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Breaking a longstanding impasse in our understanding of olfaction,

scientists at UC San Francisco (UCSF) have created the first
molecular-level, 3D picture of how an odor molecule activates a human
odorant receptor, a crucial step in deciphering the sense of smell.
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The findings, appearing online March 15, 2023, in Nature, are poised to reignite interest in
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the science of smell with implications for fragrances, food science, and beyond. Odorant
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receptors -- proteins that bind odor molecules on the surface of olfactory cells -- make up
half of the largest, most diverse family of receptors in our bodies; A deeper understanding
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of them paves the way for new insights about a range of biological processes.

"This has been a huge goal in the field for some time," said Aashish Manglik, MD, PhD, an
associate professor of pharmaceutical chemistry and a senior author of the study. The
dream, he said, is to map the interactions of thousands of scent molecules with hundreds of
odorant receptors, so that a chemist could design a molecule and predict what it would
smell like.

"But we haven't been able to make this map because, without a picture, we don't know how
odor molecules react with their corresponding odor receptors," Manglik said.

A Picture Paints the Scent of Cheese

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Smell involves about 400 unique receptors. Each of the hundreds of thousands of scents
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we can detect is made of a mixture of different odor molecules. Each type of molecule may
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be detected by an array of receptors, creating a puzzle for the brain to solve each time the
nose catches a whiff of something new.

"It's like hitting keys on a piano to produce a chord," said Hiroaki Matsunami, PhD,
professor of molecular genetics and microbiology at Duke University and a close
collaborator of Manglik. Matsunami's work over the past two decades has focused on
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decoding the sense of smell. "Seeing how an odorant receptor binds an odorant explains
how this works at a fundamental level."

To create that picture, Manglik's lab used a type of imaging called cryo-electron microscopy
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(cryo-EM), that allows researchers to see atomic structure and study the molecular shapes
of proteins. But before Manglik's team could visualize the odorant receptor binding a scent
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molecule, they first needed to purify a sufficient quantity of the receptor protein.
Odorant receptors are notoriously challenging, some say impossible, to make in the lab for
such purposes.
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The Manglik and Matsunami teams looked for an odorant receptor that was abundant in
both the body and the nose, thinking it might be easier to make artificially, and one that also
could detect water-soluble odorants. They settled on a receptor called OR51E2, which is
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known to respond to propionate -- a molecule that contributes to the pungent smell of Swiss
cheese.

But even OR51E2 proved hard to make in the lab. Typical cryo-EM experiments require a
milligram of protein to produce atomic-level images, but co-first author Christian
Billesbøelle, PhD, a senior scientist in the Manglik Lab, developed approaches to use only
1/100th of a milligram of OR51E2, putting the snapshot of receptor and odorant within
reach.

"We made this happen by overcoming several technical impasses that have stifled the field
for a long time," said Billesbøelle. "Doing that allowed us to catch the first glimpse of an
odorant connecting with a human odorant receptor at the very moment a scent is detected."

This molecular snapshot showed that propionate sticks tightly to OR51E2 thanks to a very
specific fit between odorant and receptor. The finding jibes with one of the duties of the
olfactory system as a sentinel for danger.

While propionate contributes to the rich, nutty aroma of Swiss cheese, on its own, its scent
is much less appetizing.

"This receptor is laser focused on trying to sense propionate and may have evolved to help
detect when food has gone bad," said Manglik. Receptors for pleasing smells like menthol
or caraway might instead interact more loosely with odorants, he speculated.

Just a Whiff

Along with employing a large number of receptors at a time, another interesting quality of
the sense of smell is our ability to detect tiny amounts of odors that can come and go. To
investigate how propionate activates this receptor, the collaboration enlisted quantitative
biologist Nagarajan Vaidehi, PhD, at City of Hope, who used physics-based methods to
simulate and make movies of how OR51E2 is turned on by propionate.

