Diet affects mix of intestinal bacteria, risk of inflammatory bone disease

Diet-induced changes in the gut’s bacterial ecosystem can alter susceptibility to an autoinflammatory bone disease by modifying the immune response, St. Jude Children’s Research Hospital scientists reported. The findings appeared September 28 as an advanced online publication of the scientific journal Nature.

The research provides insight into how the thousands of bacteria and other microorganisms that live in the intestines affect health. The microbes make up the intestinal microbiome, a diverse evolving ecosystem that aids digestion and helps to educate the immune cells that guard against infection. Growing evidence suggests that changes in the microbiome composition may contribute to development of diseases ranging from cancer to chronic inflammatory disorders such as multiple sclerosis. The mechanisms involved, however, were poorly understood.

“These results are exciting because they help to explain how environmental factors like diet can influence susceptibility to autoinflammatory diseases,” said the study’s corresponding author Thirumala-Devi Kanneganti, Ph.D., a member of the St. Jude Department of Immunology. “While multiple lines of evidence have suggested that diet can impact human disease, the scientific mechanism involved was a mystery. Our results demonstrate that diet can influence immune-mediated disorders by shaping the composition of the gut microbiome, which our findings suggest play a role in immune regulation.”

The study was done in a mouse model of the devastating inflammatory childhood bone disorder chronic recurrent multifocal osteomyelitis (CRMO). The mice carry a mutation in the Pstpip2 gene that leads to osteomyelitis early in life.

Researchers showed that changing the nutritional composition of the animals’ diets led to marked increases and decreases of certain intestinal bacteria. Affected bacteria included Prevotella, which have been implicated in causing osteomyelitis, arthritis, periodontal disease and other inflammatory disorders in humans.

A diet that limited intestinal Prevotella growth also protected the mutant mice from developing osteomyelitis. The same diet was associated with reduced production of the immune molecule interleukin-1 beta (IL-1 beta) that promotes inflammation. Earlier work from Kanneganti’s laboratory demonstrated that IL-1 beta fueled osteomyelitis in the mutant mice. In this study, researchers reported that dietary changes impacted the supply of IL-1 beta in immune cells called neutrophils.

To confirm the connection between the intestinal microbiome and osteomyelitis, researchers treated mice that were fed the disease-promoting diet with a cocktail of broad-spectrum antibiotics. Treatment was followed by a reduction in Prevotella as well as intestinal levels of Il-1 beta. In addition, fewer mice developed osteomyelitis.

In a series of probiotic experiments, investigators demonstrated that transplanting the intestinal microbiome from healthy mice protected the at-risk, mutant mice from osteomyelitis. Probiotics are bacteria and other microorganisms with a demonstrated health benefit. “The results suggest probiotics might provide a more targeted method for suppressing production of IL-1 beta and protecting against autoinflammatory diseases,” said first author John Lukens, Ph.D., a St. Jude postdoctoral fellow.

The research also provided key details about IL-1 beta production and regulation in neutrophils, which are part of the body’s first line of defense. Investigators identified the two enzymes capable of converting the immune molecule from its inactive form to the pro-inflammatory IL-1 beta. The enzymes are caspases 1 and 8. Deleting both enzymes led to a dramatic decline in IL-1 beta in the susceptible mice and protected the animals from osteomyelitis.

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Beer from 1840 shipwreck: Scientists developing new taste sensations for beer lovers from old beer

VTT Technical Research Centre of Finland was commissioned to analyse the bottles of beer salvaged from the 1840s shipwreck found near the Åland Islands in 2010. Living bacteria found in the bottles were subject to further tests to find out how the cells had survived for so long in the wreck. VTT also develops new brewery processes and beers. VTT was founded in 1942, and beer and brewery research is one of the institute's oldest research areas.

Both beer lovers and breweries are always looking for new taste sensations. New beer flavours can be created by developing new yeast cultures and by making use of naturally occurring yeast and bacteria. New kinds of yeast are needed, for instance, in the manufacture of non-alcoholic beers. The lager yeast Saccharomyces pastorianus is a natural hybrid of two yeast strains. One of VTT's most recently introduced research areas relates to the development of new hybrid yeast strains that have new kinds of taste profiles or a better ability to turn sugar into alcohol than the currently available lager yeasts.

