Up to 1,000 fans are allowed inside each stadium in Taiwan's Chinese Professional Baseball League

ONLINE HIGH-LEVEL DIALOGUE Moderated by Jorge Ramos (journalist & author, Univision)

 
4 May 2020, 17:00-18:15 CET (GMT+2) / 11:00am-12:15pm EDT

 
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The post Press Freedom and Tackling Disinformation in the COVID-19 context appeared first on Inter Press Service.

Dr. Azza Karam is the Secretary General of Religions for Peace International and Professor of Religion and Development at the Vrije Universiteit (VU), Amsterdam; Dr. Mustafa Y. Ali is the Secretary General of the Global Network of Religions for Children (GNRC) based in Nairobi, Kenya.

The post Religion & its Discontents: Considerations Around COVID-19 & Africa appeared first on Inter Press Service.

Facebook's new content oversight board will include a former prime minister, a Nobel Peace Prize laureate and several constitutional law experts and rights advocates in its first 20 members.

Facebook's new content oversight board will include a former prime minister, a Nobel Peace Prize laureate and several constitutional law experts and rights advocates in its first 20 members.

Title: HIV 'Cure' Looks 'Promising,' Danish Scientists Contend
Category: Health News
Created: 4/29/2013 12:35:00 PM
Last Editorial Review: 4/30/2013 12:00:00 AM

Title: NIH Launches $500 Million Contest to Produce Best COVID-19 Test
Category: Health News
Created: 4/29/2020 12:00:00 AM
Last Editorial Review: 4/30/2020 12:00:00 AM

For any journal issue that has at least one open access or early access article, PMC is now displaying the table of contents (TOC) in advance of the whole issue becoming available. Not to worry, though—only those articles specified for early release are immediately viewable in PMC. As consistent with the terms of access in the journal agreement, the other articles will only become available on their specified release date, as shown in the TOC below.

The journal's accessiblity, as indicated on the PMC Journal list also has not changed; for example, Plant Physiology's embargo period is still 12 months. What has changed is that the issues with “preview” TOCs now additionally appear on the journal's archive page. Publishers and others can rest assured, however, that no access terms for any journal have been changed with the unveiling of this new format.

There is a need to develop novel approaches to improve the balance between efficacy and toxicity for transcription factor–targeted therapies. In this study, we exploit context-dependent differences in RNA polymerase II processivity as an approach to improve the activity and limit the toxicity of the EWS-FLI1–targeted small molecule, mithramycin, for Ewing sarcoma. The clinical activity of mithramycin for Ewing sarcoma is limited by off-target liver toxicity that restricts the serum concentration to levels insufficient to inhibit EWS-FLI1. In this study, we perform an siRNA screen of the druggable genome followed by a matrix drug screen to identify mithramycin potentiators and a synergistic "class" effect with cyclin-dependent kinase 9 (CDK9) inhibitors. These CDK9 inhibitors enhanced the mithramycin-mediated suppression of the EWS-FLI1 transcriptional program leading to a shift in the IC₅₀ and striking regressions of Ewing sarcoma xenografts. To determine whether these compounds may also be liver protective, we performed a qPCR screen of all known liver toxicity genes in HepG2 cells to identify mithramycin-driven transcriptional changes that contribute to the liver toxicity. Mithramycin induces expression of the BTG2 gene in HepG2 but not Ewing sarcoma cells, which leads to a liver-specific accumulation of reactive oxygen species (ROS). siRNA silencing of BTG2 rescues the induction of ROS and the cytotoxicity of mithramycin in these cells. Furthermore, CDK9 inhibition blocked the induction of BTG2 to limit cytotoxicity in HepG2, but not Ewing sarcoma cells. These studies provide the basis for a synergistic and less toxic EWS-FLI1–targeted combination therapy for Ewing sarcoma.

