Objective

Polygenic risk scores (PRSs) are used to quantify the cumulative effects of a number of genetic variants, which may individually have a very small effect on susceptibility to a disease; we used PRSs to better understand the genetic contribution to common epilepsy and its subtypes.

Objective

To specifically report on ataxic-hypotonic cerebral palsy (CP) using registry data and to directly compare its features with other CP subtypes.

Although pain is a prevalent nonmotor symptom in Parkinson’s disease (PD), it is undertreated, in part because of our limited understanding of the underlying mechanisms. Considering that the basal ganglia are implicated in pain sensation, and that their synaptic outputs are controlled by the subthalamic nucleus (STN), we hypothesized that...

ABSTRACT

The chemical structures of soluble fiber carbohydrates vary from source to source due to numerous possible linkage configurations among monomers. However, it has not been elucidated whether subtle structural variations might impact soluble fiber fermentation by colonic microbiota. In this study, we tested the hypothesis that subtle structural variations in a soluble polysaccharide govern the community structure and metabolic output of fermenting microbiota. We performed in vitro fecal fermentation studies using arabinoxylans (AXs) from different classes of wheat (hard red spring [AX_HRS], hard red winter [AX_HRW], and spring red winter [AX_SRW]) with identical initial microbiota. Carbohydrate analyses revealed that AX_SRW was characterized by a significantly shorter backbone and increased branching compared with those of the hard varieties. Amplicon sequencing demonstrated that fermentation of AX_SRW resulted in a distinct community structure of significantly higher richness and evenness than those of hard-AX-fermenting cultures. AX_SRW favored OTUs within Bacteroides, whereas AX_HRW and AX_HRS favored Prevotella. Accordingly, metabolic output varied between hard and soft varieties; higher propionate production was observed with AX_SRW and higher butyrate and acetate with AX_HRW and AX_HRS. This study showed that subtle changes in the structure of a dietary fiber may strongly influence the composition and function of colonic microbiota, further suggesting that physiological functions of dietary fibers are highly structure dependent. Thus, studies focusing on interactions among dietary fiber, gut microbiota, and health outcomes should better characterize the structures of the carbohydrates employed.

IMPORTANCE Diet, especially with respect to consumption of dietary fibers, is well recognized as one of the most important factors shaping the colonic microbiota composition. Accordingly, many studies have been conducted to explore dietary fiber types that could predictably manipulate the colonic microbiota for improved health. However, the majority of these studies underappreciate the vastness of fiber structures in terms of their microbial utilization and omit detailed carbohydrate structural analysis. In some cases, this causes conflicting results to arise between studies using (theoretically) the same fibers. In this investigation, by performing in vitro fecal fermentation studies using bran arabinoxylans obtained from different classes of wheat, we showed that even subtle changes in the structure of a dietary fiber result in divergent microbial communities and metabolic outputs. This underscores the need for much higher structural resolution in studies investigating interactions of dietary fibers with gut microbiota, both in vitro and in vivo.

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.

Random transposon mutagenesis is a powerful and unbiased genetic approach to answer fundamental biological questions. Here, we introduce an improved mariner-based transposon system with enhanced stability during propagation and versatile applications in mutagenesis. We used a low-copy-number plasmid as a transposon delivery vehicle, which affords a lower frequency of unintended recombination during vector construction and propagation in Escherichia coli. We generated a variety of transposons allowing for gene disruption or artificial overexpression, each in combination with one of four different antibiotic resistance markers. In addition, we provide transposons that will report gene/protein expression due to transcriptional or translational coupling. We believe that the TnFLX system will help enhance the flexibility of future transposon modification and application in Bacillus and other organisms.

IMPORTANCE The stability of transposase-encoding vectors during cloning and propagation is crucial for the reliable application of transposons. Here, we increased the stability of the mariner delivery vehicle in E. coli. Moreover, the TnFLX transposon system will improve the application of forward genetic methods with an increased number of antibiotic resistance markers and the ability to generate unbiased green fluorescent protein (GFP) fusions to report on protein translation and subcellular localization.

Purpose:

To provide a better understanding of the interplay between the immune system and brain metastases to advance therapeutic options for this life-threatening disease.

