviral vector. Expression of both TCRs in human PBLs demonstrated Ag-specific reactivity against a range of melanoma and nonmelanoma tumor cells. The TCR against MAGE-A3: 112-120 was selected for further development based on superior reactivity against tumor target cells. Interestingly, peptide epitopes from MAGE-A3 and MAGE-A12 (and to a lesser extent, peptides from MAGE-A2 and MAGE-A6) were recognized by PBLs engineered to express this TCR. To further improve TCR function, single amino acid variants of the CDR3 α-chain were generated. Substitution of alanine to threonine at position 118 of the α-chain in the CDR3 region of the TCR improved its functional avidity in CD4 and CD8 cells. On the basis of these results, a clinical trial is planned in which patients bearing a variety of tumor histologies will receive autologous PBLs that have been transduced with this optimized anti-MAGE-A3 TCR.
Inhibition of erythropoietin gene expression signaling involves the transcription factors GATA‐2 and NF‐κB (2002)

The anemia of chronic inflammatory and malignant diseases is partly due to impaired synthesis of the hormone erythropoietin (Epo). The proinflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor a (TNF-alpha) suppress in vitro Epo gene expression and Epo protein secretion. However, the molecular mechanisms of this inhibition are poorly understood. The human Epo promoter and the 5' flanking region contain several recognition sequences for transcription factors acting either positively or negatively. Herein, we investigated the roles of the transcription factors GATA-2 and NF-kappaB in the modulation of Epo gene expression by IL-1beta and TNF-alpha in the human hepatoma cell line HepG2. Electrophoretic mobility shift assays revealed increased GATA-2 and NF-kappaB DNA binding in cells treated with IL-1beta or TNF-alpha. Reporter gene assays with a sequence from the Epo promoter in front of the firefly luciferase gene showed that the cytokines reduced Epo reporter gene activity. Functional inactivation of GATA-2 and NF-kappaB by oligo-decoy techniques prevented the inhibition of Epo production by IL-1beta and TNF-alpha. In HepG2 cells stably transfected with a dominant-negative form of IkappaBalpha, the activation of NF-kappaB was inhibited, while Epo mRNA levels and Epo secretion increased. Thus, both GATA-2 and NF-kappaB seem to be involved in the suppression of Epo gene expression by IL-1beta and TNF-alpha in vitro and may be responsible for impaired Epo synthesis in inflammatory diseases in vivo.
Development of a non-surfactant formulation for alfaxalone through the use of chemically-modified cyclodextrins. (1990)

The poor water solubility of alfaxalone (less than 5 micrograms/mL), a useful steroid anesthetic agent, was dramatically increased via complexation with a series of four cyclodextrins. The most effective agent was 2-hydroxypropyl-beta-cyclodextrin (2HPCD) which solubilized alfaxalone in a linear manner as a function of concentration. At a 2HPCD concentration of 50% w/v, approximately 80 mg/mL of alfaxalone was dissolved indicating an increase in aqueous solubility of over four orders of magnitude. The cyclodextrin solution was stable to autoclaving and could be conveniently lyophilized to yield a solid product.
Comparing time and frequency domain for audio event recognition using deep learning (2016)

Recognizing acoustic events is an intricate problem for a machine and an emerging field of research. Deep neural networks achieve convincing results and are currently the state-of-the-art approach for many tasks. One advantage is their implicit feature learning, opposite to an explicit feature extraction of the input signal. In this work, we analyzed whether more discriminative features can be learned from either the time-domain or the frequency-domain representation of the audio signal. For this purpose, we trained multiple deep networks with different architectures on the Freiburg-106 and ESC-10 datasets. Our results show that feature learning from the frequency domain is superior to the time domain. Moreover, additionally using convolution and pooling layers, to explore local structures of the audio signal, significantly improves the recognition performance and achieves state-of-the-art results.
Electrically pumped hybrid evanescent Si/InGaAsP lasers (2009)

Hybrid Si/III-V, Fabry-Perot evanescent lasers are demonstrated, utilizing InGaAsP as the III-V gain material for the first time to our knowledge. The lasing threshold current of 300-mum-long devices was as low as 24 mA, with a maximal single facet output power of 4.2 mW at 15 degrees C. Longer devices achieved a maximal single facet output power as high as 12.7 mW, a single facet slope efficiency of 8.4%, and a lasing threshold current density of 1 kA/cm2. Continuous wave laser operation was obtained up to 45 degrees C. The threshold current density, output power, and efficiency obtained improve upon those of previously reported devices having a similar geometry. Facet images indicate that the output light is largely confined to the Si waveguide.
Dynamics of Streptococcus mutans Transcriptome in Response to Starch and Sucrose during Biofilm Development (2010)

