Earth

Researchers at the University of Illinois Chicago have shown that even after lung tissue has been damaged, it may be possible to reverse fibrosis and promote tissue repair through treatment with microgel-coated mesenchymal stromal cells.

Pulmonary fibrosis is a chronic disease caused by environmental toxins, medications or medical conditions like pneumonia and rheumatoid arthritis. It is characterized by the formation of scar tissue due to damage or an unchecked immune response, and it can cause mild to severe difficulty breathing and oxygen deprivation. Fibrosis is currently thought to be mostly irreversible, as current drug treatments are only mildly effective at managing symptoms and generally cause significant side effects.

Mesenchymal stromal cells, or MSCs, are multipotent and self-renewing, much like stem cells, and they have been studied for their potential to treat conditions like fibrosis.

"While previous studies tested the therapeutic effects of MSCs - which are known to suppress inflammation and to adapt to different tissue environments - their efficacy has so far been limited to early phases of the disease, when inflammation levels are high and scar tissue is still forming" said Jae-Won Shin, UIC assistant professor of pharmacology and bioengineering at the College of Medicine and corresponding author of the study. "Our approach was to optimize MSC-based therapeutics to work after inflammation has been reduced, which is when most people are diagnosed with fibrosis."

As described in a new paper published in Nature Biomedical Engineering, the UIC researchers engineered a thin microgel that, when designed in a specific way, can boost the therapeutic potential of MSCs to degrade scar tissue and regenerate healthy tissue in mouse models of fibrosis.

Shin and his colleagues engineered the microgel, which is as soft as healthy lung tissue, and incorporated a small protein called tumor necrosis factor-alpha. Also known as TNF-alpha, this protein acts as an inflammatory signal that encourages MSCs to synthesize collagenase. Collagenase is an enzyme that degrades excess collagen in fibrotic tissues and promotes the restoration of damaged tissues.

To optimize the MSCs with the microgel, the UIC researchers designed a microfluidic device to encapsulate individual cells rapidly and consistently in the thin gel.

"We miniaturized down to the small scale, the individual cell, which is important for delivery of the therapeutic into the tiny airways of the lungs," said study first author Sing-Wan Wong, a UIC postdoctoral research associate in the department of pharmacology and regenerative medicine.

In models of fibrotic injury, the UIC researchers observed reduced indicators of scaring and increased indicators of healthy lung tissue, such as normal collagen levels and architecture, only among the mice treated with MSCs coated in their TNF-alpha-incorporated gel via single cell encapsulation.

"This is really one of the first scientific demonstrations that collagen levels can be normalized well after fibrotic injury, and that the cell environment, not just the cells themselves, can be designed at the single-cell level in a precise manner," Shin said. "Our results suggest a feasible approach to predictively program cellular functions for desired therapeutic outcomes."

The analysis of very old plant fossils discovered in South Africa and dating from the Lower Devonian period documents the transition from barren continents to the green planet we know today. Cyrille Prestianni, a palaeobotanist at the EDDy Lab at the University of Liège (Belgium), participated in this study, the results of which have just been published in the journal Scientific Reports.

The greening of continents - or terrestrialisation - is undoubtedly one of the most important processes that our planet has undergone. For most of the Earth's history, the continents were devoid of macroscopic life, but from the Ordovician period (480 million years ago) green algae gradually adapted to life outside the aquatic environment. The conquest of land by plants was a very long process during which plants gradually acquired the ability to stand upright, breathe in the air or disperse their spores. Plant fossils that document these key transitions are very rare. In 2015, during the expansion of the Mpofu Dam (South Africa), researchers discovered numerous plant fossils in geological strata dated to the Lower Devonian (420 - 410 million years ago), making this a truly exceptional discovery.