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-1_LAI 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.

Background:

Lipid traits have been inconsistently linked to risk of non-Hodgkin lymphoma (NHL). We examined the association of genetically predicted lipid traits with risk of diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), and marginal zone lymphoma (MZL) using Mendelian randomization (MR) analysis.

Subtractive immunization is useful for directing the immune response away from dominant epitopes to allow antibodies against less immunogenic antigens to be developed. It is also useful when there is a need to downplay the response to carriers added to peptides and recombinant proteins, such as Gst and Ig, to aid in production and purification. Subtractive immunization protocols also can be helpful if the target protein is part of a mixture (such as a cell lysate) or present on the surface of transfected cells.

BACKGROUND AND PURPOSE:

Not all tandem occlusions diagnosed on traditional vascular imaging modalities, such as MRA, represent actual complete ICA occlusion. This study aimed to explore the utility of high-resolution vessel wall imaging in identifying true ICA tandem occlusions and screening patients for their suitability for endovascular recanalization.

Get ready for the first scored event in DARPA's latest Grand Challenge

Roboticists share what they've learned so far from DARPA's Subterranean Challenge, and how they readied their bots for the next event—the Tunnel Circuit

How autonomous robots in the underground scavenger hunt pick up points for their teams

Supporting long-range communications inside of a mine is extremely difficult, so DARPA SubT teams are trying out some creative approaches

It's about more than just first place as teams look toward more competitions in 2020

What is likely to be Kimi Raikkonen's final Formula 1 victory at the 2018 US Grand Prix is being live-streamed by F1 today. The high point of a disappointing second spell at Ferrari, it nonetheless gave the 2007 world champion a chance to prove a point.

The boss of Airbus has warned that it is "bleeding cash" at such a rapid rate during the coronavirus lockdowns that its survival is in doubt.

Covid-19 could be 'antidote to complacency' among those on the fence about vaccines, scientists say

Prime Minister Justin Trudeau described Canada’s current economic situation as a recession on Friday, and that should come as no surprise, says Finance Minister Bill Morneau, as the latest economic figures show two consecutive months of major job losses.

'If I'm not acting, I'm not sure who I am,' the True Blood star said

'Without subtitles and the British accent, its a no from me'

Hakim Ziyech insists his Chelsea future was never in doubt and claims he was always intent on joining the club in July.

Welcome to the Evening Standard's LIVE coverage as the coronavirus crisis continues to heavily impact sport across the globe.

Kevin De Bruyne has revealed the outcome of Manchester City's appeal against their Champions League ban may determine his future at the club.

Up to 50 Premier League players are planning to revolt against plans to restart the season, according to reports.

It is one of the most popular and important websites for cattle producers, rangers and carbon farmers in northern Australia, but its funding is about to run out.

Valtteri Bottas is a doubt for the Australian Grand Prix after suffering back pain during qualifying and being taken to hospital for further checks on Saturday evening

Valtteri Bottas remains a doubt for Sunday's Australian Grand Prix after spending the night in hospital with soft tissue damage to his back

Traders on Thursday priced in a negative federal funds rate by December 2020, lasting at least to January 2022

Experts warn that vaccine timelines look ambitious and argue more thought is needed on manufacturing.

Joint statement insists return will not happen until stringent ‘test and trace’ regime in place

Ministers’ plans to reopen schools as early as 1 June are in serious doubt after unions representing teachers and school staff insisted that they would not consider a return without a stringent coronavirus “test and trace” regime.

In an unusual joint statement, which one senior union official said indicated that an early return to a normal school timetable was “off the menu”, the Trades Union Congress said that there should be “no increase in pupil numbers until full rollout of a national test and trace scheme”, and called for the establishment of a Covid-19 taskforce with government, unions and others to agree on the safe reopening of schools.

A 40-year-old man allegedly killed his wife and later committed suicide by hanging himself in Thane on Thursday. Sunil Sangle, an auto driver, on Wednesday night strangled his wife Archana Sangle (35), to death at their home in Sri Nagar locality and later hanged himself on Thursday afternoon, said police inspector Sulabha Patil.

