gebhart/patrepeval huggingface dataset:
TAX1BP1 and A20 Inhibit Antiviral Signaling by Targeting TBK1-IKKi Kinases (2010)

Induction of type I interferons by the transcription factor IRF3 is essential in the initiation of antiviral innate immunity. Activation of IRF3 requires C-terminal phosphorylation by the upstream kinases TBK1-IKKi, where IRF3 phosphorylation promotes dimerization, and subsequent nuclear translocation to the IFNbeta promoter. Recent studies have described the ubiquitin-editing enzyme A20 as a negative regulator of IRF3 signaling by associating with TBK1-IKKi; however, the regulatory mechanism of A20 inhibition remains unclear. Here we describe the adaptor protein, TAX1BP1, as a key regulator of A20 function in terminating signaling to IRF3. Murine embryonic fibroblasts (MEFs) deficient in TAX1BP1 displayed increased amounts of IFNbeta production upon viral challenge compared with WT MEFs. TAX1BP1 inhibited virus-mediated activation of IRF3 at the level of TBK1-IKKi. TAX1BP1 and A20 blocked antiviral signaling by disrupting Lys(63)-linked polyubiquitination of TBK1-IKKi independently of the A20 deubiquitination domain. Furthermore, TAX1BP1 was required for A20 effector function because A20 was defective for the targeting and inactivation of TBK1 and IKKi in Tax1bp1(-)(/)(-) MEFs. Additionally, we found the E3 ubiquitin ligase TRAF3 to play a critical role in promoting TBK1-IKKi ubiquitination. Collectively, our results demonstrate TBK1-IKKi to be novel substrates for A20 and further identify a novel mechanism whereby A20 and TAX1BP1 restrict antiviral signaling by disrupting a TRAF3-TBK1-IKKi signaling complex.
Diversity Considerations in HIV-1 Vaccine Selection (2002)

Globally, human immunodeficiency virus-type 1 (HIV-1) is extraordinarily variable, and this diversity poses a major obstacle to AIDS vaccine development. Currently, candidate vaccines are derived from isolates, with the hope that they will be sufficiently cross-reactive to protect against circulating viruses. This may be overly optimistic, however, given that HIV-1 envelope proteins can differ in more than 30% of their amino acids. To contend with the diversity, country-specific vaccines are being considered, but evolutionary relationships may be more useful than regional considerations. Consensus or ancestor sequences could be used in vaccine design to minimize the genetic differences between vaccine strains and contemporary isolates, effectively reducing the extent of diversity by half.
Self-Rated Effectiveness of Microdosing With Psychedelics for Mental and Physical Health Problems Among Microdosers (2019)

<b>Background:</b> There is a growing interest in the use of psychedelic substances for health related purposes, including symptom relief for disorders like anxiety, depression, and pain. Although the focus of recent clinical trials has been on high doses of these substances, anecdotal evidence suggests that low (micro) doses are also effective, and may be more suitable for certain conditions. Nonetheless, empirical evidence regarding the efficacy of microdosing with psychedelics for symptomatic relief is lacking. The present study aimed to investigate, by means of an online questionnaire, the self-rated effectiveness (SRE) of microdosing with psychedelics (MDP) for mental and physiological disorders compared to the conventional prescribed treatment and to regular doses of psychedelics. <b>Methods:</b> An online questionnaire was launched on several websites and fora between March and July 2018. Respondents who had consented, were 18 years of age or older, had experience with microdosing and were diagnosed with at least one mental or physiological disorder by a medical doctor or therapist (<i>N</i> = 410; 7.2%) were included in the analyses. Odds ratio were calculated to compare the SRE of MDP with conventional treatment, and regular psychedelic doses for mental and physiological diagnoses for each of the three effectiveness questions ("Did it work," "Symptom disappear," "Quality of life improved"). <b>Results:</b> Odds ratio showed that SRE of MDP was significantly higher compared to that of conventional treatments for both mental and physiological diagnoses; and that these effects were specific for ADHD/ADD and anxiety disorders. In contrast, SRE of MDP was lower compared to that of higher, regular psychedelic doses for mental disorders such as anxiety and depression, while for physiological disorders no difference was shown. <b>Conclusion:</b> This study demonstrates that SRE of MDP to alleviate symptoms of a range of mental or physiological diagnoses is higher compared to conventionally offered treatment options, and lower than regular ('full') psychedelic doses. Future RCTs in patient populations should objectively assess the effectivity claims of psychedelics, and whether these are dose related, disorder specific, and superior to conventional treatments.
An observational prospective study of topical acidified nitrite for killing methicillin-resistant Staphylococcus aureus (MRSA) in contaminated wounds (2011)

