A team led by University of Alabama at Birmingham researcher Charitharth Vivek Lal, M.D., found that a human fetal microbiome DNA signature is present in lungs as early as the first trimester. This fetal lung microbiome showed changes in diversity during fetal development, suggesting microbiome maturation with advancing gestational age. Finally, a placental microbiome was also present in human fetal tissue, and this microbiome signature showed some taxonomic overlap with the corresponding human fetal lung microbiome.

“We speculate that maternal-fetal microbial DNA transfer — and perhaps of other microbial products and whole live or dead bacteria — is a realistic possibility,” said Lal, an associate professor in the UAB Pediatrics Division of Neonatology. “This may serve to ‘prime’ the developing innate immune system of the fetus and help in establishment of a normal host-commensal relationship.”

Denise Al Alam, Ph.D., investigator in The Saban Research Institute of Children’s Hospital Los Angeles and assistant professor of pediatrics at University of Southern California, is the first-author who spearheaded the concept of the study, which is published in the American Journal of Respiratory and Critical Care Medicine.

Study details

Researchers, including Lal and colleagues, have previously seen that the lungs of infants, sampled immediately after birth, are colonized with bacteria. Furthermore, similar microbiome profiles are found after either cesarean or vaginal delivery, which suggested that microbes somehow are able to reach the lungs before birth.

In the new study, 31 samples of lung, placenta and intestine tissue from fetuses between 11 and 20 weeks of gestation were collected. Duplicate, independent tests done in labs at Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, and at UAB detected bacterial DNA in all samples. The two labs used different DNA extraction kits and different microbiome analysis pipelines.

Bacterial DNA was detected through targeted analysis of the bacterial gene for 16S ribosomal RNA, which is a standard method to distinguish different microbial taxa. The initial 16S analysis in Singapore showed 48 unique taxa in the lung samples, 11 unique taxa in placenta samples and 24 shared taxa.

The 16S analysis of the same samples at UAB showed two separate human fetal lung microbiome groups, based on fetal age — one group at 11 to 15 weeks’ gestation, and the other at 16 to 20 weeks’ gestation. Furthermore, the two gestational age groups showed a significant change in microbiome diversity with time.

“Overall, at both lab sites,” Lal said, “analysis of the bacterial taxa distribution and diversity showed some overlap in microbiome signatures of fetal lungs and matched placentas.”

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Materials provided by University of Alabama at Birmingham. Original written by Jeff Hansen. Note: Content may be edited for style and length.

The leaders behind this work agree that ambitious goals are important if humanity is going to avoid the worst effects of climate change. However, a new paper in Conservation Letters has generated the first comprehensive data set that describes how countries are doing so far — and it’s not looking good. The paper looked at 62 countries that have made restoration commitments, and reports that 54 percent of the Bonn Challenge’s goal area for 2020 has not yet been pledged. It then digs into the data to understand why some countries are doing better than others, and what could help those that are struggling.

Aiming high

The authors found that most of the gap between goals and reality exists in the global South, a group of nations generally south of the equator previously referred to as developing countries. These are also the countries that pledged to restore the greatest amounts of land, the paper reports. For example, Rwanda pledged to restore 81 percent of its total land area, and Burundi pledged 79 percent. One-third of the countries pledged greater than 10 percent of their total area, which would require significant shifts in land use and food production.

The authors hypothesize multiple reasons for the large pledges from global South countries. “It could be that global South countries are more aware of the risks they face from climate change, and are therefore more interested in doing something about it,” says Matthew Fagan, assistant professor of geography and environmental systems at UMBC and lead author on the paper. “They also generally have lower labor and land costs, making it easier for them to do restoration.” On the other hand, they could be trying to access more dollars from international donor organizations to reach these aspirational goals, or could have underestimated the challenges of restoration at that scale.

The paper also attempted to predict which countries would have the greatest difficulty meeting their goals based on a dozen factors the team analyzed, such as population growth, government corruption, and previous deforestation rates.

Justin Drew ’20, computer science, and a co-author on the paper, compiled the data for all 12 factors by writing computer code to pull quantitative information from public international databases. He also scoured the internet for information on individual countries’ progress. Drew collected reliable information on the 12 factors for all 62 countries making restoration commitments, and progress information for 12 of them. “When we asked how they did based on these twelve factors, we found they did about as well as we expected,” says Fagan. Countries with the lowest combined score considering all the implementation factors tended to be farther from meeting their goals.

