Possible bacterial drivers of IBD identified

Yale University researchers have identified a handful of bacterial culprits that may drive inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis, using patients' own intestinal immune responses as a guide.

The findings are published Aug. 28 in the journal Cell.

Trillions of bacteria exist within the human intestinal microbiota, which plays a critical role in the development and progression of IBD. Yet it's thought that only a small number of bacterial species affect a person's susceptibility to IBD and its potential severity.

"A handful of bad bacteria are able to attain access to the immune system and get right at the gut," said Richard Flavell, the Sterling Professor of Immunobiology at the Yale School of Medicine. "If you look at the bacteria to which we have made an immune response, you can begin to find these bad actors."

Flavell's research team focused on antibody coatings on the surface of bacteria. In particular, Yale researchers looked at bacteria with high concentrations of an antibody coating called Immunoglobulin A (IgA).

"The coating is our body's attempt to neutralize the bacteria," Flavell said. "It binds to the bad bacteria. We only make these IgA responses to a limited number of organisms."

He and his team confirmed a correlation between high levels of IgA coating and inflammatory responses in the human intestine. To do this, the team collected "good" and "bad" bacteria from a small group of patients and transplanted them into mice. In healthy mice, there was no influence on intestinal inflammation; in mice with induced colitis, those with the suspected "bad" bacteria showed signs of excessive inflammation and other IBD symptoms.

Flavell warned that more research is necessary to learn how many bacterial species fall into the "bad" category and whether those populations are common to all IBD patients or are unique to each patient.

But the study's results indicate that anti-bacterial therapies for IBD are possible, Flavell said. Such anti-bacterial approaches might include highly specific antibiotics, vaccines, and probiotics.

"We believe an anti-bacterial strategy has a place in treating IBD," Flavell said.

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The above story is based on materials provided by Yale University . The original article was written by Jim Shelton. Note: Materials may be edited for content and length.

Three Pathways Into the 1980s

Boeing/NASA

In the 1966-1967 period, NASA began serious planning for its post-Apollo future. Alas, Apollo was widely seen as a means of demonstrating U.S. technological might on the world stage, not as a first small step beyond Earth. Our society’s rapid abandonment of the moon causes me to question whether we have every truly qualified as a spacefaring people.

Had it been otherwise, what pathway might NASA have followed into the future? There were many possibilities, but in my forthcoming book I will describe in detail only three. I call these “moon base,” “space base,” and “flyby.” All might have led to humans on Mars in the 1980s, though in none of them was this a requirement.

NASA planners expected that, after a few early Apollo missions, advanced lunar missions in the Apollo Applications Program (AAP) would commence. These would lead by the mid-1970s to two-week lunar-surface stays. Some of these expeditions would have taken astronauts to the lunar Farside, where relay satellites in Earth-moon L2 Halo Orbit would have linked them with Earth. Others would have surveyed potential outpost and base sites.

By 1980, a space tug – a new upper stage for the Saturn V rocket – would have transported crews directly from Earth to the moon. Some tugs might have established a lunar-orbital way station (image at top of post). Others would have carried surface base modules and supplies. By 1985, humankind’s first permanent base on another world could have been established.

Space tugs might have gone on to serve as propulsion stages for piloted voyages to Mars. Perhaps lunar-produced liquid oxygen would have combined in the space tug engines with liquid hydrogen launched from Earth to propel astronauts beyond the moon.

That was the “moon base” pathway. The “space base” pathway would also have grown from AAP, though not from planned AAP lunar missions. NASA planners expected to launch increasingly sophisticated AAP space stations into Earth orbit beginning as early as late 1968. By 1975, a single-launch space station for from six to 12 astronauts was expected.

After that, modules based on the single-launch station design would have been joined together to form a nuclear-powered Space Base with a crew of from 50 to 100 people. The Space Base would have revolved to provide its inhabitants with artificial gravity. Fully reusable space shuttles would have rotated crews, delivered supplies, and returned experiment results and (possibly) space-made products to Earth.

