The bone marrow niche is a complex and dynamic structure composed of a multitude of cell types which functionally create an interactive network facilitating hematopoietic stem cell development and maintenance. Its specific role in the pathogenesis, response to therapy, and transformation of myeloproliferative neoplasms has only recently been explored. Niche functionality is likely affected not only by the genomic background of the myeloproliferative neoplasm-associated mutated hematopoietic stem cells, but also by disease-associated ‘chronic inflammation’, and subsequent adaptive and innate immune responses. ‘Cross-talk’ between mutated hematopoietic stem cells and multiple niche components may contribute to propagating disease progression and mediating drug resistance. In this timely article, we will review current knowledge surrounding the deregulated bone marrow niche in myeloproliferative neoplasms and suggest how this may be targeted, either directly or indirectly, potentially influencing therapeutic choices both now and in the future.

To better understand how associated microorganisms ("microbiota") influence organismal aging, we focused on the model organism Drosophila melanogaster. We conducted a metagenome-wide association (MGWA) as a screen to identify bacterial genes associated with variation in the D. melanogaster life span. The results of the MGWA predicted that bacterial cysteine and methionine metabolism genes influence fruit fly longevity. A mutant analysis, in which flies were inoculated with Escherichia coli strains bearing mutations in various methionine cycle genes, confirmed a role for some methionine cycle genes in extending or shortening fruit fly life span. Initially, we predicted these genes might influence longevity by mimicking or opposing methionine restriction, an established mechanism for life span extension in fruit flies. However, follow-up transcriptome sequencing (RNA-seq) and metabolomic experiments were generally inconsistent with this conclusion and instead implicated glucose and vitamin B₆ metabolism in these influences. We then tested if bacteria could influence life span through methionine restriction using a different set of bacterial strains. Flies reared with a bacterial strain that ectopically expressed bacterial transsulfuration genes and lowered the methionine content of the fly diet also extended female D. melanogaster life span. Taken together, the microbial influences shown here overlap with established host genetic mechanisms for aging and therefore suggest overlapping roles for host and microbial metabolism genes in organismal aging.

IMPORTANCE Associated microorganisms ("microbiota") are intimately connected to the behavior and physiology of their animal hosts, and defining the mechanisms of these interactions is an urgent imperative. This study focuses on how microorganisms influence the life span of a model host, the fruit fly Drosophila melanogaster. First, we performed a screen that suggested a strong influence of bacterial methionine metabolism on host life span. Follow-up analyses of gene expression and metabolite abundance identified stronger roles for vitamin B₆ and glucose than methionine metabolism among the tested mutants, possibly suggesting a more limited role for bacterial methionine metabolism genes in host life span effects. In a parallel set of experiments, we created a distinct bacterial strain that expressed life span-extending methionine metabolism genes and showed that this strain can extend fly life span. Therefore, this work identifies specific bacterial genes that influence host life span, including in ways that are consistent with the expectations of methionine restriction.

Background:

Despite smoking being a well-established risk factor for pancreatic cancer, there is a need to further characterize pancreatic cancer risk according to lifespan smoking patterns and other smoking features, such as tobacco type. Our aim was to deeply investigate them within a large European case–control study.

Methods:

Tobacco smoking habits and other relevant information were obtained from 2,009 cases and 1,532 controls recruited in the PanGenEU study using standardized tools. Multivariate logistic regression analysis was performed to evaluate pancreatic cancer risk by smoking characteristics and interactions with other pancreatic cancer risk factors. Fractional polynomials and restricted cubic splines were used to test for nonlinearity of the dose–response relationships and to analyze their shape.

Results:

Relative to never-smokers, current smokers [OR = 1.72; 95% confidence interval (95% CI), 1.39–2.12], those inhaling into the throat (OR = 1.48; 95% CI, 1.11–1.99) or chest (OR = 1.33; 95% CI, 1.12–1.58), and those using nonfiltered cigarettes (OR = 1.69; 95% CI, 1.10–2.61), were all at an increased pancreatic cancer risk. Pancreatic cancer risk was highest in current black tobacco smokers (OR = 2.09; 95% CI, 1.31–3.41), followed by blond tobacco smokers (OR = 1.43; 95% CI, 1.01–2.04). Childhood exposure to tobacco smoke relative to parental smoking was also associated with increased pancreatic cancer risk (OR = 1.24; 95% CI, 1.03–1.49). Dose–response relationships for smoking duration, intensity, cumulative dose, and smoking cessation were nonlinear and showed different shapes by tobacco type. Effect modification by family history of pancreatic cancer and diabetes was likely.

Conclusions:

This study reveals differences in pancreatic cancer risk by tobacco type and other habit characteristics, as well as nonlinear risk associations.

