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The Transcriptional Aftermath in Two Independently Formed Hybrids of the Opportunistic Pathogen Candida orthopsilosis

ABSTRACT

Interspecific hybridization can drive evolutionary adaptation to novel environments. The Saccharomycotina clade of budding yeasts includes many hybrid lineages, and hybridization has been proposed as a source for new pathogenic species. Candida orthopsilosis is an emerging opportunistic pathogen for which most clinical isolates are hybrids, each derived from one of at least four independent crosses between the same two parental lineages. To gain insight into the transcriptomic aftermath of hybridization in these pathogens, we analyzed allele-specific gene expression in two independently formed hybrid strains and in a homozygous strain representative of one parental lineage. Our results show that the effect of hybridization on overall gene expression is rather limited, affecting ~4% of the genes studied. However, we identified a larger effect in terms of imbalanced allelic expression, affecting ~9.5% of the heterozygous genes in the hybrids. This effect was larger in the hybrid with more extensive loss of heterozygosity, which may indicate a tendency to avoid loss of heterozygosity in these genes. Consistently, the number of shared genes with allele-specific expression in the two independently formed hybrids was higher than random expectation, suggesting selective retention. Some of the imbalanced genes have functions related to pathogenicity, including zinc transport and superoxide dismutase activities. While it remains unclear whether the observed imbalanced genes play a role in virulence, our results suggest that differences in allele-specific expression may add an additional layer of phenotypic plasticity to traits related to virulence in C. orthopsilosis hybrids.

IMPORTANCE How new pathogens emerge is an important question that remains largely unanswered. Some emerging yeast pathogens are hybrids originated through the crossing of two different species, but how hybridization contributes to higher virulence is unclear. Here, we show that hybrids selectively retain gene regulation plasticity inherited from the two parents and that this plasticity affects genes involved in virulence.




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Systematic Genetic Study of Youth With Diabetes in a Single Country Reveals the Prevalence of Diabetes Subtypes, Novel Candidate Genes, and Response to Precision Therapy

Identifying gene variants causing monogenic diabetes (MD) increases understanding of disease etiology and allows for implementation of precision therapy to improve metabolic control and quality of life. Here, we aimed to assess the prevalence of MD in youth with diabetes in Lithuania, uncover potential diabetes-related gene variants, and prospectively introduce precision treatment. First, we assessed all pediatric and most young-adult patients with diabetes in Lithuania (n = 1,209) for diabetes-related autoimmune antibodies. We then screened all antibody-negative patients (n = 153) using targeted high-throughput sequencing of >300 potential candidate genes. In this group, 40.7% had MD, with the highest percentage (100%) in infants (diagnosis at ages 0–12 months), followed by those diagnosed at ages >1–18 years (40.3%) and >18–25 years (22.2%). The overall prevalence of MD in youth with diabetes in Lithuania was 3.5% (1.9% for GCK diabetes, 0.7% for HNF1A, 0.2% for HNF4A and ABCC8, 0.3% for KCNJ11, and 0.1% for INS). Furthermore, we identified likely pathogenic variants in 11 additional genes. Microvascular complications were present in 26% of those with MD. Prospective treatment change was successful in >50% of eligible candidates, with C-peptide >252 pmol/L emerging as the best prognostic factor.




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Evolutionary insights in Amazonian turtles (Testudines, Podocnemididae): co-location of 5S rDNA and U2 snRNA and wide distribution of Tc1/Mariner [RESEARCH ARTICLE]

Manoella Gemaque Cavalcante, Cleusa Yoshiko Nagamachi, Julio Cesar Pieczarka, and Renata Coelho Rodrigues Noronha

