In multiple sclerosis, inflammation spurs the immune system to strip away the protective myelin coating around nerve fibers in the brain’s cortex, hampering electrical signals sent and received by the brain. Atrophy of the cortex in MS patients is associated with permanent worsening of disability, such as cognitive decline, visual impairment, weakness and sensory loss.

No currently available treatments for MS can repair damage to myelin. Instead, these treatments target inflammation to reduce symptom flare-ups and new nerve tissue scarring. Previous UCLA-led research found that estriol, a type of estrogen hormone produced in pregnancy, reduced brain atrophy and improved cognitive function in MS patients.

In the new study, researchers treated a mouse model of MS with estriol and found that it prevented brain atrophy and induced remyelination in the cortex, indicating that the treatment can repair damage caused by MS, rather than just slow the destruction of myelin.

This is the first study to identify a treatment that could repair myelin in the cortex, undoing some of the damage caused by MS.

Allan MacKenzie-Graham, an associate professor of neurology, is the study’s corresponding author. Other authors include Cassandra Meyer, Andrew Smith, Aitana A. Padilla-Requerey, Vista Farkhondeh, Noriko Itoh, Yuichiro Itoh, Josephine Gao, Patrick Herbig, Quynhanh Nguyen, Katelyn Ngo, Mandavi Oberoi, Prabha Siddarth and Rhonda R. Voskuhl, all of UCLA.

Dr Ashleigh Wiseman has 3D-modelled the leg and pelvis muscles of the hominin Australopithecus afarensis using scans of ‘Lucy’: the famous fossil specimen discovered in Ethiopia in the mid-1970s.

Australopithecus afarensis was an early human species that lived in East Africa over three million years ago. Shorter than us, with an ape-like face and smaller brain, but able to walk on two legs, it adapted to both tree and savannah dwelling — helping the species survive for almost a million years.

Named for the Beatles classic ‘Lucy in the Sky with Diamonds’, Lucy is one of the most complete examples to be unearthed of any type of Australopithecus — with 40% of her skeleton recovered.

Wiseman was able to use recently published open source data on the Lucy fossil to create a digital model of the 3.2 million-year-old hominin’s lower body muscle structure. The study is published in the journal Royal Society Open Science.

The research recreated 36 muscles in each leg, most of which were much larger in Lucy and occupied greater space in the legs compared to modern humans.

For example, major muscles in Lucy’s calves and thighs were over twice the size of those in modern humans, as we have a much higher fat to muscle ratio. Muscles made up 74% of the total mass in Lucy’s thigh, compared to just 50% in humans.

Paleoanthropologists agree that Lucy was bipedal, but disagree on how she walked. Some have argued that she moved in a crouching waddle, similar to chimpanzees — our common ancestor — when they walk on two legs. Others believe that her movement was closer to our own upright bipedalism.

Research in the last 20 years have seen a consensus begin to emerge for fully erect walking, and Wiseman’s work adds further weight to this. Lucy’s knee extensor muscles, and the leverage they would allow, confirm an ability to straighten the knee joints as much as a healthy person can today.

“Lucy’s ability to walk upright can only be known by reconstructing the path and space that a muscle occupies within the body,” said Wiseman, from Cambridge University’s McDonald Institute for Archaeological Research.

“We are now the only animal that can stand upright with straight knees. Lucy’s muscles suggest that she was as proficient at bipedalism as we are, while possibly also being at home in the trees. Lucy likely walked and moved in a way that we do not see in any living species today,” Wiseman said.

“Australopithecus afarensis would have roamed areas of open wooded grassland as well as more dense forests in East Africa around 3 to 4 million years ago. These reconstructions of Lucy’s muscles suggest that she would have been able to exploit both habitats effectively.”

Lucy was a young adult, who stood at just over one metre tall and probably weighed around 28kg. Lucy’s brain would have been roughly a third of the size of ours.

To recreate the muscles of this hominin, Wiseman started with some living humans. Using MRI and CT scans of the muscle and bone structures of a modern woman and man, she was able to map the “muscle paths” and build a digital musculoskeletal model.

