Economist Nouriel Roubini correctly predicted the 2008 financial crisis. Now, he believes that stock markets will plunge by 30 to 40 percent because of the coronavirus. And that Trump will lose his re-election bid.

The desperate search for two teens who vanished while tubing in Utah continued on Saturday, days after the pair were swept up in an intense storm.

At the core of quantum computing is the qubit. The best ones have a few defining traits, and scientists are looking to everything from lasers to Russian diamonds to help refine the best qubits for the next generation of quantum computing.

The desperate search for two teens who vanished while tubing in Utah continued on Saturday, days after the pair were swept up in an intense storm.

On 23 September 2019, we published an article headlined 'Labour's tax bombshell: Corbyn's benefits splurge plot would cost taxpayers £520 billion' the article focused on Labour's potential objective of introducing a universal basic income and its associated costs.

ON MAY 7, 1945, General Alfred Jodl, the commander of German forces in western Europe, walked into a technical college in the city of Reims which served as General Eisenhower's HQ in France.

The University of California announced that an artificial intelligent system has solved the puzzle in just over a second, besting the human world record by more than two seconds.

The goal, researchers say, was to create a robot that learns the way humans do — through trial and error. Eventually, those robots could be used to complete tasks — in a warehouse or perhaps on the surface of a new planet — with more autonomy.

Histone H2B monoubiquitylation (H2Bub1) has central functions in multiple DNA-templated processes, including gene transcription, DNA repair, and replication. H2Bub1 also is required for the trans-histone regulation of H3K4 and H3K79 methylation. Although previous studies have elucidated the basic mechanisms that establish and remove H2Bub1, we have only an incomplete understanding of how H2Bub1 is regulated. We report here that the histone H4 basic patch regulates H2Bub1. Yeast cells with arginine-to-alanine mutations in the H4 basic patch (H42RA) exhibited a significant loss of global H2Bub1. H42RA mutant yeast strains also displayed chemotoxin sensitivities similar to, but less severe than, strains containing a complete loss of H2Bub1. We found that the H4 basic patch regulates H2Bub1 levels independently of interactions with chromatin remodelers and separately from its regulation of H3K79 methylation. To measure H2B ubiquitylation and deubiquitination kinetics in vivo, we used a rapid and reversible optogenetic tool, the light-inducible nuclear exporter, to control the subcellular location of the H2Bub1 E3 ligase, Bre1. The ability of Bre1 to ubiquitylate H2B was unaffected in the H42RA mutant. In contrast, H2Bub1 deubiquitination by SAGA-associated Ubp8, but not by Ubp10, increased in the H42RA mutant. Consistent with a function for the H4 basic patch in regulating SAGA deubiquitinase activity, we also detected increased SAGA-mediated histone acetylation in H4 basic patch mutants. Our findings uncover that the H4 basic patch has a regulatory function in SAGA-mediated histone modifications.

Ivan Matic
Jan 1, 2008; 7:132-144
Research

Tamar Geiger
Mar 1, 2012; 11:M111.014050-M111.014050
Special Issue: Prospects in Space and Time