The couple often had fights over domestic issues and apparently the man also suspected his wife’s character, and this may have triggered the murder, police said. According to Hindustan Times, Sunil Sangle was an auto-rickshaw driver and his wife worked as a security guard at an IT park in the city. A probe is underway, the police added.

In a similar case, a 38-year-old man was arrested for allegedly killing a man suspecting him of having an extra-marital affair with his wife in outer Delhi, police said Saturday. The accused identified as Anil Chaudhary, a resident of Nangloi, used to work in a shoe factory.

Other two men, Bakil (38) and Kamrul Huda (27) who allegedly robbed the victim after he was killed by the accused Chaudhary, were also arrested, police said. On Thursday, Nihal Vihar Police station was informed by Satya Bhama Hospital that a person has been brought dead in the hospital, Rajendra Singh Sagar, Additional Deputy Commissioner of Police (Outer) said.

The victim was identified as Vikas Yadav by his relatives. He used to work as a labourer in a chemical factory. On interrogation, the accused Chaudhary revealed he suspected Yadav of having an illicit relationship with his wife since a year. So, he decided to eliminate Yadav and on Wednesday night, he fired at Yadav, the officer said. Yadav was carrying two mobile phones and Rs 15,000 which were missing from his possession, the officer added.

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Illustration/Devdutt Pattanaik

In the beginning, people said homosexuality is unnatural. Then scientists showed them that hundreds of species of animals do indulge in homosexuality. So people started saying homosexuality may be natural, but it is best restricted to animals. Amongst humans, it is a social disease. This unscientific understanding is popularised by many religious leaders, who are clueless about science, though they insist that the Vedas/Quran/Agama/Tripitaka/Talmud are essentially scientific.

These religious leaders fall into two categories. The first category is the 'liberal' guru who says sex is great for spirituality, provided it is heterosexual. The second category is the 'conservative' guru who says sex is not great for spirituality, and if you must indulge in it, do it for babies.

A gay man heard how a broad-minded Indian guru presented sexuality as an integral part of spirituality, and so decided to read a bit more of the guru's writings. He was suitably impressed, there was a lot of talk of how exploring sexual desires authentically enhances spiritual growth. But then came the horror! When the guru spoke of sexuality, he was referring only to heterosexuality and was essentially promoting orgies as a tool to liberate yourself. He saw homosexuality as a social disease resulting from heterosexuality being suppressed when men are locked with men in monasteries and prisons and women are locked with women in nunneries. This was his fantasy, which he marketed as mystical knowledge of the East!

A lesbian woman came upon a guru who gave her a sympathetic ear, and who confidently asserted that ancient mystical sages (all male, of course) had revealed to him that natural sexual activity is for making babies only, and that pleasure is just nature's way of incentivising you to make more babies. It is the human perversion to bypass the baby-making and focus on pleasure. Such value placed on pleasure comes from stress, hormones, and a lack of spiritual grounding. He insisted that homosexuality is a social pathology, not a natural physiology. She could stay a single woman if she did not wish to be a man's wife, but she had to engineer her life towards spirituality rather than sexuality if she sought fulfilment and happiness. Her libido, he insisted, was in dire need of fixing!

Most of these gurus do oppose the criminalising of homosexuality, and so appear to be modern. However, they do see homosexuality as a deviance (or its Sanskrit equivalent), or a 'fluidity' that needs explanation, management and re-alignment. They mirror the homophobia directed at queer people (pandakas, napunsakas) that we find in ancient monastic orders such as Buddhism and Jainism. Their discomfort with queerness is similar to their well-disguised discomfort with gender equality: 'Women are as good as men, provided they put the man's needs first.' Essentially, these gurus preach qualified equality, where their personal comfort zone (heterosexuality, celibacy, masculinity) remains privileged.

It is important to recognise gurus as political figures. They are today clearly political vote banks, with a vast number of followers who do whatever the guru tells them to do. Hence the power of their spiritual discourses to influence social and political direction needs to be acknowledged.