Lactic acid bacteria found in shipwreck beer bottles subject to further tests

The Åland-based brewery Stallhagen has embarked on a quest to recreate the 170-year-old recipe and start reproducing the beer. Both the product development process and the brewing technique were selected based on the thorough physico-chemical and microbiological analyses carried out at VTT Technical Research Centre of Finland.

One of VTT's triumphs was isolating living lactic acid bacteria from the bottles. This type of bacteria plays an important role in the brewing of the recreated beer. The production process was developed in collaboration with Stallhagen and the Belgian university KU Leuven, a frontrunner in yeast and bacteria fermentation.

"We are probably talking about the oldest living non-spore forming bacteria ever found in beer. The beer brewing techniques used in the old days typically caused these kinds of bacteria to grow alongside yeast," explains Key Account Manager Annika Wilhelmson from VTT Technical Research Centre of Finland.

What scientists now want to know is why and how the lactic acid bacteria survived in such extreme conditions. VTT and the University of Saskatchewan are studying the DNA of the bacteria to find answers to these questions. Bacterial strains extracted from the bottles could prove useful to the food and drinks industry in the future.

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Dang good paper [Pharyngula]

All right, Larry Moran, why did you post about this paper now? I finished the unit on the origins of life in my cell biology class over a week ago, and this summary of the metabolism first model of abiogenesis would have been very helpful. I first gave them a review of redox reactions in chemistry, and then some general ideas about events in deep sea vents that generate a source of energy that early chemistry could have tapped, but this paper is full of specifics — probably a bit too heavy going for college sophomores, but they could have appreciated some of the diagrams.

Like this one:

Also…the paper is open access! Everyone go read!

Sousa, F.L., Thiergart, T., Landan, G., Nelson-Sathi, S., Pereira, I. A., Allen, J.F., Lane, N. and Martin, W.F. (2013) Early bioenergetic evolution. Philosophical Transactions of the Royal Society B: Biological Sciences 368:20130088. [doi: 10.1098/rstb.2013.0088]

Dembski: Still wrong [Pharyngula]

William Dembski spoke at the University of Chicago in August, and a video of the talk is available. I tried to watch it, I really did, but I ended up skipping through most of it (one of the advantages of seeing it on youtube!). Here’s my rather stream-of-consciousness monolog as I was flicking like a damselfly over the stagnant pond of his words:

“Get to the point, Bill. Skip. No biology. Skip. No biology yet. Skip. Wait, that model is anti-biology…evolution doesn’t work like that. Watches a short segment. Nope, nonsense. Skip. No biology, skip. Oh, “specified complexity”…does he define it? Listens intently for a bit. Nope. Skip. Dawkins’ weasel program? He still doesn’t understand it! No biology, no biology, no biology, I’m done.”

I know, that wasn’t very informative, but then, neither was the talk. There were a few shots of the audience, and they didn’t seem particularly enthralled, either.

Joe Felsenstein watched the whoooole thing, though, and has some very sharp observations on Dembski’s model.

The most damning thing about the Dembski model, other than the fact that the authors seem to know absolutely nothing about biology, is that they build their argument on a bizarre foundation in which nothing in the genome is interconnected, where changes in a sequence lack any possibility of generating a graded response, and in which every point mutation has as much likelihood of generating a phenotypic variant as a complete scrambling of the genome. That’s the tellingly abiological part of the story — as Felsenstein notes, fitness is a random function of the whole genome:

What if, instead of changing one base, we took the drastic step of mutating all of the bases in the genotype at the same time? If the Bernoulli Principle applied, we would get to a genotype whose fitness was also chosen at random. So in that case, on average, that would be no better and no worse than changing just one base. In other words, when fitnesses are randomly assigned to genotypes making a single typographical error is exactly as bad as changing every letter in the text .

Real biology doesn’t work anything like that. Making one mutation in one of my genes will on average make it worse, though sometimes not. If it produces a protein, a single amino acid change often leaves the protein still functioning. But making changes in every site of its DNA is the same as replacing every protein by a random string of amino acids. Which will be a complete disaster.