Sebastian A. Wagner
Oct 1, 2011; 10:M111.013284-M111.013284
Research

Christian Tagwerker
Apr 1, 2006; 5:737-748
Research

DL Brasaemle
Nov 1, 1997; 38:2249-2263
Articles

The autosomal dominant disorder Schnyder corneal dystrophy (SCD) is caused by mutations in UbiA prenyltransferase domain-containing protein-1 (UBIAD1), which uses geranylgeranyl pyrophosphate (GGpp) to synthesize the vitamin K₂ subtype menaquinone-4 (MK-4). SCD is characterized by opacification of the cornea, owing to aberrant build-up of cholesterol in the tissue. We previously discovered that sterols stimulate association of UBIAD1 with ER-localized HMG-CoA reductase, which catalyzes a rate-limiting step in the synthesis of cholesterol and nonsterol isoprenoids, including GGpp. Binding to UBIAD1 inhibits sterol-accelerated ER-associated degradation (ERAD) of reductase and permits continued synthesis of GGpp in cholesterol-replete cells. GGpp disrupts UBIAD1-reductase binding and thereby allows for maximal ERAD of reductase as well as ER-to-Golgi translocation of UBIAD1. SCD-associated UBIAD1 is refractory to GGpp-mediated dissociation from reductase and remains sequestered in the ER to inhibit ERAD. Here, we report development of a biochemical assay for UBIAD1-mediated synthesis of MK-4 in isolated membranes and intact cells. Using this assay, we compared enzymatic activity of WT UBIAD1 with that of SCD-associated variants. Our studies revealed that SCD-associated UBIAD1 exhibited reduced MK-4 synthetic activity, which may result from its reduced affinity for GGpp. Sequestration in the ER protects SCD-associated UBIAD1 from autophagy and allows intracellular accumulation of the mutant protein, which amplifies the inhibitory effect on reductase ERAD. These findings have important implications not only for the understanding of SCD etiology but also for the efficacy of cholesterol-lowering statin therapy, which becomes limited, in part, because of UBIAD1-mediated inhibition of reductase ERAD.

Dong-Jae Jun
May 1, 2020; 61:746-757
Research Articles

It's episode 105, and David Price takes on hosting duties as the team dissect the best and absolute worst of the week's tech developments.

Scott Carey talks us through the troubling and wide-ranging allegations of sexual misconduct at Google, and discusses how this relates to the tech industry's culture of protected privilege, and to the #metoo movement.

Then Henry Burrell, fresh from a briefing at Apple HQ, reports his distinctly positive first impressions of the iPhone XR, which he would gladly recommend to tech newbie grandmas, and also to Scott.

See acast.com/privacy for privacy and opt-out information.

The autosomal dominant disorder Schnyder corneal dystrophy (SCD) is caused by mutations in UbiA prenyltransferase domain-containing protein-1 (UBIAD1), which uses geranylgeranyl pyrophosphate (GGpp) to synthesize the vitamin K₂ subtype menaquinone-4 (MK-4). SCD is characterized by opacification of the cornea, owing to aberrant build-up of cholesterol in the tissue. We previously discovered that sterols stimulate association of UBIAD1 with ER-localized HMG-CoA reductase, which catalyzes a rate-limiting step in the synthesis of cholesterol and nonsterol isoprenoids, including GGpp. Binding to UBIAD1 inhibits sterol-accelerated ER-associated degradation (ERAD) of reductase and permits continued synthesis of GGpp in cholesterol-replete cells. GGpp disrupts UBIAD1-reductase binding and thereby allows for maximal ERAD of reductase as well as ER-to-Golgi translocation of UBIAD1. SCD-associated UBIAD1 is refractory to GGpp-mediated dissociation from reductase and remains sequestered in the ER to inhibit ERAD. Here, we report development of a biochemical assay for UBIAD1-mediated synthesis of MK-4 in isolated membranes and intact cells. Using this assay, we compared enzymatic activity of WT UBIAD1 with that of SCD-associated variants. Our studies revealed that SCD-associated UBIAD1 exhibited reduced MK-4 synthetic activity, which may result from its reduced affinity for GGpp. Sequestration in the ER protects SCD-associated UBIAD1 from autophagy and allows intracellular accumulation of the mutant protein, which amplifies the inhibitory effect on reductase ERAD. These findings have important implications not only for the understanding of SCD etiology but also for the efficacy of cholesterol-lowering statin therapy, which becomes limited, in part, because of UBIAD1-mediated inhibition of reductase ERAD.

