pli China’s Strategic Motivations in the Indo-Pacific and Implications for US-China Competition By www.eastwestcenter.org Published On :: Thu, 16 Jul 2020 23:12:13 +0000 China’s Strategic Motivations in the Indo-Pacific and Implications for US-China Competition China’s Strategic Motivations in the Indo-Pacific and Implications for US-China Competition ferrard Thu, 07/16/2020 - 13:12 Jun 24, 2020 Jun 24, 2020 Politics & International Relations Politics & International Relations China China United States United States Web Article Home EWC Feeds Recent online articles and analysis that have been published on the East-West Center website. Explore search All Programs All Regions All Topics Release Date Filters Reset filters Web Article Home EWC Feeds Recent online articles and analysis that have been published on the East-West Center website. Explore search All Programs All Regions All Topics Release Date Filters Reset filters Full Article
pli Implications of Trump’s election on SA and global trade By www.iol.co.za Published On :: Tue, 12 Nov 2024 16:24:59 GMT Full Article
pli China clamps down on quest for soup dumplings by 'Night Riding Army' By www.voanews.com Published On :: Mon, 11 Nov 2024 00:08:46 -0500 BEIJING — Police in central China imposed traffic curbs at the weekend to halt a viral craze in which thousands of university students borrowed shared bikes to ride overnight to the city of Kaifeng in search of breakfast. The "Night Riding Army," as some participants described it, clogged a highway on Friday, pictures posted on social media showed, a surge in turnout for a rolling flash mob that had been gathering riders for months. "Last night's 'Night Riding Army' was spectacular!" one rider posted. "Two lanes were opened, but that simply was not enough: The cycling army accounted for four!" The event was part of a trend of young Chinese traveling on the cheap - "like special forces" - and spending as little as possible at a time of scarce job prospects, when wages are under pressure. The riders traveled on a straight road more than 60 km (37 miles) long beside the Yellow River that links Zhengzhou, the largest city in Henan province, with Kaifeng, an ancient capital famed for its soup dumplings. The trend was set off in June, Chinese media said, after four women college students chronicled their ride on social media to eat dumplings in the morning. "The Night Ride to Kaifeng: Youth is priceless, enjoy it in time," was the hashtag on social media for the ride, which state broadcaster CMG said tens of thousands of students had completed by the weekend. Key to its success was a glut of shared bikes, which can be rented for as little as $1.95 a month. Pictures posted by riders showed thousands of the bikes had overrun downtown Kaifeng by Saturday. In addition to the traffic controls, the largest bike-sharing platforms, Hellobike, DiDi Bike, and Mobile, said their vehicles would lock down if ridden out of a designated zone, while media told the students to grow up. "Youthful freedom does not mean following the trend and indulging oneself," one news outlet admonished in a comment. "Kaifeng is worth arriving slowly and savoring carefully," read the headline of another. Chinese authorities have cracked down on other spontaneous gatherings. Last month, police turned out in force in the commercial hub of Shanghai to deter a repeat of 2023 Halloween celebrations in which some revelers wore costumes poking fun at issues such as the stock market, youth unemployment and tough COVID-19 curbs. Full Article China News East Asia
pli Asia Studies Visiting Fellowship Application By www.eastwestcenter.org Published On :: Mon, 17 Oct 2022 14:40:13 +0000 Asia Studies Visiting Fellowship Application lynchk Mon, 10/17/2022 - 04:40 Jan 10, 2021 Education & Exchange Leadership Full Article
pli Congressional Staff Program on Korea Application By www.eastwestcenter.org Published On :: Mon, 17 Oct 2022 18:09:53 +0000 Congressional Staff Program on Korea Application lynchk Mon, 10/17/2022 - 08:09 Mar 26, 2023 North Korea South Korea Economics Environment & Climate Governance Leadership Politics & International Relations Science & Technology Full Article
pli Women in Buddhism Application Information By www.eastwestcenter.org Published On :: Tue, 08 Nov 2022 19:32:32 +0000 Women in Buddhism Application Information watanabe Tue, 11/08/2022 - 09:32 Dec 1, 2022 Full Article