Cyrille Prestianni, a palaeobotanist at the EDDy Lab (Evolution and Diversity Dynamics Lab) at the University of Liège, explains: "The discovery quickly proved to be extraordinary, since we are in the presence of the oldest fossil flora in Africa and it is very diversified and of exceptional quality. It is thanks to a collaboration between the University of Liège, the IRSNB (Royal Belgian Institute of Natural Sciences) and the New Albany Museum (South Africa) that this incredible discovery could be studied. The study, which has just been published in the journal Scientific Reports, describes this particularly diverse fossil flora with no less than fifteen species analysed, three of which are new to science. Dr. Prestianni adds : &laquo This flora is also particularly interesting because of the quantity of complete specimens that have been discovered," says the researcher. These plants are small, with the largest specimens not exceeding 10 cm in height. They are simple plants, consisting of axes that divide two or three times and end in reproductive structures called sporangia. »

The fossil flora of Mpofu allows us today to imagine what the world might have been like when the largest plants were no taller than our ankle and almost no animals had yet been able to free themselves from the aquatic environment. It gives us a better understanding of how our Earth went from a red rock devoid of life to the green planet we know today. These plants, simple as they are, are a crucial step in the construction of the environments that hosted the first land animals, arthropods. They form the basis of the long history of life on Earth, which continues today from dense tropical forests to the arid tundra of the north.

Researchers from the Hong Kong University of Science and Technology (HKUST) and Beijing Tiantan Hospital have recently uncovered a new gene mutation responsible for the non-familial patients of cerebral cavernous malformation (CCM) - a brain vascular disorder which inflicted about 10~30 million people in the world.

While the mutation of three genes: namely CCM1, CCM2, and CCM3, were known to be a cause of CCM - they mostly targeted patients who has family history in this disorder - which only account for about 20 per cent of the total inflicted population. The cause for the remaining 80 per cent non-familial cases, however, were not known.

Now, using next-generation sequencing and computational approach, a research team led by Prof. WANG Jiguang, Assistant Professor from HKUST's Division of Life Science and Department of Chemical and Biological Engineering, in collaboration with Prof. CAO Yong from the Beijing Tiantan Hospital, analyzed the genomic data of 113 CCM patients and identified another mutation called MAP3K3 c.1323C>G, which is found to be responsible for almost all the tested cases who developed popcorn-like lesions in their brain arteries - the most common one among the four types of CCM lesions (type II CCM).

At present, magnetic resonance imaging (MRI) is a commonly used non-intrusive means that doctors can base upon for diagnosis and treatment. However, the MRI images can only tell the size and type of the lesions, but not the gene responsible for the problem - which can only be ascertained by surgery and laboratory tests. Now, the HKUST research team designed a computational method that could help assess the probability of connection between the lesion shown in the MRI image to the genetic mutation MAP3K3 c.1323C>G. So CCM patients with this gene mutation may be able to receive more targeted treatment without having to undergo surgery - which could bear serious risks including cerebral hemorrhage or new focal neurological deficits.

Prof. Wang from HKUST said, "Our research opens a new direction to the genetic landscape of CCM and uncovers clues to the correlation between MAP3K3 c.1323C>G gene mutation and type II CCM. The design of the computational method, or decision-tree model takes us a step closer to non-invasive diagnosis of CCM cause, and we hope the discovery could help pave way for candidate drug target and therapy development, bringing benefits to patients in the near future."

The findings were recently published in The American Journal of Human Genetics.

Of all the different types of cancer known, a subtype of pancreatic cancer called pancreatic ductal adenocarcinoma (PDAC) is among the most aggressive and deadly. This disease begins in the cells that make up certain small ducts in the pancreas and progresses silently, usually causing no symptoms until advanced tumors actually obstruct these ducts or spread to other places. PDAC is not only difficult to diagnose, but also very unresponsive to available treatments. In particular, researchers have noted that PDAC cells can usually survive radiotherapy through mechanisms that remain largely unknown.

Part of the Radiation and Cancer Biology Group of the National Institutes for Quantum and Radiological Science and Technology, Japan, Dr. Sumitaka Hasegawa and colleagues Motofumi Suzuki and Mayuka Anko are currently studying what makes PDAC cells so radiation-resistant, and if there's a way to break through their defenses. In their latest study, published in the International Journal of Radiation Oncology, Biology, Physics, they've managed to uncover some of the mysteries underlying the curious relationship between treatment resistance in PDAC, the cell cycle, and a process called autophagy--or "self-digestion."

