expression Expression of Interest to be released for Federation Square East By www.invest.vic.gov.au Published On :: Mon, 01 Sep 2014 16:14:00 +1000 The Victorian Government is calling for Expressions of Interest to develop Federation Square East – an iconic site in the heart of Melbourne. Global developers are invited to respond to the EOI which will be officially released to the market on Monday 15 September 2014, presenting an exciting opportunity to create a vibrant, mixed use development that may incorporate commercial components — including shops, bars and even accommodation. Full Article
expression Limassol gallery presents journey of expression By cyprus-mail.com Published On :: 2024-11-13T19:49:00+02:00 The Limassol art scene is about to welcome a new exhibition. The Larnaca-born artist, Nikolas Antoniou, returns to Lumiere Gallery in Limassol for the second time to present his exhibition titled Vibrations of Being. The showcase will run from November 20 to December 7, inviting viewers into the artist’s vivid creative journey of expression. “Antoniou’s […] Full Article Entertainment What's On whatson
expression BJP’s win in recent polls is expression of people’s faith in govt. policies: Haryana Governor By www.thehindu.com Published On :: Thu, 14 Nov 2024 07:50:35 +0530 Full Article Haryana
expression Expressions of God's love By www.om.org Published On :: Fri, 22 Jul 2011 09:43:24 +0000 OM Belgium and OM Arts creatively connect with the local community through drawings, song, poetry and flowers. Full Article
expression Coconut Grove Arts Festival set to Celebrate 60 Years of Artistic Expression By www.prleap.com Published On :: Thu, 11 Jan 2024 00:00:00 PST Considered one of the top 10 outdoor art shows in the country, the Coconut Grove Arts Festival will once again bring Miami's beloved neighborhood to life as it celebrates six decades of creativity during President's Day weekend. Full Article
expression 2002 Renault Laguna Hatchback - Expression from Croatia By www.carsurvey.org Published On :: Avoid Full Article
expression Expressions - $20 Cashback on any purchase By www.allonlinecoupons.com Published On :: $20 Cashback on any purchase Full Article
expression Expressionery - 30% off any purchase By www.allonlinecoupons.com Published On :: 30% off any purchase Full Article
expression Improving the Accuracy of Facial Micro-Expression Recognition: Spatio-Temporal Deep Learning with Enhanced Data Augmentation and Class Balancing By Published On :: 2024-10-22 Aim/Purpose: This study presents a novel deep learning-based framework designed to enhance spontaneous micro-expression recognition by effectively increasing the amount and variety of data and balancing the class distribution to improve recognition accuracy. Background: Micro-expression recognition using deep learning requires large amounts of data. Micro-expression datasets are relatively small, and their class distribution is not balanced. Methodology: This study developed a framework using a deep learning-based model to recognize spontaneous micro-expressions on a person’s face. The framework also includes several technical stages, including image and data preprocessing. In data preprocessing, data augmentation is carried out to increase the amount and variety of data and class balancing to balance the distribution of sample classes in the dataset. Contribution: This study’s essential contribution lies in enhancing the accuracy of micro-expression recognition and overcoming the limited amount of data and imbalanced class distribution that typically leads to overfitting. Findings: The results indicate that the proposed framework, with its data preprocessing stages and deep learning model, significantly increases the accuracy of micro-expression recognition by overcoming dataset limitations and producing a balanced class distribution. This leads to improved micro-expression recognition accuracy using deep learning techniques. Recommendations for Practitioners: Practitioners can utilize the model produced by the proposed framework, which was developed to recognize spontaneous micro-expressions on a person’s face, by implementing it as an emotional analysis application based on facial micro-expressions. Recommendation for Researchers: Researchers involved in the development of a spontaneous micro-expression recognition framework for analyzing hidden emotions from a person’s face are playing an essential role in advancing this field and continue to search for more innovative deep learning-based solutions that continue to explore techniques to increase the amount and variety of data and find solutions to balancing the number of sample classes in various micro-expression datasets. They can further improvise to develop deep learning model architectures that are more