The combination of sucrose and starch in the presence of surface-adsorbed salivary α-amylase and bacterial glucosyltransferases increase the formation of a structurally and metabolically distinctive biofilm by Streptococcus mutans. This host-pathogen-diet interaction may modulate the formation of pathogenic biofilms related to dental caries disease. We conducted a comprehensive study to further investigate the influence of the dietary carbohydrates on S. mutans-transcriptome at distinct stages of biofilm development using whole genomic profiling with a new computational tool (MDV) for data mining. S. mutans UA159 biofilms were formed on amylase-active saliva coated hydroxyapatite discs in the presence of various concentrations of sucrose alone (ranging from 0.25 to 5% w/v) or in combination with starch (0.5 to 1% w/v). Overall, the presence of sucrose and starch (suc+st) influenced the dynamics of S. mutans transcriptome (vs. sucrose alone), which may be associated with gradual digestion of starch by surface-adsorbed amylase. At 21 h of biofilm formation, most of the differentially expressed genes were related to sugar metabolism, such as upregulation of genes involved in maltose/maltotriose uptake and glycogen synthesis. In addition, the groEL/groES chaperones were induced in the suc+st-biofilm, indicating that presence of starch hydrolysates may cause environmental stress. In contrast, at 30 h of biofilm development, multiple genes associated with sugar uptake/transport (e.g. maltose), two-component systems, fermentation/glycolysis and iron transport were differentially expressed in suc+st-biofilms (vs. sucrose-biofilms). Interestingly, lytT (bacteria autolysis) was upregulated, which was correlated with presence of extracellular DNA in the matrix of suc+st-biofilms. Specific genes related to carbohydrate uptake and glycogen metabolism were detected in suc+st-biofilms in more than one time point, indicating an association between presence of starch hydrolysates and intracellular polysaccharide storage. Our data show complex remodeling of S. mutans-transcriptome in response to changing environmental conditions in situ, which could modulate the dynamics of biofilm development and pathogenicity.
Intranasal pediatric parainfluenza virus-vectored SARS-CoV-2 vaccine candidate is protective in macaques (2022)

Pediatric SARS-CoV-2 vaccines are needed that elicit immunity directly in the airways, as well as systemically. Building on pediatric parainfluenza virus vaccines in clinical development, we generated a live-attenuated parainfluenza virus-vectored vaccine candidate expressing SARS-CoV-2 prefusion-stabilized spike (S) protein (B/HPIV3/S-6P) and evaluated its immunogenicity and protective efficacy in rhesus macaques. A single intranasal/intratracheal dose of B/HPIV3/S-6P induced strong S-specific airway mucosal IgA and IgG responses. High levels of S-specific antibodies were also induced in serum, which efficiently neutralized SARS-CoV-2 variants of concern. Furthermore, B/HPIV3/S-6P induced robust systemic and pulmonary S-specific CD4<sup>+</sup> and CD8<sup>+</sup> T-cell responses, including tissue-resident memory cells in lungs. Following challenge, SARS-CoV-2 replication was undetectable in airways and lung tissues of immunized macaques. B/HPIV3/S-6P will be evaluated clinically as pediatric intranasal SARS-CoV-2/parainfluenza virus type 3 vaccine.
Vascular Differences Detected by MRI for Metastatic Versus Nonmetastatic Breast and Prostate Cancer Xenografts (2001)

Several studies have linked vascular density, identified in histologic sections, to "metastatic risk." Functional information of the vasculature, not readily available from histologic sections, can be obtained with contrast-enhanced MRI to exploit for therapy or metastasis prevention. Our aims were to determine if human breast and prostate cancer xenografts preselected for differences in invasive and metastatic characteristics established correspondingly different vascular volume and permeability, quantified here with noninvasive MRI of the intravascular contrast agent albumin-GdDTPA. Tumor vascular volume and permeability of human breast and prostate cancer xenografts were characterized using MRI. Parallel studies confirmed the invasive behavior of these cell lines. Vascular endothelial growth factor (VEGF) expression in the cell lines was measured using ELISA and Western blots. Metastasis to the lungs was evaluated with spontaneous as well as experimental assay. Metastatic tumors formed vasculature with significantly higher permeability or vascular volume (P<.05, two-sided unpaired t test). The permeability profile matched VEGF expression. Within tumors, regions of high vascular volume usually exhibited low permeability whereas regions of low vascular volume exhibited high permeability. We observed that although invasion was necessary, without adequate vascularization it was not sufficient for metastasis to occur.
Streptococcus equi with truncated M-proteins isolated from outwardly healthy horses The EMBL accession numbers of the M-protein gene partial sequences of S. equi isolates A1–A3 and B–E are AJ249868–AJ249874, respectively. (2000)