An intensive Earth-orbital program might have yielded specialized Space Bases such as zero-gee hospitals and assembly bases for Solar Power Satellites. Or, just possibly, a space base might have been fitted out with nuclear-electric thrusters – beefed-up versions of thrusters used to maintain the Space Bases in their orbits about the Earth – and relocated to Mars orbit. Space Base components might also have been combined in new ways to build a large Mars ship.

The “flyby” pathway would also have grown from AAP space stations, but would have aimed directly for Mars at an early date. A flyby spacecraft with only enough modification to enable it to serve as an Earth-orbital station would have been launched into Earth orbit as early as 1972. There, astronauts would have simulated a two-year piloted Mars flyby mission.

If the Earth-orbital test was a success, then a second flyby spacecraft outfitted for interplanetary travel would have left Earth orbit on a free-return path in September 1975. As it passed Mars, its crew would have released robotic probes, including Mars sample collectors, which they would have operated on Mars by remote control. The flyby spacecraft would have entered the inner Asteroid Belt before falling back to Earth.

NASA might have taken advantage of opportunities for a Venus-Mars-Venus flyby starting in 1977 and a Venus-Mars flyby starting in 1979. The experience gained through these relatively cheap combined human-robotic missions could have led to a “minimum-energy” Mars landing mission as early as 1981. Mars landings might have occurred every 26 months throughout the 1980s. By the end of that decade, an operational Mars refueling station would have permitted establishment of a Mars base.

NASA planners expected that the “Moon Base” and “Space Base” pathways would in their early years have required NASA budgets of about $5 billion per year adjusted for inflation, rising to about $9 billion by 1980. The “Flyby” pathway would have been cheaper; it would have called for a NASA budget through 1980 of about $5 billion per year adjusted for inflation. These estimates assumed that other NASA programs, such as aeronautics development, would continue as they had during the 1960s.

To place these costs in perspective: $5 billion per year, equivalent to NASA’s peak Apollo-era budget in Fiscal Year 1965, amounted to about 1% of the Federal budget. By 1968, the war in Indochina cost about $5 billion every 75 days. The entire Apollo Program from 1961 to 1972 cost a little less than $25 billion. The upshot of this is, these proposed space programs were remarkably cheap. Only an intense myopia – nearly a belief that the universe revolves around the Earth, or that the sky is a painted dome – prevented us a half-century ago from seeing the boundless frontier around us and prevents us from seeing it now.

Hydrogen powers important nitrogen-transforming bacteria

Nitrite-oxidizing bacteria are key players in the natural nitrogen cycle on Earth and in biological wastewater treatment plants. For decades, these specialist bacteria were thought to depend on nitrite as their source of energy. An international team of scientists led by Holger Daims, a microbiologist at the University of Vienna, has now shown that nitrite-oxidizing bacteria can use hydrogen as an alternative source of energy. The oxidation of hydrogen with oxygen enables their growth independent of nitrite and a lifestyle outside the nitrogen cycle. The study is published in the current issue of the journal Science.

Nitrogen, an essential chemical element for life, is transformed into its different chemical forms in numerous steps of the global nitrogen cycle. Nitrite-oxidizing bacteria are important players in nitrogen cycling since they convert the toxic nitrite to the less harmful nitrate. "Humans exploit this process in biological wastewater treatment. Moreover, the formed nitrate is a substrate for other important microbial processes and a source of nitrogen for many plants" explains Hanna Koch, first author of the study and Ph.D. student at the Department of Microbiology and Ecosystem Science of the University of Vienna. Since the description of the first nitrite-oxidizing bacteria in the 19th century, scientists have assumed that the survival of these microorganisms would depend on nitrite as their source of energy. Therefore, the presence of nitrite-oxidizing bacteria in the environment and in wastewater treatment plants has commonly been associated with the nitrogen cycle.