pli US-Korea Commercial Relations Beyond Washington & Seoul Application By www.eastwestcenter.org Published On :: Wed, 08 Mar 2023 15:52:41 +0000 US-Korea Commercial Relations Beyond Washington & Seoul Application jacksonl Wed, 03/08/2023 - 05:52 Mar 26, 2023 South Korea Economics Education & Exchange Governance Science & Technology Full Article
pli 전문가 교류 및 공동연구 프로그램 - KIET Applicants By www.eastwestcenter.org Published On :: Mon, 27 Mar 2023 04:33:25 +0000 전문가 교류 및 공동연구 프로그램 - KIET Applicants jacksonl Sun, 03/26/2023 - 18:33 Mar 26, 2023 South Korea Economics Education & Exchange Governance Urbanization Full Article
pli 한국-미국 비즈니스 및 경제 관계 – 서울과 워싱턴 DC를 넘어서 (KITA applicants) By www.eastwestcenter.org Published On :: Mon, 27 Mar 2023 05:48:28 +0000 한국-미국 비즈니스 및 경제 관계 – 서울과 워싱턴 DC를 넘어서 (KITA applicants) jacksonl Sun, 03/26/2023 - 19:48 Mar 26, 2023 South Korea Economics Education & Exchange Governance Urbanization Full Article
pli Summer Institute 2023: Women in Buddhism Application By www.eastwestcenter.org Published On :: Tue, 08 Nov 2022 19:20:08 +0000 Summer Institute 2023: Women in Buddhism Application watanabe Tue, 11/08/2022 - 09:20 Dec 1, 2022 Arts & Culture Education & Exchange Gender Equality Full Article
pli Congressional Program on US-Japan Relations and the Indo-Pacific Application By www.eastwestcenter.org Published On :: Wed, 30 Nov 2022 16:49:07 +0000 Congressional Program on US-Japan Relations and the Indo-Pacific Application lynchk Wed, 11/30/2022 - 06:49 Dec 5, 2023 Japan Governance Leadership Politics & International Relations Full Article
pli Next-Generation Vision Consortium on ROK-US and the Indo-Pacific Application By www.eastwestcenter.org Published On :: Mon, 17 Oct 2022 16:58:48 +0000 Next-Generation Vision Consortium on ROK-US and the Indo-Pacific Application lynchk Mon, 10/17/2022 - 06:58 Oct 23, 2022 East Asia South Korea United States Pacific South Asia Southeast Asia Economics Leadership Politics & International Relations Science & Technology Full Article
pli Congressional Staff Program on Australia (CSPAUS) Application By www.eastwestcenter.org Published On :: Mon, 07 Aug 2023 16:47:29 +0000 Congressional Staff Program on Australia (CSPAUS) Application jacksonl1 Mon, 08/07/2023 - 06:47 Aug 7, 2023 Australia Politics & International Relations Full Article
pli Summer Institute 2023: Modern China in Three Keys Application By www.eastwestcenter.org Published On :: Wed, 02 Nov 2022 20:48:20 +0000 Summer Institute 2023: Modern China in Three Keys Application watanabe Wed, 11/02/2022 - 10:48 Nov 2, 2022 China Arts & Culture Education & Exchange Full Article
pli Summer Institute 2024: Modern Southeast Asia Application By www.eastwestcenter.org Published On :: Thu, 10 Aug 2023 23:03:30 +0000 Summer Institute 2024: Modern Southeast Asia Application watanabe Thu, 08/10/2023 - 13:03 Nov 1, 2023 Southeast Asia Arts & Culture Education & Exchange Full Article
pli Project Governance Graduate Fellowship Application By www.eastwestcenter.org Published On :: Fri, 14 Oct 2022 01:07:45 +0000 Project Governance Graduate Fellowship Application fairfieb Thu, 10/13/2022 - 15:07 Aug 1, 2023 Pacific Education & Exchange Governance Full Article
pli Obuchi Student Scholarship Application By www.eastwestcenter.org Published On :: Fri, 14 Oct 2022 01:01:56 +0000 Obuchi Student Scholarship Application fairfieb Thu, 10/13/2022 - 15:01 Aug 2, 2024 Japan Education & Exchange Full Article
pli Financial mismanagement: Gauteng Health Department’s R743 million debt to suppliers By www.iol.co.za Published On :: Sun, 10 Nov 2024 11:57:00 GMT Full Article
pli Una tumba vacía con una explicación angelical A By feeds.gracia.org Published On :: Tue, 26 Mar 2024 00:00:00 PST La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.Click the icon below to listen. Full Article
pli Una tumba vacía con una explicación angelical B By feeds.gracia.org Published On :: Wed, 27 Mar 2024 00:00:00 PST La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.Click the icon below to listen. Full Article
pli Actitudes cristianas fundamentales: Disciplina personal, 1ª Pte. A By feeds.gracia.org Published On :: Wed, 05 Jun 2024 00:00:00 PST La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.Click the icon below to listen. Full Article
pli Actitudes cristianas fundamentales: Disciplina personal, 1ª Pte. B By feeds.gracia.org Published On :: Thu, 06 Jun 2024 00:00:00 PST La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.Click the icon below to listen. Full Article
