Discovery could lead to more long-lived, inexpensive rechargeable batteries
A new process for seeing how electricity flows at the surface of electrodes will give a boost to efforts to improve rechargeable batteries
Discover Waterton Lakes National Park, jewel of the Rockies
This stunning park isn't as famous as Banff and Jasper, but it has every reason to be.
Fonts, fabulous fonts: How to use the @font-face rule with popular font services
Discover how to use the @font-face CSS rule to place real fonts on your website with popular font services.
Browser testing across devices with Adobe Edge Inspect
Discover how to test your websites and web apps in the browser across desktops and mobile devices using Adobe Edge Inspect.
Discovered a multilayer haze system on Saturn's Hexagon
The most extensive system of haze layers ever observed in the solar system have been discovered and characterised on the planet Saturn.
Discordance between Etravirine Phenotype and Genotype-Based Predicted Phenotype for Subtype C HIV-1 from First-Line Antiretroviral Therapy Failures in South Africa [Antiviral Agents]
Etravirine (ETR) is a nonnucleoside reverse transcriptase inhibitor (NNRTI) used in treatment-experienced individuals. Genotypic resistance test-interpretation systems can predict ETR resistance; however, genotype-based algorithms are derived primarily from HIV-1 subtype B and may not accurately predict resistance in non-B subtypes. The frequency of ETR resistance among recombinant subtype C HIV-1 and the accuracy of genotypic interpretation systems were investigated. HIV-1LAI containing full-length RT from HIV-1 subtype C-positive individuals experiencing virologic failure (>10,000 copies/ml and >1 NNRTI resistance-associated mutation) were phenotyped for ETR susceptibility. Fold change (FC) was calculated against a composite 50% effective concentration (EC50) from treatment-naive individuals and three classifications were assigned: (i) <2.9-FC, susceptible; (ii) ≥2.9- to 10-FC, partially resistant; and (iii) >10-FC, fully resistant. The Stanford HIVdb-v8.4 was used for genotype predictions merging the susceptible/potential low-level and low-level/intermediate groups for 3 x 3 comparison. Fifty-four of a hundred samples had reduced ETR susceptibility (≥2.9-FC). The FC correlated with HIVdb-v8.4 (Spearman’s rho = 0.62; P < 0.0001); however, 44% of samples were partially (1 resistance classification difference) and 4% completely discordant (2 resistance classification differences). Of the 34 samples with an FC of >10, 26 were HIVdb-v8.4 classified as low-intermediate resistant. Mutations L100I, Y181C, or M230L were present in 27/34 (79%) of samples with an FC of >10 but only in 2/46 (4%) of samples with an FC of <2.9. No other mutations were associated with ETR resistance. Viruses containing the mutation K65R were associated with reduced ETR susceptibility, but 65R reversions did not increase ETR susceptibility. Therefore, genotypic interpretation systems were found to misclassify ETR susceptibility in HIV-1 subtype C samples. Modifications to genotypic algorithms are needed to improve the prediction of ETR resistance for the HIV-1 subtype C.
Discontinuation of RAAS Inhibition in Children with Advanced CKD
Although renin-angiotensin-aldosterone system inhibition (RAASi) is a cornerstone in the treatment of children with CKD, it is sometimes discontinued when kidney function declines. We studied the reasons of RAASi discontinuation and associations between RAASi discontinuation and important risk markers of CKD progression and on eGFR decline in the Cardiovascular Comorbidity in Children with CKD study. In this study, 69 children with CKD (67% male, mean age 13.7 years, mean eGFR 27 ml/min per 1.73 m2) who discontinued RAASi during prospective follow-up were included. Initial change in BP, albuminuria, and potassium after discontinuation were assessed (median time 6 months). Rate of eGFR decline (eGFR slope) during a median of 1.9 years before and 1.2 years after discontinuation were estimated using linear mixed effects modeling. Physician-reported reasons for RAASi discontinuation were increase in serum creatinine, hyperkalemia, and symptomatic hypotension. After discontinuation of RAASi, BP and albuminuria increased, whereas potassium decreased. eGFR declined more rapidly after discontinuation of RAASi (–3.9 ml/min per 1.73 m2 per year; 95% confidence interval, –5.1 to –2.6) compared with the slope during RAASi treatment (–1.5 ml/min per 1.73 m2 per year; 95% confidence interval, –2.4 to –0.6; P=0.005). In contrast, no change in eGFR slope was observed in a matched control cohort of patients in whom RAASi was continued. Discontinuation of RAASi in children with CKD is associated with an acceleration of kidney function decline, even in advanced CKD.