Impact:

This characterization of smoking-related pancreatic cancer risk profiles may help in defining pancreatic cancer high-risk populations.

Mammographic breast density is a strong risk factor for breast cancer. We comprehensively investigated the associations of body mass index (BMI) change from ages 10, 18, and 30 to age at mammogram with mammographic breast density in postmenopausal women. We used multivariable linear regression models, adjusted for confounders, to investigate the associations of BMI change with volumetric percent density, dense volume, and nondense volume, assessed using Volpara in 367 women. At the time of mammogram, the mean age was 57.9 years. Compared with women who had a BMI gain of 0.1–5 kg/m² from age 10, women who had a BMI gain of 5.1–10 kg/m² had a 24.4% decrease [95% confidence interval (CI), 6.0%–39.2%] in volumetric percent density; women who had a BMI gain of 10.1–15 kg/m² had a 46.1% decrease (95% CI, 33.0%–56.7%) in volumetric percent density; and women who had a BMI gain of >15 kg/m² had a 56.5% decrease (95% CI, 46.0%–65.0%) in volumetric percent density. Similar, but slightly attenuated associations were observed for BMI gain from ages 18 and 30 to age at mammogram and volumetric percent density. BMI gain over the life course was positively associated with nondense volume, but not dense volume. We observed strong associations between BMI change over the life course and mammographic breast density. The inverse associations between early-life adiposity change and volumetric percent density suggest that childhood adiposity may confer long-term protection against postmenopausal breast cancer via its effect of mammographic breast density.

* Khởi công xây dựng: Quý 3 / 2019. * Bàn giao căn hộ: Quý 2 / 2021. * Tầng 1 - Tầng 5: Thương mại, Dịch vụ, tiện ích ngoài trời, bãi giữ xe,.. * Tầng 5 - Tầng 28: Căn hộ ở. * Diện tích căn hộ: 1PN: 33 - 43m2. - 2PN, 2WC: 59m2 - 65m2. - 3PN: Trên 70m2. - Lý do bạn nên đầu tư tại Ecolife Riverside. + Căn hộ chuẩn xanh quốc tế EDGE đầu tiên tại Quy Nhơn. + Mức giá chỉ ...

Sở hữu Căn hộ cao cấp Ecolife Riverside với giá tốt nhất tại trung tâm TP Quy Nhơn. Sau chuỗi ngày dài mệt mỏi với bộn bề công việc, được trở về căn hộ Ecolife Riverside đó là một cảm giác thật tuyệt vời. - Căn hộ Ecolife Riverside đạt chuẩn Xanh - EDGE quốc tế tiết kiệm nă...

These findings suggest that scientists may need to broaden their definition of what a life-supporting planet might look like.

NASA’s Mars 2020 rover will search for signs of life on Mars, and New Scientist’s Leah Crane visited it in the clean room where it is being assembled

We may not have found alien life yet, but new methods and the discovery of exoplanets and extreme life on Earth is revolutionising the hunt, says the doyenne of SETI research

Out of 28,000 suggestions, NASA selected the name Perseverance for its Mars 2020 rover, which will search for signs of life on the Red Planet

Proxima Centauri b, a planet orbiting our nearest stellar neighbour, is being blasted with cosmic rays and solar flares – which could make it warm enough to host life

When Mars was young, parts of the planet may have been able to sustain RNA, a molecule that probably played a key role in the beginnings of life on Earth

Could life on Mars have hidden from extreme weather in a cavern on the Pavonis Mons volcano? This 2011 orbiter image of an otherworldly crater has NASA asking just that

Extraterrestrial oceans are an obvious place to search for alien life, but getting there and having a look won't be easy, says NASA's Kevin Hand in his book Alien Oceans

A new computational method allows robotic characters to perform fast motions without excessive vibrations

If Stephen King keeps writing ‘em, we’ll keep seeing ‘em.

Because we don't have enough on our plates as it is, now we've got 'murder hornets' flying around the United States. Murder hornets (actually Asian Giant Hornets, but that name didn't strike enough fear into the masses) have a sting powerful enough that China recommends medical treatment if stunk more than ten times, and emergency treatment if stung more than 30. *pours out a little liquor for Macaulay Culkin in My Girl*. And where is his glasses?! He can't see without his glasses! Put his glasses on! Here's a video of Coyote Peterson getting stung by one (the Japanese Giant Hornet was previously believed to be a subspecies of the Asian Giant Hornet, but has since been recategorized as a color morph). This is a video of a praying mantis eating a Giant Asian hornet until it's just a pile of limbs. So yeah, praying mantises -- start breeding them. And make sure to selectively breed them too so we can produce them bigger and bigger until they're preying on us because the way things are going how is that not how this ends? Keep going for the video while I surround my Animal Crossings town with preying mantises to protect my villagers and keep my five-star rating (okay, three).