pli Actitudes cristianas fundamentales: Disciplina personal, 2ª Pte. A By feeds.gracia.org Published On :: Fri, 07 Jun 2024 00:00:00 PST La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.Click the icon below to listen. Full Article
pli Actitudes cristianas fundamentales: Disciplina personal, 2ª Pte. B By feeds.gracia.org Published On :: Mon, 10 Jun 2024 00:00:00 PST La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.Click the icon below to listen. Full Article
pli 2 lotto bettors split P118.9 million prize By www.philstar.com Published On :: Wed, 13 Nov 2024 00:00:00 +0800 Two bettors won the P118.9-million jackpot in the 6/45 Mega Lotto draw on Monday night. Full Article
pli Film Commission delays in funds and rebate crippling local productions – MEIA By www.maltatoday.com.mt Published On :: Tue,12 Nov 2024 12:24:32 +0100 Maltese producers raise alarm over ripple effect of late payments in funding and services to creatives from Malta Film Commission Full Article
pli BIR to monitor online sellers' tax compliance during holiday season By business.inquirer.net Published On :: Wed, 13 Nov 2024 14:14:09 +0800 MANILA, Philippines – The Bureau of Internal Revenue (BIR) will closely monitor the tax compliance of online marketplaces and online sellers during the holiday season, Commissioner Romeo Lumagui Jr. has said. In a statement Wednesday, Lumagui warned that online businesses violating tax laws would be blocked. Section 115 of the National Internal Revenue Code, as […]...Keep on reading: BIR to monitor online sellers' tax compliance during holiday season Full Article
pli COP29: Making Space Applications Work for Women in Agriculture By www.ipsnews.net Published On :: Tue, 12 Nov 2024 07:29:41 +0000 When the first woman in space, Valentina Tereshkova, orbited the Earth in 1963, there were only three active Earth observation satellites. Today, the number is 114 times greater. With more and better satellites, the impacts of advances in the space sector are particularly evident in agriculture, where space data improves insights into the individual components […] Full Article Climate Action Climate Change COP29 Environment Featured Global Headlines Human Rights Humanitarian Emergencies Sustainable Development Goals TerraViva United Nations IPS UN Bureau
pli Warmer climate, forest cover loss flood Bicol farmers’ plight By www.bulatlat.com Published On :: Tue, 12 Nov 2024 01:52:07 +0000 Days before Kristine (international name: Trami) developed into a severe tropical storm, the Philippine Sea was warmer than usual. Under the warming climate, the typhoon-prone Bicol Region is more vulnerable with decimated forests. Both Camarines Sur and Albay saw a net loss of tree cover from 2000 to 2020, according to Global Forest Watch. Full Article * Latest Posts Environment & Climate Crisis Top Stories Bicol disaster farmers affected by typhoon Typhoon Kristine
pli Replicating ADB Projects from the People's Republic of China By www.adb.org Published On :: 2024-10-30 This video introduces a new publication presenting five case studies of projects in the People's Republic of China that illustrate how effective solutions to environmental and social problems have been applied in different contexts. Full Article
pli Senior Compliance Review Officer By www.adb.org Published On :: 2024-10-30 ADB has a vacancy for the position of Senior Compliance Review Officer in the Office of the Compliance Review Panel. The deadline for submitting applications is on 21-NOV-2024. Full Article
pli Prospects of India–Bangladesh Economic Cooperation: Implications for South Asian Regional Cooperation By www.adb.org Published On :: Bangladesh and India should pursue bilateral economic cooperation to enhance South Asian regional cooperation. Full Article Publications/Papers and Briefs
pli Corporate Governance in the Republic of Korea and Its Implications for Firm Performance By www.adb.org Published On :: This paper is part of a cross-country study on corporate governance in Asia. A consensus has yet to be reached about exactly what factors were behind the crisis of 1998 and how these factors interacted in bringing about the crisis. Full Article Publications/Papers and Briefs