Nitrospira: Nitrite oxidizers with surprising features

The environmentally most widespread nitrite oxidizers belong to the genus Nitrospira. These bacteria occur in the most different habitats such as soil, rivers, lakes and oceans, and even in hot springs. In addition, Nitrospira are the key nitrite-oxidizing bacteria in wastewater treatment plants. A team of scientists from Austria, Denmark, Germany, and France has now revealed surprising facts about these microorganisms. "The genome analysis of a Nitrospira species indicated that this bacterium might use hydrogen as an alternative source of energy" says Holger Daims from the Department of Microbiology and Ecosystem Science of the University of Vienna. The potential of Nitrospira to use hydrogen was then studied in detail.

NanoSIMS at the University of Vienna for high-resolution single-cell analyses

The hydrogen-dependent growth of Nitrospira could be visualized in individual bacterial cells by using the high-resolution secondary ion mass spectrometer, also called "NanoSIMS," at the University of Vienna. Under high vacuum conditions like in space, this method shoots small particles out of single bacterial cells for subsequent identification by mass spectrometry. "This exciting approach is feasible at very few research institutions worldwide," says Daims about this high-tech equipment. The scientists could show that Nitrospira cells, which use hydrogen as the source of energy, incorporate carbon dioxide into their biomass. This metabolic activity is linked to cell proliferation and was important evidence that the Nitrospira bacteria indeed use hydrogen for growth. These newly discovered features raise numerous questions about the lifestyle of the "free-living" close relatives of this Nitrospira species in the environment and wastewater treatment plants.

New insights into the ecology of nitrite oxidizers

"The oxidation of hydrogen not only enables Nitrospira to colonize unexpected habitats, but also sustains their activity when nitrite is not available" explains Hanna Koch. Holger Daims adds: "This discovery was a great surprise to us. In the next step, we will explore how extensively environmental nitrite oxidizers use hydrogen as an energy source. Our goal is to better understand the ecology of these important bacteria and their significance for the global cycles of nitrogen and carbon."

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Homosexuality and evolution [Pharyngula]

I made the mistake of reading some of the comments on those last youtube videos. There were some good ones, but they were also laced with the usual grunting assholes complaining about gays and “trannies” and quoting the Bible and making racist remarks about Africans. Let us pass over those contemptible arguments; there’s no dealing with them rationally. Spit and move on.

But there’s another flavor of argument that annoys me to no end: people who cite science and evolution to support their ignorant misconceptions about human nature. I want to address two, one anti-gay and the other pro-gay, both wrong.

First, there is the reductionist who knows a tiny bit about selection.

interesting point of view, but no. Evolution is all about competition. If you dont produce offspring, you take yourself out of the running. They may help the larger group, but that is more along the lines of the group exploiting a weakness. Their genes do not pass on. In the evolutionary crucible, thats a game over. It doesn’t matter what disease you cure, what philosophy you teach, biologically, you lose. Now, again, in modern society, things are more complex. There are more qualities to a life than how many mini-me’s you can make, but for the purposes of biology, it ends there.

If evolution is all about competition, how come reproduction in sexual species requires cooperation between two individuals to occur? Have you ever noticed that reproduction isn’t actually literally replication? You take your complement of 20,000 pairs of genes, and you throw half of them away, splice the remainder into different combinations, and then you merge those with the similarly mangled set of genes from another person, and you produce a unique individual. Not a clone of either of you — someone completely different.

That should tell you right away that you aren’t the focal point of evolution. You are a test platform for a battery of genes, genes that are shared with other members of your community. Evolution sees the propagation of a pool of genes that tends to produce successful individuals; look up inclusive fitness sometime. You share genes and combinations of genes with your siblings, your cousins, and more distant relatives — there’s more than one way for your population to propagate itself than for every individual to maximize the number of offspring they produce.

I also have to laugh every time some oblivious multicellular animal announces that evolution is all about competition, and that all that matters is how many progeny you produce. Do you realize that your existence is entirely a product of cooperation? Your parents were made up of trillions of cells, almost all of them dedicated to specialized, non-reproductive functions, all in support of a tiny minority of cells that can produce gametes. And of all those gametes, only two combined to make you — the great lumbering mass of agglomerated metazoan cells that were your parents then dedicated themselves to cooperatively nurturing the little zygote that was you (and which was not genetically identical to either) into a roughly similar lumbering mass.