"We performed computer simulations to understand how propionate causes a shape

change in the receptor at an atomic level," said Vaidehi. "These shape changes play a
critical role in how the odorant receptor initiates the cell signaling process leading to our
sense of smell."

The team is now developing more efficient techniques to study other odorant-receptor
pairs, and to understand the non-olfactory biology associated with the receptors, which
have been implicated in prostate cancer and serotonin release in the gut.

Manglik envisions a future where novel smells can be designed based on an understanding
of how a chemical's shape leads to a perceptual experience, not unlike how pharmaceutical
chemists today design drugs based on the atomic shapes of disease-causing proteins.

"We've dreamed of tackling this problem for years," he said. "We now have our first
toehold, the first glimpse of how the molecules of smell bind to our odorant receptors. For
us, this is just the beginning."

Funding: This work was supported by NIH grants R01DC020353, K99DC018333 and the
UCSF Program for Breakthrough Biomedical Research, funded in part by the Sandler
Foundation. Cryo-EM equipment at UCSF is partially supported by NIH grants
S10OD020054 and S10OD021741. For other funding, please see the paper.

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Public acceptance of fossil fuel subsidy removal

could be improved in developing countries

Date:
March 21, 2023
Source:
University of Gothenburg
Summary:
People might be more positive to the removal of fuel subsidies if told where the
money would be spent instead. This has been shown in a study which investigated
attitudes towards removing fossil fuel subsidies in five developing countries.

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People might be more positive to the removal of fuel subsidies if told

where the money would be spent instead. This has been shown in a
study from the University of Gothenburg, which investigated attitudes
towards removing fossil fuel subsidies in five developing countries.

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The countries of the world have agreed to take joint responsibility for reducing greenhouse
gas emissions and an increasing number have introduced, or are considering introducing, a
carbon tax. Figures from the OECD for example also show that in 2021 alone, 51 countries
provided tax relief in the form of fossil fuel subsidies -- at a cost of USD 697 billion. This
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was double that of the previous year and three times the amount needed to fight extreme
poverty globally each year.

"One of the most important measures by far to reduce carbon emissions is the removal of
fossil fuel subsidies. They encourage increased production and consumption of fossil fuels
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and are counter-productive for effective carbon pricing. Removing fossil fuel subsidies
would also free up public funds for investment in social and economic development,
especially in developing countries," says Niklas Harring, docent in political science.

Highest subsidies in developing countries

Many of the countries that subsidise the consumption of fossil fuels are in fact developing
countries. Removing subsidies on coal, gas and oil, for example, would result in
significantly higher costs for both business and private consumers.

"Transitioning to a fossil-free society is a huge challenge in many developing countries, and

increased fuel prices risk hitting the most vulnerable the hardest. The political feasibility of
removing fossil fuel subsidies very much depends on the extent to which the public accept
(or reject) such a change, and our study is the first to investigate this," says Sverker C.
Jagers, Professor of Political Science.

Niklas Harring and Sverker C. Jagers, together with colleagues at the University of
Gothenburg, Luleå Technical University and the University of Delaware, compared people's
attitudes to climate policy instruments in Ecuador, Egypt, India, Indonesia and Mexico.
These are some of the countries that currently subsidise their production and consumption
of fossil fuels the most. In the study involving close to 7,000 respondents, the researchers
looked at differences in attitudes to the introduction of a domestic carbon tax and to a
proposal to remove subsidies on fossil fuels.
"The respondents were as opposed to a carbon tax as they were to removing fossil fuel
subsidies," says Niklas Harring.

Importance of policy design

The researchers investigated whether the respondents' attitudes to removing subsidies on

fossil fuels for private consumption would change if told where the revenue would be used
instead -- termed revenue recycling. They formulated a policy proposal for the removal of
fossil fuel subsidies that was combined with examples of various investments that could be
made with the money instead: investments in welfare systems, income tax reductions,
investments in climate adaptation measures, and cash transfers to the poorest and most
affected households.

