Daily Archives: May 14, 2020

New progress reported from researchers investigating Strep zoo in North American pigs – The Pig Site

Posted: May 14, 2020 at 5:47 pm

Over the past 14 months swine health officials and scientists have been tracking the movement of a novel bacterial infection in swine, Streptococcus zooepidemicus.

The infection, which results in sudden death, was identified in Canada in March 2019 and has since been found in several US states.

Speaking to Farmscape, Dr Matheus Costa, an Adjunct Professor with the University of Saskatchewan's Western College of Veterinary Medicine and an Assistant Professor with the University of Minnesota, says Strep zoo is a normal part of the microbiome of several species and typically doesn't cause disease.

"Streptococcus zooepidemicus is present in healthy pigs so that becomes a bit of a challenge when differentiating who could be carrying a potentially dangerous Streptococcus zooepidemicus versus the other pigs that are carrying the normal ones that don't do anything to pigs," explains Dr Costa.

"We're trying to explore that right now in order to prevent and control the disease.

"The other thing we have learned is that there seems to be a very specific Streptococcus zooepidemicus called ST-194 that causes disease in pigs.

"That's what we're working on right now is, what makes this Streptococcus zooepidemicus type problematic for pigs in comparison to the other ones that they have had for years.

"It really looks like this disease flares up once pigs have been exposed to some kind of intense stress event, such as a long haul or even a comingling of many different animals from many different sources.

"If you can minimise stress at any point, that is always welcome and it seems to help prevent flareups of disease associated with Strep zoo."

Dr Costa acknowledges this infection is rare and scientists are just scratching the surface trying to deal with this bug.

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Good Weather Allowed Crop Planting to Progress, Frost and Freeze Warnings A Concern Last Week – kwbg.com

Posted: at 5:47 pm

DES MOINES, IowaIowa Secretary of Agriculture Mike Naig Monday commented on the Iowa Crop Progress and Condition report released by the USDA National Agricultural Statistics Service. The report is released weekly from April through November.

Planting has moved at a near-record pace this spring and with that comes the risk of a late frost. Most of the state was under frost and freeze warnings over the weekend and some stations set new record lows, said Secretary Naig. We expect warmer and wetter weather towards the end of the week, which is welcome news for farmers who are closely monitoring emerging corn and soybean crops.

The weekly report is also available on the USDAs site atnass.usda.gov/ia.

Crop Progress

There were 4.7 days suitable for field work during the week ending May 10, 2020, according to the USDA, National Agricultural Statistics Service. Showers early in the week briefly slowed planting progress and below normal temperatures delayed emergence.

Topsoil moisture levels rated 4% very short, 15% short, 78% adequate and 3% surplus. Subsoil moisture levels rated 2% very short, 8% short, 86% adequate and 4% surplus.

Iowa farmers have planted 91% of the expected corn crop, almost a month ahead of last year and 2 weeks ahead of the 5-year average. Less than 5% of the crop remains to be planted in Northwest and North Central Iowa. One-third of the expected corn crop has emerged. The soybean crop moved to 71% planted, a full month ahead of last year and over 2 weeks ahead of the average. Northwest and North Central Iowa also lead the way in soybean planting with less than 20% remaining to be planted. Only 2% of Iowas expected oat crop remains to be planted, with 77% of the oat crop emerged. The first oat condition rating of the season was 0% very poor, 2% poor, 19% fair, 67% good and 12% excellent.

The first hay condition rating of the season was 0% very poor, 3% poor, 26% fair, 61% good and 10% excellent. Pasture condition rated 62% good to excellent. Cooler than normal temperatures slowed growth in pastures and hay fields. Livestock conditions were good with little to no stress reported.

Preliminary Weather SummaryProvided by Justin Glisan, Ph.D., State Climatologist, Iowa Department of Agriculture and Land Stewardship

Iowa experienced cooler and drier conditions during the first full week of May. Measurable rain was reported statewide, though a majority of stations observed below average totals. A notable Arctic air intrusion brought below average coldness towards the end of the reporting period. Temperature departures were six to ten degrees below normal with eastern Iowa experiencing the coldest conditions. The statewide average temperature was 48.9 degrees, 9.0 degrees below normal.

