The Growth Study is an ongoing prospective, multicenter, longitudinal cohort study investigating sex differences in growth impairment in children with Crohn’s disease. For their current analysis, lead author Dr. Neera Gupta, principal investigator for The Growth Study, director of research for the Pediatric Inflammatory Bowel Disease (PIBD) Program and an associate professor of pediatrics at Weill Cornell Medicine and a pediatric gastroenterologist at NewYork-Presbyterian Komansky Children’s Hospital, and colleagues examined a range of variables associated with statural growth by sex for 113 children with Crohn’s disease, such as disease characteristics, patient-reported symptoms at onset and the use of certain medications.

Among 41 female patients, an initial classification of IBD as Crohn’s disease or perianal disease at diagnosis were associated with better growth. However, patient-reported joint pain at symptom onset or the use of probiotics or azathioprine/6-mercaptopurine were associated with worse growth.

Variables associated with statural growth were markedly different for 72 male patients. Patient-reported poor growth at symptom onset or the use of infliximab, biologics, methotrexate or vitamin D were associated with better growth. In contrast, an initial classification of IBD as Crohn’s disease or patient-reported anorexia or mouth sores at symptom onset were associated with worse growth.

The authors noted that female patients appear to grow better independent of disease severity/inflammatory burden and medication interventions. Their findings suggest sex-specific molecular pathways lead to growth impairment in children with Crohn’s disease, and that there may be a difference in the response of these sex-specific molecular pathways to current medications used to treat pediatric Crohn’s disease. Sex will likely be an important future determinant of treatment decisions, which will represent a major advancement in clinical decision making for pediatric Crohn’s disease.

“Through the Growth Study, we aim to transform the care of pediatric patients with Crohn’s disease by providing an evidence-based approach for the appropriate early introduction of aggressive therapy in patients with high risk for each sex because there is only a narrow therapeutic window available for intervention to improve statural growth,” the authors wrote.

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Head circumference may indicate a head growth issue, which could be further investigated to determine if there is an issue with brain size or extra fluid. But now, in the age of noninvasive brain scanning such as magnetic resonance imaging (MRI), could researchers develop normalized growth curve charts for the brain?

That was the question Steven Schiff, Brush Chair Professor of Engineering at Penn State, and his multi-institution research team set out to answer. They published their results today (July 9) in the Journal of Neurosurgery, Pediatrics.

“Brain size research also has a very unfortunate history, as it was often used to attempt to scientifically prove one gender or race or culture of people as better than another,” said Schiff, also a professor of engineering science and mechanics in the College of Engineering and of neurosurgery in the College of Medicine. “In this paper, we discuss the research going back about 150 years and then look at what the data of a contemporary cohort really tells us.”

The researchers analyzed 1,067 brain scans of 505 healthy children, ages 13 days to 18 years old, from the National Institutes of Health (NIH) Pediatric MRI Repository. To ensure a representative sample population across sex, race, socioeconomic status and geographic location, the MRI scans were taken sequentially over several years at hospitals and medical schools in California, Massachusetts, Missouri, Ohio, Pennsylvania and Texas. To ensure calibrated results, one person was established as a control and scanned at each site.

“The study of brain size and growth has a long and contentious history — even in the era of MRI, studies defining normal brain volume growth patterns often include small sample sizes, limited algorithm technology, incomplete coverage of the pediatric age range and other issues,” said first author Mallory R. Peterson, a Penn State student who is pursuing both a doctorate in engineering science and mechanics in the College of Engineering and a medical degree in the College of Medicine. She earned her bachelor of science degree in biomedical engineering from Penn State in 2016. “These studies have not addressed the relationship between brain growth and cerebrospinal fluid in depth, either. In this paper, we resolve both of these issues.”

The first startling finding, according to Schiff and Peterson, was the difference in brain volume between male and female children. Even after adjusting for body size, males exhibited larger overall brain volume — but specific brain structures did not differ in size between sexes, nor did cognitive ability.

“Clearly, sex-based differences do not account for intelligence — we have known that for a long time, and this does not suggest differently,” Schiff said. “The important thing here is that there is a difference in how the brains of male and female children grow. When you’re diagnosing or treating a child, we need to know when a child’s brain isn’t growing normally.”