"The respondents who were told where the money would go instead turned out to be more
positive towards the proposal than those who were not given any information about
alternative revenue use. Climate adaptation measures were most likely to increase support
for the removal of fuel subsidies in Mexico and Ecuador, although this proposal did not
increase this support in Egypt, for example."

The results indicate that decision-makers should take country-specific circumstances into
account when designing policy proposals.
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"For us, it's important to understand why some policy proposals encounter public resistance
and not others, but also to better understand how policy design can help to influence
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people's attitudes towards climate policy. Our study shows that policy design can also play
a role," says Sverker C. Jagers.

Evolution of dinosaur body size through different

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developmental mechanisms
Date:
February 23, 2023
Source:
Ohio University
Summary:
The meat-eating dinosaurs known as theropods that roamed the ancient Earth
ranged in size from the bus-sized T. rex to the smaller, dog-sized Velociraptor.
Scientists puzzling over how such wildly different dinosaur sizes evolved recently
 found -- to their surprise -- that smaller and larger theropod dinosaurs like these
didn't necessarily get that way merely by growing slower or faster.

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FULL STORY

The meat-eating dinosaurs known as theropods that roamed the

ancient Earth ranged in size from the bus-sized T. rex to the smaller,
dog-sized Velociraptor. Scientists puzzling over how such wildly
different dinosaur sizes evolved recently found -- to their surprise- that
smaller and larger theropod dinosaurs like these didn't necessarily get
that way merely by growing slower or faster.

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In a new paper published in Science, "Developmental strategies underlying gigantism and

miniaturization in non-avialan theropod dinosaurs," researchers including Ohio University
professor Patrick O'Connor and Ph.D. student Riley Sombathy discovered through
examining the bones of dinosaurs that there was no relationship between growth rate and
body size.
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"Most animals are thought to evolve to be larger by growing faster than their ancestors, but
this study shows that it's just as likely that bigger and smaller animals grew for longer or
shorter periods of time during growth spurts," said Michael D. D'Emic, a paleontologist at
Adelphi University and lead author of the study.

The bones of many animals, including dinosaurs, slowed or paused growth every year,
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leaving marks like tree rings that indicate the animal's age and can be used to estimate the
rate of growth. "Rings like these are called cortical growth marks," said D'Emic. "Widely
spaced rings indicate faster growth and narrowly spaced rings tell us that an animal was
growing more slowly."
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D'Emic, O'Connor, Sombathy and a team of international researchers measured about 500
such growth rings in about 80 different theropod bones, the two-legged, mostly meat-eating
species of dinosaurs closely related to birds.
"We found that there was no relationship between growth rate and size," said D'Emic.
"Some gigantic dinosaurs grew very slowly, slower than alligators do today. And some
smaller dinosaurs grew very fast, as fast as mammals that are alive today." This made
sense to co-author Thomas Pascucci, whose graduate thesis contributed to the project:
"Extinct animals like dinosaurs inspire awe because of how different they seem from our
modern world, but they were animals that grew under similar constraints and environmental
factors as those that exist today."
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According to O'Connor, this study opens the door to future investigations of how animals
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regulate their growth. "Alteration of different growth control mechanisms, at molecular or
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genetic levels, likely accounts for the range of developmental strategies our team observed
in theropod dinosaurs. Future studies of living organisms provide an opportunity to
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elucidate mechanisms related to the evolution of body size in vertebrates more generally."

Sombathy hopes to take up some of those investigations, adding "One of the things that
interests me most about the results is the apparent decoupling between growth rate and
body size. My Ph.D. dissertation will investigate the impacts of growth rate and body size
on bone shape and function."

"This has really important implications because changes in rate versus timing can correlate
to many other things, like how many or how large your offspring are, how long you live, or
how susceptible to predators you are," D'Emic added. "Hopefully this research spurs
investigations into other groups, both alive and extinct, to see what developmental
mechanisms are most important in other types of animals."