Histone H2B monoubiquitylation (H2Bub1) has central functions in multiple DNA-templated processes, including gene transcription, DNA repair, and replication. H2Bub1 also is required for the trans-histone regulation of H3K4 and H3K79 methylation. Although previous studies have elucidated the basic mechanisms that establish and remove H2Bub1, we have only an incomplete understanding of how H2Bub1 is regulated. We report here that the histone H4 basic patch regulates H2Bub1. Yeast cells with arginine-to-alanine mutations in the H4 basic patch (H42RA) exhibited a significant loss of global H2Bub1. H42RA mutant yeast strains also displayed chemotoxin sensitivities similar to, but less severe than, strains containing a complete loss of H2Bub1. We found that the H4 basic patch regulates H2Bub1 levels independently of interactions with chromatin remodelers and separately from its regulation of H3K79 methylation. To measure H2B ubiquitylation and deubiquitination kinetics in vivo, we used a rapid and reversible optogenetic tool, the light-inducible nuclear exporter, to control the subcellular location of the H2Bub1 E3 ligase, Bre1. The ability of Bre1 to ubiquitylate H2B was unaffected in the H42RA mutant. In contrast, H2Bub1 deubiquitination by SAGA-associated Ubp8, but not by Ubp10, increased in the H42RA mutant. Consistent with a function for the H4 basic patch in regulating SAGA deubiquitinase activity, we also detected increased SAGA-mediated histone acetylation in H4 basic patch mutants. Our findings uncover that the H4 basic patch has a regulatory function in SAGA-mediated histone modifications.

From online petitions to organized walkouts, corporate America is facing increasing employee activism over its business involvement with agencies implementing the federal government's immigration policies. This "cubicle activism," seen at companies ranging from Amazon and Google to Bank of America and Wayfair, has garnered mixed success to date, forcing divestiture from private prison contractors but fewer results in other contexts, as this article explores.

Sexually transmitted infections (STIs) are on the rise, and many people are curious about the reasons why. While the cause is obviously multifactorial, some have suggested that at least part of the rise in STIs may be due to increasing rates of pubic hair grooming in men and women alike. Given that it’s not uncommon for people to experience cuts and skin irritation from genital grooming practices, it at least sounds plausible in theory that pubic hair shaving could potentially increase infection risk. But what does the research actually say?

Ubiquity Press is an open access publisher of peer-reviewed, academic journals and books. It was founded by researchers at University College London (UCL) in 2012.

Paris : Doin, 1896.

London : Macmillan, 1896.

Berlin : Heuser, 1889.

Breslau : Hirt, 1871.

Gottingae : Typis Jo. Christian. Dieterich, [1793]

Paris : V.A. Delahaye, 1880.

London : Cleanair (33 Stillness Rd, London, SE23 1NG), [198-?]

JS Taube
Feb 1, 1990; 10:420-435
Articles

Ethnomusicologists visited a North African country to help local singers and a Sudanese Nubian believer write a worship song in his language and style.

It was 3pm on May 8 1945 when Prime Minister Sir Winston Churchill addressed the nation from the Cabinet Room announcing that “we may allow ourselves a brief period of rejoicing,” but that message instead led to three days of partying in Glasgow’s George Square, children were given time off school and families were looking forward to being reunited again.

Predischarge serum or transcutaneous bilirubinometry (TcB) measurements are recommended as appropriate screening options for identifying infants at risk for neonatal hyperbilirubinemia (NH). Visual inspection for jaundice is not reliable at identifying infants with NH in the community.

When compared with visual inspection alone, coordinated TcB screening for NH in acute-care and community settings is associated with significant improvements in laboratory utilization, patient care, convenience, and safety. (Read the full article)

Transcutaneous bilirubinometry was originally developed as a potential replacement for invasive blood sampling, but its clinical application is still limited to a screening method for hyperbilirubinemia. Reasons for this limited clinical value may be diverse.

This study provides insight into the reasons for the limited clinical value of transcutaneous bilirubinometry. This aids to both better interpretation of the measured TcB value from a patient and to possible improvement of the clinical value of the technique. (Read the full article)

Neonatal hyperbilirubinemia may progress to bilirubin encephalopathy. Findings from previous studies on long-term development of neonatal hyperbilirubinemia are conflicting.