pli Aid groups slam Israeli duplicity on relief delivery By www.dawn.com Published On :: Wed, 13 Nov 2024 07:48:40 +0500 JERUSALEM: Aid agencies slammed Israel for continuing to obstruct the delivery of aid to Gaza, despite Tel Aviv’s claims that it had opened an additional crossing into the besieged territory on the eve of a US deadline to boost relief deliveries. The United States last month warned Israel to improve the humanitarian conditions in Gaza or risk a cut to its military support. A day before the deadline, the Israeli military said it opened the Kissufim crossing “as part of the effort and commitment to increase the volume and routes of aid” to Gaza. But the UN agency for Palestinian refugees (UNRWA) and eight humanitarian groups said Israel was still not doing enough to get aid in as the situation in the besieged north becomes especially “catastrophic”. On eve of US deadline to restore aid supplies to Gaza, Tel Aviv claims to have opened another border crossing The eight organisations, including Oxfam and Save The Children, said Israel “failed to comply” with US demands — “at enormous human cost for Palestinian civilians in Gaza”. “The humanitarian situation in Gaza is now at its worst point since the war began in October 2023,” they said in a joint statement. Asked about whether there were signs the situation had improved ahead of Wednesday’s deadline, Louise Wateridge, an UNRWA emergencies officer, highlighted that “aid entering the Gaza Strip is at its lowest level in months”. No food was permitted to enter besieged northern Gaza for an entire month, Wateridge said, adding that UN requests to access the area have been repeatedly denied. Wateridge said that testimonies from the north painted “an endlessly horrific” picture that was becoming “more critical” by the hour. “Hospitals have been bombed, the doctors inform us that they have run out of blood supplies, they have run out of medicine… there are bodies in the streets.” Separately, a spokesperson for the Norwegian Refugee Council told Al Jazeera that Israelis were obstructing aid from entering through the crossings. “Aid is arbitrarily rejected and essential supplies are not allowed in, including timber to help people build shelters as they face winter. Sometimes the requests to access those crossings are denied for over a month,” Shaina Low, NRC’s communications adviser, told Al Jazeera. Once the aid enters Gaza, aid workers must request safe routes through which they can safely distribute the aid. “Israel often denies requests to move from place to place in order to reach Palestinian families that are in desperate need,” Low said. However, the US State Department on Tuesday said that Israel was not violating US law on the level of aid entering Gaza, but called for further progress. Asked if Israel had met the US demands, State Department spokesman Vedant Patel said of Israel, “We have not made an assessment that they are in violation of US law,” but added: “The overall humanitarian situation in Gaza continues to be unsatisfactory”. “But in the context of the letter, it’s not about whether we find something satisfactory or not; it’s what are the actions that we’re seeing,” he said, adding that Tel Aviv was taking steps in the right direction. Attacks on Gaza Gaza’s civil defence agency said that at least 14 people were killed in Israeli strikes on Tuesday. On Tuesday, residents said Israeli tanks advanced deeper in Beit Hanoun and besieged four displaced families before ordering them to leave towards Gaza City. The health ministry in Gaza said on Tuesday that at least 43,665 people have been killed in more than 13 months. Published in Dawn, November 13th, 2024 Full Article World
pli university paper application By english.al-akhbar.com Published On :: university paper application Full Article
pli to write a high school scholarship application letter By english.al-akhbar.com Published On :: to write a high school scholarship application letter Full Article
pli Physicists are grappling with their own reproducibility crisis By www.newscientist.com Published On :: Fri, 17 May 2024 21:58:32 +0100 A contentious meeting of physicists highlighted concerns, failures and possible fixes for a crisis in condensed matter physics Full Article
pli Evidence of consciousness in newborns has implications for their care By www.newscientist.com Published On :: Wed, 12 Jun 2024 19:00:00 +0100 Babies cannot tell us what they are experiencing, so it is hard to know what they are conscious of. But new research suggesting they perceive the world consciously could change how we care for them, says Claudia Passos-Ferreira Full Article
pli Vitamins May Lower Risk of Birth Complication By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Vitamins May Lower Risk of Birth ComplicationCategory: Health NewsCreated: 8/20/2011 11:00:00 AMLast Editorial Review: 8/22/2011 12:00:00 AM Full Article