Every cell in our body is the result of the completion of countless cell cycles, from one cellular division to the next. Each cell cycle, shown schematically in Figure 1, is a chemically orchestrated sequence of phases in which a multitude of proteins actively control the growth of the cell and ensure it divides safely. When DNA damage is encountered, the cell cycle is halted at what's called the G2 checkpoint and division is postponed until the problem is fixed. In many types of cancers including PDAC, the G2 checkpoint is strongly activated after irradiation, which has been shown to increase resistance to therapy.

On the other hand, autophagy is a natural mechanism by which a cell digests some of its own organelles and proteins, especially damaged or unnecessary ones, to reclaim nutrients and maintain proper internal conditions, among other functions. While essential for healthy cells, researchers have found that autophagy increases in cancer cells right after radiation treatment and that it actually helps them endure and survive therapy.

Most interestingly, because autophagy and the G2 checkpoint share some of the same chemical signals, it has been suggested that these two processes are interrelated. "Although a relationship had been proposed, the mechanistic details of the interactions between autophagy and the G2 checkpoint after irradiation were unclear. Thus, in our recent study, we sought to understand more about the link between these processes, especially in PDAC cells," explains Dr. Hasegawa.

After numerous experiments in PDAC cell cultures, the team of scientists led by Dr. Hasegawa determined that irradiation-induced autophagy is dependent on the G2 checkpoint being activated. Moreover, they showed that autophagy helped the irradiated PDAC cells generate more energy (in the form of a molecule called ATP), which in turned led to their survival. Thus, the team proceeded to analyze what happened to irradiated PDAC cells when the G2 checkpoint was chemically inhibited. These irradiated cells, which could not activate the G2 checkpoint, did not undergo autophagy, and thus were much more likely to die post-radiation (Figure 2).

These promising results were then tested in mice onto which PDAC cells were transplanted to produce tumors. By treating these mice with both radiation and the G2 checkpoint inhibitor, the scientists managed to greatly suppress tumor growth compared to when irradiation was administered alone (Figure 3). In essence, this means that suppressors of the G2 checkpoint, which also mitigate autophagy, could be effectively used as tools to lower the radiation resistance of PDAC cells. "Our research," concludes Dr. Hasegawa, "should facilitate the development of radiosensitizers or new radiotherapeutic strategies for PDAC. In turn, this could largely improve the survival rate of patients with this type of cancer."

Further studies will be needed to better understand the connection between the G2 checkpoint and autophagy and how these processes make cancer cells more resistant. Let us hope scientists eventually find ways to effectively combat particularly difficult cancer types, such as PDAC, and give more years of life to affected people.

BINGHAMTON, N.Y. -- New research from Binghamton University, State University of New York shows the human trauma and family separation that resulted from the Trump Administration's zero tolerance policy on undocumented immigration.

The news reports surrounding the Trump Administration's "zero tolerance" policy on undocumented immigration were stark: children separated from their parents, uncertain whether they would ever see them again.

All told, the official zero tolerance policy lasted only a few months, from April to June 2018. But family separations occurred before and after those dates: at least 5,512 children were separated from their families since July 2017, and 1,142 families were separated even after the policy formally ended.

Along with four Binghamton students, Assistant Professor of Human Development Óscar F. Gil-García put a human face on these tragic statistics in "'It felt like my son had died': Zero tolerance and the trauma of family separation," recently published in the journal Latino Studies, the article documents the impact of immigration policy on a Central American family that became separated in 2017 from their son David, a minor and a United States citizen.

As the Biden administration begins to reunify families, the case of David and his family provides an opportunity to comprehend the long-term harm inflicted by family separations, said Gil-García, who is also affiliated with Latin and Caribbean Area Studies (LACAS).

"Immigration policies in the U.S. and Mexico are really damaging to migrant populations; they paint migrant populations as not human, but as criminals and as undeserving," said co-author Sarah Vener '22, an English and political science dual major. "We see that this creates human rights abuses that have real impacts on people throughout their lives -- and those impacts last."