Spotty showers moved through central Iowa during the late morning hours on Sunday (3rd) though partly to mostly sunny skies were reported for the rest of the day. Highs reached the mid to upper 70s, with locally warmer spots, under variable winds shifting out of the northeast into early Monday (4th) morning. Temperatures remained in the 40s and low 50s in southwest Iowa, slightly warmer than average. Another wave of light to moderate rain pushed into the state during the day ahead of a low pressure system over the Dakotas, leaving measurable rain across much of Iowa. The system spun into southern Minnesota early Tuesday (5th) propagating southeast through central Iowa and clearing the states southeast corner close to midnight. Daytime conditions were unseasonably cold with statewide highs averaging 54 degrees, 14 degrees colder than normal. Two-day rain totals reported at 7:00 am on Wednesday (6th) were highest in eastern Iowa with multiple stations in Scott County reporting from 0.97 inch to 1.07 inches. Totals into western Iowa were generally between 0.25 inch to 0.50 inch; the statewide average was 0.42 inch. Winds shifted to the northwest through the day under cloudy conditions as highs stayed in the upper 50s and low 60s.

Starry skies greeted Iowa overnight into Thursday (7th) with morning lows in the 40s; upper 30s were reported in western Iowa. Another low pressure center moved slowly through western Iowa into the evening hours, bringing moderate rainfall across the region. Rain totals were generally at or under 0.50 inch in Iowas southwest corner with lighter amounts moving into central Iowa; Clarinda (Page County) observed 0.54 inch while on the eastern periphery of the system, Indianola (Warren County) reported 0.05 inch. Skies cleared into Friday (8th) with gusty northerly winds as daytime temperatures remained unseasonably cool in the low to mid 50s. A late season cold blast blanketed much of the upper Midwest, prompting freeze warnings overnight into Saturday (9th) with morning lows plummeting into the upper 20s and low 30s across Iowa. Several stations reported record lows for the date with Waterloo (Black Hawk County) reporting 27 degrees, breaking the station record set in 1945; the statewide average was 29 degrees, 17 degrees below normal. Temperatures quickly rebounded under southerly winds and mostly sunny skies. Daytime highs peaked in the mid 60s though a cold front swept west to east across Iowa into the nighttime hours, bringing light showers and localized gusty winds. Rain totals reported Sunday (10th) morning were under 0.20 inch with the highest totals in northern Iowa; New Hampton (Chickasaw County) reported 0.17 inch. Morning lows combined with strong northerly winds were brisk, generally in the upper 30s west to low 40s east.

Weekly rain totals ranged from 0.10 inch at Oelwein (Fayette County) to 1.07 inches at a rain gauge in Le Claire (Scott County). The statewide weekly average precipitation was 0.56 inch while the normal is 0.99 inch. Clarion (Wright County) reported the weeks high temperature of 83 degrees on the 4th, 16 degrees above average. Elkader (Clayton County) and Stanley (Buchanan County) reported the weeks low temperature of 21 degrees on the 9th, on average 23 degrees below normal. Four-inch soil temperatures were in the low to mid 50s as of Sunday.

(contributed press release)

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GM CEO Mary Barra Is Very Pleased With GM Cruise Progress – GM Authority

Posted: at 5:47 pm

General Motors recently posted its Q1 2020 financial results, surprising analysts and Wall Street with $300 million in income on $32.7 billion in revenue. GM was the only one of the big three U.S. automakers to post a profit. During the recent first-quarter 2020 earnings call, GM CEO Mary Barra addressed a number of crucial topics, including an indication that the automakers highly profitable full-size SUVs were on-track for shipping in June, and that the companys future EVs were on track despite disruptions from the COVID-19 pandemic. Whats more Barra said she was very pleased with the progress made by the GM Cruise autonomous vehicle division.

During a Q&A session, Bank of America-Merrill Lynch analyst John Murphy asked Barra if she was rethinking the dollar commitment required to develop the GM Cruise autonomous vehicle technology, citing a $1 billion annual investment without any associated revenue.