Wiseman then used existing virtual models of Lucy’s skeleton to “rearticulate” the joints — that is, put the skeleton back together. This work defined the axis from which each joint was able to move and rotate, replicating how they moved during life.

Finally, muscles were layered on top, based on pathways from modern human muscle maps, as well as what little “muscle scarring” was discernible (the traces of muscle connection detectable on the fossilised bones). “Without open access science, this research would not have been possible,” said Wiseman.

These reconstructions can now help scientists understand how this human ancestor walked. “Muscle reconstructions have already been used to gauge running speeds of a T-Rex, for example,” said Wiseman. “By applying similar techniques to ancestral humans, we want to reveal the spectrum of physical movement that propelled our evolution — including those capabilities we have lost.”

But the bacteria can sometimes change their behavior and enter the bloodstream, causing chronic localized infections to become acute and potentially fatal. Despite decades of studying the transition in lab environments, how and why the switch happens in humans has remained unknown.

However, researchers at the Georgia Institute of Technology have identified the major mechanism behind the transition between chronic and acute P. aeruginosa infections. Marvin Whiteley — professor in the School of Biological Sciences and Bennie H. and Nelson D. Abell Chair in Molecular and Cellular Biology — and Pengbo Cao, a postdoctoral researcher in Whiteley’s lab, discovered a gene that drives the switch. By measuring bacterial gene expression in human tissue samples, the researchers identified a biomarker for the transition.

Their research findings, published in Nature, can inform the development of future treatments for life-threatening acute infections.

According to Whiteley and Cao, bacteria, like animals, are versatile and behave differently depending on their environment. A person with a chronic infection might be fine one day, but environmental changes in the body can cause bacteria to change their behavior. This can lead to acute infection, and a person could develop sepsis that requires immediate treatment.

“For years, people have been studying these bacteria in well-controlled lab environments, even though the lab is a place most microbes have never seen,” said Whiteley. “Our study took a novel approach to look directly into the bacterium’s behavior in the human host.”

The researchers chose to look at human tissue samples of chronic bacterial lung and wound infections. Using genetic sequencing technologies, Whiteley and Cao measured the levels of all types of mRNA present in the bacteria. The mRNAs encode the proteins that do all the work in a cell, so by measuring a bacterium’s mRNA level, one can infer the bacterium’s behavior.

While P. aeruginosa has roughly 6,000 genes, Whiteley and Cao found that one gene in particular — known as PA1414 — was more highly expressed in human tissue samples than all the other thousands of genes combined. The levels were so high that, at first, Cao and Whiteley thought the amount of PA1414 mRNA might be an artifact — a glitch associated with the sequencing methods.

“This particular gene is not expressed in the standard lab environment very much, so it was striking to see these levels,” Cao said. “And at this point, the function of the gene was unknown.”

The researchers also found that low oxygen drives the high expression of the gene. This is a common environmental characteristic of bacterial infections, as bacteria frequently encounter oxygen deprivation during chronic infections. Further tests showed that the gene also regulates bacterial respiration under low oxygen conditions.

Interestingly, the researchers found that rather than encoding a protein, the gene encodes a small RNA that plays a vital role in bacterial respiration. They named the small RNA SicX (sRNA inducer of chronic infection X).

The researchers then tested the functions of the gene in different animal infection models. They observed that when SicX wasn’t present, the bacteria easily disseminated from chronic infections throughout the body, causing systemic infection. The comparison allowed the researchers to determine that the gene is important for promoting chronic localized infection. Moreover, researchers also showed that the expression of SicX immediately decreased during the transition from chronic to acute infection, suggesting SicX potentially serves as a biomarker for the chronic-to-acute switch.

“In other words, without the small RNA, the bacteria become restless and go looking for oxygen, because they need to breathe like we need to breathe,” Whiteley said. “That need causes the bacteria to enter the bloodstream. Now, we know that oxygen levels are regulating this transition.”

Having a better indication of when an infection might enter the bloodstream would be a paradigm shift for treatments.