The new Nightlife reactive skin is now live ahead of the Fortnite Party Royale event which starts later today.

Extra Life 2014 Details

We played some games, talked some news, and healed some kids. It was a good way to spend a Saturday. Thanks for your donations and...

XSEED and Natsume make up. Chris rubs his sore feet. Emmanuel’s ear drums get blown out by a Shenmue fan. Alex is STILL posting stories....

Sarah and Alice join Anna Marie and Chris for our annual charity podcast. Kids need healing, you need RPG news, and Alice needs to deliver...

An affectionate and absorbing documentary from film-maker Rachel Mason about her devout parents, who ran a famous adult bookstore in early-80s LA

Here is a documentary with an absorbing and unexpectedly complicated story to tell, whose paradoxes and sadnesses are not entirely resolved by the end. Artist and film-maker Rachel Mason has created an affectionate portrait of her elderly parents, Karen and Barry, who in many ways are like one of the (fictional) old couples in When Harry Met Sally.

Karen is a former journalist, devoutly Jewish, and Barry is a former special visual effects engineer who worked on Stanley Kubrick’s 2001 and invented a modification for kidney dialysis machines. But they found themselves in a tough financial spot in the early 1980s and took over Circus of Books, a gay porn bookstore in Los Angeles that also sold movies called things like Confessions of a Two Dick Slut and Don’t Drop the Soap, and was one of Larry Flynt’s first distribution points. Under their shrewd management, the store boomed, opened another branch and became a well-known meeting place for LGBT people, while all the time, the Masons were a conventional family who kept their three children well away from the business. Karen movingly – and honestly – recounts how upset she was to discover that one of her sons was gay: the business and family life were that separate.

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Giant elliptical galaxies are not as likely as previously thought to be cradles of complex life, according to a paper published in the Monthly Notices of the Royal Astronomical Society. In 2015, University of Durham astronomer Pratika Dayal and colleagues concluded that large elliptical galaxies have up to 10,000 times more habitable planets than the [...]

A team of researchers at the Massachusetts Institute of Technology (MIT) has demonstrated that single-celled microorganisms such as Escherichia coli and Saccharomyces cerevisiae that normally do not inhabit hydrogen-rich environments can survive and grow in a 100% hydrogen atmosphere. “There’s a diversity of habitable worlds out there, and we have confirmed that Earth-based life can [...]

The covid-19 pandemic has led to rushed guidelines for doctors making treatment decisions, and has encouraged more people to make advance decisions on CPR and ventilation

The 'Wrecking Ball' hitmaker is aware many people are struggling with social distancing measures because they may have lost their job

Astronomers have more places to look for signs of intelligent life and more advanced tools to find it

Debate over Earth’s oldest fossils fuels the search for our deepest origins

Lendbreen, a pass high in the Norwegian mountains, was an important route from the Roman era until the late Middle Ages

Data centres and digital information processors are reaching their capacity limits and producing heat. Foundational work here on optical-acoustic microchips opens door to low-heat, low-energy, fast internet.

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

The Prime Minister has thanked NHS staff at St Thomas' Hospital in central London for saving his life while he underwent treatment in intensive care for coronavirus.

Read our live coronavirus blog HERE

The family of a London care home worker who died with Covid-19 today described how she "gave her life to nursing".

A man in his 40s is fighting for life after a shooting in Brent.

Police are hunting two masked men who set off a bomb inside an Indian restaurant outside Toronto, injuring at least 15 people.

RAF plane still awaiting go-ahead for flight to Turkey to collect supplies

This is the heartwarming moment more than 100 NHS staff applaud a nurse as she leaves intensive care after spending 23 days in the ward fighting for her life against coronavirus.

Two doctors in Wuhan who survived coronavirus after long battles on life support found their skin changed colour as a result of their treatment.

A man in his 50s is fighting for his life after a stabbing in Notting Hill.

A man in his 20s is fighting for his life after an assault in east London this lunchtime.

A woman in her 80s is fighting for her life after she was hit by a van in front of shocked onlookers on a major south London road.

A police officer has died and another is fighting for his life after a shooting in Louisiana.

A top New York City doctor has taken her own life after battling coronavirus on the frontline, officials have said.

The family of a four-year-old boy with a rare form of cancer is raising money to take him to New York for a potentially life-saving vaccine.

Neighbours have described their shock after a boy suffered "possibly life-changing" injuries after being shot in east London.

Boris Johnson and Carrie Symonds have named their baby boy Wilfred Lawrie Nicholas Johnson.

A woman in her 20s is fighting for her life in hospital with "slash injuries" after a street fight in north-west London.