Barra backed the companys commitment to AVs, saying: Well, first, Im very pleased with the progress that were making from a technology perspective at Cruise. Just reviewed that earlier this week. So I think that we are continuing to hit milestone after milestone there.

Barra did not elaborate on exactly what those milestones were. However, in response to a question proposed by Murphy with regard to integrating GM Cruise technology into the existing GM product portfolio, Barra talked about the GM Super Cruise semi-autonomous driver assist feature, saying:

As it relates to bringing the technology into our fleet of vehicles on the road today, thats really occurring through Super Cruise and we continue to add miles, add roads, add features, and youll see us as we spread it across the portfolio, starting with Cadillac and then moving to others.

As was announced last June, the Super Cruise semi-autonomous driver system gained an additional 70,000 miles of usable highway driving last year, bringing the grand total to 200,000 miles of divided highway driving throughout the U.S. and Canada for customers. The GM Cruise-derived technology will see widespread implementation throughout the Cadillac lineup, including with the all-new 2021 Cadillac Escalade, while availability is expected to expand to 22 vehicles total by 2023, and will include non-Cadillac vehicles as well.

Meanwhile, the Cruise Origin driverless taxi was unveiled back in January.

Check out a full transcript of the earnings call below, and subscribe to GM Authority for ongoing GM news coverage.

GM Q1 2020 Earnings Call - Mary Barra On GM Cruise Progress

John Murphy Bank of America-Merrill Lynch Analyst

Okay. And then just a second question, I mean the commitment to Cruise, seems like its unwavering. But there is about $1 billion a year going out the door without any revenue. Im just curious if youre rethinking that dollar commitment on an annual basis, the potential business and monetization of it. And one phrase that I think you mentioned superhuman driving experience sounds really appealing to me. Is there the potential that you could lead some of this technology into your existing product portfolio over the next few years if you dont see the monetization of an AMoD fleet anytime in the near future?

Mary T. Barra GM Chairman and Chief Executive Officer

Well, first, Im very pleased with the progress that theyre making from a technology perspective at Cruise. Just reviewed that earlier this week. So I think that we are continuing to hit milestone after milestone there. So Im very positive about whats happening at Cruise from that perspective. So I see huge opportunity. And so our commitment, as you said, is unwavering.

As it relates to bringing the technology into the our fleet of vehicles on the road today, thats really occurring through Super Cruise and we continue to add miles, add roads, add features and youll see us as well as spread it across the portfolio, starting with Cadillac and then moving to others. So definitely have an aggressive plan to further roll out and improve the capability of Super Cruise.

Jonathan Lopez

Jonathan is an automotive journalist based out of Southern California. He loves anything and everything on four wheels.

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Pilgrims’ progress – The Tablet

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A Furnace Full of God: A Holy Year on the Camino de SantiagoREBEKAH SCOTT(PEACEABLE PUBLISHING, 264 PP, 12.21)

According to a pre-lockdown double-page spread in The Times, pilgrimages are making a comeback. For 2,000, one can enjoy a mentally and spiritually refreshing walking holiday organised by the Catholic Herald. But there are cheaper options, and to prove it this author has published an illuminating report of how, in 2006, she and her husband left journalistic jobs in the United States to found a refuge their home to this day for some of the pilgrims who hit the road to the shrine city of Santiago de Compostela, Spain, every year: 300,000 of them in the Holy Year of 2010 alone.

Glamorous is hardly the word to describe life in Moratinos, a tiny, sparsely populated town in the middle of the 500-mile, 1,000-year-old pilgrim trail, but Rebekah Scott has turned their adventure, and the adventures of the disparate wayfarers who passed through Peaceable Kingdom the name they gave their far-from-luxurious farmhouse into a beacon of warmth on the way west via Palencia.

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LeBrun: Bill Daly provides update on NHL’s progress toward a resumed season – The Athletic

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The NHL and NHL Players Association were in discussion again Tuesday through the Return to Play Committee, trying to navigate through a number of issues and eventually finding a path to a potential puck drop.

