The study was published in the journal Development, and was conducted by physician-scientists and researchers at the UMSOM Department of Otorhinolaryngology Head and Neck Surgery and the UMSOM Institute for Genome Sciences (IGS), in collaboration with researchers at the Sackler School of Medicine at Tel Aviv University in Israel.

Hearing relies on the proper functioning of specialized cells within the inner ear called hair cells. When the hair cells do not develop properly or are damaged by environmental stresses like loud noise, it results in a loss of hearing function.

In the United States, the prevalence of hearing loss doubles with every 10-year increase in age, affecting about half of all adults in their 70s and about 80 percent of those who are over age 85. Researchers have been focusing on describing the developmental steps that lead to a functional hair cell, in order to potentially generate new hair cells when old ones are damaged.

Hair cells in the inner ear

To conduct her latest study, Dr. Hertzano and her team utilized cutting-edge methods to study gene expression in the hair cells of genetically modified newborn mice that did not produce GFI1. They demonstrated that, in the absence of this vital protein, embryonic hair cells failed to progress in their development to become fully functional adult cells. In fact, the genes expressed by these cells indicated that they were likely to develop into neuron-like cells.

“Our findings explain why GFI1 is critical to enable embryonic cells to progress into functioning adult hair cells,” said Dr. Hertzano. “These data also explain the importance of GFI1 in experimental protocols to regenerate hair cells from stem cells. These regenerative methods have the potential of being used for patients who have experienced hearing loss due to age or environmental factors like exposure to loud noise.”

Dr. Hertzano first became interested in GFI1 while completing her M.D., Ph.D. at Tel Aviv University. As part of her dissertation, she discovered that the hearing loss resulting from mutations in another protein called POU4F3 appeared to largely result from a loss of GFI1 in the hair cells. Since then, she has been conducting studies to discover the role of GFI1 and other proteins in hearing. Other research groups in the field are now testing these proteins to determine whether they can be used as a “cocktail” to regenerate lost hair cells and restore hearing.

“Hearing research has been going through a Renaissance period, not only from advances in genomics and methodology, but also thanks to its uniquely collaborative nature among researchers,” said Dr. Herzano.

The new study was funded by the National Institute on Deafness and Other Communication Disorders (NIDCD) which is part of the National Institutes of Health (NIH). It was also funded by the Binational Scientific Foundation (BSF).

“This is an exciting new finding that underscores the importance of basic research to lay the foundation for future clinical innovations,” said E. Albert Reece, MD, PhD, MBA, Executive Vice President for Medical Affairs, UM Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor and Dean, University of Maryland School of Medicine. “Identifying the complex pathways that lead to normal hearing could prove to be the key for reversing hearing loss in millions of Americans.”

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

Alcoholic cirrhosis can happen after years of drinking too much alcohol. According to the researchers, discovering more about this illness couldn’t come at a more important time.

“Based on U.S. data, alcohol-associated liver disease is on the rise in terms of the prevalence and incidents and it is happening more often in younger patients,” said Suthat Liangpunsakul, MD, professor of medicine, dean’s scholar in medical research for the Department of Medicine Division of Gastroenterology and Hepatology, and one of the principal investigators of the study. “There’s a real public health problem involving the consumption of alcohol and people starting to drink at a younger age.”

The team describes their findings in a new paper published in Hepatology. The GenomALC Consortium was funded by the National Institutes on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institute of Health (NIH). This genome-wide association study began several years ago and is one of the largest studies related to alcoholic cirrhosis ever performed. DNA samples were taken from over 1,700 patients from sites in the United States, several countries in Europe and Australia and sent to IU School of Medicine where the team performed the DNA isolation for genome analysis. The patients were divided into two groups — one made up of heavy drinkers that never had a history of alcohol-induced liver injury or liver disease and a second group of heavy drinkers who did have alcoholic cirrhosis.