Vener has spent three years as a research assistant under Gil-García, exploring the effects of U.S. and Mexican immigration policy on indigenous Maya refugees. Co-authors also include Francesca Bové '21, who recently graduated with a master's in public administration; psychology major Luz Velazquez '21; and sociology, human development and LACAS triple-major Alexandra Miranda '22.

The interview with David came out of a larger project that Gil-García has been working on since around 2012, concerning members of a Maya community living in the Mexican state of Chiapas. Gil-García worked with these stateless individuals on obtaining legal status in Mexico; David's parents, Evelyn and Carlos, were among them.

The two had fled Guatemala in 1985 to escape that nation's civil war. Lacking legal status and job opportunities in Mexico, they crossed the border to work at an Alabama sweatshop. David was born in the United States in 2003, making him a U.S. citizen.

He first became separated from his father at only 4 years old, when he and his mother returned to Mexico, concerned about rising deportations; Carlos joined them two years later. At the age of 14, David expressed interest in returning to the United States for his education. His father joined him, believing that his son's U.S. citizenship meant that he could accompany him. That proved not to be the case.

The two were immediately separated by immigration officials. After two months' detention, Carlos was deported to Mexico in February 2018. David ended up in the Arizona foster care system, and neither knew the whereabouts of the other for months.

Frantic, Carlos and Evelyn enlisted Gil-García's help in tracking down their son, who ended up in three different foster-care facilities. Unable to speak English, he was at times unable to communicate in his group home, and struggled with eating and sleeping. Gil-García worked with David's family to expedite his release. Just as the coronavirus began to spread, David was finally able to leave the foster care system and live with a family member in California.

While David's story may seem uniquely tragic, he's not alone, the researchers stress; more than 5.9 million children who are citizens of the United States have at least one undocumented parent and live with the constant fear of family separation.

Such separations have long-lasting health consequences for both the children and their families, including forms of post-traumatic stress disorder (PTSD), anxiety, depression and other conditions that can shorten life expectancy. Family separations also meet the definition of an enforced disappearance, which is considered a crime in international law -- and even the United Nations' definition of torture, the researchers note.

For all the pain they inflict, zero tolerance policies are largely ineffective in deterring migration; in fact, they have the opposite effect, Gil-García noted.

"These kinds of separations are actually creating new forms of migration and compelling these individuals to re-migrate," he said.

Gil-García and his research team have other projects in the works concerning experiences like that of David and his family. One will conceptualize a heuristic model for practitioners who want to help unaccompanied minors cope with the trauma of family separation.

Forty years ago, the first cases of HIV/AIDS in the U.S began to raise public awareness- but new research highlights the struggle people living with the disease still face against stigma, discrimination and negative labelling in their own families, communities and even amongst healthcare professionals.

A new study by Flinders University researchers interviewed 20 HIV healthcare providers including doctors, nurses, and counsellors in Yogyakarta and Belu districts, Indonesia to examine their experiences when treating patients with HIV. Their responses indicated admission of personal stigma and discrimination towards people living with HIV.

Although there is no significant differences in the number of HIV cases in the two settings, where Yogyakarta reports 1,353 HIV cases and Belu reporting 1,200 cases, Yogyakarta is a traditionally Muslim area with the majority of people following Javanese culture, while Belu is a traditionally Christian area where the majority of people follow Timorese culture.

The research, published in Frontiers in Medicine, coincides with the 30th anniversary of Princess Diana's speech that it is okay to hug those with HIV/AIDS, bringing to the forefront discussion about the disease which had up to that point created misconceptions in society.

A Flinders University Researcher, Nelsensius Fauk, the lead author of the study, says people living with HIV/AIDS are being significantly discriminated in a wide range of ways. For example, they may be subjected to separation of their personal belongings by family members, be avoided physically by community members, and they may go through a rejection or not being provided treatment by the healthcare providers.