Hockey fans are hungry for answers. Hey, so are the media.

What about the draft? The playoff format? The hub cities in the proposed four-site scenario? What about Phase 2, which is the next step?

The NHL and NHLPA are plugging away at it.

The reality is that its still a very fluid situation, Bill Daly told The Athletic on Tuesday night after another long day of meetings and phone calls for the NHLs deputy commissioner.

Look, I think theres some optimism, Daly said. The trending is positive right now in most of our markets. We have businesses and economies opening up, and thats a good thing. Dont know yet what it means to us. But were going in a positive...

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Main St update: Work in progress this spring to be completed this fall – mysouthborough

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Above: Construction workers are back on the job for the Main Street Reconstruction Project. (photos by Cassie Melo)

At readers request, I checked in with Public Works on Friday for an update on the Main Street Reconstruction project. I learned that work resumed last week.

Below are some photos from work in progress this morning (click to enlarge):

Earlier this spring, Public Works Superintendent Karen Galligan told selectmen that she expected construction to start in late April. She noted then that the MassDOT* schedule was fluid.

Last spring, the Town posted an overview timeline with the reminders:

The Main Street Project is a State project, not a local project. Details of the schedule are determined by the State and the contractor, although the Town will have input and access to the information, we will not necessarily have day to day information.

Select Main Street Project Updates through the E-Alert system to receive notification of any updates we post. . .

Project completion is scheduled for November 15, 2020.

As work was winding down last fall for the winter, Public Works update explained that starting this spring:

Underground [utility] work will begin east of Route 85, granite for sidewalks will be installed west of Route 85.

Work will proceed eastward all summer and landscaping should close out the project late next fall.

In early March, an update shared that over the winter some overhead utility work continued and traffic lights were installed.

Earlier last week, Galligan was expecting the project to resume this week or next. On Friday, Galligan learned that they restarted work that day. She was able toupdate:

Work continues on the stone walls for the next several weeks.

Drainage work is starting on the east side of Route 85.

Water work will begin within the next two to three weeks, this includes by-pass piping, new main installation and other associated work.

*The Main Street project is run by the Mass Dept of Transportation.

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Gamergate – Wikipedia

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Reproductively viable female worker ant

A gamergate ( GAMM-r-gayt) is a mated worker ant that is able to reproduce sexually, i.e., lay fertilized eggs that will develop as females. Gamergates are restricted to taxa where the workers have a functional sperm reservoir ('spermatheca'). In various species, gamergates reproduce in addition to winged queens (usually upon the death of the original foundress), while in other species the queen caste has been completely replaced by gamergates. In gamergate species, all workers in a colony have similar reproductive potentials, but as a result of physical interactions, a dominance hierarchy is formed and only one or a few top-ranking workers can mate (usually with foreign males) and produce eggs. Subsequently however, aggression is no longer needed as gamergates secrete chemical signals that inform the other workers of their reproductive status in the colony.

Depending on the species, there can be one gamergate per colony (monogyny) or several gamergates (polygyny). Most gamergate species have colonies with a few hundred or fewer workers.

"Gamergate" derives from the Greek words (gmos) and (ergts) and means "married worker". It was coined in 1983 by geneticist William L. Brown[1] and was first used in scientific literature by entomologists Christian Peeters and Robin Crewe in a 1984 paper published in Naturwissenschaften.[2] The definition typically found in entomological dictionaries is "mated, egg-laying worker",[3][4] and is drawn from the glossary of Bert Hlldobler and E. O. Wilson's 1990 book, The Ants.[3]

There are 100200 different species in which gamergates reproduce (roughly 1% of all ants), most of which fall within the poneromorph subfamilies. Whereas workers (which are all females) in most ant species are morphologically incapable of storing sperm, in gamergate species one or several workers mate and have active ovaries.[5] Gamergate lifespan is short compared to queens in queenright colonies, but gamergates can be replaced by other dominant workers in the colony without risking colony survival. Reproductive investment in gamergate females is thus optimized because non-differentiated gamergates (i.e. reproductively inactive workers) function as laborers.[6]