ABSTRACT

Microbes affect vertebrates on timescales from daily to evolutionary, and the cumulative effect of these interactions is immense. However, how microbiomes compare across (host) species is poorly understood, as most studies focus on relatively few species. A recent mBio article by S. J. Song, J. G. Sanders, F. Delsuc, J. Metcalf, et al. (mBio 11:e02901-19, 2019, https://doi.org/10.1128/mBio.02901-19) expands our collective understanding of the vertebrate microbiome by analyzing ~900 species. They demonstrate that patterns within mammals contrast with those within birds. Their results suggest many hypotheses about the role of host ecology and evolution on microbiome variation. Bats, the only volant mammals, appear to contradict many of the general mammal microbiome trends, in some ways resembling birds. What role has powered flight, and the evolution thereof, played in microbiome structure and function? Comparative methods, mechanistic hypotheses, and theory will elucidate this exciting question (and others) that we can ask using Song, Sanders et al.’s data and results.

ABSTRACT

Pseudomonas aeruginosa is an opportunistic human pathogen, particularly noted for causing infections in the lungs of people with cystic fibrosis (CF). Previous studies have shown that the gene expression profile of P. aeruginosa appears to converge toward a common metabolic program as the organism adapts to the CF airway environment. However, we still have only a limited understanding of how these transcriptional changes impact metabolic flux at the systems level. To address this, we analyzed the transcriptome, proteome, and fluxome of P. aeruginosa grown on glycerol or acetate. These carbon sources were chosen because they are the primary breakdown products of an airway surfactant, phosphatidylcholine, which is known to be a major carbon source for P. aeruginosa in CF airways. We show that the fluxes of carbon throughout central metabolism are radically different among carbon sources. For example, the newly recognized "EDEMP cycle" (which incorporates elements of the Entner-Doudoroff [ED] pathway, the Embden-Meyerhof-Parnas [EMP] pathway, and the pentose phosphate [PP] pathway) plays an important role in supplying NADPH during growth on glycerol. In contrast, the EDEMP cycle is attenuated during growth on acetate, and instead, NADPH is primarily supplied by the reaction catalyzed by isocitrate dehydrogenase(s). Perhaps more importantly, our proteomic and transcriptomic analyses revealed a global remodeling of gene expression during growth on the different carbon sources, with unanticipated impacts on aerobic denitrification, electron transport chain architecture, and the redox economy of the cell. Collectively, these data highlight the remarkable metabolic plasticity of P. aeruginosa; that plasticity allows the organism to seamlessly segue between different carbon sources, maximizing the energetic yield from each.

IMPORTANCE Pseudomonas aeruginosa is an opportunistic human pathogen that is well known for causing infections in the airways of people with cystic fibrosis. Although it is clear that P. aeruginosa is metabolically well adapted to life in the CF lung, little is currently known about how the organism metabolizes the nutrients available in the airways. In this work, we used a combination of gene expression and isotope tracer ("fluxomic") analyses to find out exactly where the input carbon goes during growth on two CF-relevant carbon sources, acetate and glycerol (derived from the breakdown of lung surfactant). We found that carbon is routed ("fluxed") through very different pathways during growth on these substrates and that this is accompanied by an unexpected remodeling of the cell’s electron transfer pathways. Having access to this "blueprint" is important because the metabolism of P. aeruginosa is increasingly being recognized as a target for the development of much-needed antimicrobial agents.

Axonal protein synthesis has been shown to play a role in developmental and regenerative growth, as well as in the maintenance of the axoplasm in a steady state. Recent studies have begun to identify the mRNAs localized in axons, which could be translated locally under different conditions. Despite that by now hundreds or thousands of mRNAs have been shown to be localized into the axonal compartment of cultured neurons in vitro, knowledge of which mRNAs are localized in mature myelinated axons is quite limited. With the purpose of characterizing the transcriptome of mature myelinated motor axons of peripheral nervous systems, we modified the axon microdissection method devised by Koenig, enabling the isolation of the axoplasm RNA to perform RNA-seq analysis. The transcriptome analysis indicates that the number of RNAs detected in mature axons is lower in comparison with in vitro data, depleted of glial markers, and enriched in neuronal markers. The mature myelinated axons are enriched for mRNAs related to cytoskeleton, translation, and oxidative phosphorylation. Moreover, it was possible to define core genes present in axons when comparing our data with transcriptomic data of axons grown in different conditions. This work provides evidence that axon microdissection is a valuable method to obtain genome-wide data from mature and myelinated axons of the peripheral nervous system, and could be especially useful for the study of axonal involvement in neurodegenerative pathologies of motor neurons such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophies (SMA).