Discovering Associated Data in PMC
In the NLM Strategic Plan released earlier this year, we noted that “[c]reating efficient ways to link the literature with associated datasets enables knowledge generation and discovery.” To that end, PMC is now aggregating data citations, data availability statements and supplementary materials, as available, in an Associated Data box. This box will only display on articles that have one or more of these features in the article.
To limit your search to records with an Associated Data box, you can use the new "Associated Data" facet on the search results page:
We hope that exposing this content in a consistent format and in an easy to find and easy to access manner, you will more readily find the datasets you need to further accelerate discovery and advance health. As part of our ongoing commitment to making data findable, accessible, interoperable, and re-usable (FAIR), we encourage you to contact us with your feedback on these updates and with any other suggestions you may have for improving discovery of related data in PMC.
Discover how to sit to dodge the dangers of inactivity
Inactivity is the new smoking and is linked to heart disease and cancer, but we can learn from kids and modern hunter-gatherers to make sitting less dangerous
Discover the Next Level of Experiences with HARMAN at CES 2020
Each year, HARMAN kicks off the New Year at CES, the premier consumer electronics show that takes place each January in Las Vegas. From the legendary HARMAN showcase at the Hard Rock, we’ll be once again showing what’s coming next when it comes to...
Ancient site older than Göbeklitepe unearthed
Discoveries at Boncuklu Tarla in the southeastern province of Mardin are around 1,000 years older than those in Göbeklitepe
Rising ‘over-dues’ of discoms: NTPC bites back at states, seeks to invoke three-way agreement
Discoms’ over-dues — bills that remained unpaid for more than 60 days — have been rising almost relentlessly over the years, and spiraled 242% on year, to a level of Rs 10,500 crore by FY20 end.
Discovering Jesus
Through community development projects, workers in Central Asia meet people interested in Jesus.
Discomfort and Pain in Newborns With Myelomeningocele: A Prospective Evaluation
Active termination of life in newborns with myelomeningocele because of assumed suffering in these newborns has been extensively discussed. However, the level of discomfort and pain in these newborns has never been substantially assessed.
This is the first study presenting quantitative data on discomfort and pain in newborns with myelomeningocele. Therefore, it can be of guidance in the choice of treatment: either active treatment or palliative care in the context of end-of-life decisions. (Read the full article)
Discover what’s new in SOLIDWORKS Education 2020-2021
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DC Deals - Mount Vernon: George Washington's Estate & Gardens - Attractions
Discover the real George Washington through his restored home and gardens, over 1,000 artifacts, and an immersive Revolutionary War "snow" experience
Discover Protestant nonconformity in England and Wales / Paul Blake.
Dissenters, Religious -- Great Britain.
Discourses : biological & geological : essays / by Thomas H. Huxley.
Discourse on the enlarged and pendulous abdomen : showing it to be a visceral affection, attended with important consequences in the human economy : with cursory observations on diet, exercise, and the general management of health : for the use of the dys
London : Longman, Brown, Green, and Longmans, 1842.
Disco embraces fresh start after tough end to '18
Reds starting pitcher Anthony DeSclafani hated how his 2018 season ended and didn't need any motivation to make improvements over the winter.