Within gamergate colonies, all workers are born reproductively viable and are thus potential gamergates. Prior to differentiation as a gamergate, a dominant worker must physically inhibit its sisters. For example, in the case of Diacamma australe, the first female to become reproductively active will clip off the thoracic gemmae of her sisters, thus greatly reducing their sexual attractiveness. In other genera, persistent domination of worker females by gamergates via physical aggression all but ensure that they will not produce male offspring.[7] In Diacamma nilgiri, gamergates use dominance interactions to monopolize reproduction without mutilation of sister workers.[8] The same is true for Streblognathus peetersi, which engage in non-injurious aggression to determine dominance.[2] For most gamergate species, the start of ovarian activity eliminates the need to physically dominate nestmate workers. Instead newly produced pheromones or signaling chemicals ensure that workers remain nonreproductive. Although it is unknown to what degree these chemicals act as pheromones or as signals, support for the signaling hypothesis can be found in the loss of reproductive inhibition of workers as the gamergate grows older and her fecundity diminishes.[7]

Mechanisms of gamergate replacement vary among monogynous and polygynous species. When a gamergate dies, it is usually replaced by a formerly submissive worker who proceeds to mate and begins ovarian activity. A new gamergate often originates from a younger cohort. For example, when the original founding queen dies in a Harpegnathos saltator colony, younger workers begin to fight for dominance and some become the next reproductives.[9] Because reproductively inactive workers are able to activate their ovaries after the death of the gamergate, some gamergate species can be considered cooperative breeders rather than truly eusocial insects.[10]

In colonies with both queens and gamergates, the latter function as secondary reproductives.[5] Research on Amblyoponinae species has shown that there is a fecundity-based hierarchy among gamergates. In Stigmatomma reclinatum, it was found that higher-ranked gamergates had more fully developed oocytes than low-ranked gamergates.[11] In Streblognathus peetersi, only the alpha worker mates and becomes the gamergate; younger workers await a chance to reproduce when the current gamergate exhibits decreased fecundity or dies.[2] Challenges to gamergates from subordinate workers are risky because the gamergate in species like Dinoponera quadriceps may mark the challenger by rubbing special chemicals produced only by the gamergate. These chemicals signal to other workers to immobilize the challenger by biting her appendages and immobilizing her for a few days until her hormonal levels return to normal.[12] Subordinate workers play an important policing role in the selection of future gamergates and are thus able to increase their indirect fitness.[5]

There is much variation in the social structure of ant colonies with gamergates. Some species such as Harpegnathos saltator,[13] Pseudoneoponera tridentata, Gnamptogenys menadensis, and Rhytidoponera confusa have a winged alate queen caste as well as gamergates.[14] Queenless species with only gamergates and workers may have a monogynous structure with a single gamergate or they may have a polygynous structure with multiple gamergates. Examples of monogynous queenless species include Pachycondyla krugeri, P. sublaevis, Diacamma australe, D. rugosum, Dinoponera quadriceps, Platythyrea lamellosa, and Streblognathus aethiopicus.[15] Examples of polygynous queenless species include Ophthalmopone berthoudi, O. hottentota, and all known queenless species of Rhytidoponera.[15] In the queenless Ophthalmopone berthoudi, foreign males visit underground nests to mate with young workers.[16]

Ecologically, gamergate species from different tribes and genera often tend to share certain characteristics. Many gamergate species are solitary generalist foragers living in arid environments.[6] Similar to species with ergatoid queens, the evolution of gamergate reproduction is hypothesized to be associated with a shift to colonial fission. Myrmecologists Christian Peeters and Fuminori Ito have also suggested that "the evolution of gamergate reproduction appears strongly associated with the adaptive benefits of secondary polygyny (e.g. increased colony lifespan and resource inheritance), and it is the preferred option in species having workers able to store sperm."[14]