Nitric oxide and acidified nitrite offer a novel therapy for control of MRSA in wounds. Wounds that were not cleared of infection may have been re-contaminated or the bioavailability of acidified nitrite impaired by local factors in the tissue.
The pattern of flavan-3-ols in relation to scab resistance of apple cultivars (1990)

Amounts and types of flavan-3-ols in leaves and fruit skins of scab-resistant and susceptible apple cultivars were determined by the combined use of HPLC and CRD (chemical reaction detection). The latter is necessary because the UV absorption spectra of flavanols are generally uninformative. Resistant cultivars had higher quantities of fla- van-3-ols in leaf tissue and fruit skin than susceptible ones: levels were 6.5 fold higher in leaves and 3 fold higher in fruit skins. Approximately twice the number of different fla- van-3-ols were found in leaves and fruit skin of the resistant group than in the susceptible one.
Methanesulfonic acid catalyzed cyclization of 3-arylpropanoic and 4-arylbutanoic acids to 1-indanones and 1-tetralones (1981)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMethanesulfonic acid catalyzed cyclization of 3-arylpropanoic and 4-arylbutanoic acids to 1-indanones and 1-tetralonesVuppalapaty Premasagar, Venkatapuram A. Palaniswamy, and Edmund J. EisenbraunCite this: J. Org. Chem. 1981, 46, 14, 2974–2976Publication Date (Print):July 1, 1981Publication History Published online1 May 2002Published inissue 1 July 1981https://pubs.acs.org/doi/10.1021/jo00327a028https://doi.org/10.1021/jo00327a028research-articleACS PublicationsRequest reuse permissionsArticle Views1249Altmetric-Citations66LEARN 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-Alertsclose Get e-Alerts
Olanzapine‐Associated Diabetes Mellitus (2002)

Number of reports, temporal relationship to start of olanzapine therapy, relatively young age, and improvement on drug withdrawal suggest that olanzapine may precipitate or unmask diabetes in susceptible patients.
Nitrogen-15 nuclear magnetic resonance spectroscopy. XIII. Pyridine-15N (1971)

From high-resolution proton, ^(13)C, and ^(15)N nuclear magnetic resonance spectra of ^(15)N-enriched pyridine and its hydrochloride, all of the chemical shifts, ^(15)N-H, and ^(l5)N-^(13)C coupling constants have been obtained. Attention is centered on the coupling constants, which are compared with other values and discussed in light of the known inapplicability to pyridine of the average energy approximation. The coupling ^2J_(NH)exhibits the normal dependence on geometry, and the algebraic increase observed on protonation parallels the behavior exhibited by other acyclic compounds with unsaturated nitrogen. The coupling ^1J_(NC) in pyridine increases 30-fold on protonation, which accords with qualitative predictions. In contrast to the absence of C-N coupling over more than one bond in saturated systems (glycine, alanine, 1,l-dimethylhydrazine), pyridine and pyridinium ion display substantial C-N couplings over two and three bonds. Because large two-bond C-N couplings are also observed in methylnitrosamine as well as in some amides, the presence of a π system is felt to be important for the longer range couplings. Substantial solvent effects are observed on these couplings which may be attributed to increasing hydrogen bonding at nitrogen. On the basis of changes in ^(15)N chemical shifts and ^(15)N-H coupling constants, ^lJ_(NC) is shown to very likely undergo a change in sign when the nitrogen is protonated.
Drug Delivery for Treatment of Inner Ear Disease: Current State of Knowledge (2010)