The importance of noncoding RNA sequences has become increasingly clear over the past decade. New RNA families are often detected and analyzed using comparative methods based on multiple sequence alignments. Accordingly, a number of programs have been developed for aligning and deriving secondary structures from sets of RNA sequences. Yet, the best tools for these tasks remain unclear because existing benchmarks contain too few sequences belonging to only a small number of RNA families. RNAconTest (RNA consistency test) is a new benchmarking approach relying on the observation that secondary structure is often conserved across highly divergent RNA sequences from the same family. RNAconTest scores multiple sequence alignments based on the level of consistency among known secondary structures belonging to reference sequences in their output alignment. Similarly, consensus secondary structure predictions are scored according to their agreement with one or more known structures in a family. Comparing the performance of 10 popular alignment programs using RNAconTest revealed that DAFS, DECIPHER, LocARNA, and MAFFT created the most structurally consistent alignments. The best consensus secondary structure predictions were generated by DAFS and LocARNA (via RNAalifold). Many of the methods specific to noncoding RNAs exhibited poor scalability as the number or length of input sequences increased, and several programs displayed substantial declines in score as more sequences were aligned. Overall, RNAconTest provides a means of testing and improving tools for comparative RNA analysis, as well as highlighting the best available approaches. RNAconTest is available from the DECIPHER website (http://DECIPHER.codes/Downloads.html).

Loess, a wind-blown silty soil, can be deposited under a variety of moisture conditions, including dry deposition, wet deposition and gravitational settling of aggregations formed in moist air by capillary forces at grain contacts. This experimental study uses single and double oedometer tests to assess the effect of depositional water content on the collapse potential of reconstituted samples of the Langley Silt Member, known as Brickearth, a natural loessic soil. A freefall sample preparation technique was used to mimic loess formation and environmental scanning electron microscopy was used to relate the observed behaviour to sample fabric. The results show that loess deposited at higher water contents has a greater collapse potential, which is shown to be related to its looser, more granular fabric.

Q fever, caused by Coxiella burnetii, is a worldwide zoonotic disease that may cause severe forms in humans and requires a specific and prolonged antibiotic treatment. Although current serological and molecular detection tools allow a reliable diagnosis of the disease, culture of C. burnetii strains is mandatory to assess their susceptibility to antibiotics and sequence their genome in order to optimize patient management and epidemiological studies. However, cultivating this fastidious microorganism is difficult and restricted to reference centers, as it requires biosafety level 3 laboratories and relies on cell culture performed by experienced technicians. In addition, the culture yield is low, which results in a small number of isolates being available. In this work, we developed a novel high-content screening (HCS) isolation strategy based on optimized high-throughput cell culture and automated microscopic detection of infected cells with specifically designed algorithms targeting cytopathic effects. This method was more efficient than the shell vial assay, at the level of time dependency, when applied to both frozen specimens (7 isolates recovered by HCS only, sensitivity 91% versus 78% for shell vial) and fresh samples (1 additional isolate using HCS, sensitivity 7% versus 5% for shell vial), for which most strains were recovered more rapidly with the new technique. In addition, detecting positive cultures by an automated microscope reduced the need for expertise and saved 24% of technician working time. Application of HCS to antibiotic susceptibility testing of 12 strains demonstrated that it was as efficient as the standard procedure that combines shell vial culture and quantitative PCR.

Accumulation of lipid in skeletal muscle is thought to be related to the development of insulin resistance and type 2 diabetes. Initial work in this area focused on accumulation of intramuscular triglyceride; however, bioactive lipids such as diacylglycerols and sphingolipids are now thought to play an important role. Specific species of these lipids appear to be more negative toward insulin sensitivity than others. Adding another layer of complexity, localization of lipids within the cell appears to influence the relationship between these lipids and insulin sensitivity. This article summarizes how accumulation of total lipids, specific lipid species, and localization of lipids influence insulin sensitivity in humans. We then focus on how these aspects of muscle lipids are impacted by acute and chronic aerobic and resistance exercise training. By understanding how exercise alters specific species and localization of lipids, it may be possible to uncover specific lipids that most heavily impact insulin sensitivity.