We must also recognise the power of followers over gurus. Gurus are expected to be superhuman, and 'pure and pious'. We don't mind them dancing to Bollywood songs or playing golf. But if they were to talk too much in favour of sex and pleasure, we will see them as less than spiritual. In our hearts, many of us are convinced spirituality is an adversary of sexuality. We see Shiva who burnt Kama to ash. We refuse to see Shiva who was enchanted by Kamakshi and Mohini.

The author writes and lectures on the relevance of mythology in modern times. Reach him at devdutt@devdutt.com

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The Belgian Formula One Grand Prix scheduled for August 30 is in doubt after the country's ban on public gatherings was extended until the end of that month, organisers said. "All scenarios are being studied: postponement, holding it behind closed doors, or cancelling it. No-one can say what the situation will be in four and a half months," Vanessa Maes, the grand prix's director general, told Belga news agency.

Holding the event behind closed doors is unlikely with local backers unhappy with the financial fallout, according to the newspaper La Derniere Heure. The race is expected to join nine other grands prix that have already been cancelled or postponed this season as Formula One grapples with the consequences of the coronavirus pandemic.

"Our absolute priority remains the health of the Belgian people and the spectators who come to Spa-Francorchamps," the race venue, said Maes.
The French Grand Prix scheduled for June 28 is also in doubt. A decision on whether to go ahead with the race behind closed doors or to postpone or scrap the event is expected in the coming days.

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After the government's protocol of social distancing and self-quarantine, many people have found ways to keep themselves busy into the four walls. Speaking of which, Janhvi Kapoor was seen cooking and trying her hand into various dishes. But guess who turns the judge of her experimentation cooking classes? It's none other than baby sister Khushi Kapoor.

Last time, the actress baked a carrot cake, and once again, it was fed to Khushi Kapoor first. Janhvi shared the review video as her Instagram story, and Khushi liked the cake baked by her sister. Take a look at the video here.

 

 

 

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A post shared by Manav Manglani (@manav.manglani) onApr 21, 2020 at 10:21am PDT

Now, once again, Janhvi Kapoor wore the chef's cap and made 'banana toffee,' and shared a video as her story. As soon as Khushi Kapoor tried the dish, she couldn't help it but subtly reject what Janhvi cooked for her. We can't stop laughing her Khushi's various expressions in one bite of 'banana toffee.'

Speaking of Khushi Kapoor, the star kid was in New York for her further studies, but papa Boney Kapoor brought her back as soon as the coronavirus outbreak started to take over the world slowly. Now, the duo has been living with papa at their Mumbai residence.

On the work front, Janhvi Kapoor will be next seen in Gunjan Saxena, where the actress is portraying a real-life person for the first time in her career. Based on Gunjan Saxena, who is one of the first female pilots to fly in combat, Janhvi plays an important role in rescuing injured soldiers during the Kargil War in 1999 and was awarded the gallantry Shaurya Vir Award for displaying courage during the war.

Directed by Sharan Sharma, the film also stars Vineet Kumar Singh, Angad Bedi and Manav Vij in pivotal roles. She will also be seen in Karan Johar's multi-starrer Takht alongside Kareena Kapoor Khan, Ranveer Singh, Alia Bhatt, Vicky Kaushal, Bhumi Bednekar and Anil Kapoor, and Roohi Afza opposite Rajkummar Rao.

Apart from Gunjan Saxena and Takht, Janhvi Kapoor will be seen in Dostana 2 and Roohi Afzana.

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The White House released new guidelines Monday aimed at answering criticism that America's coronavirus testing has been too slow, and President Donald Trump tried to pivot toward a focus on 'reopening' the nation. Still, there were doubts from public health experts that the White House's new testing targets were sufficient. Monday's developments were meant to fill critical gaps in White House plans to begin easing restrictions, ramping up testing for the virus while shifting the president's focus toward recovery from the economic collapse caused by the outbreak. The administration unveiled a 'blueprint' for states to scale up their testing in the coming week, a tacit admission, despite public statements to the contrary, that testing capacity and availability over the past two months have been lacking.