Discovery of a Redox Thiol Switch: Implications for Cellular Energy Metabolism [Research]
The redox-based modifications of cysteine residues in proteins regulate their function in many biological processes. The gas molecule H2S has been shown to persulfidate redox sensitive cysteine residues resulting in an H2S-modified proteome known as the sulfhydrome. Tandem Mass Tags (TMT) multiplexing strategies for large-scale proteomic analyses have become increasingly prevalent in detecting cysteine modifications. Here we developed a TMT-based proteomics approach for selectively trapping and tagging cysteine persulfides in the cellular proteomes. We revealed the natural protein sulfhydrome of two human cell lines, and identified insulin as a novel substrate in pancreatic beta cells. Moreover, we showed that under oxidative stress conditions, increased H2S can target enzymes involved in energy metabolism by switching specific cysteine modifications to persulfides. Specifically, we discovered a Redox Thiol Switch, from protein S-glutathioinylation to S-persulfidation (RTSGS). We propose that the RTSGS from S-glutathioinylation to S-persulfidation is a potential mechanism to fine tune cellular energy metabolism in response to different levels of oxidative stress.
Discovery of Species-unique Peptide Biomarkers of Bacterial Pathogens by Tandem Mass Spectrometry-based Proteotyping [Research]
Mass spectrometry (MS) and proteomics offer comprehensive characterization and identification of microorganisms and discovery of protein biomarkers that are applicable for diagnostics of infectious diseases. The use of biomarkers for diagnostics is widely applied in the clinic and the use of peptide biomarkers is increasingly being investigated for applications in the clinical laboratory. Respiratory-tract infections are a predominant cause for medical treatment, although, clinical assessments and standard clinical laboratory protocols are time-consuming and often inadequate for reliable diagnoses. Novel methods, preferably applied directly to clinical samples, excluding cultivation steps, are needed to improve diagnostics of infectious diseases, provide adequate treatment and reduce the use of antibiotics and associated development of antibiotic resistance. This study applied nano-liquid chromatography (LC) coupled with tandem MS, with a bioinformatics pipeline and an in-house database of curated high-quality reference genome sequences to identify species-unique peptides as potential biomarkers for four bacterial pathogens commonly found in respiratory tract infections (RTIs): Staphylococcus aureus; Moraxella catarrhalis; Haemophilus influenzae and Streptococcus pneumoniae. The species-unique peptides were initially identified in pure cultures of bacterial reference strains, reflecting the genomic variation in the four species and, furthermore, in clinical respiratory tract samples, without prior cultivation, elucidating proteins expressed in clinical conditions of infection. For each of the four bacterial pathogens, the peptide biomarker candidates most predominantly found in clinical samples, are presented. Data are available via ProteomeXchange with identifier PXD014522. As proof-of-principle, the most promising species-unique peptides were applied in targeted tandem MS-analyses of clinical samples and their relevance for identifications of the pathogens, i.e. proteotyping, was validated, thus demonstrating their potential as peptide biomarker candidates for diagnostics of infectious diseases.
Discovery of a Redox Thiol Switch: Implications for Cellular Energy Metabolism
Xing-Huang Gao
May 1, 2020; 19:852-870
Research
Discontinuous critical Fujita exponents for the heat equation with combined nonlinearities
Mohamed Jleli, Bessem Samet and Philippe Souplet
Proc. Amer. Math. Soc. 148 (2020), 2579-2593.
Abstract, references and article information
Discovery of a Redox Thiol Switch: Implications for Cellular Energy Metabolism [Research]
The redox-based modifications of cysteine residues in proteins regulate their function in many biological processes. The gas molecule H2S has been shown to persulfidate redox sensitive cysteine residues resulting in an H2S-modified proteome known as the sulfhydrome. Tandem Mass Tags (TMT) multiplexing strategies for large-scale proteomic analyses have become increasingly prevalent in detecting cysteine modifications. Here we developed a TMT-based proteomics approach for selectively trapping and tagging cysteine persulfides in the cellular proteomes. We revealed the natural protein sulfhydrome of two human cell lines, and identified insulin as a novel substrate in pancreatic beta cells. Moreover, we showed that under oxidative stress conditions, increased H2S can target enzymes involved in energy metabolism by switching specific cysteine modifications to persulfides. Specifically, we discovered a Redox Thiol Switch, from protein S-glutathioinylation to S-persulfidation (RTSGS). We propose that the RTSGS from S-glutathioinylation to S-persulfidation is a potential mechanism to fine tune cellular energy metabolism in response to different levels of oxidative stress.