pli How Reliable Are Medical Studies? Half of Findings Couldn't Be Replicated By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: How Reliable Are Medical Studies? Half of Findings Couldn't Be ReplicatedCategory: Health NewsCreated: 8/27/2015 12:00:00 AMLast Editorial Review: 8/28/2015 12:00:00 AM Full Article
pli Toppling TVs, Furniture Sending Many Young Children to ERs By www.medicinenet.com Published On :: Mon, 29 Aug 2022 00:00:00 PDT Title: Toppling TVs, Furniture Sending Many Young Children to ERsCategory: Health NewsCreated: 8/27/2021 12:00:00 AMLast Editorial Review: 8/27/2021 12:00:00 AM Full Article
pli Seamless, rapid, and accurate analyses of outbreak genomic data using split k-mer analysis [METHODS] By genome.cshlp.org Published On :: 2024-10-29T06:46:08-07:00 Sequence variation observed in populations of pathogens can be used for important public health and evolutionary genomic analyses, especially outbreak analysis and transmission reconstruction. Identifying this variation is typically achieved by aligning sequence reads to a reference genome, but this approach is susceptible to reference biases and requires careful filtering of called genotypes. There is a need for tools that can process this growing volume of bacterial genome data, providing rapid results, but that remain simple so they can be used without highly trained bioinformaticians, expensive data analysis, and long-term storage and processing of large files. Here we describe split k-mer analysis (SKA2), a method that supports both reference-free and reference-based mapping to quickly and accurately genotype populations of bacteria using sequencing reads or genome assemblies. SKA2 is highly accurate for closely related samples, and in outbreak simulations, we show superior variant recall compared with reference-based methods, with no false positives. SKA2 can also accurately map variants to a reference and be used with recombination detection methods to rapidly reconstruct vertical evolutionary history. SKA2 is many times faster than comparable methods and can be used to add new genomes to an existing call set, allowing sequential use without the need to reanalyze entire collections. With an inherent absence of reference bias, high accuracy, and a robust implementation, SKA2 has the potential to become the tool of choice for genotyping bacteria. SKA2 is implemented in Rust and is freely available as open-source software. Full Article
pli Theoretical framework for the difference of two negative binomial distributions and its application in comparative analysis of sequencing data [METHODS] By genome.cshlp.org Published On :: 2024-10-29T06:46:08-07:00 High-throughput sequencing (HTS) technologies have been instrumental in investigating biological questions at the bulk and single-cell levels. Comparative analysis of two HTS data sets often relies on testing the statistical significance for the difference of two negative binomial distributions (DOTNB). Although negative binomial distributions are well studied, the theoretical results for DOTNB remain largely unexplored. Here, we derive basic analytical results for DOTNB and examine its asymptotic properties. As a state-of-the-art application of DOTNB, we introduce DEGage, a computational method for detecting differentially expressed genes (DEGs) in scRNA-seq data. DEGage calculates the mean of the sample-wise differences of gene expression levels as the test statistic and determines significant differential expression by computing the P-value with DOTNB. Extensive validation using simulated and real scRNA-seq data sets demonstrates that DEGage outperforms five popular DEG analysis tools: DEGseq2, DEsingle, edgeR, Monocle3, and scDD. DEGage is robust against high dropout levels and exhibits superior sensitivity when applied to balanced and imbalanced data sets, even with small sample sizes. We utilize DEGage to analyze prostate cancer scRNA-seq data sets and identify marker genes for 17 cell types. Furthermore, we apply DEGage to scRNA-seq data sets of mouse neurons with and without fear memory and reveal eight potential memory-related genes overlooked in previous analyses. The theoretical results and supporting software for DOTNB can be widely applied to comparative analyses of dispersed count data in HTS and broad research questions. Full Article