suitable and relevant according to the needs of recognition tasks and the various characteristics of different datasets. Impact on Society: The proposed framework could significantly impact society by providing a reliable model for recognizing spontaneous micro-expressions in real-world applications, ranging from security systems and criminal investigations to healthcare and emotional analysis. Future Research: Developing a spontaneous micro-expression recognition framework based on spatial and temporal flow requires the learning model to classify optimal features. Our future work will focus more on exploring micro-expression features by developing various alternative learning models and increasing the weights of spatial and temporal features. Full Article
expression Using Photos and Visual-Processing Assistive Technologies to Develop Self-Expression and Interpersonal Communication of Adolescents with Asperger Syndrome (AS) By Published On :: Full Article
expression Brintons Fall 2024 Self Expression Woven Carpet Collection Hiraeth By www.floortrendsmag.com Published On :: Wed, 02 Oct 2024 09:00:00 -0400 The new collection is inspired by the countryside and includes eight distinct patterns. Full Article
expression Official Development Assistance: Global Innovation Fellowships (Expressions of interest must be submitted by 6 Nov) By ifp.nyu.edu Published On :: Tue, 29 Oct 2024 03:34:53 +0000 The post Official Development Assistance: Global Innovation Fellowships (Expressions of interest must be submitted by 6 Nov) was curated by information for practice. Full Article Funding
expression Conspiracy Theories: Groups, Ideology, and Status as Three Distinct Bases for Expressions in Society By ifp.nyu.edu Published On :: Mon, 04 Nov 2024 20:58:49 +0000 Current Directions in Psychological Science, Ahead of Print. Conspiracy theories have been treated mostly as a homogeneous phenomenon in empirical research. However, to fully understand their causes and consequences, a multifaceted approach to conspiracy theories would be useful. Here, we propose an organizational framework with three facets (groups, ideology, and status) to conceptualize conspiracy theories. […] The post Conspiracy Theories: Groups, Ideology, and Status as Three Distinct Bases for Expressions in Society was curated by information for practice. Full Article Journal Article Abstracts
expression CfP: Patient preferences in psychotherapy (Deadline for expressions of interest: Oct 31) By ifp.nyu.edu Published On :: Wed, 09 Oct 2024 22:48:34 +0000 The post CfP: Patient preferences in psychotherapy (Deadline for expressions of interest: Oct 31) was curated by information for practice. Full Article Calls & Consultations
expression Call for expressions of interest: Director – IDPC Board of Directors (Deadline 1 Nov) By ifp.nyu.edu Published On :: Fri, 11 Oct 2024 21:52:43 +0000 The post Call for expressions of interest: Director – IDPC Board of Directors (Deadline 1 Nov) was curated by information for practice. Full Article Calls & Consultations
expression Call for expression of interest: National Centre for Research Methods (NCRM) By ifp.nyu.edu Published On :: Mon, 14 Oct 2024 00:03:48 +0000 The post Call for expression of interest: National Centre for Research Methods (NCRM) was curated by information for practice. Full Article Calls & Consultations
expression NIHR Global Health Mentoring Programme Research PILOT – Mentor Expression of Interest By ifp.nyu.edu Published On :: Tue, 05 Nov 2024 04:49:12 +0000 The post NIHR Global Health Mentoring Programme Research PILOT – Mentor Expression of Interest was curated by information for practice. Full Article Calls & Consultations
expression Expression, purification and crystallization of the photosensory module of phytochrome B (phyB) from Sorghum bicolor By journals.iucr.org Published On :: 2024-02-20 Sorghum, a short-day tropical plant, has been adapted for temperate grain production, in particular through the selection of variants at the MATURITY loci (Ma1–Ma6) that reduce photoperiod sensitivity. Ma3 encodes phytochrome B (phyB), a red/far-red photochromic biliprotein photoreceptor. The multi-domain gene product, comprising 1178 amino acids, autocatalytically binds the phytochromobilin chromophore to form the photoactive holophytochrome (Sb.phyB). This study describes the development of an efficient heterologous overproduction system which allows the production of large quantities of various holoprotein constructs, along with purification and crystallization procedures. Crystals of the Pr (red-light-absorbing) forms of NPGP, PGP and PG (residues 1–655, 114–655 and 114–458, respectively), each C-terminally tagged with His6, were successfully produced. While NPGP crystals did not diffract, those of PGP and PG diffracted to 6 and 2.1 Å resolution, respectively. Moving the tag to the N-terminus and replacing phytochromobilin with phycocyanobilin as the ligand produced PG crystals that diffracted to 1.8 Å resolution. These results demonstrate that the diffraction quality of challenging protein crystals can be improved by removing flexible regions, shifting fusion tags and altering small-molecule ligands. Full Article text