“If you can predict when an acute infection will occur, a patient could take a diagnostic test at home to determine if and when they may need to get treatment — before the infection becomes life-threatening,” Whiteley said.

The study provides answers to the long-standing questions about how and why chronic infections become acute. The researchers’ findings also open opportunities to develop therapeutics that target this specific molecular behavior associated with P. aeruginosa infections.

“The chronic Pseudomonas infection is usually highly resistant to first-line antibiotics,” Cao said. “By targeting this small RNA, we could potentially change the lifestyle of the bacteria to make it more susceptible to antibiotic treatments and achieve greater clearance of these dangerous infections.”

“In the past, marital conflict has always been considered a negative thing in reference to various aspects of child development. But what’s more important than having conflict is how people deal with it. Our study looked at whether constructive conflict resolution could buffer some of the negative influence of marital conflict on parenting practices,” said lead author Qiujie Gong, a doctoral student in the Department of Human Development and Family Studies (HDFS) in the College of Agricultural, Consumer and Environmental Sciences at Illinois.

Some studies have shown father-child relationships may be more impacted by conflict than mother-child relationships, and can lead to negative development for kids. That’s why the authors chose to focus on fathers in their study.

“We wanted to pay more attention to fathers, because while mothers have always been considered the main caregiver, fathers can also significantly influence children’s development,” Gong said.

The authors, including HDFS professors Karen Kramer and Kelly Tu, accessed a longitudinal dataset from the U.S. Department of Education tracing children’s experiences from 9 months to kindergarten. Recognizing the importance of the preschool years for learning socioemotional skills, they analyzed the subset of data for families with 4-year-olds and, controlling for mother’s parenting styles, honed in on fathers’ responses to survey questions about marital conflict and resolution strategies. Building links in a chain, they connected fathers’ reports of conflict to their parenting practices, then to the socioemotional impacts of those practices on children.

“Beyond looking separately at mothers, fathers, and conflict, as previous studies have done, we put it all together in one model, not only to see the family as an interconnected system but also to not forget the father: How his perceptions of conflict and approaches to resolution affect child socioemotional development,” said Kramer. “That’s the uniqueness of this study.”

Analyzing a diverse sample of 3,955 heterosexual families with resident fathers, the authors found when fathers reported more frequent marital conflict, it increased their parenting stress and decreased their warmth toward their child. According to the analysis, those factors then decreased the child’s socioemotional skills reported by mothers in the surveys.

Gong emphasizes preschool-age children are at a crucial stage for developing socioemotional skills. These early experiences set the stage for later peer relationships, mental health, and more, so parents of small children should consider how their interactions may spill over to their kids, she says.

Next, Gong factored in how fathers resolved conflict.

“We found fathers who reported using more constructive conflict resolution — like open communication and reaching compromise, as opposed to hitting, criticizing, or throwing things — showed more involvement and warmth toward their kids, compared to their counterparts,” she said.

Not surprisingly, children benefited from these warmer interactions with their dads.

“Fathers using constructive conflict resolution led to more parental involvement, which led to more positive child development,” Kramer said. “Destructive conflict has the opposite effect on kids.”

In the end, Gong says parents shouldn’t shy away from conflict. Instead, what’s more important is to find constructive resolution strategies that minimize stress and maintain a father’s ability to interact warmly with his children.

“If we could have more clinical or educational programs that teach parents how to openly communicate with each other, how to listen to each other, and maintain good relationships with family members, it might be effective in promoting healthier family and child development,” Gong said. “It’s also important to not only consider the amount of parenting, but the quality of parenting. Even if fathers have a lot of involvement, if their warmth is super low, that might not be beneficial for the child.”

Kramer adds that although the study focused exclusively on married couples, fathers in other family arrangements can still learn from the study.

“These lessons don’t only apply to married couples. In fact, I would say they are even more important when you are not living together, or you’re separated or divorced,” she said. “You might have even more conflict in those cases, so the process of solving it might be even more important to the development of the child.”