pli Chromatin interaction maps identify oncogenic targets of enhancer duplications in cancer [RESEARCH] By genome.cshlp.org Published On :: 2024-10-29T06:46:07-07:00 As a major type of structural variants, tandem duplication plays a critical role in tumorigenesis by increasing oncogene dosage. Recent work has revealed that noncoding enhancers are also affected by duplications leading to the activation of oncogenes that are inside or outside of the duplicated regions. However, the prevalence of enhancer duplication and the identity of their target genes remains largely unknown in the cancer genome. Here, by analyzing whole-genome sequencing data in a non-gene-centric manner, we identify 881 duplication hotspots in 13 major cancer types, most of which do not contain protein-coding genes. We show that the hotspots are enriched with distal enhancer elements and are highly lineage-specific. We develop a HiChIP-based methodology that navigates enhancer–promoter contact maps to prioritize the target genes for the duplication hotspots harboring enhancer elements. The methodology identifies many novel enhancer duplication events activating oncogenes such as ESR1, FOXA1, GATA3, GATA6, TP63, and VEGFA, as well as potentially novel oncogenes such as GRHL2, IRF2BP2, and CREB3L1. In particular, we identify a duplication hotspot on Chromosome 10p15 harboring a cluster of enhancers, which skips over two genes, through a long-range chromatin interaction, to activate an oncogenic isoform of the NET1 gene to promote migration of gastric cancer cells. Focusing on tandem duplications, our study substantially extends the catalog of noncoding driver alterations in multiple cancer types, revealing attractive targets for functional characterization and therapeutic intervention. Full Article
pli AGAP duplicons associate with structural diversity at Chromosome 10q11.22 [RESEARCH] By genome.cshlp.org Published On :: 2024-10-29T06:46:07-07:00 The 10q11.22 chromosomal region is a duplication-rich interval of the human genome and one of the last to be fully assembled. It carries copy number–variable genes associated with intellectual disability, bipolar disorder, and obesity. In this study, we characterized the structural diversity at this locus by analyzing 64 haploid assemblies produced by the Human Pangenome Reference Consortium. We identified 11 alternative haplotypes that differ in the copy number and/or orientation of large genomic segments, ranging from hundreds of kilobase pairs (kbp) to over one megabase pair (Mbp). We uncovered a 2.4 Mbp size difference between the shortest and longest haplotypes. Breakpoint analysis revealed that genomic instability results from nonallelic homologous recombination between segmental duplication (SD) pairs with varying similarity (94.4%–99.6%). Nonetheless, these pairs generally recombine at positions where their identity is higher (>99.6%). Recurrent inversions occur with different breakpoints within the same inverted SD pair. Inversion polymorphisms shuffle the entire SD arrangement, creating new predispositions to copy-number variations. The SD architecture is associated with a catarrhine-specific subgroup of the AGAP gene family, which likely triggered the accumulation of SDs at this locus over the past 25 million years of human evolution. Our results reveal extensive structural diversity and genomic instability at the 10q11.22 locus, and expand the general understanding of the mutational mechanisms behind SD-mediated rearrangements. Full Article
pli The Evolution of Intermittent Mandatory Ventilation: Update and Implications for Home Care By rc.rcjournal.com Published On :: 2024-10-25T05:44:13-07:00 Full Article
pli A circular split nanoluciferase reporter for validating and screening putative internal ribosomal entry site elements [METHOD] By rnajournal.cshlp.org Published On :: 2024-10-16T07:18:13-07:00 Internal ribosomal entry sites (IRESs) recruit the ribosome to promote translation, typically in an m7G cap-independent manner. Although IRESs are well-documented in viral genomes, they have also been reported in mammalian transcriptomes, where they have been proposed to mediate cap-independent translation of mRNAs. However, subsequent studies have challenged the idea of these "cellular" IRESs. Current methods for screening and discovering IRES activity rely on a bicistronic reporter assay, which is prone to producing false positive signals if the putative IRES sequence has a cryptic promoter or cryptic splicing sites. Here, we report an assay for screening IRES activity using a genetically encoded circular RNA comprising a split nanoluciferase (nLuc) reporter. The circular split nLuc reporter is less susceptible to the various sources of false positives that adversely affect the bicistronic IRES reporter assay and provides a streamlined method for screening IRES activity. Using the circular split nLuc reporter, we find that nine reported cellular IRESs have minimal IRES activity. Overall, the circular split nLuc reporter offers a simplified approach for identifying and validating IRESs and exhibits reduced propensity for producing the types of false positives that can occur with the bicistronic reporter assay. Full Article