Delivery of medications to the inner ear has been an area of considerable growth in both the research and clinical realms during the past several decades. Systemic delivery of medication destined for treatment of the inner ear is the foundation on which newer delivery techniques have been developed. Because of systemic side effects, investigators and clinicians have begun developing and using techniques to deliver therapeutic agents locally. Alongside the now commonplace use of intratympanic gentamicin for Meniere's disease and the emerging use of intratympanic steroids for sudden sensorineural hearing loss, novel technologies, such as hydrogels and nanoparticles, are being explored. At the horizon of inner ear drug-delivery techniques, intracochlear devices that leverage recent advances in microsystems technology are being developed to apply medications directly into the inner ear. Potential uses for such devices include neurotrophic factor and steroid delivery with cochlear implantation, RNA interference technologies, and stem-cell therapy. The historical, current, and future delivery techniques and uses of drug delivery for treatment of inner ear disease serve as the basis for this review.
Worldwide variation in the performance of children and adolescents: An analysis of 109 studies of the 20-m shuttle run test in 37 countries (2006)

This study is a meta-analysis of 109 reports of the performance of children and adolescents on the 20-m shuttle run test (20-mSRT). The studies were performed in 37 countries and included data on 418,026 children, tested between 1981 and 2003. Results were expressed as running speed (km x h(-1)) at the final completed stage of the 20-mSRT. Raw data were combined with pseudodata using Monte Carlo simulation. The 20-mSRT performances were expressed as z-scores relative to all children of the same age and sex from all countries. An overall "performance index" was derived for each country as the average of the age- and sex-specific z-scores for all children from that country. Factorial analysis of variance was used to compare scores among countries and regions, and between boys and girls of the same age. There was wide and significant (P < 0.0001) global variability in the performance of children. The best performing children were from the Northern European countries Estonia, Iceland, Lithuania, and Finland (0.6 - 0.9 standard deviations above the global average). The worst performing children were from Singapore, Brazil, USA, Italy, Portugal, and Greece (0.4 - 0.9 standard deviations below the global average). There is evidence that performance was negatively related to being overweight, as well as to a country's average temperature.
Stimulation of CD5 enhances signal transduction by the T cell antigen receptor. (1990)

After the addition of a CD3 monoclonal antibody to peripheral T cells that have been previously stimulated with phytohemagglutinin, inositol phosphates are produced at a rapid rate for 2 min and at a much slower rate thereafter. Stimulation of CD5 allows CD3-mediated production of inositol phosphates to be sustained at a brisk rate for greater than 20 min and augments the initial CD3-mediated increase in inositol trisphosphate and release of intracellular Ca2+. Thus, perturbation of CD5 by monoclonal antibody enhances the ability of the CD3-antigen receptor complex to couple to the inositol phospholipid pathway. This effect of CD5 is independent of any direct effect of the CD5 monoclonal antibody on the levels of inositol phosphates.
Vagal nerve stimulation improves cerebellar tremor and dysphagia in multiple sclerosis (2007)

Vagus nerve stimulation (VNS), an adjunctive approach for the treatment of epilepsy, was performed in three multiple sclerosis (MS) patients displaying postural cerebellar tremor (PCT) and dysphagia. Following VNS, improvement of PCT and dysphagia was manifested over a period of two and three months, respectively. In view of the involvement of the main brainstem visceral component of the vagus, the nucleus tractus solitarius (NTS), in modulating central pattern generators (CPGs) linked to both olive complex pathway and swallowing, improvement is likely to be VNS related. The results obtained suggest an additional therapeutic application for VNS and may represent a novel form of treatment in patients with severe MS.
Thrombospondin-1 and Pathogenesis of Age-Related Macular Degeneration (2015)