Further, if that’s too abstract for you, consider this: you’d most likely be dead right now if scientists hadn’t collaborated to make vaccines against childhood diseases, if doctors and family hadn’t worked to keep you healthy and educated. Imagine all those carpenters who built your house and plumbers who put in the pipes and electricians who wired it up; imagine the vast combines that work to deliver fuel for heating and food for eating. Everything that you think is important about you was created by cooperation.

If you think otherwise, go masturbate into a mud puddle and hope that some of your offspring can make it without any assistance.

Here’s the pro-gay argument based on evolution. It’s just as annoying.

from a view strictly based in the ideas of natural evolution, i always assumed “homosexuality” was as old as the species… and that it was evolution’s way of both keeping the growth of the species in check (since humans are one of the few species that have sex for pleasure) and ensuring orphaned younglings have a chance at receiving care, guidence, and protection in their formative years. mind you this is just a personal theory based on the nature of nature…

Do not anthropomorphize evolution. Evolution is not an entity that plans and manages populations, it is not a nanny that cares about youngsters — if they are orphaned, one evolutionary outcome is for them to die, another is for survivors to support them, and all that matters is whether the population persists. In particular, evolution isn’t concerned with keeping populations in check — it’s simply a ratchet that permits populations to strive, and eventually and inevitably they hit physical and biological limitations, or pressure from some other growing population, and then physics happens.

Nothing personal. Evolution doesn’t play favorites. It can’t: it’s just the outcome of chance and physical laws interacting in particular environments.

Here’s my perspective on evolution and homosexuality.

Humans are complex organisms whose development is plastic and strongly dependent on environmental influences. There is selection pressure for the population reproduce, which we social beings accomplish with a significant subset of individuals providing sufficient progeny to replenish the population each generation, and with a similarly significant subset of the population working cooperatively to provide a supportive environment.

Evolution doesn’t care. All that matters is that the population thrives into the next generation, and that requires that individuals cooperate. Evolution is not a micromanager, either; we acquire random variations purely by chance, some work, some don’t, and in general, there are so many competing factors driving our survival that selection cannot possibly fine-tune emergent properties of behavior to such a degree that biology can specify exactly who you will bump genitals with. We are dealing with general tendencies expressed to varying degrees in individuals within a population.

If there is one biological imperative for humans, it is this: love one another. Build communities. Cooperate. Help each other in adversity. Successful populations will express these behaviors to a greater degree.

There are also biases towards favoring sexual interactions with members of a different sex, but that’s a secondary priority. Even if sexual preference were non-existent and totally random, women would pair up with men half the time, which would be more than sufficient to propagate our species, especially if the other half are working cooperatively to build safe homes and stable food supplies and provide loving educational environments.

From my biological perspective, the negative behavior that affects the survival of the species isn’t homosexuality, but anything that disrupts the cooperative bonds of community and foments hate — homophobia in humans is the destructive behavior that selection should work against. But keep in mind that if God has lousy aim, evolution is even worse…so we should also encourage behaviors that discourage attitudes that work against our survival.

Surprising discovery: HIV hides in gut, evading eradication

Researchers at UC Davis have made some surprising discoveries about the body's initial responses to HIV infection. Studying simian immunodeficiency virus (SIV), the team found that specialized cells in the intestine called Paneth cells are early responders to viral invasion and are the source of gut inflammation by producing a cytokine called interleukin-1 beta (IL-1β).

Though aimed at the presence of virus, IL-1β causes breakdown of the gut epithelium that provides a barrier to protect the body against pathogens. Importantly, this occurs prior to the wide spread viral infection and immune cell killing. But in an interesting twist, a beneficial bacterium, Lactobacillus plantarum, helps mitigate the virus-induced inflammatory response and protects gut epithelial barrier. The study was published in the journal PLoS Pathogens.