pli Abolished frameshifting for predicted structure-stabilizing SARS-CoV-2 mutants: implications to alternative conformations and their statistical structural analyses [ARTICLE] By rnajournal.cshlp.org Published On :: 2024-10-16T07:18:13-07:00 The SARS-CoV-2 frameshifting element (FSE) has been intensely studied and explored as a therapeutic target for coronavirus diseases, including COVID-19. Besides the intriguing virology, this small RNA is known to adopt many length-dependent conformations, as verified by multiple experimental and computational approaches. However, the role these alternative conformations play in the frameshifting mechanism and how to quantify this structural abundance has been an ongoing challenge. Here, we show by DMS and dual-luciferase functional assays that previously predicted FSE mutants (using the RAG graph theory approach) suppress structural transitions and abolish frameshifting. Furthermore, correlated mutation analysis of DMS data by three programs (DREEM, DRACO, and DANCE-MaP) reveals important differences in their estimation of specific RNA conformations, suggesting caution in the interpretation of such complex conformational landscapes. Overall, the abolished frameshifting in three different mutants confirms that all alternative conformations play a role in the pathways of ribosomal transition. Full Article
pli Branch site recognition by the spliceosome [REVIEW] By rnajournal.cshlp.org Published On :: 2024-10-16T07:18:13-07:00 The spliceosome is a eukaryotic multimegadalton RNA–protein complex that removes introns from transcripts. The spliceosome ensures the selection of each exon-intron boundary through multiple recognition events. Initially, the 5' splice site (5' SS) and branch site (BS) are bound by the U1 small nuclear ribonucleoprotein (snRNP) and the U2 snRNP, respectively, while the 3' SS is mostly determined by proximity to the branch site. A large number of splicing factors recognize the splice sites and recruit the snRNPs before the stable binding of the snRNPs occurs by base-pairing the snRNA to the transcript. Fidelity of this process is crucial, as mutations in splicing factors and U2 snRNP components are associated with many diseases. In recent years, major advances have been made in understanding how splice sites are selected in Saccharomyces cerevisiae and humans. Here, I review and discuss the current understanding of the recognition of splice sites by the spliceosome with a focus on recognition and binding of the branch site by the U2 snRNP in humans. Full Article
pli Multidisciplinary management of adult patients with chylothorax: a consensus statement By erj.ersjournals.com Published On :: 2024-11-07T00:35:55-08:00 The management of chylothorax remains challenging given the limited evidence and significant heterogeneity in practice. In addition, there are no practical guidelines on the optimal approach to manage this complex condition. We convened an international group of 27 experts from 20 institutions across five countries and four specialties (pulmonary, interventional radiology, thoracic surgery and nutrition) with experience and expertise in managing adult patients with chylothorax. We performed a literature and internet search for reports addressing seven clinically relevant PICO (Patient, Intervention, Comparison and Outcome) questions pertaining to the management of adult patients with chylothorax. This consensus statement, consisting of best practice statements based on expert consensus addressing these seven PICO questions, was formulated by a systematic and rigorous process involving the evaluation of published evidence, augmented with provider experience. Panel members participated in the development of the final best practice statements using the modified Delphi technique. Our consensus statement aims to offer guidance in clinical decision making when managing patients with chylothorax while also identifying gaps in knowledge and informing future research. Full Article