System sensor The kidney is made up of miles of minuscule tubes, twisted into an exquisite lacework. Threaded through these is a system of blood vessels, and in places where these and the kidney's ...

1. Scent and taste receptors found all over the body,
including sperm, bladder, gut, muscle tissue and
brain
System sensor The kidney is made up of miles of minuscule tubes, twisted into an exquisite lacework.
Threaded through these is a system of blood vessels, and in places where these and the kidney's ...
System sensor The kidney is made up of miles of minuscule tubes, twisted into an exquisite lacework.
Threaded through these is a system of blood vessels, and in places where these and the kidney's tubes
are especially intertwined, water, nutrients and other molecules seep through the walls and pass between
the two. What the blood doesn't need is passed off to the urine forming in the tubes, and what it does
have a use for – keeping blood pressure stable, for instance – goes back. If this process stops working the
body will soon shut down, poisoned by its own exhaust fumes. Peering more closely down the microscope
at that slice of kidney, Pluznick saw the fluorescent glow was emanating from the macula densa, a group
of cells that play a central role in this chemical back-and-forth, sampling the forming urine as it goes by
and sending out alerts to adjust the blood filtration rate. “The macula densa is the only cell type in the
kidney that you would think of as being a chemical sensor,” says Pluznick. “It made a hell of a lot of sense,
and it made me think it was real.” The next step was to figure out what would happen if these receptors
were absent in this region of the kidney. A team led by neuroscientist Stuart Firestein, at Columbia
University in New York had engineered mice that lacked one of scent receptors Pluznick identified in the
kidney, called Olfr78. Further tests revealed these mice had kidney problems involving their blood
filtration rate and the production of renin, a hormone which stimulates the constriction of blood vessels

2. to increase blood pressure. Both of these are controlled by the macula densa. Pluznick now began to
devote herself full-time to the puzzle. Identifying which chemical "keys" – known as ligands – were
binding to the Olfr78 receptor "locks" would help her understand the bigger picture of what the receptor
was responding to. In doing so, her work took her from one weird and wonderful discovery in biology to
another: the microbiome. Our bodies contain trillions of bacteria, fungi, and other microorganisms. Those
in the human gut fulfil various important functions, such as breaking down certain foods into energy and
useful nutrients, suppressing harmful microbes, preventing allergies and assisting the immune system in
a number of other ways. The evidence that the balance of different microbes we have inside us is
important to our health has been growing rapidly in recent years. People with irritable bowel syndrome,
obesity, Alzheimer's disease, Parkinson's and depression have been shown to have differences in gut
bacteria when compared to healthy people. As a study published by Pluznick last March showed, Olfr78's
ligands are short-chain fatty acids, molecules produced when gut bacteria digest components of
plant-based foods. Other scientists have documented their roles in human health, such as stimulating
immune-cell production, reducing heart-disease risk, stabilising blood glucose levels and protecting the
colon lining. Pluznick acknowledges the picture is a complex and incomplete one, further work indicates
another receptor that also binds to short-chain fatty acids has a greater and opposite effect. However,
she believes the work shows the scent receptors she accidentally discovered are a previously unknown
means for bacteria to tell the kidney to make blood pressure changes that allow them to best carry out
their health-related functions. Bitter truth As Pluznick was unravelling this mystery, other researchers
were investigating taste and scent receptors elsewhere in the body. Yehuda Ben-Shahar, now a professor
at Washington University in St. Louis, found cells in the human airway equipped with bitter receptors.
These cells are covered in microscopic hair-like protrusions called cilia which flap when dangerous
chemicals are breathed in, helping to flush them out of the body. Bitter receptors in the tongue are
thought to have evolved to help us identify poisons, and Ben-Shahar wondered whether those in the
airway might be protecting us in a similar way. He and his collaborators found that when receptors in
these cells were exposed to certain noxious molecules, it triggered a cascade of events that culminated in
the flapping of the cilia. This made Ben-Shahar think that what we know as bitter receptors might better
be called danger receptors. “We call them bitter but that's only because when we taste with them that's
what we get," he says. "Probably what's uniting them is things that we try not to take in." In fact, work by
Noam Cohen, an ear, nose and throat doctor at University of Pennsylvania Medical School, suggests an
intriguing role for bitter receptors recently discovered in the sinuses. He found one particular type can
intercept the chemical signals that bacteria send to each other when they are coming together to form
biofilms, a manoeuvre that greatly strengthens their defences against immune-system attacks. When the
bitter receptors in the sinuses pick up these signals, they set in motion an attack against the bacteria,
causing cells to release toxic gas and cilia to flap. If people have a genetic variant that produces a
different form of this bitter receptor, however, they are deaf to this back-channel bacterial chatter, and
are more prone to severe sinus infections. Patients who regularly get serious sinus infections often opt
for surgery. However Cohen, who, along with Ben-Shahar, presented some of his findings at April's
Association for Chemoreception Sciences meeting in Huntington Beach, California, speculates this may
not help those with bitter receptors that can't pick up these signals. Since the bitter receptors in an
individual's sinuses are the same as those on their tongue, Cohen suggests a test that tells clinicians
which version of the receptor patients have on their tongues could help guide treatment.

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