The second finding was one of striking similarity rather than differences.

“Regardless of the sex or the size of the child, we unexpectedly found that the ratio between the size of the child’s brain and the volume of fluid within the head — cerebrospinal fluid — was universal,” Schiff said. “This fluid floats and protects the brain, serving a variety of functions as it flows through the brain. Although we have not recognized this tight normal ratio before, this relationship of fluid to brain is exactly what we try to regulate when we treat children for excess fluid in conditions of hydrocephalus.”

The researchers plan to continue studying the ratio and its potential functions, as well as underlying mechanisms, in children and across the life span.

“The apparent universal nature of the age-dependent brain-cerebrospinal fluid ratio, regardless of sex or body size, suggests that the role of this ratio offers novel ways to characterize conditions affecting the childhood brain,” Peterson said.

The researchers also settled a longstanding controversy in terms of the temporal lobe, according to Schiff. After two years of age, the left side of this brain structure — where language function is typically localized — was clearly larger than the right side throughout childhood. A portion of the temporal lobe called the hippocampus, which can be a cause of epilepsy, was larger on the right than the left as it grew during childhood.

“These normal growth curves for these critical structures often involved in epilepsy will help us determine when these structures are damaged and smaller than normal for age,” said Schiff.

This approach to normal brain growth during childhood could help researchers understand normal from excessive volume loss throughout the later lifespan, according to Schiff.

“Brain volume peaks at puberty,” Schiff said. “It then decreases as we age, and it decreases more rapidly in people with certain types of dementia. If we can better understand both brain growth and the ratio of brain to fluid at every age, we can not only improve how we diagnose clinical conditions, but also how we treat them.”

The X-rays are part of Jupiter’s aurora — bursts of visible and invisible light that occur when charged particles interact with the planet’s atmosphere. A similar phenomenon occurs on Earth, creating the northern lights, but Jupiter’s is much more powerful, releasing hundreds of gigawatts of energy, enough to briefly power all of human civilisation*.

In a new study, published in Science Advances, researchers combined close-up observations of Jupiter’s environment by NASA’s satellite Juno, which is currently orbiting the planet, with simultaneous X-ray measurements from the European Space Agency’s XMM-Newton observatory (which is in Earth’s own orbit).

The research team, led by UCL and the Chinese Academy of Sciences, discovered that X-ray flares were triggered by periodic vibrations of Jupiter’s magnetic field lines. These vibrations create waves of plasma (ionised gas) that send heavy ion particles “surfing” along magnetic field lines until they smash into the planet’s atmosphere, releasing energy in the form of X-rays.

Co-lead author Dr William Dunn (UCL Mullard Space Science Laboratory) said: “We have seen Jupiter producing X-ray aurora for four decades, but we didn’t know how this happened. We only knew they were produced when ions crashed into the planet’s atmosphere.

“Now we know these ions are transported by plasma waves — an explanation that has not been proposed before, even though a similar process produces Earth’s own aurora. It could, therefore, be a universal phenomenon, present across many different environments in space.”

X-ray auroras occur at Jupiter’s north and south poles, often with clockwork regularity — during this observation Jupiter was producing bursts of X-rays every 27 minutes.

The charged ion particles that hit the atmosphere originate from volcanic gas pouring into space from giant volcanoes on Jupiter’s moon, Io.

This gas becomes ionised (its atoms are stripped free of electrons) due to collisions in Jupiter’s immediate environment, forming a donut of plasma that encircles the planet.

Co-lead author Dr Zhonghua Yao (Chinese Academy of Sciences, Beijing) said: “Now we have identified this fundamental process, there is a wealth of possibilities for where it could be studied next. Similar processes likely occur around Saturn, Uranus, Neptune and probably exoplanets as well, with different kinds of charged particles ‘surfing’ the waves.”

Co-author Professor Graziella Branduardi-Raymont (UCL Mullard Space Science Laboratory) said: “X-rays are typically produced by extremely powerful and violent phenomena such as black holes and neutron stars, so it seems strange that mere planets produce them too.