The new testing targets would ensure states had enough COVID-19 tests available to sample at least 2.6 per cent of their populations each month, a figure already met by a majority of states. Areas that have been harder hit by the virus would be able to test at double that rate, or higher, the White House said. The testing issue has bedeviled the administration for months. Trump told reporters on March 6 during a visit to the CDC in Atlanta that 'anybody that wants a test can get a test,' but the reality has proved to be vastly different. The initial COVID-19 test developed by the Centers for Disease Control and Prevention was contaminated, and early kits operated only on platforms able to perform a small number of test per day. While the rate of testing increased as tests developed for higher-capacity platforms, they were still limited by shortages of supplies, from nasal swabs to the reagents used to process the samples.

Administration officials maintained Monday that the limiting factor now is actually the availability of samples from people who have been tested ' either because guidelines on who could be tested are too stringent or because there are not enough health workers able to take nasal swab samples from them. The CDC moved to address one of those concerns Monday, expanding the list of people to be prioritized for virus testing to include those who show no symptoms but are in high-risk settings like nursing homes. And Trump met with leaders of businesses including CVS, Walmart and Kroger, who said they were working to expand access to tests across the country. 'Testing is not going to be a problem at all,' Trump said later in the Rose Garden.

However, many of the administration's past pledges and goals on testing have not been met. Jeremy Konyndyk, a disaster preparedness expert who helped lead the Obama administration response to Ebola, said the administration's testing plans are well short of what is needed. Researchers at Harvard have estimated the country needs to be testing a minimum of 500,000 people per day, and possibly many more. Konyndyk said the aim should be 2 million to 3 million per day. Trump said the current total, up sharply in recent days, is over 200,000 per day. Konyndyk said, 'Over the past month, we've doubled or if you want to be really generous tripled the testing capacity in this country. We need to take where we are now and expand it 10-fold."

The testing blueprint for states provides details missing from the administration's guidelines for them to return to normal operations that were released more than a week ago. It includes a focus on surveillance testing as well as 'rapid response' programs to isolate those who test positive and identify those with whom they had come in contact. The administration aims to have the market 'flooded' with tests for the fall, when COVID-19 is expected to recur alongside the seasonal flu. Trump and administration medical experts outlined the plan on a call with governors Monday afternoon, before unveiling them publicly in a Rose Garden press conference. The White House announcements came as Trump sought to regain his footing after weeks of criticism and detours created in part by his press briefings.

Days after he set off a firestorm by publicly musing that scientists should explore the injection of toxic disinfectants as a potential virus cure, Trump said he found little use for his daily task force briefings, where he has time and again clashed with medical experts and reporters. Trump's aides had been trying to move the president onto more familiar and, they hope, safer, ground: talking up the economy in more tightly controlled settings. Republican Party polling shows Trump's path to a second term depends on the public's perception of how quickly the economy rebounds from the state-by-state shutdowns meant to slow the spread of the virus.

On Monday, the White House initially announced there would be a Trump briefing, but canceled it as Trump's greatest asset in the reelection campaign ' his ability to dominate headlines with freewheeling performances ' was increasingly seen as a liability. But hours later, Trump it became clear Trump had other ideas. He held court in the Rose Garden for a bit less than an hour. Spokeswoman Kayleigh McEnany said that briefings would be held later in the week but 'they might have a new look to them, a new focus to them.' Trump said he hoped that virus deaths would end up no more than 60,000 to 70,000, slightly revising upward his public estimate of recent days as the U.S. toll neared 56,000 on nearly 1 million cases.

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The new review has described the growing skepticism regarding adoption of chloroquine and hydroxychloroquine for COVID-19 patients. The review is published in FASEB journal.

In kidneys from living donors, subtle structural features help predict the risk of transplant failure in recipients, revealed Mayo Clinic researchers.

Britain is haunted by past industrial decline and the buccaneering raids of the 1980s

Mexican government’s rescue plan for debt-laden state oil group underwhelms

Minister omits eastern leg to Yorkshire in statement on high-speed rail project

We’ve spent so long asking tech to turn its attention to real-world problems. Let’s not complain when they do so now. 

Serena Williams rolled her right ankle but that didn't seem to slow her down in a 6-3, 6-4 victory over Petra Martic that moved her into the U.S. Open quarterfinals for a 16th time.