In contrast to the general belief that the airways of an infant are sterile until after birth, University of Alabama at Birmingham researchers and colleagues have found that the infant airway is already colonised with bacteria or bacterial DNA when a baby is born — and this is true for infants born as early as 24 weeks gestation.

How microbes get into the airways and the purpose of this pre-birth colonisation are still unclear, but the pattern of colonisation appears to have an important link to later severe neonatal lung disease.

An early microbial imbalance, or dysbiosis, is predictive for the development of bronchopulmonary dysplasia, or BPD, a chronic lung disease of prematurity. The extremely low birth-weight, or ELBW, infants in this study had an average birth weight of 1 pound, 8 ounces. Researchers found that the ELBW infants who went on to develop life-threatening BPD showed abnormal microbial colonisation patterns at birth, as compared to pre-term infants who did not get BPD.

“Right at birth, your respiratory microbiome can possibly predict your risk for BPD,” said Charitharth Vivek Lal, M.D., assistant professor in the UAB Pediatrics Division of Neonatology and the lead investigator of this study.
Extremely premature infants are at risk for BPD, which is the most common lung pathology of these tiny infants and a significant cause of morbidity, mortality and health care expenditures. Adults and children who had BPD as infants have lungs that failed to develop properly and are more prone to worse lung function, asthma, lung infections and pulmonary hypertension.

The researchers also looked at the airway microbiomes of 18 ELBW infants with established BPD and found that their microbiomes had a decreased diversity of types of microbes, and the pattern was very different from those of ELBW infants shortly after birth or full-term infants at birth.

As to specific groups of microbes, the phylum Proteobacteria, which includes bacteria like E. coli, appeared to be involved in BPD pathology, and the genus Lactobaccillus, part of the phylum Firmicutes, appeared to be involved in disease protection.

Lal and colleagues found decreased Lactobacillus abundance in the airway microbiomes of 10 infants born to mothers who had chorioamnionitis — an infection of the membranes of the placenta and an independent risk factor for BPD — as well as decreased Lactobacillus abundance at birth in the airways of the BPD-predisposed, ELBW infants, as compared to BPD-resistant infants. Research elsewhere has suggested a beneficial role for Lactobacillus against airway diseases and for lung development.

“I predict that researchers will study the use of respiratory probiotics, and the role of the gut-lung microbiome axis in the future,” Lal said.

For five ELBW infants who later developed BPD, the researchers collected periodic airway microbiome samples from birth through 9 weeks and saw extremely similar patterns of change in the microbiomes over time.

As for the source of the microbes, Lal and colleagues wrote, “As it is commonly believed that colonization of neonates originates in the birth canal, we were surprised to find that the airway microbiome of vaginally delivered and caesarean section-delivered neonates were similar, which suggests that the microbial DNA in the airways is probably transplacentally derived, consistent with reports that the placenta has a rich microbiome.”

The researchers speculate that this transmission of bacteria or bacterial DNA to the in-utero infant could be via blood or amniotic fluid.

University of Alabama at Birmingham www.uab.edu/news/innovation/item/7505-discovery-of-infants-airway-microbiomes-may-help-predict-lung-disease

Ribonucleic acid (RNA) binding fluorescent probes have been powerful and important analytical tools for the study of RNA structures and functions.

A research group led by Professor Seiichi Nishizawa at Tohoku University’s Graduate School of Science has reported a new RNA probe that binds to double-stranded RNA (dsRNA) in a sequence-specific manner.

The probe has a weak response to mismatch-containing dsRNA sequences, thus enabling sequence-selective fluorescence sensing of dsRNA at the single-base pair resolution. It also shows a preference for binding with dsRNA over dsDNA, which is an important selective process for future applications in a cellular environment where RNA and DNA co-exist.

In contrast to the conventional analytical method which is limited to single-stranded regions of RNA, the new analytical method allows for fluorescent sensing of target dsRNA structure and sequence for the first time.

It is expected that the probe will open up new possibilities for analysing the functions of dsRNA-containing structures, which are closely related to various biological phenomena and diseases.

Tohoku University www.tohoku.ac.jp/en/press/fluorescence_detection_of_rna.html

A research team at the Krembil Research Institute has discovered a pair of tissue biomarkers that directly contribute to the harmful joint degeneration associated with spine osteoarthritis.

The study is the first to show that elevated levels of both of these biomarkers cause inflammation, cartilage destruction and collagen depletion.

‘These biomarkers are actively involved in increasing inflammation and destructive activities in spine cartilage and assist in its destruction,’ says principal investigator Dr. Mohit Kapoor, Senior Scientist at the Krembil Research Institute and Associate Professor in the Department of Surgery and the Department of Laboratory Medicine and Pathobiology at the University of Toronto. Dr. Kapoor specializes in arthritis research.

Osteoarthritis affects about three million Canadians and is characterized by a breakdown of the protective cartilage found in the body’s spine, hand, knee and hip joints. There is no known cure.

The study involved tissue biopsies from 55 patients undergoing decompression or discectomy at the Krembil Neuroscience Centre at Toronto Western Hospital. As part of the study, the research team – led by Dr. Kapoor and comprising Dr. Akihiro Nakamura, a post-doctoral fellow, and Dr. Y. Raja Rampersaud, a clinical expert and spine surgeon – explored the role, function and signaling mechanisms of two tissue biomarkers: microRNA-181a-5p and microRNA-4454.