Eukaryotic genomes exhibit substantial accumulation of repetitive DNA sequences. These sequences can participate in chromosomal reorganization events and undergo molecular cooption to interfere with the function and evolution of genomes. In turtles, repetitive DNA sequences appear to be accumulated at probable break points and may participate in events such as non-homologous recombination and chromosomal rearrangements. In this study, repeated sequences of 5S rDNA, U2 snRNA and Tc1/Mariner transposons were amplified from the genomes of the turtles, Podocnemis expansa and Podocnemis unifilis, and mapped by fluorescence in situ hybridization. Our data confirm the 2n=28 chromosomes for these species (the second lowest 2n in the order Testudines). We observe high conservation of the co-located 5S rDNA and U2 snRNA genes on a small chromosome pair (pair 13), and surmise that this represents the ancestral condition. Our analysis reveals a wide distribution of the Tc1/Mariner transposons and we discuss how the mobility of these transposons can act on karyotypic reorganization events (contributing to the 2n decrease of those species). Our data add new information for the order Testudines and provide important insights into the dynamics and organization of these sequences in the chelonian genomes.




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Enhanced Efflux Pump Expression in Candida Mutants Results in Decreased Manogepix Susceptibility [Mechanisms of Resistance]

Manogepix is a broad-spectrum antifungal agent that inhibits glycosylphosphatidylinositol (GPI) anchor biosynthesis. Using whole-genome sequencing, we characterized two efflux-mediated mechanisms in the fungal pathogens Candida albicans and Candida parapsilosis that resulted in decreased manogepix susceptibility. In C. albicans, a gain-of-function mutation in the transcription factor gene ZCF29 activated expression of ATP-binding cassette transporter genes CDR11 and SNQ2. In C. parapsilosis, a mitochondrial deletion activated expression of the major facilitator superfamily transporter gene MDR1.




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Ironbark: Did two spies really prevent all-out nuclear war?

Ironbark is one of 2020’s anticipated movies. Benedict Cumberbatch plays the MI6 handler of a Russian spy who may have helped prevent nuclear war




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TikTok: How did the video-sharing app get so big so quickly?

TikTok's rise has been meteoric. With more than 3 million people a day now downloading the app, its success is down to more than just luck




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Alison Roman Bashed Marie Kondo and Chrissy Teigen, and It Did Not Spark Joy

Photo Illustration by Lyne Lucien/The Daily Beast/Getty

Alison Roman’s latest comments about Marie Kondo have not sparked joy.

In an interview with The New Consumer about her increased popularity and the avenues she might pursue to capitalize on it, the popular food columnist discussed her hesitance to put her name on a product line—citing the Japanese organization maven and Chrissy Teigen as examples of what she did not foresee in her own future.

“I have a collaboration coming out with [the cookware startup] Material, a capsule collection,” Roman said. “It’s limited edition, a few tools that I designed that are based on tools that I use that aren’t in production anywhere—vintage spoons and very specific things that are one-offs that I found at antique markets that they have made for me.”

Read more at The Daily Beast.




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Mega Millions Results, Numbers for 5/8/20: Did Anyone Win the $231 Million Jackpot Prize Last Night?

The winners and results of last night's Mega Millions lottery, plus how to avoid falling victim to a lottery scam.




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Ousted Scientist Tears Up While Ripping Trump Coronavirus Response: 'We Could've Done Something And We Didn't'

Trump administration whistleblower Rick Bright teared up while ripping the Trump's response to the coronavirus: "We could've done something and we didn't."




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Raptorial Dinosaurs Did Not Hunt in Coordinated Packs, Paleontologists Say

An analysis of the fossilized teeth of Deinonychus antirrhopus, a species of wolf-sized dromaeosaurid dinosaur that lived between 115 and 108 million years ago (Cretaceous period) in what is now the United States, adds to the growing evidence that this and other raptors were not complex social hunters by modern mammalian standards. The image of [...]




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The hunt for patient zero: Where did the coronavirus outbreak start?

Growing evidence suggests the covid-19 outbreak may not have started at Wuhan’s Huanan Seafood Market in December after all. Finding its origins may help us stop it happening again




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Trump says he did not wear mask at Honeywell facility after consulting CEO

U.S. President Donald Trump said on Wednesday he did not wear a mask during a tour on Tuesday of a Honeywell International Inc factory in Arizona after consulting the company's chief executive, despite requirements at the plant that workers wear them.