“We can never visit black holes, as they are beyond space travel, but Jupiter is on our doorstep. With the arrival of the satellite Juno into Jupiter’s orbit, astronomers now have a fantastic opportunity to study an environment that produces X-rays up close.”

For the new study, researchers analysed observations of Jupiter and its surrounding environment carried out continuously over a 26-hour period by the Juno and XMM-Newton satellites.

They found a clear correlation between waves in the plasma detected by Juno and X-ray auroral flares at Jupiter’s north pole recorded by X-MM Newton. They then used computer modelling to confirm that the waves would drive the heavy particles towards Jupiter’s atmosphere.

Why the magnetic field lines vibrate periodically is unclear, but the vibration may result from interactions with the solar wind or from high-speed plasma flows within Jupiter’s magnetosphere.

Jupiter’s magnetic field is extremely strong — about 20,000 times as strong as Earth’s — and therefore its magnetosphere, the area controlled by this magnetic field, is extremely large. If it was visible in the night sky, it would cover a region several times the size of our moon.

The work was supported by the Chinese Academy of Sciences, the National Natural Science Foundation of China, and the UK’s Science and Technology Facilities Council (STFC), Royal Society, and Natural Environment Research Council, as well as ESA and NASA.

* Jupiter’s X-ray aurora alone releases about a gigawatt, equivalent to what one power station might produce over a period of days.

The stomatal pores are surrounded by two guard cells. If the internal pressure of these cells drops, they slacken and close the pore. If the pressure rises, the cells move apart and the pore widens.

The stomatal movements are thus regulated by the guard cells. Signalling pathways in these cells are so complex that it is difficult for humans to intervene with them directly. However, researchers of the Julius-Maximilians-Universität (JMU) Würzburg in Bavaria, Germany, nevertheless found a way to control the movements of stomata remotely — using light pulses.

Light-sensitive protein from algae used

The researchers succeeded in doing this by introducing a light-sensitive switch into the guard cells of tobacco plants. This technology was adopted from optogenetics. It has been successfully exploited in animal cells, but the application in plant cells it is still in its infancy.

The team led by JMU biophysicist and guard cell expert Professor Rainer Hedrich describes their approach in the scientific journal Science Advances. JMU researchers Shouguang Huang (first author), Kai Konrad and Rob Roelfsema were significantly involved.

The group used a light-sensitive protein from the alga Guillardia theta as a light switch, namely the anion channel ACR1 from the group of channelrhodopsins. In response to light pulses, the switch ensures that chloride flows out of the guard cells and potassium follows. The guard cells lose internal pressure, slacken and the pore closes within 15 minutes. “The light pulse is like a remote control for the movement of the stomata,” says Hedrich.

Anion channel hypothesis confirmed

“By exposing ACR1 to light, we have bridged the cell’s own signalling chain, thus proving the hypothesis that the opening of anion channels is essential and sufficient for stomatal closure,” Hedrich summarises the results of the study. The exposure to light had almost completely prevented the transpiration of the plants.

With this knowledge, it is now possible to cultivate plants with an increased number of anion channels in the guard cells. Plants equipped in this way should close their stomata more quickly in response to approaching heat waves and thus be better able to cope with periods of drought.

“Plant anion channels are activated during stress; this process is dependent on calcium. In a follow up optogenetics project, we want to use calcium-conducting channelrhodopsins to specifically allow calcium to flow into the guard cells cell through exposure to light and to understand the mechanism of anion channel activation in detail,” Hedrich outlines the upcoming goals of his research.

Basic scientific research can also benefit from the results from Würzburg: “Our new optogenetic tool has enormous potential for research,” says the JMU professor. “With it, we can gain new insights into how plants regulate their water consumption and how carbon dioxide fixation and stomatal movements are coupled.”

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Materials provided by University of Würzburg. Original written by Robert Emmerich. Note: Content may be edited for style and length.

