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Bacteria Use Different Strategies To Divide And Survive Under Stress

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Under laboratory conditions, many common bacteria reproduce and divide into symmetrical halves. In the real world with limited resources, however, conditions aren’t always ideal for this kind of carefully planned growth.

A new study by scientists from the University of Chicago shows how cyanobacteria (bacteria that produce energy through photosynthesis like plants) change the way they grow and divide in response to different levels of light. With typical light conditions, the cells remain relatively short and divide symmetrically. But as light dims, the cells grow longer and divide unevenly, resulting in two daughter cells of different lengths. The researchers believe this may be a survival strategy that evolved to help these bacteria survive in less than ideal conditions.

“In the real world, most bacteria are living in some growth limited, nutrient poor condition and they just get an occasional puff of something they can eat,” said Michael Rust, PhD, associate professor of molecular genetics, cell biology and physics, and senior author of the study.

“Probably what evolution is selecting for is the ability to tolerate starvation for a long time and use those rare resources as efficiently as possible.”

In the new study, featured as the cover article in the latest issue of Cell Systems, Rust and Yi Liao, PhD, a postdoctoral researcher in his lab, used time-lapse imaging to track cell division in Synechococcus elongatus, a rod-shaped cyanobacterium. The researchers saw that under dim light conditions, which cause stress for cells by limiting their energy source, the S. elongatuscells grow longer than usual. When the lights are turned back up, cells shorter than eight micrometers still divide symmetrically, but above this length the divisions become uneven, typically producing one short daughter (about three micrometers) and a longer one.

In many bacteria, the position where a mother cell splits into two is controlled by something called the Min system, a group of proteins that moves around inside the cell. In a typical short cell, one of the proteins, MinC, pools in one end and then every few minutes moves to the opposite end. As they bounce back and forth, the MinC proteins spend more time at the ends and less at mid-cell, like squeezing a water balloon in the middle and wiggling it back and forth. Since MinC inhibits cell division, this oscillation creates a sort of weak point in the middle where the cell can divide.

To see whether the Min system is also responsible for asymmetric divisions seen in longer cells, Liao and Rust tagged the MinC protein with a fluorescent marker that lets them follow its movements. They found that the Min system exhibits different patterns depending on the cell length. The proteins kept up a characteristic, back-and-forth oscillatory pattern in short cells, but they formed a variety of dynamic patterns in longer cells, including multi-band oscillations, traveling waves, and other more complex patterns. In all of these patterns in long cells, a region without MinC was always seen about three micrometers from the end of the cell, allowing cells to divide off-center and make a short daughter of a specific size.

“We think the patterns change because it’s geometrically sensitive, so it can adapt to a changing cell size,” Liao said.

“The ability to form these different patterns allows both shorter cells to divide symmetrically and longer cells to produce short daughter cells.”

Rust and Liao said they aren’t sure why bacteria divide into different lengths under stressful conditions or whether one length provides an advantage over another. It could be that smaller cells are able to maneuver better to find resources. Elongating themselves could give the cell more surface area to absorb light in dim conditions. There is even evidence that length is a defense mechanism for pathogens, because it’s harder for an immune cell to engulf a really long bacterial cell.

Either way, Rust said understanding how bacteria grow and divide under real world conditions could help strategies for using antibiotics. For example, cells might need to be a certain length to be able to infect someone, or they just elongate themselves and don’t divide as a way of riding out the tough times. Researchers could use this to their advantage and design ways to interfere with the Min system and disrupt the bacteria’s tricks for survival.

“There’s this whole hidden world of the biology of suboptimal conditions,” Rust said.

“We can understand how organisms are growing and thriving in difficult circumstances that may unveil new rules of how life behaves.”

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Hypertonic Saline May Help Babies with Cystic Fibrosis Breathe Better

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Nov. 9, 2018─Babies with cystic fibrosis may breathe better by inhaling hypertonic saline, according to a randomized controlled trial conducted in Germany and published in the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine.

In “Preventive Inhalation of Hypertonic Saline in Infants with Cystic Fibrosis (PRESIS): A Randomized, Double-blind, Controlled Study,” Mirjam Stahl, MD, and  co-authors describe a study of 40 young infants (average age three months at enrollment) with CF. The babies were randomly assigned to receive either hypertonic saline (saline with a 6 percent salt concentration) or isotonic (.9 percent) saline. They were followed for 12 months.