Local engagement

But all is not lost. “We’ve identified countries that need help” to achieve their ambitious environmental goals, says Fagan. “It’s clear that there’s a whole set of countries that are facing headwinds, and if we expect them to be able to accomplish their goals, then the international community needs to support them.”

Increased financial aid is important, but so are other means of support. That might mean providing technical tools and training to help governments and local communities make informed decisions about restoration efforts. Above all, it means listening to local communities’ needs and working in collaboration to create solutions.

“Restoration efforts have a better chance of achieving sustained improvement when local communities have a voice early in the process, feel empowered to participate actively throughout, and can experience direct and long-term benefits from these efforts,” says Maggie Holland. She is an associate professor of geography and environmental systems at UMBC and a co-author on the paper.

In one location, the best solution might be planting trees on agricultural land, such as shade-grown coffee. Other places, it might be tree plantations, reclaiming agricultural land for forest, or thinning existing forests to prevent fires.

“Different efforts will yield different benefits for mitigating climate change, for helping people, for restoring ecosystem health and conserving biodiversity,” Holland says. She suggests that more social science research on the results of different strategies is needed to deploy them most effectively.

There are other, less direct, efforts that can also have a huge effect on forests. “Even if countries haven’t necessarily made big strides in restoration, in some cases they’re making big policy changes that will hopefully result in restoration in the longer term,” Fagan says. For example, bringing electricity to more rural communities reduces the need for fuel wood and charcoal. That reduces forest loss while also improving human health by removing smoke from homes.

Investing in the foundation

Ultimately, the researchers argue that while it may sound good to pledge huge areas of land, that might not be the best strategy to reach the goals of combating climate change, improving people’s lives, and protecting species from extinction. If countries feel pressured to meet their ambitious goals, they might employ the easiest restoration strategies, such as thinning forest. The U.S., for example, has already met its goal of 15 million hectares, and the vast majority of it was through this method. That may have some beneficial effects, like decreasing the chance of forest fires, but it’s not the same as planting trees on agricultural land or shifting land use patterns.

In addition to supporting countries in need, “I think the wealthier countries need to get on this bandwagon and do more themselves as well,” Fagan says. Ambitious, but realistic, and locally appropriate goals are the best way to succeed, Fagan and Holland agree.

Overall, Fagan is “guardedly optimistic.” “There’s a lot of potential and a lot of interesting policy work going on. I believe, though, that there’s a time to build your castles in the air, and now it’s time to put foundations under them. We’re underinvesting in the foundations, and we need to spend more international aid money on helping countries figure out how to meet these commitments,” he says.

“I’d like to hope that this article helps generate more support for that kind of work,” Fagan shares, “because I think it is possible to make this kind of change.”

Since so-called boronic acid derivatives are very versatile and reliably applicable in their variants, chemists often use them to build up important carbon-carbon couplings (C-C couplings). The most important process using boronic acid derivatives is the Nobel Prize-winning Suzuki-Miyaura coupling. Also widely used in synthesis are the so-called allylboronic esters, which also belong to this class of boron compounds.

In their current study, the chemists headed by Prof. Armido Studer of the Organic Chemical Institute at Münster University are now presenting C-C couplings in which the boron unit from the starting material is retained in the product. The scientists use methods of so-called radical chemistry for this purpose. The principle works like this: The boron unit “migrates” from one carbon atom to the neighbouring atom, thus enabling a second C-C coupling.

Using this method, the chemists can gradually incorporate individual building blocks of molecules at different points in the basic structure. “Since the boron unit remains in the product molecule, i.e. is ‘preserved’, it can be replaced by another molecular unit, which can be done using the entire spectrum of industrial methods. The commercially available allylboronic esters thus appear in a new guise,” says Armido Studer, the lead author of the study. The new method may in future be relevant for the production of drugs. In the future, the new method may be relevant for the production of pharmaceuticals, among other things.

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Materials provided by University of Münster. Note: Content may be edited for style and length.

Conventional wisdom renders there’s one circuit in the brain that suppresses eating — it comes from the stomach and makes you feel sick if you activate it too hard. Eating a portioned meal makes your body happy, though, even while stimulating a signal to the brain to stop eating, according to Michigan Diabetes Research Center’s director, Martin Myers Jr., M.D. Ph.D.

“Therefore, there must be a circuit that stops normal feeding without the adverse effects, right?” says Myers.

Now, a Cell Metabolism study may have discovered this second circuit in mice. Myers, Randy Seeley, Ph.D, the director of the Michigan Nutrition Obesity Research Center, and a team of researchers sought to better understand which part of the brain curbs appetite and which neurons play a role in making mice want to eat or not eat.