expression Expression Central on a Mission to Make Freedom Go Viral By www.24-7pressrelease.com Published On :: Tue, 17 Sep 2024 08:00:00 GMT The Message: Don't Keep it to Yourself – Share It Full Article
expression TeeStitch Apparel: A New Voice in Sustainable Fashion Blending Artistic Expression with Eco-Friendly Streetwear By www.24-7pressrelease.com Published On :: Thu, 03 Oct 2024 08:00:00 GMT TeeStitch Apparel introduces its eco-friendly streetwear collection, offering exclusive global artist designs on sustainable, 100% organic cotton garments. Full Article
expression Suggested reading: Hallnäs, L., & Redström, J. (2002). From use to presence: On the expressions and aesthetics of everyday computational things. By densitydesign.org Published On :: Mon, 18 Jul 2022 13:38:47 +0000 When investigating how we frame technology in the design process,... more Full Article Uncategorized critical design suggested reading
expression Regexes Got Good: The History And Future Of Regular Expressions In JavaScript By smashingmagazine.com Published On :: Tue, 20 Aug 2024 15:00:00 GMT Although JavaScript regexes used to be underpowered compared to other modern flavors, numerous improvements in recent years mean that’s no longer true. Steven Levithan evaluates the history and present state of regular expressions in JavaScript with tips to make your regexes more readable, maintainable, and resilient. Full Article
expression Atlanta Amends Anti-Discrimination Ordinance to Include Protections for Gender Expression and Criminal Histories By www.littler.com Published On :: Thu, 10 Nov 2022 15:20:07 +0000 The City Council of Atlanta, Georgia recently passed an ordinance that amends its existing anti-discrimination law to include protection on the basis of “criminal history status” as well as “gender expression.” The ordinance is effective immediately. With regard to gender expression, the law simply amends existing law to include “gender expression” as an additional protected characteristic. Full Article
expression Atlanta Amends Anti-Discrimination Ordinance to Include Protections for Gender Expression and Criminal Histories By www.littler.com Published On :: Wed, 16 Nov 2022 15:41:49 +0000 Rachel P. Kaercher, Wendy Buckingham and William J. Simmons examine a new ordinance passed by the Atlanta City Council that amends its existing anti-discrimination law to include protections on the basis of criminal history status and gender expression. SHRM Online View (Subscription required.) Full Article
expression Proteomics analysis reveals the differential protein expression of female and male adult Toxocara canis using Orbitrap Astral analyzer - Infectious Diseases of Poverty - BioMed Central By news.google.com Published On :: Wed, 09 Oct 2024 07:00:00 GMT Proteomics analysis reveals the differential protein expression of female and male adult Toxocara canis using Orbitrap Astral analyzer Infectious Diseases of Poverty - BioMed Central Full Article
expression Decrypting the molecular basis of cellular drug phenotypes by dose-resolved expression proteomics - Nature.com By news.google.com Published On :: Tue, 07 May 2024 07:00:00 GMT Decrypting the molecular basis of cellular drug phenotypes by dose-resolved expression proteomics Nature.com Full Article
expression Optimizing differential expression analysis for proteomics data via high-performing rules and ensemble inference - Nature.com By news.google.com Published On :: Thu, 09 May 2024 07:00:00 GMT Optimizing differential expression analysis for proteomics data via high-performing rules and ensemble inference Nature.com Full Article
expression Writers and human rights experts call on India to repeal laws that threaten free expression in world’s largest democracy - Writers and human rights experts call on India to repeal laws that threaten free expression in world’s largest democracy By media.utoronto.ca Published On :: Tue, 26 May 2015 17:09:57 +0000 Writers and human rights experts call on India to repeal laws that threaten free expression in world’s largest democracyToronto, ON – Earlier this year, India’s Ministry of Home Affairs used an extensive arsenal of vague and overbroad laws to muzzle the world’s largest environmental watchdog, Greenpeace International. Using seemingly innocuous provisions in the Indian Foreign Contribution (Regulation) Act […] Full Article Law Media Releases