The utility of "gamergate" as a morphological designation is not without critics. Within the field of myrmecology it is a matter of dispute whether caste should be defined primarily by reproductive role or by physical morphology. Notably, Alfred Buschinger has argued that the term "worker" should be applied only to those ants who make up the non-reproductive caste and "queen" should be applied only to reproductively viable female ants regardless of their physical appearance. Hlldobler and Wilson suggest that the two positions can be semantically resolved and that the most fruitful approach would be to keep classification "somewhat loose, incorporating either anatomy or roles in a manner that maximizes convenience, precision, and clarity of expression."[17]

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What Does Gamergate Mean? | Pop Culture by Dictionary.com

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Gamergate was originally coined by Firefly actor Adam Baldwin as a hashtag, #GamerGate. It was created on August 27, 2014, in response to a controversy involving the gameDepression Quest, developed by Zo Quinn. Gamers criticized the games simplicity and its departure from standard gaming formats, and people claimed the game didnt warrant its positive and extensive press coverage. Not long after, Quinns ex-boyfriend wrote a blog post falsely detailing how Quinn had cheated on him with five different guys, one of whom was a gaming journalist who worked for Kotaku. (Notably, said journalist never reviewed the game)

An online campaign accusing Quinn of exchanging sex for press coverage followed, and users across online communities (including 4chan, Twitter, and Reddit) all jumped on board.Threats and harassment ensued, and users leaked Quinns and others personal information in a practice known as doxxing. Another notable target was Anita Sarkeesian, an outspoken feminist media critic and blogger, who was forced to cancel a speaking engagement due to Gamergate-related threats on her life.

Supporters ofGamergateclaimedto shed light on the sometimes unethical relationship between developers and journalists, as the two are often too close on a personal level. Their goal was to snuff out corruption and to spearhead an ethics reform in the industry. Despite this stated goal, the movement produced countless attacks on women who commented on the situation. As a result, Gamergate raised concerns about anti-women views in gaming as a whole.

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This free photography game lets you explore the beautiful wilderness of Iceland – PC Gamer

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Released on Steam earlier this year, Mrdalssandur, Iceland is a minimalist exploration game set on the Nordic island's southern coast. I've been to Iceland myself a few times, and every time I go I fall in love with the quiet beauty of its volcanic landscapesa feeling this game captures perfectly.

It really is lovely to look at, using realistic photo-scanned 3D models from Quixel to great effect. Wandering this stark, barren terrain, I see black volcanic sand, glacial rivers, moss-covered rocks, cascading waterfalls, and grass-sprinkled mountains far in the distance. It's incredibly atmospheric.

I would've been happy just wandering around here aimlessly, but there's an interactive element to Mrdalssandur. As I explore I find an old camera and a board of photos to replicate. These include a windy stretch of coastline, a rock yellowed by sulphur, and a vast glacier looming over the landscape.

Snap the correct scene and its corresponding photo will disappear from the board. Complete them all and a gate unlocks, giving you access to a new part of the map with a stunning vista. It's a lean experience, clocking in at about 25 minutes, but in that short amount of time it makes a big impact.

And that's really all there is to it. You walk around, listen to a mellow ambient soundtrack (including a track from Minecraft composer C418), and take photographs. And I appreciate it for that. Games like this don't always need a story: sometimes an evocative environment is enough on its own.

Mrdalssandur is free to play, but you can pay $5 to experience it in VR. Developer Caves RD has other, similarly well-realised locations to explore, including New Zealand's Wakamarina Valley and the Fushimi Inari shrine in the foothills of Kyoto, Japan. With no end to the coronavirus lockdown in sight, this kind of virtual tourism is more valuable than ever.

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How "Dark Matter" Regions of the Genome Affect Inflammatory Diseases – Technology Networks

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A study led by researchers at the Babraham Institute in collaboration with the Wellcome Sanger Institute has uncovered how variations in a non-protein coding dark matter region of the genome could make patients susceptible to complex autoimmune and allergic diseases such as inflammatory bowel disease. The study in mice and human cells reveals a key genetic switch that helps immune responses remain in check. Published in Nature, the research, involving collaborations with research institutions in the UK and worldwide, identified a new potential therapeutic target for the treatment of inflammatory diseases.Over the last twenty years, the genetic basis of susceptibility to complex autoimmune and allergic diseases, such as Crohns disease, ulcerative colitis, type 1 diabetes and asthma, has been narrowed down to a particular region of chromosome 11. This work has involved large scale genome-wide association studies (GWAS), a genome-wide spot-the-difference comparison between the genomes of individuals with or without a disease, to highlight regions of variation in the DNA code. This can identify potential genetic causes, and reveal possible drug targets.