Human epithelia are tissues found in several parts of the body (such as the epidermis and internal mucosa). They are composed of layers of contiguous cells that serve as a physical and chemical barrier. This role is constantly being put to the test by both the outside environment and their own renewal. Tissue renewal involves the formation of new cells by cell division and the elimination of dead cells. The mechanisms that regulate the ability of epithelia to maintain their integrity in contexts involving large numbers of eliminated cells remain poorly understood, despite the fact that this situation occurs regularly during embryogenesis or the maintenance of adult tissues. For example, more than ten billion cells can be eliminated every day in an adult intestine. How are these eliminations orchestrated to maintain tissue integrity and connectivity?

Scientists from the Institut Pasteur and the CNRS set out to identify the mechanisms involved in epithelial integrity and the conditions that can affect epithelial connectivity by using Drosophila (or vinegar flies), an organism studied in the laboratory with a similar epithelial architecture to humans.

Using protein-sensitive fluorescent markers, the research team revealed that when a cell dies, the EGFR-ERK pathway — a cell activation signaling pathway known for its involvement in the regulation of cell survival — is temporarily activated in the neighboring cells. The scientists observed that the activation of the EGFR-ERK pathway protected neighboring cells from cell death for approximately one hour, thereby preventing the simultaneous elimination of a group of cells. “We already knew that this pathway plays a key role in regulating cell survival in epithelial tissue, but we were surprised to observe such protective dynamics between cells,” comments Romain Levayer, Head of the Cell Death and Epithelial Homeostasis Unit at the Institut Pasteur and last author of the study.

The scientists’ research also shows that inhibiting this protective mechanism has a drastic effect on epithelial tissue: cell elimination becomes random and neighboring cells can be eliminated simultaneously, leading to repeated losses of connectivity. The elimination of groups of neighboring cells is never observed in epithelial tissue in normal conditions, when the EGFR-ERK pathway is not deliberately inhibited, even if a large number of cells are eliminated.

By using a new optogenetic tool that can control cell death in time and space and bypass the protective mechanism, the scientists confirmed that epithelial integrity was compromised when neighboring cells were eliminated simultaneously. “Surprisingly, epithelial tissue is highly sensitive to the spatial distribution of eliminated cells. Although it can withstand the elimination of a large number of cells, epithelial integrity is affected if just three neighboring cells are eliminated simultaneously,” explains Léo Valon, a scientist in the Cell Death and Epithelial Homeostasis Unit at the Institut Pasteur and first author of the study.

The scientists’ observations confirm that tissues need to develop mechanisms preventing the elimination of neighboring groups of cells. “These observations are important as they illustrate the incredible self-organizing ability of biological tissues, a property that enables them to withstand stressful conditions. So there is no need for a conductor to orchestrate where and when the cells should die; everything is based on highly local communications between neighboring cells,” adds Romain Levayer.

This process seems to have been conserved during evolution. The same protective mechanism based on local EGFR-ERK activation was discovered independently in human cell lines by the research group led by Olivier Pertz at the University of Bern in Switzerland (the results are published in the same journal2). The results of the other study suggest that the protective mechanism is conserved between species separated by hundreds of millions of years, indicating that it is a relatively universal mechanism.

Future research will reveal whether disruption to this cell death coordination mechanism and repeated loss of connectivity in epithelial tissue could be one of the roots of chronic inflammation, a phenomenon responsible for various diseases that are currently among the leading causes of death worldwide.

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To understand the connection between human activity and a type of tumorlike disease called growth anomalies (GAs), researchers at the National Institute of Standards and Technology (NIST) have collaborated with the U.S Geological Survey (USGS) and the National Oceanic and Atmospheric Administration (NOAA) to use an emerging molecular profiling method to identify 18 small molecules that promise to help them better understand the series of molecular reactions that lead to the disease.

GAs affect both the coral skeleton and its soft tissues. Scientists don’t know the cause of the disease or how it spreads but have hypothesized that there is a strong correlation between GA prevalence in coral colonies and human population density nearby.

Almost all types of corals are made of hundreds to millions of individual soft-bodied animals called polyps. The polyps secrete calcium carbonate to form a hard skeleton that lays the foundation for the coral colony. GAs affect corals through irregular and accelerated growth of their skeleton, causing it to be less dense and filled with holes. This results in a tumorlike mass in the skeleton of a coral colony with fewer polyps and a diminished ability to reproduce.