expression PEN and IHRP report on India reveals culture of stifling dissent, criminalising free expression By media.utoronto.ca Published On :: Mon, 19 Sep 2016 16:07:50 +0000 Toronto, ON – An inefficient legal system and what amounts to unchecked abuse of vague and overbroad legislation have contributed to a chilling effect on free speech within India’s society and throughout its public sphere according to a report released today by PEN International, PEN Canada and International Human Rights Program (IHRP) at the University of […] Full Article Law Media Releases University of Toronto
expression SELF EXPRESSION By www.thecollectionshop.com Published On :: 4/10/2007 10:01:00 AM SELF EXPRESSION by Hessam is a(n) Limited Edition. The Edition is Limited to Limited Edition pcs Full Article
expression OSCE Mission in Kosovo helps youth pursue careers in journalism, promote freedom of expression By feeds.osce.org Published On :: Mon, 09 May 2016 12:33:03 +0000 PRISHTINË/PRIŠTINA, 9 May 2016 – A ten-day school of journalism organized by the OSCE Mission for around 20 young people from northern Kosovo started today in Mitrovica/Mitrovicё North. In the course of the programme, led by Davor Glavaš, a renowned journalist and lecturer at the University of Zagreb, participants will gain practical knowledge in reporting, writing skills and the use of social media and new technologies, such as blogs and web portals. Enhancing these skills will help them in their careers as well as contribute to media pluralism in Kosovo. “For democratic societies it is crucial to have well educated journalists able to report in an objective, factual and independent manner. It is also important to provide aspiring young people with education opportunities to pursue a career in journalism,” said Christopher Tuetsch, Director of the OSCE Mission in Kosovo Democratization Department. “With this activity the OSCE Mission aims to help media outlets in northern Kosovo strengthen their human capacities and enhance information pluralism offered to the public.” Following the successful completion of the programme, the top four candidates will be selected to participate in a six-month apprenticeship programme, to be implemented jointly with four media outlets in northern Kosovo: TV Mir, Radio Kosovska Mitrovica, Radio Kontakt Plus and the KoSSev web portal. The OSCE Mission in Kosovo is mandated with human rights protection and promotion, democratization and public safety sector development. It helps safeguard freedom of the media and freedom of expression, and supports media development.Related StoriesMini-Olympic Games 2016OSCE Mission-organized Junior Basketball TournamentOSCE Mission, police to discuss how to help prevent violent extremism and radicalization in Kosovo Full Article OSCE Mission in Kosovo Media freedom and development South-Eastern Europe Press release
expression [ X.1215 (01/19) ] - Use cases for structured threat information expression By www.itu.int Published On :: Fri, 05 Apr 2019 07:35:00 GMT Use cases for structured threat information expression Full Article
expression Fragments of metropolis Berlin : Berlins expressionistisches Erbe = Berlin's expressionist legacy / By search.lib.uiowa.edu Published On :: 02/22/2017 12:00 Library - Art Library, Location - LIB, Call number - NA1085 .L44 2016 Full Article
expression Four expressions I didn't know until today came from rhyming slang By johnfinnemore.blogspot.com Published On :: Sat, 26 Aug 2023 13:13:00 +0000 - Scarper; British slang for 'run away'. From Scapa Flow - Go. - Grass; as in informant. From Grasshopper - copper (and from there to copper's nark) - Dukes; slang for fists, as in 'duking it out'. From Duke of York - Fork. ('Forks' being now-forgotten slang for hands.) - Donkey's years; a long time. From Donkey's Ears, rhyming slang for Years... but then the Y crept back in. Alt Text: Donkey's ears. And between them, a donkey. Well, I suppose there's always a donkey between a donkey's ears. I mean: another one, framed in the photo between the ears of the first donkey. Glad we've got that clear. It doesn't matter in the least. Full Article Didn't Know That Yesterday Unfierce Creatures
expression Comparative Proteomic Analysis of Eleven Common Cell Lines Reveals Ubiquitous but Varying Expression of Most Proteins By www.mcponline.org Published On :: 2012-03-01 Tamar GeigerMar 1, 2012; 11:M111.014050-M111.014050Special Issue: Prospects in Space and Time Full Article
expression Complementary Profiling of Gene Expression at the Transcriptome and Proteome Levels in Saccharomyces cerevisiae By www.mcponline.org Published On :: 2002-04-01 Timothy J. GriffinApr 1, 2002; 1:323-333Research Full Article
expression Discordant Protein and mRNA Expression in Lung Adenocarcinomas By www.mcponline.org Published On :: 2002-04-01 Guoan ChenApr 1, 2002; 1:304-313Research Full Article