The cardinal features of age-related macular degeneration (AMD) are the accumulation of subretinal debris, subretinal inflammation, neovascularization, and degeneration of the photoreceptors and retinal pigment epithelium (RPE). Thrombospondin-1 (TSP-1) is a major matricellular protein that is physiologically expressed in the RPE and choroid, but severely diminished in eyes with AMD. TSP-1 plays an important role in phagocytosis, potently inhibits neovascularization, and mediates immune suppression and immune privilege. The lack of TSP-1 could have a central role in the pathogenesis of AMD as it is implicated in the major pathways that seem to be deficient in the disease. We here give an overview of the major functions of TSP-1 and how it could intervene in AMD pathogenesis.
Role of Protein Translocation Pathways across the Endoplasmic Reticulum in Trypanosoma brucei (2008)

The translocation of secretory and membrane proteins across the endoplasmic reticulum (ER) membrane is mediated by co-translational (via the signal recognition particle (SRP)) and post-translational mechanisms. In this study, we investigated the relative contributions of these two pathways in trypanosomes. A homologue of SEC71, which functions in the post-translocation chaperone pathway in yeast, was identified and silenced by RNA interference. This factor is essential for parasite viability. In SEC71-silenced cells, signal peptide (SP)-containing proteins traversed the ER, but several were mislocalized, whereas polytopic membrane protein biogenesis was unaffected. Surprisingly trypanosomes can interchangeably utilize two of the pathways to translocate SP-containing proteins except for glycosylphosphatidylinositol-anchored proteins, whose level was reduced in SEC71-silenced cells but not in cells depleted for SRP68, an SRP-binding protein. Entry of SP-containing proteins to the ER was significantly blocked only in cells co-silenced for the two translocation pathways (SEC71 and SRP68). SEC63, a factor essential for both translocation pathways in yeast, was identified and silenced by RNA interference. SEC63 silencing affected entry to the ER of both SP-containing proteins and polytopic membrane proteins, suggesting that, as in yeast, this factor is essential for both translocation pathways in vivo. This study suggests that, unlike bacteria or other eukaryotes, trypanosomes are generally promiscuous in their choice of mechanism for translocating SP-containing proteins to the ER, although the SRP-independent pathway is favored for glycosylphosphatidylinositol-anchored proteins, which are the most abundant surface proteins in these parasites.
246. Optical Control of Mammalian Endogenous Transcription and Epigenetic States (2014)

The dynamic nature of gene expression enables cellular programming, homeostasis and environmental adaptation in living systems. Dissection of causal gene functions in cellular and organismal processes therefore necessitates approaches that enable spatially and temporally precise modulation of gene expression. Recently, a variety of microbial and plant-derived light-sensitive proteins have been engineered as optogenetic actuators, enabling high-precision spatiotemporal control of many cellular functions. However, versatile and robust technologies that enable optical modulation of transcription in the mammalian endogenous genome remain elusive. Here we describe the development of light-inducible transcriptional effectors (LITEs), an optogenetic two-hybrid system integrating the customizable TALE DNA-binding domain with the light-sensitive cryptochrome 2 protein and its interacting partner CIB1 from Arabidopsis thaliana. LITEs do not require additional exogenous chemical cofactors, are easily customized to target many endogenous genomic loci, and can be activated within minutes with reversibility. LITEs can be packaged into viral vectors and genetically targeted to probe specific cell populations. We have applied this system in primary mouse neurons, as well as in the brain of freely behaving mice in vivo to mediate reversible modulation of mammalian endogenous gene expression as well as targeted epigenetic chromatin modifications. We explore the modularity of the LITE approach through the development of CRISPR/Cas9 transcriptional effectors in either constitutively active or light-inducible contexts. The LITE system establishes a novel mode of optogenetic control of endogenous cellular processes and enables direct testing of the causal roles of genetic and epigenetic regulation in normal biological processes and disease states.
X‐Ray absorption fine structure analysis of the local environment of zinc in dentine treated with zinc compounds (2005)