One of the biggest obstacles to complete viral eradication and immune recovery is the stable HIV reservoir in the gut. There is very little information about the early viral invasion and the establishment of the gut reservoir.

"We want to understand what enables the virus to invade the gut, cause inflammation and kill the immune cells," said Satya Dandekar, lead author of the study and chair of the Department of Medical Microbiology and Immunology at UC Davis.

"Our study has identified Paneth cells as initial virus sensors in the gut that may induce early gut inflammation, cause tissue damage and help spread the viral infection. Our findings provide potential targets and new biomarkers for intervening or blocking early spread of viral infection," she said.

In the study, the researchers detected a very small number of SIV infected cells in the gut within initial 2.5 days of viral infection; however, the inflammatory response to the virus was playing havoc with the gut lining. IL-1β was reducing the production of tight-junction proteins, which are crucial to making the intestinal barrier impermeable to pathogens. As a result, the normally cohesive barrier was breaking down.

Digging deeper, the researchers found the inflammatory response through IL-1β production was initiated in Paneth cells, which are known to protect the intestinal stem cells to replenish the epithelial lining. This is the first report of Paneth cell sensing of SIV infection and IL-1β production that links to gut epithelial damage during early viral invasion. In turn, the epithelial breakdown underscores that there's more to the immune response than immune cells.

"The epithelium is more than a physical barrier," said first author Lauren Hirao. "It's providing support to immune cells in their defense against viruses and bacteria."

The researchers found that addition of a specific probiotic strain, Lactobacillus plantarum, to the gut reversed the damage by rapidly reducing IL-1β, resolving inflammation, and accelerating repair within hours. The study points to interesting possibilities of harnessing synergistic host-microbe interactions to intervene early viral spread and gut inflammation and to mitigate intestinal complications associated with HIV infection.

"Understanding the players in the immune response will be important to develop new therapies," said Hirao. "Seeing how these events play out can help us find the most opportune moments to intervene."

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The above story is based on materials provided by University of California - Davis Health System . Note: Materials may be edited for content and length.

Prions can trigger 'stuck' wine fermentations, researchers find

A chronic problem in winemaking is "stuck fermentation," when yeast that should be busily converting grape sugar into alcohol and carbon dioxide prematurely shuts down, leaving the remaining sugar to instead be consumed by bacteria that can spoil the wine.

A team of researchers including UC Davis yeast geneticist Linda Bisson has discovered a biochemical communication system behind this problem. Working through a prion -- an abnormally shaped protein that can reproduce itself -- the system enables bacteria in fermenting wine to switch yeast from sugar to other food sources without altering the yeast's DNA.

"The discovery of this process really gives us a clue to how stuck fermentations can be avoided," said Bisson, a professor in the Department of Viticulture and Enology. "Our goal now is to find yeast strains that essentially ignore the signal initiated by the bacteria and do not form the prion, but instead power on through the fermentation."

She suggests that the discovery of this biochemical mechanism, reported Aug. 28 in the journal Cell, may also have implications for better understanding metabolic diseases, such as Type 2 diabetes, in humans.

Bacteria, yeast and fermentation

Biologists have known for years that an ancient biological circuit, based in the membranes of yeast cells, blocks yeast from using other carbon sources when the sugar glucose is present.

This circuit, known as "glucose repression," is especially strong in the yeast species Saccharomyces cerevisiae, enabling people to use that yeast for practical fermentation processes in winemaking, brewing and bread making, because it causes such efficient processing of sugar.

Prions play key role

In this study, the researchers found that the glucose repression circuit is sometimes interrupted when bacteria jump-start the replication of the prions in membranes of yeast cells. The interference of the prions causes the yeast to process carbon sources other than glucose and become less effective in metabolizing sugar, dramatically slowing down the fermentation until it, in effect, becomes "stuck."

"This type of prion-based inheritance is useful to organisms when they need to adapt to environmental conditions but not necessarily permanently," Bisson said. "In this case, the heritable changes triggered by the prions enable the yeast to also change back to their initial mode of operation if environmental conditions should change again."