expression Integrated Genomic and Proteomic Analyses of Gene Expression in Mammalian Cells By www.mcponline.org Published On :: 2004-10-01 Qiang TianOct 1, 2004; 3:960-969Research Full Article
expression Analysis of the Human Tissue-specific Expression by Genome-wide Integration of Transcriptomics and Antibody-based Proteomics By www.mcponline.org Published On :: 2014-02-01 Linn FagerbergFeb 1, 2014; 13:397-406Research Full Article
expression Stable Isotope Labeling by Amino Acids in Cell Culture, SILAC, as a Simple and Accurate Approach to Expression Proteomics By www.mcponline.org Published On :: 2002-05-01 Shao-En OngMay 1, 2002; 1:376-386Research Full Article
expression Gene expression regulation by retinoic acid By www.jlr.org Published On :: 2002-11-01 James E. BalmerNov 1, 2002; 43:1773-1808Reviews Full Article
expression Role of the peroxisome proliferator-activated receptor (PPAR) in mediating the effects of fibrates and fatty acids on gene expression By www.jlr.org Published On :: 1996-05-01 K SchoonjansMay 1, 1996; 37:907-925Reviews Full Article
expression The regional and international implications of restrictions to online freedom of expression in Asia By www.chathamhouse.org Published On :: Fri, 12 Mar 2021 12:25:49 +0000 The regional and international implications of restrictions to online freedom of expression in Asia 25 March 2021 — 12:30PM TO 1:30PM Anonymous (not verified) 12 March 2021 Online Panellists discuss the latest developments affecting online freedom of expression in the Asia region. Please note this is an online event. Please register using the link below to finalize your registration. In recent years, state-led clampdowns on online freedom of expression have become widespread in several countries across Asia, further intensified by the COVID-19 crisis. The reasons for this are complex and diverse – drawing upon history, culture and politics, in addition to external influences. Across the region, governments have been accused of silencing online criticism and failing to uphold rights to free speech. Individuals have been arrested, fined or attacked for the alleged spread of ‘fake news’, raising concern among human rights organizations. In some countries, this has culminated in the imposition of new social media rules, which could require social media companies to censor posts and share decrypted messages. In China, the government’s restrictive online regime has relied on a combination of legal, technical and manipulation tactics to manage control of the internet, and now includes attempts at censorship beyond its borders. Panellists will discuss the latest regional developments affecting online freedom of expression in the Asia region, and will consider the broader regional and international implications for technology governance. This webinar launches the publication Restrictions on online freedom of expression in China: The domestic, regional and international implications of China’s policies and practices. Full Article
expression MicroRNA-98 reduces nerve growth factor expression in nicotine-induced airway remodeling [Gene Regulation] By www.jbc.org Published On :: 2020-12-25T00:06:30-08:00 Evolving evidence suggests that nicotine may contribute to impaired asthma control by stimulating expression of nerve growth factor (NGF), a neurotrophin associated with airway remodeling and airway hyperresponsiveness. We explored the hypothesis that nicotine increases NGF by reducing lung fibroblast (LF) microRNA-98 (miR-98) and PPARγ levels, thus promoting airway remodeling. Levels of NGF, miR-98, PPARγ, fibronectin 1 (FN1), endothelin-1 (EDN1, herein referred to as ET-1), and collagen (COL1A1 and COL3A1) were measured in human LFs isolated from smoking donors, in mouse primary LFs exposed to nicotine (50 μg/ml), and in whole lung homogenates from mice chronically exposed to nicotine (100 μg/ml) in the drinking water. In selected studies, these pathways were manipulated in LFs with miR-98 inhibitor (anti-miR-98), miR-98 overexpression (miR-98 mimic), or the PPARγ agonist rosiglitazone. Compared with unexposed controls, nicotine increased NGF, FN1, ET-1, COL1A1, and COL3A1 expression in human and mouse LFs and mouse lung homogenates. In contrast, nicotine reduced miR-98 levels in LFs in vitro and in lung homogenates in vivo. Treatment with anti-miR-98 alone was sufficient to recapitulate increases in NGF, FN1, and ET-1, whereas treatment with a miR-98 mimic significantly suppressed luciferase expression in cells transfected with a luciferase reporter linked to the putative seed sequence in the NGF 3'UTR and also abrogated nicotine-induced increases in NGF, FN1, and ET-1 in LFs. Similarly, rosiglitazone increased miR-98 and reversed nicotine-induced increases in NGF, FN1, and ET-1. Taken together, these findings demonstrate that nicotine-induced increases in NGF and other markers of airway remodeling are negatively regulated by miR-98. Full Article