“Our key finding is a gene called Fas Associated Factor Family Member 2, or FAF2,” said Tae-Hwi Schwantes-An, PhD, assistant research professor of medical and molecular genetics and the lead author of the study. “There’s this convergence of findings now that are pointing to the genes involved in lipid droplet organization pathway, and that seems to be one of the biological reasonings of why certain people get liver disease and why certain people do not.”

The researchers are anticipating to study this gene more closely and looking at its relationship to other, previously-discovered genes that can make a person more likely to develop alcoholic cirrhosis.

“We know for a fact those genes are linked together in a biological process, so the logical next step is to study how the changes in these genes alter the function of that process, whether it’s less efficient in one group of people, or maybe it’s inhibited in some way,” Schwantes-An said. “We don’t know exactly what the biological underpinning of that is, but now we have a pretty well-defined target where we can look at these variants and see how they relate to alcoholic cirrhosis.”

As their research continues, the team hopes to eventually find a way to identify this genetic factor in patients with the goal of helping them prevent alcoholic cirrhosis in the future or developing targeted therapies that can help individuals in a more personalized way.

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Materials provided by Indiana University School of Medicine. Original written by Christina Griffiths. Note: Content may be edited for style and length.

The group made the discovery at the 75-acre site of Tel Kabri in Israel, which contains the ruins of a Canaanite palace and city that dates back to approximately 1900-1700 B.C. The excavations, located on land belonging to Kibbutz Kabri in the western Galilee region, are co-directed by Assaf Yasur-Landau, a professor of Mediterranean archaeology at the University of Haifa, and Eric Cline, a professor of classics and anthropology at the George Washington University.

“We wondered for several years what had caused the sudden destruction and abandonment of the palace and the site, after centuries of flourishing occupation,” Yasur-Landau said. “A few seasons ago, we began to uncover a trench which runs through part of the palace, but initial indications suggested that it was modern, perhaps dug within the past few decades or a century or two at most. But then, in 2019, we opened up a new area and found that the trench continued for at least 30 meters, with an entire section of a wall that had fallen into it in antiquity, and with other walls and floors tipping into it on either side.”

According to Michael Lazar, the lead author of the study, recognizing past earthquakes can be extremely challenging in the archaeological record, especially at sites where there isn’t much stone masonry and where degradable construction materials like sun-dried mud bricks and wattle-and-daub were used instead. At Tel Kabri, however, the team found both stone foundations for the bottom part of the walls and mud-brick superstructures above.

“Our studies show the importance of combining macro- and micro-archaeological methods for the identification of ancient earthquakes,” he said. “We also needed to evaluate alternative scenarios, including climatic, environmental and economic collapse, as well as warfare, before we were confident in proposing a seismic event scenario.”

The researchers could see areas where the plaster floors appeared warped, walls had tilted or been displaced, and mud bricks from the walls and ceilings had collapsed into the rooms, in some cases rapidly burying dozens of large jars.

“It really looks like the earth simply opened up and everything on either side of it fell in,” Cline said. “It’s unlikely that the destruction was caused by violent human activity because there are no visible signs of fire, no weapons such as arrows that would indicate a battle, nor any unburied bodies related to combat. We could also see some unexpected things in other rooms of the palace, including in and around the wine cellar that we excavated a few years ago.”

In 2013, the team discovered 40 jars within a single storage room of the palace during an expedition also supported by a National Geographic Society grant. An organic residue analysis conducted on the jars indicated that they held wine; it was described at the time as the oldest and largest wine cellar yet discovered in the Near East. Since then, the team has found four more such storage rooms and at least 70 more jars, all buried by the collapse of the building.

“The floor deposits imply a rapid collapse rather than a slow accumulation of degraded mud bricks from standing walls or ceilings of an abandoned structure,” Ruth Shahack-Gross, a professor of geoarchaeology at the University of Haifa and a co-author on the study, said. “The rapid collapse, and the quick burial, combined with the geological setting of Tel Kabri, raises the possibility that one or more earthquakes could have destroyed the walls and the roof of the palace without setting it on fire.”

The investigators are hopeful that their methodological approach can be applied at other archaeological sites, where it can serve to test or strengthen cases of possible earthquake damage and destruction.