The researchers demonstrated in this study that the process leading to a stuck fermentation benefits both the bacteria and the yeast. As sugar metabolism slows down, conditions in the fermenting wine become more conducive to bacterial growth, and the yeast benefit by gaining the ability to metabolize not only glucose but also other carbon sources as well -- maintaining and extending their lifespan.

Solutions for winemakers

Now that this communication mechanism between the bacteria and yeast is more clearly understood, winemakers should be better able to avoid stuck fermentations.

"Winemakers may want to alter the levels of sulfur dioxide used when pressing or crushing the grapes, in order to knock out bacteria that can trigger the processes that we now know can lead to a stuck fermentation," Bisson said. "They also can be careful about blending grapes from vineyards known to have certain bacterial strains or they could add yeast strains that have the ability to overpower these vineyard bacteria."

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Cicada study discovers two genomes that function as one

Two is company, three is a crowd. But in the case of the cicada, that's a good thing.

Until a recent discovery by a University of Montana research lab, it was thought that cicadas had a symbiotic relationship with two important bacteria that live within the cells of its body. Since the insect eats a simple diet consisting solely of plant sap, it relies on these bacteria to produce the nutrients it needs for survival.

In exchange, those two bacteria, Hodgkinia and Sulcia, live comfortably inside the cicada. Since all three divvy up the nutritional roles, each member of the symbiosis is completely dependent on the others for survival.

So, where does this third-wheel bacterium come into play? That is exactly what UM microbiologist John McCutcheon and his team of colleagues stumbled upon once they started delving deeper into the genome sequence of the essential bacteria. Instead of two bacterial symbionts, they actually identified three. Sulcia was predictably still there, but they found two different kinds of Hodgkinia. What previously was thought to be a tripartite, or a three-way symbiosis, is now proven to actually be a four-way symbiosis.

Their work was published in the Aug. 28 issue of Cell, a scientific journal in an article titled "Sympatric speciation in a bacterial endosymbiont results in two genomes with the functionality of one."

The researchers discovered that Hodgkinia had subtly become more complex in what McCutcheon explained as a speciation event, in which the original lineage split to produce two separate but interdependent species of Hodgkinia.

"We just didn't expect it," McCutcheon said of this discovery. "I had thought my student made a mistake, but he proved me wrong."

It took a keen eye to identify what were actually two separate versions of the bacteria that were acting as one.

"When we looked at the genes, they were clearly closely related to each other," McCutcheon said. "If there was a broken gene in one version of Hodgkinia, it would be complete and functional on the other and visa-versa. So, the functional genes in each, when working together, seem to operate as one."

Because they only are complete when they operate as a team, they are reliant on each other just as the Sulcia, and ultimately the cicada, is reliant on their contributions to the symbiotic ecosystem.

"This is an obligate symbiosis -- all of the organisms in there need each other," McCutcheon said. "We've shown that what was once a three-way symbiosis is now a four-way symbiosis."

This unexpected discovery piqued the interest of McCutcheon, who theorizes that this evolutionary development is a result of "slop and chance." However, this accidental evolution may answer some questions about how other organisms have evolved and become more sophisticated over time.

Hodgkinia's development closely parallels that of a path of some organelles. Essentially, organelles are to cells what an organ is to the human body. Mitochondria of our own cells are organelles, and like Hodgkinia, are derived from symbiotic bacteria.

In the case of the cicada, Hodgkinia's speciation event added a new member to the symbiotic team but it did not add any new functionality to the symbiosis. McCutcheon writes in the paper that, "this process parallels what is observed in some organelles, where massive genome expansions result in little if any observable increase in function."

Understanding the development of organelles is fundamental to understanding the development of life. Because organelles arose such a long time ago, it's impossible to trace back to the specific events that allowed the organelle to become what it is today. By examining Hodgkinia's evolution, researchers in McCutcheon's lab are hoping to gain insight into the storied pasts of organelles whose history has since been erased.

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