Similarly, in statements in English, one typographical error might change “to be or not to be that is the question” into “to be or not to de that is the question”. Changing all letters would give something like “bdglvwujzib lxmoxg rjdg a ohlowugrbl owj”. It should be obvious that the latter is far less functional. The comprehensibility of English sentences is more like the actual fitness of organisms, and not like the fitness of the organisms Dembski and Marks imagine.

So, basically, by building a model in which the accumulation of mutations to improve fitness is impossible, they proved that the accumulation of mutations to improve fitness is impossible. What a stunning accomplishment!

Before creationists leap in an argue that he’s not a biologist, he’s a mathematician, and he’s carrying out an analysis of the underlying mathematics of evolution, he’s not even competent at that. One point mentioned in the talk is Dawkins’ “Weasel” model of how selection can lead to refinement of a sequence. It’s a very simple, fundamentally inarguable demonstration of how selection can work, and yet, for years Dembski & Co. have gotten it completely wrong, been unable to puzzle out exactly how it works, and have distorted both its purpose and its algorithm. He’s still getting it wrong.

One should note in passing Dembski’s use of Richard Dawkins’s “Methinks It Is a Weasel” model. In his Chicago talk, Dembski portrays Dawkins as arguing that the Weasel model shows that natural selection can originate information, and portrays Dawkins as claiming that it is a realistic model of evolution. Dawkins was not arguing that it was a realistic model of evolution, or that this evolution originated new information. Dawkins’s model was a teaching example to show why creationist debaters who argue that natural selection is doing a “random” search are disingenuous. The Weasel search succeeds in about 1000 steps, while a truly random search would take astronomical numbers of steps. Dawkins’s model is an effective teaching device. It is routinely misrepresented in the creationist and ID literature as intended to be a realistic model of evolution, and intended to prove assertions about where the information in life originates. Unfortunately Dembski has followed this sad tradition.

You know, when you can’t puzzle out a simple BASIC program written by a biologist, I don’t think you have any credibility in your assertion that your vast logic and math skills have sussed out all of biology and evolution.

How the Klingon and Dothraki Languages Conquered Hollywood

Lieutenant Commander Worf, from Star Trek: The Next Generation. Paramount

One great strength of science fiction is that it creates new worlds. The downside is that creating new worlds is hard. Many science fiction films cut corners, falling back on convenient but scientifically dubious notions such as that faster-than-light travel is no big deal, or that aliens all look like (and can mate with) humans, or that everyone in the galaxy speaks English. For the most part science fiction fans have had to grit their teeth and suspend disbelief, but one recent trend offers hope: The rising use of constructed languages, or “conlangs,” for movie aliens.

“Not having them talk to you in a Brooklyn accent or use Valley slang from Southern California helps transport you into that world,” says Lawrence M. Schoen, director of the Klingon Language Institute. “And I think that Hollywood has seen that’s very effective, and is a lot cheaper than CGI.”

Klingon was the first Hollywood conlang to achieve widespread notice. It was invented on the set of Star Trek by actor James Doohan (“Scotty”) and developed into a full language by linguist Marc Okrand. But writers and directors of subsequent TV spinoffs were often careless about sticking to the established grammar and pronunciation, figuring no one cared. They were wrong.

“Paramount has learned, often to its regret, how rabid and enthusiastic Star Trek fans are,” says Schoen, who points out that digital recording and the internet have made it much easier for fans to notice and complain if an imaginary world doesn’t hold together.

This has led to a much greater attention to language on the part of Hollywood studios. When David Benioff and D.B. Weiss adapted George R. R. Martin’s novel A Game of Thrones for HBO, they were careful to get the conlangs right, hiring linguist David J. Peterson, co-founder of the Language Creation Society, to develop Dothraki and Valyrian into real, consistent languages. Peterson feels that Lord of the Rings and Avatar helped pave the way for the current trend of Hollywood conlangs, and also credits the success of Mel Gibson’s Passion of the Christ , which presented its dialogue in Latin, Hebrew, and Aramaic.

“That’s kind of the nudge I think a lot of producers needed to say, this is not only something that audiences will tolerate, this is something that audiences will seek out and find interesting,” he says.