Previous studies in mice found that the salt content of hypertonic saline decreased mucous plugging that can lead to airway obstruction and repeated infections. Other studies found hypertonic saline benefited older infants and children with CF.

 “Several studies from teams worldwide investigating infants and preschool children with CF identified by newborn screening revealed that CF lung disease starts in the first months of life, leaving only a narrow window of opportunity for preventive therapeutic interventions,” said Dr. Stahl, the lead study author and a pediatric pulmonologist at the Cystic Fibrosis Centre and the Translational Lung Research Center at the University of Heidelberg.

“Because lung disease is the most important factor for morbidity and mortality in patients with CF, prevention, or at least delay, of the onset and progression of CF lung disease may be a promising therapeutic strategy.”

The researchers also tested whether lung clearance index and chest magnetic resonance imaging (MRI) could be safely performed on the infants and serve as quantitative outcome measures.

Lung clearance index measures how well air is flowing through the lungs. Mucous obstruction of the smallest airways is one of the earliest features of CF lung disease, and lung clearance index can detect these changes in breathing. MRI can detect early abnormalities in lung structure.

The authors report that both procedures could be safely performed in the infants and were well tolerated, though lung clearance index in this particular study provided a better yardstick to measure the benefits of this treatment.

After one year, the infants who received the hypertonic saline had a better lung clearance index. Furthermore, they gained significantly more weight (500 grams or 1.1 pounds higher mean weight after one year of treatment) and height (1.5 centimeters or just under an inch higher mean height after one year of treatment). The weight gain confirmed previous studies of hypertonic saline in a mouse model for CF lung disease.

Pulmonary exacerbation rates and adverse events between the treatment groups were similar.

Study limitations include the fact that isotonic saline (sodium chloride concentration: .9 percent) is not a true placebo because it may, itself, have therapeutic benefits. The authors added that the infants were followed for only one year, so whether hypertonic saline therapy is beneficial over the long term is unknown.

The study is believed to be the first randomized controlled trial in infants with CF.

“We demonstrated that early studies are feasible in this challenging age group using innovative, sensitive outcome parameters such as lung clearance index,” Dr. Stahl said.

“Treatment with hypertonic saline in infants with CF is safe from diagnosis onwards, and our results suggest this preventive therapy benefits lung function and improves thriving.”

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Tiny Pacemakers Aim To Make Infant Heart Surgeries Less Invasive, While Cutting Operating Costs And Time

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WASHINGTON – At 2:15 p.m. C.T. on Sunday, Nov. 11, Rohan Kumthekar, M.D., a cardiology fellow working in Dr. Charles Berul’s bioengineering lab at the Sheikh Zayed Institute for Pediatric Surgical Innovation, part of Children’s National Health System, presents a prototype for a miniature pacemaker at the American Heart Association’s Scientific Sessions 2018. The prototype, approximately 1 cc, the size of an almond, is designed to make pacemaker procedures for infants less invasive, less painful and more efficient, measured by shorter surgeries, faster recovery times and reduced medical costs.

Kumthekar, a Cardiovascular Disease in the Young Travel Award recipient, will deliver his oral abstract, entitled “Minimally Invasive Percutaneous Epicardial Placement of a Custom Miniature Pacemaker with Leadlet under Direct Visualization,” in S101A as part of the Top Translational Science Abstracts in Pediatric Cardiology session.

“As cardiologists and pediatric surgeons, our goal is to put a child’s health and comfort first,” says Kumthekar.

“Advancements in surgical fields are tending toward procedures that are less and less invasive. There are many laparoscopic surgeries in adults and children that used to be open surgeries, such as appendix and gall bladder removals. However, placing pacemaker leads on infants’ hearts has always been an open surgery. We are trying to bring those surgical advances into our field of pediatric cardiology to benefit our patients.”

Instead of using open-chest surgery, the current standard for implanting pacemakers in children, doctors could implant the tiny pacemakers by making a relatively tiny 1-cm incision just below the ribcage.

“The advantage is that the entire surgery is contained within a tiny 1-cm incision, which is what we find groundbreaking,” says Kumthekar.