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Diddy and Justin Timberlake demand justice for murdered jogger

Prosecutor Tom Durden has vowed to convene a grand jury to discuss possible charges against the suspects - but only when coronavirus pandemic restrictions are eased, which could take several weeks.




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Justin Amash on third-party presidential campaign: 'I think it hurts both candidates'

Rep. Justin Amash believes his White House bid is bad for both President Trump and his Democratic challenger, the Michigan Libertarian indicated in a recent interview.

Mr. Amash, a former Republican who left the GOP last year, told Time that he expects his presence in the presidential race will not ...




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NOT REAL NEWS: A look at what didn't happen this week

A roundup of some of the most popular but completely untrue stories and visuals of the week. None of these are legit, even though they were shared widely on social media. The Associated Press checked them out. Here are the facts:

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CLAIM: Photo shows Joe Biden posing with former ...




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Dad of Ahmaud Arbery says of his killing: 'He didn't deserve to go out like that'

Arbery, who would have turned 26 on Friday, was shot to death after being chased by two men who thought he was a burglar.




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Justin Bieber, Hailey Baldwin open their lives for candid new series

Justin Bieber and his wife Hailey Baldwin are opening up in an intimate series for Facebook Watch in which they discuss their marriage, their problems and their lives together.




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One in 11 Covid-19 deaths did not involve underlying health conditions, ONS statistics show

Read our live coronavirus updates HERE Coronavirus: The symptoms




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Coronavirus China: When did Wuhan lockdown begin and for how long?

Follow our live Covid-19 updates HERE Coronavirus: The symptoms




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Nurse tells how she held elderly woman's hand 'during her last breaths' so she didn't die alone after coronavirus battle

A former NHS nurse who returned to the frontlines to help fight the coronavirus pandemic has shared the moment she held an elderly woman's hand during her last breaths so she didn't die alone from the virus.




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South Korean officials claim Kim Jong Un did not undergo surgery as speculation continues about ill health

North Korean leader Kim Jong Un did not undergo surgery or any other medical procedure, a South Korean official has said amid continued speculation about his health.




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Who is Professor Neil Ferguson and how did he breach lockdown?

The top scientist, Professor Neil Ferguson, whose research aided Boris Johnson's decision to impose a lockdown, has resigned after reportedly allowing a woman to visit his home in an "error of judgment".









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Did David Dobrik Just Confirm He’s In A Relationship With Madison Beer?

Fans think they might be going official




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Bella Hadid Unfollows Selena Gomez Just One Day After Refollowing Her

Fans celebrated their friendship too soon




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Fans Think Zayn Malik Is Dropping Clues That He’s Engaged To Gigi Hadid

Marriage ~and~ a baby? It's a lot to take in




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Sony says major The Last of Us Part 2 leak didn’t come from employee [Updated]

No spoilers here, but details about character relationships, fates are out there.




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'Star Wars' actor criticises 'The Last Jedi', says Rian Johnson didn't 'do his homework'

Another 'Star Wars' actor has added their voice to the criticism of Rian Johnson's movie.




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The incredible comeback you probably didn't hear about: Phil Galfond talks overcoming €900,000 deficit

Professional poker player Phil Galfond overcame a €900,000 deficit in a 25,000-hand head-to-head challenge against a pot-limit Omaha regular known as "VeniVidi1993" online.




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Gigi Hadid and Zayn Malik Reportedly Expecting a Baby

25-year-old supermodel Gigi Hadid is expecting her first child with One Direction's Zayn Malik, reports TMZ and Entertainment Tonight.




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How the coronavirus undid Florida Gov. Ron DeSantis

Long before the coronavirus outbreak turned him into one of the least popular governors in the nation, DeSantis of Florida was something of a conservative golden boy.





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How Did Ancient People Keep Their Food From Rotting?

Archaeologists have discovered methods that kept food fresh long before refrigeration.




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What Did Humans Evolve From?

A key piece of the human family tree is still missing, waiting to be found.