In light of the ongoing COVID-19 crisis, this week’s resources continue to have the dual focus of providing resources that can help us navigate this […]

The post David Kelly’s Curated L&D Content for the Week of 5/4/20 appeared first on e-Learning Feeds.

In light of the ongoing COVID-19 crisis, this week’s resources continue to have the dual focus of providing resources that can help us navigate this […]

The post David Kelly’s Curated L&D Content for the Week of 4/27/20 appeared first on e-Learning Feeds.

Honeywell, the same company that might make your humidifier or home security system, is unveiling a powerful quantum computer that will be available to the public

AI algorithms for deep-reinforcement learning have demonstrated the ability to learn at very high levels in constrained domains.

Loni SDM clarified that four employees have tested positive for coronavirus and not all of them, as claimed.

Newly released FBI documents suggest a federal judge in Washington was swayed by apparent misrepresentations from a top prosecutor when he issued a memorandum opinion in December 2019 -- a ruling that marked one of the lowest points in former U.S. national security adviser Michael Flynn's effort to withdraw a guilty plea on a charge of lying to investigators.

Smithsonian's Earth Optimism Summit features CNN's Chief Climate Correspondent Bill Weir

A woman allegedly spat at and threw the contents of a sick bowl over a nurse while being treated for Covid-19 symptoms.

In today's Diary: Unofficial Eurovision replacement planned / David Nicholls on his unkind friend / Robert Halfon has too many Whatsapp groups / Simon Hoare creates new barnet formula

UN secretary-general Antonio Guterres has called for an "all-out effort to end hate speech globally" amid what he called a "tsunami of hate and xenophobia, scapegoating and scare-mongering" unleashed during the coronavirus pandemic.

The company has faced criticism in recent years for its handling of issues ranging from user privacy to policing hate speech to stopping the spread of disinformation.

NASA has awarded the University of Washington a $499,864 grant to develop a competition that calls on students to turn a simulated lava tube into a habitat suitable for harboring humans on the moon or Mars. The exploration and habitation skills competition will be funded as part of NASA's Artemis Student Challenges program, which plays off the themes of the Artemis moon program to inspire the next generation of explorers and engineers. The competition will involve navigating a rover through a facsimile lava tube and surface structures, generating maps, identifying valuable resources and deploying an airtight barrier to seal the… Read More

Newly discovered documents have revealed the first telegraph messages and joy when England was linked for the first time with India on 23 June, 1870.

'Weekend Update' among segments returning

Live shows will begin this month

Challenges will test potential dads' parenting abilities

Darragh Ennis appeared on the show in 2017

Popular party food was the subject of disagreements on the popular quiz show

'The Mindy Project' star and writer talks to Priya Arora about breaking boundaries with her new Netflix show 'Never Have I Ever', a coming-of-age comedy about a modern-day first-generation Indian American teenage girl, much like younger herself

'The way it finished, it was heartbreaking and we did feel bad' revealed the winning pair

'Ladies and gentlemen, you have just witnessed something that never happens on our programme'

The blunder was worth $800

David Walliams and Matt Lucas's comedy comeback proved controversial

'We tried to tell that story, but it defeated us every time'

Get the royally-approved glow

They travelled the length of Central and South America for the BBC's Race Across the World, so who better to ask for travel tips?

The Workers Compensation Commission finds in favour of a former House Rules contestant who claimed she was now unemployable because of the negative way she was portrayed on the Channel Seven show.

We are a new board overseeing Facebook. Here’s what we’ll decide.Catalina Botero-Marino, Jamal Greene, Michael W. McConnell and Helle Thorning-Schmidt, The New York TimesFacebook announced the first members of its content oversight board this week, a...

Saray Carrillo felt she was being unfairly treated by the judges on the Spanish version of MasterChef - so decided to cook up a terrifying meal in revenge

The show was postponed last month because of the COVID-19 pandemic

Mental health advocate Malin Andersson reacted to the news that the ITV2 dating show has been shelved