Discordant Protein and mRNA Expression in Lung Adenocarcinomas
Guoan Chen
Apr 1, 2002; 1:304-313
Research
Here's how to find the ultimate Indianapolis eats
Discover new restaurants, the best drinks and local food at Liz Biro's new Indylicious Facebook group.
Here's how to find the ultimate Indianapolis eats
Discover new restaurants, the best drinks and local food at Liz Biro's new Indylicious Facebook group.
Discover: Aberdeen
Among the artifacts displayed at The Gordon Highlanders Museum in Aberdeen, Scotland is a flag from Hitler's staff car. (Don't ask how they got it.)
Discover: Saudi Arabia
In Saudi Arabia, you can try authentic apple-flavored Budweiser. (Non-alcoholic, of course.)
Discover: Graz
UPC Arena in Graz, Austria was renamed in 1997 to honor native son Arnold Schwarzenegger, but the old name was restored in 2005 over the governor's support of the death penalty.
Discover: Havana
For an "authentic" experience in getting around Havana via public transportation, try El Camello, a split-level bus pulled by a semi-truck, and resembling a 2-humped camel.
Discover: Santa Fe
In the celebrated art colony of Santa Fe, New Mexico, you can of course get paintings of the scenery of the southwestern United States, but did you know you can also get original paintings of Daffy Duck and Wile E. Coyote?
Discover: Kota Kinabalu
The Hall of Skulls at Monsopiad Cultural Village outside Kota Kinabalu, Malaysia features 42 skulls of enemies, all killed by the warrior-hero Monsopiad.
Discover: Lubbock
Among the objects on display at the Buddy Holly Center in Lubbock, Texas, memorializing the city's favorite son, is a giant-size replica of the rocker's trademark glasses.
Discover: Seoul
Fans of spicy fermented cabbage from all over Korea flock to the Kimchi Museum in Seoul.
Discover: Bergen
The Norwegian city of Bergen is famously rainy, but the locals say there's no such thing as bad weather, only bad clothing.
Discover: Takaoka
On your way from Takaoka to the Vladivostok ferry? Take a look out the window: the name of the Himi train line means Ice-Watching.
Discover: Cranbrook
If you visit Cranbrook, British Columbia, Canada and crave a dinner of alligator meat, you can get it at K's Amazon Eatery -- even though the Amazon and its gators are thousands of miles away.
Discover: Jakar
A cypress tree outside Kurje Lhakhang monastery in Jakar, Bhutan is claimed to have grown from Guru Rinpoche's walking stick.
Discover: Vicksburg
When you visit Vicksburg (Mississippi) National Military Park, you can see one of the first ironclad gunboats, dating back to US Civil War times.
Discover: Japan
Good things come in threes — and in Japan, the list includes views, castles, gardens, mountains, hot springs and giant Buddha statues.
Discover: Bohinj
Medieval frescoes in the Church of St. John the Baptist in Bohinj, Slovenia often show figures with large swellings of the neck (goiters), caused by lack of iodine in the local diet.
Discover: Savannah
Chippewa Square in Savannah, Georgia was the site of the bus stop in the movie Forrest Gump, but don't look for the famous bench; it was just a prop.
Discover: Kanab
When eating at Houston's restaurant in Kanab, Utah, tip the servers well; they pack pistols, although it's just for show -- allegedly.
Discover: Fukuoka
A bullet train ride on the Hakata-Minami Line in Fukuoka, Japan costs just ¥290 (under US$3). Alas, the end-to-end trip lasts just ten minutes.
Discover: Clipperton Island
If you somehow find yourself visiting Clipperton Island and lack things to do (understandably), try running around the island and timing yourself; the record circumnavigation time is one hour and 17 minutes.