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Tiger King: Rick Kirkham comes forward with disturbing Joe Exotic story that didn't make it into documentary

He called Exotic 'unbelievably cruel'




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Westworld actor Ed Harris criticises character's season 3 storyline: 'I didn't sign on to play the Man in White'

'This wasn't the most joyous season for me,' actor admitted in candid new interview




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Better Call Saul: Vince Gilligan admits he initially didn't want to bring Breaking Bad's Lalo back

'Man, I was wrong'




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Idris Elba denies calling for annual quarantine week: 'I didn't suggest an actual lockdown'

Actor was ridiculed for remarks as people pointed out they were unlikely to forget current predicament anytime soon




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The Apprentice's Lottie Lion apologises after impersonating fellow candidate in 'racist' Instagram video

Lion says she meant it as 'light entertainment for fans during these difficult times'




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The Simpsons writer concedes series really did 'predict 2020' after new double 'prediction' emerges

People have noted a certain timeliness in a clip from the 1993 episode 'Marge in Chains'




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NFL great Brett Favre to repay $1.1m he received for speeches he didn't make

  • State auditor says Favre will repay money for no-show speeches
  • Hall of Fame quarterback faces no criminal charges after report

Former NFL quarterback Brett Favre is repaying $1.1m in welfare money that he received for multiple speeches where he did not show up, the Mississippi state auditor said Wednesday.

Auditor Shad White said his office received $500,000 from Favre on Wednesday, plus a commitment that Favre will repay the other $600,000 in installments over the next few months.

Related: NFL tells teams to have facility reopening protocols in place by next week

Continue reading...




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Sydney harbour master tells Ruby Princess inquiry he 'did not understand' email

NSW Health assessment the cruise ship was ‘low risk’ introduced ‘an unfortunate element’ into his decision-making

A New South Wales harbour master has told an inquiry he “did not understand” an email that told him to treat the Ruby Princess “as if it has a positive Covid-19 result” when it came into Sydney Harbour on 18 and 19 March.

Cameron Butchart, who was the duty harbour master on 18 March, said NSW Health’s assessment that the ship was “low risk” introduced “an unfortunate element” into his decision-making.

Continue reading...




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NSW police watchdog says strip searches illegal but critics say findings ‘did not go far enough’

A 16-year-old Aboriginal boy was forced to remove his shorts and squat during a search, but disciplinary action has not been recommended

A New South Wales police watchdog investigation into seven strip searches including one in which a 16-year-old Aboriginal boy was physically forced to remove his shorts and squat has found that all of them were unlawful.

But the watchdog has been criticised for “not going far enough” in its findings, with Sarah Crellin, a principal solicitor at the Aboriginal Legal Service, saying she was “deeply disappointed that there have been no recommendations for disciplinary action” against individual officers.

Continue reading...




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‘Why didn’t he help those little boys?’: how George Pell failed the children of Ballarat

The cardinal maintains he didn’t know about the Victorian town’s notorious paedophile priests, a claim the royal commission found ‘implausible’

“Why isn’t all of Australia talking about what happened here in Ballarat?”

That’s the question Clare Linane remembers asking her husband, Peter Blenkiron, 12 years ago as they were sitting in the kitchen talking about his abuse. Linane’s husband, brother and cousin had all been abused when they were children between 1973 and 1974 by Christian Brother and now convicted paedophile Edward “Ted” Dowlan. They knew they were among thousands of people living in and around Ballarat – Victoria’s largest inland city – who had been affected by child sexual abuse perpetrated by clergy.

Continue reading...




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Dua Lipa reveals orange hair in cute quarantine snap with boyfriend Anwar Hadid

The Hotter than Hell singer has revealed her new 'do in a sweet Instagram post




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Zayn Malik and Gigi Hadid 'expecting first child'

Zayn Malik and Gigi Hadid are reportedly expecting their first child together.




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Gigi Hadid and Zayn Malik relationship timeline: From how they met to their brief split and baby rumours

The couple have been on and off since 2015