The study screened 2,100 microRNAs and found that measuring the levels of these two specific biomarkers can help clinicians determine the stage to which the disease has progressed, and provide a tool for determining the degree of cartilage destruction.

‘These are biologically active molecules. By detecting them in the tissue biopsies, we have a tool for determining the stage of spine osteoarthritis,’ says Dr. Kapoor. ‘What is really significant, however, is we have discovered that these biomarkers are actively involved in destroying cartilage and increasing inflammation. Furthermore, they promote cartilage cells to die and deplete the most important component of your cartilage, which is your collagen.’

The discovery represents the end of the first stage of research. The team is now investigating whether these biomarkers can be detected in the blood – which would help clinicians more simply determine the stage of spine osteoarthritis – and whether further studying the biomarkers will allow researchers to halt and reverse spine degeneration.

‘The most critical aspect of this discovery is that we have found that they are active. Now that we know what they are, we are currently looking at blocking them and restoring the joint,’ says Dr. Kapoor.

Krembil Research Institute www.uhn.ca/corporate/News/PressReleases/Pages/research_team_discovers_two_biomarkers_that_contribute_to_spine_osteoarthritis.aspx

Researchers from the National Institutes of Health and their colleagues identified the genetic cause and a possible therapeutic target for a rare form of paediatric progressive neuropathy. Neuropathy, damage or disease affecting the peripheral nervous system, can range from rare conditions linked to a patient’s exome to more common causes like diabetes and viral infections. Neuropathies can affect both motor and sensory neurons, producing muscle weakness, numbness, pain, and a wide range of symptoms.

These types of discoveries underscore the importance of the families who volunteer to participate in clinical research. “This case superbly illustrates how the intensive study of children with very rare neurological disorders can lead quickly to a deep knowledge of a specific genetic condition, as well as uncover mysteries of the nervous system relevant to a wide spectrum of disorders,” said Walter J. Koroshetz, M.D., director of NINDS.

In their report, researchers examined a 10-year-old child with early onset, progressive neuropathy primarily affecting his ability to walk, grasp, and perform fine motor skills. When the patient’s complete genetic makeup, or genome, was analysed, a mutation was found in the gene associated with the protein KCC3. This protein is important for the ability of cells to respond to swelling.

When a neuron swells, KCC3 is involved in the mechanism that drives fluid out, returning the cell to normal. In the absence of this protein (in what is called a loss-of-function mutation), extreme swelling of the neurons can occur, which in turn leads to nerve damage.

In the study, the patient’s mutation affected the ability of KCC3 to turn off once it was no longer needed, leading to the opposite effect—shrunken neurons that also fail to communicate properly. This is referred to as a gain-of-function mutation, causing the affected protein to behave in a new and damaging way.

“This protein, KCC3, has been connected to other forms of neuropathy in the past,” said Carsten G. Bonnemann, M.D., a senior investigator in the Neuromuscular and Neurogenetic Disorders of Childhood Section at NINDS and a senior author of the paper. “What’s unique here is that this is the first time that we have seen a gain-of-function mutation in the KCC3 protein that leads to neuropathy.”

NIH www.nih.gov/news-events/news-releases/novel-genetic-mutation-may-lead-progressive-loss-motor-function

University of Helsinki researchers have previously demonstrated that a point mutation in a gene of serotonin 2B receptor can render the carrier prone to impulsive behaviour, particularly when drunk. Now the research group has established that the same mutation may shield its bearers from obesity and insulin resistance, both of which are associated with type 2 diabetes.

The study focused on the insulin sensitivity, beta cell activity and BMI of 98 Finnish men between the ages of 25 and 30, all of whom had been diagnosed with antisocial personality disorder. The results indicate that carriers of a point mutation in a gene of serotonin 2B receptor had a lower BMI and higher insulin sensitivity than persons without the mutation. Normally, men with low testosterone levels are more susceptible to metabolic disorders, but among carriers of the point mutation, this tendency was reversed – lower levels of testosterone increased insulin sensitivity.

The results also suggest that men in their thirties with antisocial personalities may constitute a risk group for insulin resistance, and consequently type 2 diabetes later in life.

 “It is fascinating to think that this receptor mutation which has been passed through the chain of evolution would impact both the brain as impulsive behaviour and energy metabolism,” says psychiatrist, Dr Roope Tikkanen from the University of Helsinki, who led the study. 

 “We could speculate that the compound effect the mutation and testosterone have on energy metabolism may have been beneficial in the cool, nutrition-poor environment after the Ice Age, particularly for men with a high physiological level of testosterone – they would have survived with a lower calorie intake. Simultaneously, the aggression associated with high levels of testosterone may have helped them compete for food.”

In our modern society with ample food, the carriers of the mutation who have normal or low levels of testosterone may be better protected from metabolic illnesses relating to obesity, such as type 2 diabetes.

 “One would assume that the effect would be particularly pronounced in women, who naturally have lower levels of testosterone than men,” Tikkanen points out.

Over 100,000 Finns and more than 1,000 Finnish infants born every year are carriers of the point mutation in the serotonin 2B receptor. The intention is to study the national health implications of the results from the extensive FINRISKI research material through cooperation between Finnish, Swedish and American researchers.

 “Our results will further highlight the importance of Finnish diabetes research,’ Tikkanen states.

University of Helsinki www.helsinki.fi/en/news/aggressive-drunk-gene-may-protect-carriers-from-obesity