The M-protein genes of Streptococcus equi isolated from 17 outwardly healthy horses after 4 strangles outbreaks had ended, including a quarantined animal, were compared with those of S. equi isolates from 167 active cases of strangles across 4 countries. The healthy horses included 16 persistent S. equi carriers, at least one from each of the four outbreaks. These carriers, despite being outwardly healthy, had empyema of the guttural pouch(es), an enlargement of the equine Eustachian tube. A persistent carrier from two of these outbreaks, the quarantined animal and a healthy animal with normal guttural pouches, from which S. equi was isolated only once, were colonized by variant S. equi with truncated M-protein genes (24% of outwardly healthy animals with S. equi). The truncated M-protein genes had in-frame deletions in slightly different positions between the signal sequence and the central repeat region, equivalent to approximately 20% of the mature expressed protein. Immunoblotting with antibody to recombinant M-protein confirmed that the variants expressed a truncated form of the M-protein. In contrast to the outwardly healthy S. equi carriers, only 1/167 of S. equi isolates from strangles cases possessed a truncated M-protein gene (<1%; Fisher's exact test, P=0.0002). Compared with isolates from healthy horses with a truncated M-protein, much more of the N terminus of the truncated M-protein was retained in the variant S. equi from a strangles case. Variant S. equi from outwardly healthy animals were more susceptible to phagocytosis by neutrophils in vitro than typical isolates. This is the first report of detection of S. equi with a truncated M-protein. The distribution of the variants between strangles cases and carriers suggests that the 80% of the M-protein retained in the variants may contribute to colonization whilst the deleted portion of the gene may be needed for full virulence.
Cell-extracellular matrix interactions can regulate the switch between growth and differentiation in rat hepatocytes: reciprocal expression of C/EBP alpha and immediate-early growth response transcription factors. (1994)

Previous investigations have shown that culture of freshly isolated hepatocytes under conventional conditions, i.e., on dried rat tail collagen in the presence of growth factors, facilitates cell growth but also causes an extensive down-regulation of most liver-specific functions. This dedifferentiation process can be prevented if the cells are cultured on a reconstituted basement membrane gel matrix derived from the Englebreth-Holm-Swarm mouse sarcoma tumor (EHS gel). To gain insight into the mechanisms regulating this response to extracellular matrix, we are analyzing the activities of two families of transcription factors, C/EBP and AP-1, which control the transcription of hepatic and growth-responsive genes, respectively. We demonstrate that isolation of hepatocytes from the normal quiescent rat liver by collagenase perfusion activates the immediate-early growth response program, as indicated by increased expression of c-jun, junB, c-fos, and c-myc mRNAs. Adhesion of these activated cells to dried rat tail collagen augments the elevated levels of these mRNAs for the initial 1 to 2 h postplating; junB and c-myc mRNA levels then drop steeply, with junB returning to normal quiescence and the c-myc level remaining slightly elevated during the 3-day culture period. Levels of c-jun mRNA and AP-1 DNA binding activity, however, remain elevated from the outset, while C/EBP alpha mRNA expression is down-regulated, resulting in a decrease in the steady-state levels of the 42- and 30-kDa C/EBP alpha polypeptides and C/EBP alpha DNA binding activity. In contrast, C/EBP beta mRNA production remains at near-normal hepatic levels for 5 to 8 days of culture, although its DNA binding activity decreases severalfold during this time. Adhesion of hepatocytes to the EHS gel for the same period of time dramatically alters this program: it arrests growth and inhibits AP-1 DNA binding activity and the expression of c-jun, junB, and c-myc mRNAs, but, in addition, it restores C/EBP alpha mRNA and protein as well as C/EBP alpha and C/EBP beta DNA binding activities to the abundant levels present in freshly isolated hepatocytes. These changes are not due merely to growth inhibition, because suppression of hepatocyte proliferation on collagen by epidermal growth factor starvation or addition of transforming growth factor beta does not inhibit AP-1 activity or restore C/EBP alpha DNA binding activity to normal hepatic levels. These data suggest that expression of the normal hepatic phenotype requires that hepatocytes exist in a G0 state of growth arrest, facilitated here by adhesion of cells to the EHS gel, in order to express high levels of hepatic transcription factors such as C/EBP alpha.
Loss of stem cell regenerative capacity within aged niches (2007)

This work uncovers novel mechanisms of aging within stem cell niches that are evolutionarily conserved between mice and humans and affect both embryonic and adult stem cells. Specifically, we have examined the effects of aged muscle and systemic niches on key molecular identifiers of regenerative potential of human embryonic stem cells (hESCs) and post-natal muscle stem cells (satellite cells). Our results reveal that aged differentiated niches dominantly inhibit the expression of Oct4 in hESCs and Myf-5 in activated satellite cells, and reduce proliferation and myogenic differentiation of both embryonic and tissue-specific adult stem cells (ASCs). Therefore, despite their general neoorganogenesis potential, the ability of hESCs, and the more differentiated myogenic ASCs to contribute to tissue repair in the old will be greatly restricted due to the conserved inhibitory influence of aged differentiated niches. Significantly, this work establishes that hESC-derived factors enhance the regenerative potential of both young and, importantly, aged muscle stem cells in vitro and in vivo; thus, suggesting that the regenerative outcome of stem cell-based replacement therapies will be determined by a balance between negative influences of aged tissues on transplanted cells and positive effects of embryonic cells on the endogenous regenerative capacity. Comprehensively, this work points toward novel venues for in situ restoration of tissue repair in the old and identifies critical determinants of successful cell-replacement therapies for aged degenerating organs.