Shallow water corals receive food like carbohydrates and oxygen as a byproduct of photosynthesis from the symbiotic relationship they have with zooxanthellae, photosynthetic algae that live inside coral tissues. GAs can lead to fewer symbiotic zooxanthellae and therefore less energy being absorbed from photosynthesis.

Even though GAs do not typically directly lead to coral death, they do affect the overall health of coral colonies and can pose an ecological threat to coral populations. To analyze the disease, NIST researchers chose the coral species Porites compressa as their target sample.

This coral species is known as the “finger” or “hump” coral and is part of the stony coral family, which is “one of the important reef-building species in Hawaii,” said NIST chemist Tracey Schock. “They lay the foundation for the coral reef.”

P. compressa is found in shallow lagoons off the Hawaiian Islands, and the researchers obtained their coral samples from Kaneohe Bay, Oahu. The bay has been studied widely as a site affected by human activity such as sewage discharge and metal pollution. GAs have previously been observed in the coral species there.

In order to analyze and study GAs in P. compressa, researchers turned to the field of metabolomics, which is the study of small molecules, such as those making up living organisms found in tissues, blood or urine. These small molecules, known as metabolites, are the intermediate and end products in a linked series of biochemical reactions known as molecular pathways in an organism.

Some examples of such small molecules include sugars like glucose, amino acids, lipids and fatty acids. Their production can be influenced by genetic and environmental factors and can help researchers better understand the biochemical activity of tissue or cells. In this case, chemical analysis of metabolites provides significant information that helps researchers understand the physiology of the disease.

For their study, researchers sampled a coral colony that had both healthy and diseased tissue. They split up their samples so they could assess the healthy coral and diseased coral separately. They also had a separate adjacent sample that was free of diseased tissue.

The samples were frozen in liquid nitrogen, and then freeze-dried for practical sample processing while maintaining metabolic integrity. The researchers then separated the diseased parts from the healthy colony using a hammer and stainless-steel chisel and collected the tissue from the skeleton with a brush. In one of the final stages of the sample preparation, they chemically extracted the metabolites from the coral tissue using a combination of methanol, water and chloroform.

“The method is novel for coral studies,” said Schock. “With metabolomics, it is critical to preserve the state of all metabolites in a sample at the time of collection. This requires halting all biochemical activity using liquid nitrogen and maintaining this state until chemical extraction of the metabolome. The complexity of a coral structure necessitates stringent collection and processing protocols.”

The researchers then produced a metabolomic analysis of the coral samples by using a reproducible profiling technique known as proton nuclear magnetic resonance (1H NMR).

The 1H NMR technique exposes the coral extract to electromagnetic fields and measures the radio frequency signals released by the hydrogens in the sample. The various kinds of metabolites are revealed by their unique signals which inform of their chemical environment. NMR detects all signals from the magnetic nuclei within a sample, making it an unbiased “all-in-one” technique. Two-dimensional NMR experiments that can identify both hydrogens (1H) and their directly bound carbon (13C) atoms provide more chemical information, giving confidence in the accuracy of the identities of the various metabolites within a sample.

The study identified 18 different metabolites and a new GA morphological form in P. compressa. The researchers found that GA tumors have distinct metabolite profiles compared with healthy areas of the same coral colony and detected specific metabolites and metabolic pathways that may be important for these profile differences. They also discovered that the loss of internal pH regulation is seemingly responsible for the hollow skeletons that are a characteristic of GAs.

“We have not only characterized new aspects of GA physiology, but have also discovered candidate pathways that provide a clear path forward for future research efforts aiming to further understand GA formation and coral metabolism, in general,” said Schock.

As studies of this type accumulate, the researchers envision a database that could pull together coral metabolite information from multiple coral species into an accessible location for all scientists.

Collaborating with other researchers in different fields could increase understanding of the biological impacts of this disease on coral colonies. “We are going to learn which species are tolerant and which species are sensitive to stresses, and the physiological adaptations or mechanisms of both types will be important to conservation efforts,” said Schock.

For now, the researchers hope these findings will be helpful for other scientists analyzing coral species and ultimately be beneficial for the coral reefs themselves, potentially aiding efforts to better preserve them.