With the help of a patented two-channel, self-anchoring access port previously developed by Berul’ s research group, the operator can insert a camera into the chest to directly visualize the entire procedure. They can then insert a sheath (narrow tube) through the second channel to access the pericardial sac, the plastic-like cover around the heart. The leadlet, the short extension of the miniature pacemaker, can be affixed onto the surface of the heart under direct visualization. The final step is to insert the pacemaker into the incision and close the skin, leaving a tiny scar instead of two large suture lines.

The median time from incision to implantation in this thoracoscopic surgery study was 21 minutes, and the entire procedure took less than an hour on average. In contrast, pediatric open-heart surgery could take up to several hours, depending on the child’s medical complexities.

“Placing a pacemaker in a small child is different than operating on an adult, due to their small chest cavity and narrow blood vessels,” says Kumthekar.

“By eliminating the need to cut through the sternum or the ribs and fully open the chest to implant a pacemaker, the current model, we can cut down on surgical time and help alleviate pain.”

The miniature pacemakers and surgical approach may also work well for adult patients with limited vascular access, such as those born with congenital heart disease, or for patients who have had open-heart surgery or multiple previous cardiovascular procedures.

The miniature pacemakers passed a proof-of-concept simulation and the experimental model is now ready for a second phase of testing, which will analyze how the tailored devices hold up over time, prior to clinical testing and availability for infants.

“The concept of inserting a pacemaker with a 1-cm incision in less than an hour demonstrates the power of working with multidisciplinary research teams to quickly solve complex clinical challenges,” says Charles Berul, M.D., a guiding study author, electrophysiologist and the chief of cardiology at Children’s National.

Berul’s team from Children’s National collaborated with Medtronic PLC, developers of the first implantable pacemakers, to develop the prototype and provide resources and technical support to test the minimally-invasive surgery.

The National Institutes of Health provided a grant to Berul’s research team to develop the PeriPath, the all-in-one 1-cm access port, which cut down on the number of incisions by enabling the camera, needle, leadlet and pacemaker to be inserted into one port, through one tiny incision.

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Grief Linked To Sleep Disturbances That Can Be Bad For The Heart

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HOUSTON – (Nov. 9, 2018) – People who have recently lost a spouse are more likely to have sleep disturbances that exacerbate levels of inflammation in the body, according to new research from Rice University and Northwestern University. These elevated levels of inflammation may increase risk for cardiovascular illness and death.

The study, “Bereavement, self-reported sleep disturbances and inflammation: Results from Project HEART,” was recently published in Psychosomatic Medicine. It compared the self-reported sleep habits of recently widowed people to a control group. Both groups had sleep disturbances, such as insomnia.

The researchers found that the link between sleep disturbances and inflammation was two to three times higher for the bereaved spouses. Inflammation was measured by the level of proinflammatory cytokines, which are designed to be short-term fighters of disease but are linked to long-term risk for health problems including cardiovascular disease.

Corresponding author Diana Chirinos, a research assistant professor of preventive medicine at the Northwestern University Feinberg School of Medicine who began examining the topic as a Rice Academy postdoctoral fellow in Rice’s Department of Psychological Sciences, said the study suggests that these bereaved individuals are more susceptible to the negative health effects of poor sleep.

“The death of a spouse is an acutely stressful event and they have to adapt to living without the support of the spouse,” she said. “Add sleep disturbance to their already stressful situation and you double the stressor. As a result, their immune system is more overactivated.”

Chirinos said she and her fellow researchers already knew widowed individuals had higher levels of inflammation. Prior work revealed that in the first six months after the loss of a spouse, widows and widowers are at a 41 percent higher risk of mortality, and 53 percent of this increased risk is due to cardiovascular disease. However, they wanted to find the specific cause.

“Now we know it’s not the grief itself; it is the sleep disturbance that arises from that grief,” Chirinos said.

Chris Fagundes, an assistant professor of psychological sciences at Rice and the principal investigator for Project HEART, said the finding is another revelation in the study of how human behaviors and activities impact inflammation, and it adds to a growing body of work about how bereavement can affect health. His initial work showed why people who have been widowed are at higher risk of cardiovascular problems and premature death by comparing their inflammation with matched controls.

“While working in my laboratory as a post-doctoral fellow, Diana did a great job incorporating her expertise in sleep data collection into this project,” he said.

Ultimately, the researchers hope the findings will help to design better health interventions for those suffering from loss.

The study included 101 people with an average age of 67. Half were bereaved (identified through obituaries), and the rest made up the control group.

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