Obesity is considered to be a global public health concern, but experts still disagree about the precise origins and causes of rising obesity rates. One topic under debate is whether a person’s individual genetics and behaviors are more or less important than environmental factors, like socioeconomic status, in developing obesity.

In the new study, researchers estimated the impact of several factors on a person’s weight, including societal factors, like a person’s job type, as well as early life factors, like a person’s birth order, how they were delivered and whether their mother smoked or was obese. They looked specifically at whether a person was overweight, obese or severely obese at age 16 and age 42. They also looked at participants’ weight between ages 16 to 42, a range that spans the rise in obesity rates in the United Kingdom. The data came from the 1958 National Child Development Study, a long-term study that followed the lives of more than 17,000 people born in a single week in March 1958 across England, Scotland and Wales.

The analysis showed that if a mother was obese or if she smoked, her child was more likely to be obese or severely obese at each of the ages examined. The findings demonstrate that these early life factors can have a persistent effect on a person’s weight. Notably, these factors were just as powerful before and after the start of the rise in obesity rates in the UK, suggesting that the impact of individual factors, like behaviors, likely did not change during that time.

The results suggest that societal and early-life risk factors could be used to target obesity prevention programs for children and adults. The researchers also conclude that, since individual risk factors have not changed as obesity rates have risen, new studies are needed to identify societal factors that may have caused the current obesity pandemic.

The authors add: “Our research shows that the effect of maternal influences persists through to age 42 and that strikingly, those predictors were just as powerful (and prevalent) in the era before the current obesity pandemic began. This suggests that, as Geoffrey Rose pointed out, novel studies are needed of factors at the community/societal level that may have caused the current obesity pandemic, since individual-level risk factors appear not to have changed over the time period spanning the pandemic’s onset and growth.”

Peter Dempsey, PhD, professor of pediatrics-developmental biology in the CU School of Medicine, and Justin Brumbaugh, PhD, assistant professor of molecular, cellular, and developmental biology at CU Boulder, recently published a paper in the journal Nature Cell Biology showing the importance of the H3K36 methylation process in regulating plasticity and regeneration in intestinal cells.

“The intestine has an enormous ability to regenerate itself after injury, and it does this through a model of dedifferentiation,” Dempsey explains. “The cells dedifferentiate back into a type of regenerative stem cell after injury, and those stem cells eventually recover the intestine and turn back to normal cells.”

Finding the switch

Scientists have been looking for a long time for the “switch” that turns regular intestinal cells back into regenerative stem cells, Brumbaugh says. Using animal models, he, Dempsey, and the rest of their research team found that H3K36 methylation — a biochemical process that occurs within the H3 histone protein — is responsible for turning that plastic state on and off. Their research was funded by a grant from the CU Cancer Center.

“If you think about it, those cells that are normally in the intestine have to maintain their identity so they’re functional,” Brumbaugh says. “You have to be sure that they don’t flip when they’re not supposed to, because you lose their specialized function — which is also a hallmark of cancer. There has been other research on histone modifications, because epigenetics makes sense to study in this context. It makes sense that you have this form of regulation that will prevent reversion and lock in cell fate.”

Next steps

With H3K36 methylation identified as the process responsible for the switch between normal cells and regenerative cells, the researchers say the next step is to look for ways to target the process to turn it off or on as needed to treat colorectal cancer and intestinal conditions that can lead to cancer.

“H3K36 methylation seems to be directly involved in differentiating the cells, but if you take it away, the cells revert to this regenerative stem cell state,” Dempsey says. “That regenerative state is important when you have injury and repair, but there also are certain colorectal cancers that have exactly this regenerative gene signature. Chronic colitis, inflammatory bowel disease, is a repetitive injury system, and leads to a higher risk of colorectal cancer. We think we have a mechanism that could be directly applied to those types of cancers, and that’s something we want to study.”

Outside of colon cancer, the methylation process also may have implications for resistance to chemotherapy and radiation, Dempsey says.

“When the cells switch into this regenerative stem cell state, they become more resistant to certain treatments, and that’s a problem,” he says. “If you have a patient who’s not a colon cancer patient but is undergoing chemotherapy or radiation therapy, one of the side effects of those therapies is that you get destruction of intestinal stem cells. In some patients, if it’s not dosed correctly, you can actually strip the whole lining of the intestine. If you could understand how to turn that state back on, you may be able to get the cells to be more protected.”

Future applications

Brumbaugh emphasizes that the recently published research is just the first step in understanding a process that could have a significant role in treating diseases in the future.

“As stem cell biologists, we want to understand the nuts and bolts of this process, because if you do, then you can manipulate it,” he says. “You might want to manipulate it for drug testing, for disease modeling — even if it’s not something where we have a direct therapy that we’re applying to patients, if we can understand how a disease works, then that provides options and opportunities to inform therapies.

“This would be far off in the future, but creating certain cell types for transplantation therapies is something that is very exciting in the stem cell arena,” he adds. “We’re not anywhere close to that, but if you understand how to manipulate the process, you can start thinking about these types of things.”

Now, applied physicists at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) have invented a new type of interferometer that allows precise control of light’s frequency, intensity and mode in one compact package.

Called a cascaded-mode interferometer, it is a single waveguide on a silicon-on-insulator platform that can create multiple signal paths to control the amplitude and phase of light simultaneously, a process known as optical spectral shaping. By combining mechanisms to manipulate different aspects of light into a single waveguide, the device could be used in advanced nanophotonic sensors or on-chip quantum computing.

Published in Science Advances, the research was led by postdoctoral fellow Jinsheng Lu, who works in the lab of Federico Capasso, the Robert L. Wallace Professor of Applied Physics and Vinton Hayes Senior Research Fellow in Electrical Engineering. Federal support for the work included award No. FA9550-23-1-0699 from the Air Force Office of Scientific Research under. Devices were made at Harvard’s Center for Nanoscale Systems, supported by the National Science Foundation under award No. ECCS-2025158.

“Conceptually, this is a very big step forward compared to the state of the art for commercial high-speed modulators that are particularly used for communications,” Capasso said.

The most widely used such devices, known as Mach-Zehnder interferometers, work by splitting a beam of light down two paths to toggle its output. Despite their widespread use, Mach-Zehnder interferometers have their limitations — they are not very good at simultaneously controlling different aspects of light. Today, multiple interferometers are needed in succession to make up for these limitations, taking up space and restricting the amount of signal that can travel through.

The new cascaded-mode interferometer is a reimagining of a Mach-Zehnder device integrated into a single-chip waveguide. Rather than the traditional split beam, the new interferometer has a unique, nanoscale pattern of gratings etched into the waveguide that control the energy exchange between different modes of light.

This makes the new interferometer able to control the spectrum of light passing through by finely adjusting the intensity and characteristics of different colors. Light can move through in different patterns, or transverse modes. And the device allows for precise, sharp lines of color, or light waves with distinct features.

In the paper, the team not only demonstrates the capabilities of their new interferometer but also lays out the theoretical framework for extending the physics of the device to many different modes of light.