Listen to our complete interview with Lawrence M. Schoen and David J. Peterson in Episode 119 of the Geek’s Guide to the Galaxy podcast (above), and check out a few highlights from the discussion below.

Lawrence M. Schoen on writing aliens who are truly alien:

“By definition a truly alien language is going to be one you can’t comprehend. You can’t grok it, so to speak. I had a story where the aliens show up and they’re lumps of igneous rock, as far as we can tell. And they throw Earth’s best linguist in a room with one of these aliens, and they won’t let either of them out until they communicate. And it’s horrible, they’re making no progress at all. The rock every now and then emits a little ammonia, it paints colors on the wall or something. The guy is trying to talk to it, he’s doing dialects, he’s trying every different grammatical category he can think of, and finally after weeks of this he starts banging the walls in frustration. And the rock can relate to this, because it’s frustrated too. And now we have a common ground to build communication from.”

Lawrence M. Schoen on realistic nuance in conlangs:

“I don’t know a lot of people who have degrees [in linguistics] who are writing science fiction. They’re getting the physics right. They can tell you everything about the gravity of the planet and the density of the core and all that, but the aliens land and they all sound identical. I always say I want to hear alien speech impediments, I want to hear the Martian equivalent of ‘you know’ and ‘um.’ And I don’t want to talk to the officer on the bridge who’s gone to all the best schools, and had diction lessons and all this. I want to talk to the guy who’s scrubbing out the mess, who didn’t get that education, who has a different dialect. … And then I want to take it a step further and I want figurative language. I’ve been pushing for this in Klingon for 20 years. Because if you really are driving your conlang, then you should be able to use metaphors in that language and be understood.”

David J. Peterson on hostility toward conlangs:

“Linguistics is often under fire, and so I think anything that’s related to linguistics that could possibly diminish the field, linguists will sometimes react defensively, and they certainly did that over the years with constructed languages, especially when one of the most prominent examples of constructed languages was Esperanto, which carried with it a political agenda. But I think that many linguists—not all, certainly—but many linguists are really getting it now, that those who create languages and those who are interested in creating languages are really interested in language, period, and that interest in language is a good thing, because it leads you to interest in other natural languages, it sometimes leads you to the study of natural language, and it also just raises your level of understanding of language in general, which as Lawrence pointed out is pretty low in America specifically.”

David J. Peterson on authors and conlangers working together:

“There are literally thousands of people all over the world who spend the better part of their free time creating languages … and a lot of them would love to be in my position. And I think that it’s going to be tough to break into television for a conlanger, but I think it might be easier to break into fiction. … It would be wonderful if there were tons of conlangers working with fantasy authors, working with science fiction authors, where the author can spend their time on the story and the conlanger can spend their time on the language, so by the time it gets picked up and it becomes the next blockbuster, whether on film or television, they actually have a language there to go along with it. … And right now the place where both conlangers can go and people interested in getting languages created can go is the Language Creation Society’s jobs board.”

This Interactive Map of NYC Is Made of 180 Morphing Speakers

There’s a permanent Sonos Studio in L.A., but the multimedia gallery and event space recently took a week-long trip to New York City. It runs through Sunday, Oct. 5 at NeueHouse near Madison Square Park, and the week-long event features a smorgasbord of daily concerts, art exhibits, and interactive workshops.

It’s basically a futuristic day camp with a lot of weird, fun things going on. In addition to daily concerts, you’ve got workstations where you can make your own Sonos speakers, a theater where you can take in an A/V installation by artist JD Walsh and the band Spoon, and a moving mercurial sculpture collaboration by musician Dev Hynes and design shop The Principals.

One of the main attractions was this massive, interactive display made of 300 Sonos Play:1 speakers and four Sonos Sub woofers. Dubbed “Sounds of NYC,” this moving map of sound uses 180 Play:1 speakers filled with LED lights as a display. Those light-up speakers act purely as “pixels”—they don’t actually produce sound because they’ve been gutted. To handle the audio, there are 120 black Play:1 units on either side of the display.

Once you stand in front of the wall, it greets you with a giant “YO!” Then the display morphs into a map of the five boroughs. A Kinect controller above the speaker wall acts as an input device, and moving your hands around selects different parts of the city. White “pixels” display the selectable locations. Once they’re selected, they pop out of the wall thanks to Arduino controllers behind the scenes. A woman’s voice announces the location and artist, and the system plays a song that represents the area.