Using Ages and Stages Questionnaire, we observed no association between bilirubin exposure and overall development in 1- to 5-year-old children who in the neonatal period had total serum bilirubin level ≥25 mg/dL and no or only minor neurologic symptoms. (Read the full article)

A dose-response relationship exists between light irradiance and decrease of total serum bilirubin concentration (TsB) at relatively low irradiances. It has been questioned whether by increasing irradiance a "saturation point" exists, above which no further decrease of TsB is seen.

We found a linear relation between light irradiance in the range of 20 to 55 μW/cm²/nm and decrease in TsB after 24 hours of therapy, with no evidence of a saturation point. (Read the full article)

The higher the predischarge bilirubin percentile reading on the hour of life–specific nomogram, the higher becomes that infant's risk of developing significant hyperbilirubinemia. Neonates in the low-risk zones (≤75th percentile) have a low risk of developing hyperbilirubinemia.

Thirty-two percent of newborns readmitted for hyperbilirubinemia had low-risk zone predischarge bilirubin percentile values, predominantly in the intermediate low-risk zone (41st–75th percentile). The intermediate low-risk zone may not be as low risk as previously thought. (Read the full article)

Although the natural course of bilirubin levels has been extensively studied in general neonatal populations, there is a paucity of data regarding bilirubin trends in neonates before the development of significant hyperbilirubinemia.

This study provides data on the natural course of transcutaneous bilirubin before the development of significant hyperbilirubinemia, and on the effect of different demographic and perinatal risk factors on the rate of bilirubin increase in neonates with borderline bilirubin values. (Read the full article)

Severe neonatal hyperbilirubinemia can lead to acute bilirubin encephalopathy and, subsequently, chronic bilirubin encephalopathy (CBE). This condition is preventable through routine identification and proper treatment; therefore, it is rare for permanent neurologic complications to occur.

This article describes the incidence of CBE in Canada, which is higher than previously reported in the literature. Furthermore, it describes the underlying causes of CBE and the spectrum of neurologic disease. (Read the full article)

Doxorubicin therapy, effective against many malignancies, is limited by cardiotoxicity. Continuous-infusion doxorubicin, compared with bolus-infusion, reduces early cardiotoxicity in adults. Its effectiveness in reducing late cardiotoxicity in children remains uncertain.

This multicenter randomized trial assessed whether continuous-infusion of doxorubicin in pediatric patients provides long-term cardioprotection or improvement in event-free survival over bolus-infusion in acute lymphoblastic leukemia. Continuous-infusion of doxorubicin provided no cardioprotection or improvement in event-free survival. (Read the full article)

For newborn infants, extreme hyperbilirubinemia (≥24.5 mg/dL) is associated with risk for severe bilirubin encephalopathy. The causal factor of extreme hyperbilirubinemia is often not established. The genotype of Gilbert syndrome, the UGT1A1*28 allele, is considered a potential risk factor.

The UGT1A1*28 allele was not associated with risk for developing extreme hyperbilirubinemia. (Read the full article)

Total serum bilirubin levels ≥30 mg/dL have been labeled as "hazardous." Levels this high are rare, occurring in 3 to 10 per 100 000 births. Few studies have examined etiologies and long-term outcomes in these infants.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a major identifiable cause, but is under-assessed. Chronic, bilirubin-induced neurotoxicity is rare and only occurred in the setting of additional risk factors (prematurity, G6PD deficiency, sepsis) and at levels far above recommended exchange transfusion thresholds. (Read the full article)

Evidence from cohort studies has consistently found that universal bilirubin screening is associated with reductions in rates of severe hyperbilirubinemia but has shown variation in other outcomes such as phototherapy use, length of stay, emergency department visits, and readmission rates.

Universal bilirubin screening may not increase neonatal length of stay or postdischarge hospital use. Preexisting trends in health care utilization have an impact on observed effects of universal bilirubin screening. (Read the full article)