The gut-brain signal that suppresses appetite is triggered by a type of neuron, containing calcitonin receptor (CALCR), which lives in a structure of the hindbrain called the medulla. Interestingly enough, these neurons didn’t need to be active in the brain for gut sickness to cause an aversive response.

“This suggested we might be able to dissociate the brainstem systems that stop feeding from those that cause nausea,” says Myers, whose group found they could genetically activate those CALCR neurons to do just that.

Singling out the responsible neuron

Since there are neurons that can suppress eating but also cause aversive effects, that must mean there are different types of neurons, or circuits, in the brain that can terminate feeding with differing emotional responses.

When the researchers inactivated the CALCR neurons, they were surprised to make another discovery, which contradicted the idea that the brain only controls short term meal sizes and consumption.

Turning these neurons “off” didn’t only interfere with the suppression of feeding by gut signals, but it also caused an ongoing increase in food intake. The mice became obese, suggesting that the brainstem systems don’t only control meal size, but the amount of food consumed long term. This created a predisposition to obesity because of the energy imbalance in the mice (more input than output).

Similarly, activating CALCR neurons decreased the mice’s food intake and body weight without any aversive gut effects. In the study, Myers and his team found another neuron, CCK, also decreased food intake and body weight but created an aversive internal response, unlike the CALCR neurons. The difference between the two neurons were found in their circuits.

“CCK activates what we would call a ‘yucky circuit’,” says Myers. “The neurons activate a certain cell, CGRP cells, which create that sick feeling.” Unlike CCK, activated CALCR neurons follow a “yummy circuit,” activating non-CGRP cells.

Potential implications in humans

Obesity affects more than one-third of the adult population in developed countries, which can lead to diabetes or other serious, long-term health conditions like heart disease, explains Myers, who is also the director of MDiabetes.

Unfortunately, many diet drugs work, but they make people feel nauseous after they take them. Obesity remains a condition difficult to pharmaceutically manage, since the treatment options have limited therapeutic utility. A drug that turns “on” CALCR and turns off “CGRP” could greatly benefit patients with obesity by suppressing feeding and creating a long term control of food intake and body weight.

“If we could figure out a drug for individuals with obesity that suppresses food intake to produce long term weight loss without the negative side effects, it could absolutely change someone’s life,” says Myers.

Some of the most critical decision-making steps taken by airlines across the world rely on tools that do not fully incorporate passengers’ preferences and the dynamics of flight scheduling, resulting in missed profits and unsatisfied passengers, according to the authors. The new paper uses 2016 data from Alaska Airlines to introduce an original integrated optimization approach to comprehensive flight timetabling and fleet assignment while taking into consideration passengers’ preferences, such as flight departure time.

“Beyond ticket prices, perhaps the biggest thing that air passengers care about is the convenience of flight schedule. Yet, due to the associated computational complexities, nobody has really tried to completely redesign an airline’s flight schedule from scratch to take passenger preference into account,” said co-author Vikrant Vaze, assistant professor of engineering at Dartmouth. “This paper does just that, by proposing a comprehensive mathematical model and a new algorithm to solve it. It aligns the flight schedules to passenger preferences, in turn maximizing airline profits.”

The model’s flexible and comprehensive approach would enable airlines to increase the number of passengers with one-stop itineraries, and, consequently, dramatically increase the total one-stop revenue and the total operating profit compared with the most advanced approaches currently used in the industry. In addition, the paper suggests that an airline using this approach would experience a significant increase in market share.

First author Keji Wei, who was an engineering PhD candidate at Dartmouth while working on the study, received the Anna Valicek Award at the Airline Group of the International Federation of Operational Research Societies (AGIFORS) Symposium last fall for his work on this paper. Wei is now a senior operations research analyst at Sabre Corporation, a leading technology solutions provider to the travel industry.

In addition to Wei and Vaze, the paper was co-authored by Alexandre Jacquillat, an assistant professor of operations research and statistics at the MIT Sloan School of Management.

The authors note that the paper doesn’t consider factors such as business strategy and aircraft orders because the data is not available, as well as airport gate and slot availability for simplicity’s sake. However, the approach is designed to be versatile and usable for a variety of strategic planning decisions made by major airlines with a realistic computational budget.

Vaze is currently working on a follow-up paper that will incorporate revenue management considerations into scheduling and fleet assignment.

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Materials provided by Thayer School of Engineering at Dartmouth. Original written by Julie Bonette. Note: Content may be edited for style and length.