In addition to O'Connor, Sombathy, and D'Emic, the paper was co-authroed by Ignacio
Cerda of Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) and
Universidad Nacional de Río Negro in Argentina, David Varricchio of Montana State
University; Diego Pol of CONICET-Museo Paleontológico Egidio Feruglio in Argentina,
Rodolfo Coria of Museo Carmen Funes in Argentina; and Kristina A. Curry Rogers of
Macalester College in Minnesota. The study was funded, in part, by the US National
Science Foundation and Adelphi University.
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Genome research: Origin and evolution of vine
Date:
March 20, 2023
Source:
Karlsruher Institut für Technologie (KIT)
 Summary:
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Cultivation and growth of grapevines have strongly influenced European
civilizations, but where the grapevine comes from and how it has spread across the
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globe has been highly disputed so far. In an extensive genome project, researchers
have determined its origin and evolution from the wild vine to today's cultivar by
analyzing thousands of vine genomes collected along the Silk Road from China to
Western Europe.

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FULL STORY

Cultivation and growth of grapevines have strongly influenced

European civilizations, but where the grapevine comes from and how it
has spread across the globe has been highly disputed so far. In an
extensive genome project, researchers from the Chinese Yunnan
Agricultural University have determined its origin and evolution from
the wild vine to today's cultivar by analyzing thousands of vine
genomes collected along the Silk Road from China to Western Europe.
The collection of wild vines of Karlsruhe Institute of Technology (KIT)
played an important role in the above project.

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Grapevine is among the world's oldest crops. Wine was one of the oldest products traded
all around the world. It pushed the exchange of cultures, ideas, and religions. At the end of
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the Ice Age, grapevine originated from the European wild vine, of which only a few relic
populations have survived to date.

One of these populations can be found on the Ketsch peninsula on the Rhine river between
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Karlsruhe and Mannheim. So far, the traces of when and where exactly wild vines were
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domesticated, of whether grapes for wine production and table grapes have the same
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origin, and how thousands of vines developed have been hidden in the mist of the
prehistoric era. Still, it is clear that grapevine survived partly drastic climate changes and
gathered a number of genes from Asia as a result of early human migration movements.
"For some years now, it has been known that today's Silk Road once was a wine road.
The Chinese symbol for alcohol is derived from Georgian wine jugs, so-called Qevri,"
explains Professor Peter Nick of KIT's Joseph-Gottlieb Kölreuter Institut for Plant Sciences
(JKIP). Nick, who had already cooperated with Chinese researchers in a previous project to
determine grapevine genomes, suggested to collect grapevines along the previous Silk
Road and to analyze their genomes.

Most Detailed Model of the Evolution and Domestication of Grapevine So Far

Nick's idea gave rise to a network of researchers from 16 countries, who contributed not
only wild vines and old species from their regions, but also knowledge on their origin and
history. Under most difficult circumstances resulting from the global political situation, DNA
samples of more than 3500 vines, including more than 1000 wild species, were sent to the
State Key Laboratory for Conservation and Utilization of Bio-Resources of Yunnan
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Agricultural University. There, the genomes were decoded under the direction of Dr. Wei
Chen and the most detailed model of the evolution and domestication of grapevines so far
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was generated. As a result, a number of new findings have been obtained. Now, the origin
of winegrowing can be dated back to earlier than 11,000 B.C. in the South Caucasus. This
means that wine is older than bread. Winegrowing technology very quickly spread across
the Mediterranean to the west. Within shortest terms, cross-breeding with local wild vines
produced a large variety of vines that were reproduced using cuttings. About 7000 years
ago in the Middle East, large-berry species developed to table vines.
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Domestication was accompanied by climatic changes, i.e. the end of the Ice Age, as well
as by the warm and moist Atlantic, a climate period between 8000 and 4000 B.C. The
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resulting human migration movements left their traces in the genome of the vines. Medieval
vines in Southwest Germany, for instance, contain genes of vines from Azerbaijan and
Central Asia