“All the songs are streamed from Google Play,” explains Brad Wolf, senior director of brand innovation at Sonos. “The back-end program is built using Flash, which controls the movement and the light of the units while also grabbing the songs from Google Play.”

The end result is a giant, interactive Lite Brite that plays music. The project started as a collaboration between California-based Sonos and Stockholm-based creative agency Perfect Fools, who worked on the piece’s overall design. The hardware and mechanics were assembled by VolvoxLabs in Brooklyn. The location-based music playlist was curated by DJ/production team Wolf+Lamb, while a second playlist of ambient noises recorded at the actual locations in the map was created by the two-piece group Big Noble.

Somehow, the project came together in three months despite the teams being scattered across the globe.

“It was a transcontinental effort to collaborate on this project,” says Wolf. “[We used] Skype for regular check-ins.”

As a music map, NYC’s playlist is rock-solid and incredibly varied: Everyone from Louis Armstrong (Queens) to Nas (Brooklyn) to soundbites from the Metropolitan Opera House (Upper West Side, Manhattan) to Afrika Bambaataa (The Bronx) is in the mix. The maps were initially planned out using Google Maps, with one or multiple song suggestions for each location. To keep it fresh—and maybe avoid debates about the best artists in each borough—Perfect Fools says it mixes up the song list from day to day.

After Sonos Studio NYC wraps up, the “Sounds of NYC” hardware will live on. However, its light show and sounds will adapt to the next place it visits.

“The beauty of the installation is that it is a flexible canvas,” says Sonos’s Wolf. “It can musically bring any city or region to life—whether that’s LA, London, New Orleans, or Beijing.”

New discovery in the microbiology of serious human disease

Previously undiscovered secrets of how human cells interact with a bacterium which causes a serious human disease have been revealed in new research by microbiologists at The University of Nottingham.

The scientists at the University's Centre for Biomolecular Sciences have shed new light on how two proteins found on many human cells are targeted by the human pathogen Neisseria meningitidis which can cause life-threatening meningitis and septicaemia.

The proteins, laminin receptor (LAMR1) and galectin-3 (Gal-3) are found in and on the surface of many human cells. Previous research has shown they play diverse roles in a variety of infectious and non-infectious diseases. For example, the LAMR1 is a key receptor targeted by disease-causing pathogens and their toxins and is also a receptor for the spread of cancer around the body and for the development of Alzheimer's.

Using the latest bimolecular fluorescence and confocal imaging techniques, the researchers have shown that these two separate proteins can form pairs made up of two similar molecules (homodimers) or one of each molecule (heterodimers) which are targeted by Neisseria meningitidis. They have also identified critical components which cause the formation of these pairs of molecules.

These new mechanistic insights into the three-way relationship between proteins and bacterial pathogens could have significant implications in the fields of infection, vaccination and cancer biology.

Associate Professor of Microbiology, Dr Karl Wooldridge, said: "We have shown evidence for the self and mutual association of these two important proteins and their distinctive surface distribution on the human cell. We've also demonstrated that they are targeted by the serious human pathogen Neisseria meningitidis. This is significant because these proteins could potentially be used to develop new vaccines and treatments which could sabotage the colonisation of these dangerous bacteria, and also which could protect the blood-brain barrier which is disrupted in cases of bacterial meningitis."

Co-investigator Dr Jafar Mahdavi added: "One of the problems of studying laminin receptors is that there are at least two forms of LAMR1 found on the cell surface, called 37LRP and 67LR, and many previous studies have not sufficiently distinguished between the two forms. There are antibodies available but the specificity for the different types of laminin receptor had not previously been adequately reported. In our research we were able to identify which antibody detects which specific type of receptor.

The paper, published in the Royal Society journal Open Biology, will inform the whole field of laminin receptor research, not just infection. The team at Nottingham says that by examining bacteria as model organisms which have learned how to manipulate cell biology systems, they may gain insights into how medical science can manipulate cell systems for cancer treatment, Alzheimer's disease and other diseases associated with the laminin receptor.

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