It has been reported that zinc oxide (ZnO) inhibits dentine demineralization. By using the X-ray absorption fine structure (XAFS) technique, our aims in this study were to provide information about the local environment of zinc atoms in dentine that had been treated with zinc compounds. We measured the Zn K-edge X-ray absorption near-edge structure (XANES) and the extended X-ray absorption fine structure (EXAFS) of dentine specimens treated with zinc chloride or ZnO. In XAFS analyses, the spectra of dentine specimens treated with ZnO (D-ZO) or with zinc chloride (D-ZC) were similar and obviously different from the reference ZnO spectrum. This suggests that most of the zinc atoms detected in D-ZO are not derived from particles of ZnO. The spectra of D-ZO and D-ZC were similar to the spectrum of the synthetic, zinc-containing hydroxyapatite, but were not similar to that of zinc in ZnCl2-treated collagen. The results of this study suggest that most of the zinc atoms detected were attached to hydroxyapatite and not to collagen.
Radionuclide photon dose kernels for internal emitter dosimetry (1996)

Photon point dose kernels and absorbed fractions were generated in water for the full photon emission spectrum of each radionuclide of interest in nuclear medicine, by simulating the transport of particles using Monte Carlo. The kernels were then fitted to a mathematical expression. Absorbed fractions for point sources were obtained by integrating the kernels over spheres. Photon dose kernels and absorbed fractions were generated for the following radionuclides: I-123, I-124, I-125, I-131, In-111, Cu-64, Cu-67, Ga-67, Ga-68, Re-186, Re-188, Sm-153, Sn-117m, Tc-99m. The Monte Carlo simulation was verified by comparing the dose kernels to published monoenergetic photon kernels. Further validation was obtained by generating an I-125 brachytherapy seed kernel and comparing it with published data. Since Monte Carlo simulation was initialized by sampling from the complete photon spectra of these radionuclides, interpolation between monoenergetic kernels and absorbed fractions was not required. The absorbed-fraction due to uniform spherical distributions can be directly applied for use in internal dosimetry. In addition, the kernels can be used as input for three-dimensional internal dosimetry calculations.
Arabidopsis Tic110 Is Essential for the Assembly and Function of the Protein Import Machinery of Plastids (2005)

The translocon at the inner envelope membrane of chloroplasts (Tic) plays a central role in plastid biogenesis by coordinating the sorting of nucleus-encoded preproteins across the inner membrane and coordinating the interactions of preproteins with the processing and folding machineries of the stroma. Despite these activities, the precise roles of known Tic proteins in translocation, sorting, and preprotein maturation have not been defined. In this report, we examine the in vivo function of a major Tic component, Tic110. We demonstrate that Arabidopsis thaliana Tic110 (atTic110) is essential for plastid biogenesis and plant viability. The downregulation of atTic110 expression results in the reduced accumulation of a wide variety of plastid proteins. The expression of dominant negative mutants of atTic110 disrupts assembly of Tic complexes and the translocation of preproteins across the inner envelope membrane. Together, these data suggest that Tic110 plays a general role in the import of nuclear-encoded preproteins as a common component of Tic complexes.
PML mediates IFN-α–induced apoptosis in myeloma by regulating TRAIL induction (2005)

Interferon (IFN) induces expression of proapoptotic genes and has been used in the clinical treatment of multiple myeloma. The promyelocytic leukemia (PML) gene is an IFN-induced target that encodes a tumor suppressor protein. PML protein is typically localized within discrete speckled nuclear structures termed PML nuclear bodies (NBs). Multiple myeloma cells demonstrate differential responses to IFN treatment, the mechanism of which is largely unknown. Herein, we show that growth inhibition effects of IFN-alpha in myeloma cells correlate with PML NBs and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induction, whereas known IFN targets including signal transducer and activator of transcription-1 (STAT1), STAT3, p38, and Daxx cannot account for these differential responses. RNAi silencing of PML blocks IFN-alpha-induced apoptosis in myeloma cells and correspondingly down-regulates TRAIL expression. Similarly, stable expression of a dominant negative TRAIL receptor DR5 partially blocks IFN-induced cell death. These results demonstrate that PML and TRAIL play important roles in IFN-induced apoptosis and identify TRAIL as a novel downstream transcriptional target of PML. Identification of PML and PML NBs as effectors of IFN responses provides insights into mechanisms by which tumor cells exhibit resistance to this class of agents and may prove useful in assessing treatment regimens.