expression Inhibition of the SUV4-20 H1 histone methyltransferase increases frataxin expression in Friedreich's ataxia patient cells [Gene Regulation] By www.jbc.org Published On :: 2020-12-25T00:06:30-08:00 The molecular mechanisms of reduced frataxin (FXN) expression in Friedreich's ataxia (FRDA) are linked to epigenetic modification of the FXN locus caused by the disease-associated GAA expansion. Here, we identify that SUV4-20 histone methyltransferases, specifically SUV4-20 H1, play an important role in the regulation of FXN expression and represent a novel therapeutic target. Using a human FXN–GAA–Luciferase repeat expansion genomic DNA reporter model of FRDA, we screened the Structural Genomics Consortium epigenetic probe collection. We found that pharmacological inhibition of the SUV4-20 methyltransferases by the tool compound A-196 increased the expression of FXN by ∼1.5-fold in the reporter cell line. In several FRDA cell lines and patient-derived primary peripheral blood mononuclear cells, A-196 increased FXN expression by up to 2-fold, an effect not seen in WT cells. SUV4-20 inhibition was accompanied by a reduction in H4K20me2 and H4K20me3 and an increase in H4K20me1, but only modest (1.4–7.8%) perturbation in genome-wide expression was observed. Finally, based on the structural activity relationship and crystal structure of A-196, novel small molecule A-196 analogs were synthesized and shown to give a 20-fold increase in potency for increasing FXN expression. Overall, our results suggest that histone methylation is important in the regulation of FXN expression and highlight SUV4-20 H1 as a potential novel therapeutic target for FRDA. Full Article
expression Importance of endothelial Hey1 expression for thoracic great vessel development and its distal enhancer for Notch-dependent endothelial transcription [Gene Regulation] By www.jbc.org Published On :: 2020-12-18T00:06:18-08:00 Thoracic great vessels such as the aorta and subclavian arteries are formed through dynamic remodeling of embryonic pharyngeal arch arteries (PAAs). Previous work has shown that loss of a basic helix-loop-helix transcription factor Hey1 in mice causes abnormal fourth PAA development and lethal great vessel anomalies resembling congenital malformations in humans. However, how Hey1 mediates vascular formation remains unclear. In this study, we revealed that Hey1 in vascular endothelial cells, but not in smooth muscle cells, played essential roles for PAA development and great vessel morphogenesis in mouse embryos. Tek-Cre–mediated Hey1 deletion in endothelial cells affected endothelial tube formation and smooth muscle differentiation in embryonic fourth PAAs and resulted in interruption of the aortic arch and other great vessel malformations. Cell specificity and signal responsiveness of Hey1 expression were controlled through multiple cis-regulatory regions. We found two distal genomic regions that had enhancer activity in endothelial cells and in the pharyngeal epithelium and somites, respectively. The novel endothelial enhancer was conserved across species and was specific to large-caliber arteries. Its transcriptional activity was regulated by Notch signaling in vitro and in vivo, but not by ALK1 signaling and other transcription factors implicated in endothelial cell specificity. The distal endothelial enhancer was not essential for basal Hey1 expression in mouse embryos but may likely serve for Notch-dependent transcriptional control in endothelial cells together with the proximal regulatory region. These findings help in understanding the significance and regulation of endothelial Hey1 as a mediator of multiple signaling pathways in embryonic vascular formation. Full Article
expression Molecular characterization of the RNA-protein complex directing -2/-1 programmed ribosomal frameshifting during arterivirus replicase expression [Protein Structure and Folding] By www.jbc.org Published On :: 2020-12-25T00:06:30-08:00 Programmed ribosomal frameshifting (PRF) is a mechanism used by arteriviruses like porcine reproductive and respiratory syndrome virus (PRRSV) to generate multiple proteins from overlapping reading frames within its RNA genome. PRRSV employs −1 PRF directed by RNA secondary and tertiary structures within its viral genome (canonical PRF), as well as a noncanonical −1 and −2 PRF that are stimulated by the interactions of PRRSV nonstructural protein 1β (nsp1β) and host protein poly(C)-binding protein (PCBP) 1 or 2 with the viral genome. Together, nsp1β and one of the PCBPs act as transactivators that bind a C-rich motif near the shift site to stimulate −1 and −2 PRF, thereby enabling the ribosome to generate two frameshift products that are implicated in viral immune evasion. How nsp1β and PCBP associate with the viral RNA genome remains unclear. Here, we describe the purification of the nsp1β:PCBP2:viral RNA complex on a scale sufficient for structural analysis using small-angle X-ray scattering and stochiometric analysis by analytical ultracentrifugation. The proteins associate with the RNA C-rich motif as a 1:1:1 complex. The monomeric form of nsp1β within the complex differs from previously reported homodimer identified by X-ray crystallography. Functional analysis of the complex via mutational analysis combined with RNA-binding assays and cell-based frameshifting reporter assays reveal a number of key residues within nsp1β and PCBP2 that are involved in complex formation and function. Our results suggest that nsp1β and PCBP2 both interact directly with viral RNA during formation of the complex to coordinate this unusual PRF mechanism. Full Article
expression Coronavirus infection and PARP expression dysregulate the NAD metabolome: An actionable component of innate immunity [Molecular Bases of Disease] By www.jbc.org Published On :: 2020-12-25T00:06:30-08:00 Poly(ADP-ribose) polymerase (PARP) superfamily members covalently link either a single ADP-ribose (ADPR) or a chain of ADPR units to proteins using NAD as the source of ADPR. Although the well-known poly(ADP-ribosylating) (PARylating) PARPs primarily function in the DNA damage response, many noncanonical mono(ADP-ribosylating) (MARylating) PARPs are associated with cellular antiviral responses. We recently demonstrated robust up-regulation of several PARPs following infection with murine hepatitis virus (MHV), a model coronavirus. Here we show that SARS-CoV-2 infection strikingly up-regulates MARylating PARPs and induces the expression of genes encoding enzymes for salvage NAD synthesis from nicotinamide (NAM) and nicotinamide riboside (NR), while down-regulating other NAD biosynthetic pathways. We show that overexpression of PARP10 is sufficient to depress cellular NAD and that the activities of the transcriptionally induced enzymes PARP7, PARP10, PARP12 and PARP14 are limited by cellular NAD and can be enhanced by pharmacological activation of NAD synthesis. We further demonstrate that infection with MHV induces a severe attack on host cell NAD+ and NADP+. Finally, we show that NAMPT activation, NAM, and NR dramatically decrease the replication of an MHV that is sensitive to PARP activity. These data suggest that the antiviral activities of noncanonical PARP isozyme activities are limited by the availability of NAD and that nutritional and pharmacological interventions to enhance NAD levels may boost innate immunity to coronaviruses. Full Article
expression FAP and PSMA Expression by Immunohistochemistry and PET Imaging in Castration-Resistant Prostate Cancer: A Translational Pilot Study By jnm.snmjournals.org Published On :: 2024-10-30T08:04:15-07:00 Visual Abstract Full Article
expression Dysregulation of hsa-miR-34a and hsa-miR-449a leads to overexpression of PACS-1 and loss of DNA damage response (DDR) in cervical cancer [Cell Biology] By www.jbc.org Published On :: 2020-12-11T00:06:20-08:00 We have observed overexpression of PACS-1, a cytosolic sorting protein in primary cervical tumors. Absence of exonic mutations and overexpression at the RNA level suggested a transcriptional and/or posttranscriptional regulation. University of California Santa Cruz genome browser analysis of PACS-1 micro RNAs (miR), revealed two 8-base target sequences at the 3' terminus for hsa-miR-34a and hsa-miR-449a. Quantitative RT-PCR and Northern blotting studies showed reduced or loss of expression of the two microRNAs in cervical cancer cell lines and primary tumors, indicating dysregulation of these two microRNAs in cervical cancer. Loss of PACS-1 with siRNA or exogenous expression of hsa-miR-34a or hsa-miR-449a in HeLa and SiHa cervical cancer cell lines resulted in DNA damage response, S-phase cell cycle arrest, and reduction in cell growth. Furthermore, the siRNA studies showed that loss of PACS-1 expression was accompanied by increased nuclear γH2AX expression, Lys382-p53 acetylation, and genomic instability. PACS-1 re-expression through LNA-hsa-anti-miR-34a or -449a or through PACS-1 cDNA transfection led to the reversal of DNA damage response and restoration of cell growth. Release of cells post 24-h serum starvation showed PACS-1 nuclear localization at G1-S phase of the cell cycle. Our results therefore indicate that the loss of hsa-miR-34a and hsa-miR-449a expression in cervical cancer leads to overexpression of PACS-1 and suppression of DNA damage response, resulting in the development of chemo-resistant tumors. Full Article