However, most of the genetic variations responsible for the susceptibility to complex immune and allergic diseases are concentrated within regions of the genome that dont encode proteins the genomes dark matter. This means theres not always a clear gene target for further investigation and the development of treatments.

Recent advances in sequencing-based approaches have shown that these disease-associated genetic changes are concentrated within regions of DNA called enhancers, which act as switches to precisely regulate the expression of genes. Further technological developments have allowed scientists to map physical interactions between different remote parts of the genome in 3D, so they can connect enhancers in non-coding regions with their target gene.

To gain insight into inflammatory disease, a large team of researchers used these methods to study an enigmatic non-protein-coding region of the genome whose genetic variations are associated with increased immune disease risk. They identified an enhancer element that is required for the immune systems peace-keepers and immune response mediators, regulatory T cells (Tregs), to balance an immune response.

Lead researcher and Babraham Institute group leader, Dr Rahul Roychoudhuri said: The immune system needs a way of preventing reactions to harmless self- and foreign substances and Treg cells play a vital role in this. Theyre also crucial in maintaining balance in the immune system, so that our immune responses are kept in check during infections. Tregs only represent a small percentage of the cells making up our complete immune system but theyre essential; without them we die from excessive inflammation. Despite this important role, there has been little evidence that unequivocally links the genetic variations that cause certain individuals to be susceptible to inflammatory diseases to changes in Treg function. It turns out that non-protein-coding regions provided us with the opportunity to address this important question in the field.

Evolution gave the researchers a helping hand. The researchers took advantage of an approach called shared synteny, where not just genes are conserved between species, but a whole section of the genome. Similar to finding part of your book collection duplicated in your neighbors house, including the order of their arrangement on the bookshelf.

They used this genomic similarity to translate what was known about the enhancer in the human genome and find the corresponding region in mice. They then explored the biological effect of removing the enhancer using mouse models.

The researchers found that the enhancer element controls the expression of a gene in Treg cells, which encodes a protein called GARP (Glycoprotein A Repetitions Predominant). They showed that deleting this enhancer element caused loss of the GARP protein in Treg cells, and an uncontrolled response to a triggered inflammation of the colon lining. This demonstrated that the enhancer is required for Treg-mediated suppression of colitis, with a role for the GARP protein in this immune system control.

There was a similar effect in human Treg cells from healthy blood donors. The researchers identified an enhancer region whose activity was impacted by genetic variation specifically in Treg cells. The enhancer directly interacted with the human form of the same gene, and the genomic variations occurring in the enhancer element were associated with reduced GARP expression.

Dr Gosia Trynka, a senior author on the paper from the Wellcome Sanger Institute and Open Targets, said: Genetic variation provides important clues into disease processes that can be targeted by drugs. In our joint efforts here, we combined human and mouse research to gain invaluable insight into complex processes underlying immune diseases. This has identified GARP as a promising new drug target and brings us a step closer to developing more efficient therapies for people suffering from diseases such as asthma or inflammatory bowel disease.

Dr Roychoudhuri concludes: Decades of research have now identified the variations in our genomes that make some of us more susceptible to inflammatory diseases than others. It has been very difficult, however, to make sense of how these variations relate to immune disease since many of them occur in non-protein-coding regions, and therefore the implications of these changes are poorly understood. Studies such as these will enable us to link the genetic switches that commonly reside in such disease-associated non-coding regions with the genes they control in different cell types. This will yield new insights into the cell types and genes underlying disease biology and provide new targets for therapeutic development.ReferenceNasrallahet al. (2020). A distal enhancer at risk locus 11q13.5 promotes suppression of colitis by Treg cells. Nature. DOI: https://doi.org/10.1038/s41586-020-2296-7

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