"Due to the lack of knowledge about HIV, there is still a fear in the community about contracting the disease from patients and a reluctance to help because of personal values, religious stances, socio cultural values and norms in these communities, which directly contribute further towards HIV stigma and discrimination of people living with HIV/AIDS."

"HIV stigma and discrimination may lead to people living with HIV concealing their condition and self- isolate, potentially hindering their access to important healthcare services. The findings indicate the importance of HIV/AIDS education programs for family and community members and for the healthcare providers to improve their awareness, so they can accept patients living with HIV."

Senior author Associate Professor Lillian Mwanri says although treatment modalities have improved significantly, and the quality of life improved where HIV patients are treated effectively, HIV stigma and discrimination remain very prevalent, leading to poor access to service by patients and healthcare providers being less familiar with how to manage and interact with HIV patients.

These in turn increase healthcare providers fear of contracting HIV from patients. This vicious cycle of HIV stigma needs to be addressed urgently to improve effective access of service and the quality of life for people living with HIV.

"Negative perceptions and judgements about people living with HIV through unprotected sex or injecting drug use (IDU), and general negative portrayals of them, are also drivers of discriminatory treatment by healthcare providers."

Other factors such as healthcare providers' gender, race and religion have also been reported to play a role in discriminatory attitudes

"Understanding the perspectives and experiences of healthcare providers related to HIV stigma and discrimination will be an important contribution to the current body of knowledge and useful for the improvement of HIV care systems and delivery, and to improve the health outcomes of people living with HIV in Indonesia and globally."

A separate study in Ethiopia has evaluated the success of HIV testing as part of UNAID's first 90 program.

A trial using mice has shown that a diet high in sugar from childhood could lead to significant weight gain, persistent hyperactivity and learning impairments

Many people on 'western' diets consume four times more the sugar recommended by the World Health Organisation (WHO)

Reducing sucrose intake in mice by four-fold prevented sugar-induced increase in weight gain, supporting the WHO's recommendations of 25g per person a day.

Children who consume too much sugar could be at greater risk of becoming obese, hyperactive, and cognitively impaired, as adults, according to the results of a new study of mice led by QUT and published by Frontiers in Neuroscience.

The study resulted in a reduced risk of sugar-induced weight gain and other health problems when the mice were given a much smaller daily dose of sucrose, supporting World Health Organisation calls for a reduction in sugar intake by humans.

One of the lead authors, QUT neuroscientist Professor Selena Bartlett, says many children, adolescents, and adults in more than 60 countries, including Australia, have a diet consisting of more than four times the sugar (100g) recommended by the World Health Organisation (25g per person per day).

"More work needs to be done in the investigation of the long-term effects of sugar on adolescents and adults but our results with the mouse model are very promising," said Professor Bartlett.

"Recent evidence shows obesity and impulsive behaviours caused by poor dietary habits leads to further overconsumption of processed food and beverages but the long-term effects on cognitive processes and hyperactivity from sugar overconsumption, beginning at adolescence, are not known," said Professor Bartlett.

"Our study found long-term sugar consumption (a 12-week period with the mice which started the trial at five weeks of age) at a level that significantly boosts weight gain, elicits an abnormal and excessive stimulation of the nervous system in response to novelty. It also alters both episodic and spatial memory. These results are like those reported in attention deficit and hyperactivity disorders.

"Human trials would need to be done but it suggests a link to the long-term overconsumption of sugar, beginning at a young age, which occurs more commonly in the Western Diet and an increased risk of developing persistent hyperactivity and neurocognitive deficits in adulthood."

Professor Bartlett said while the concept of 'sugar addiction' and the classification of sugar as a substance of abuse were still being debated, there is increasing evidence of overlap in the brain circuitry and molecular signalling pathways involved in sugar consumption and drug abuse.

"People consume sugar and food to regulate energy balance, but also for pleasure and comfort. This hedonistic desire for palatable food is reward-driven and overeating can impact upon and even override our ability to regulate," Professor Bartlett said.

"It is increasingly considered that unrestricted consumption of high-sugar food and beverages within the Western Diet might be linked to the increased obesity epidemic. A strong association between attention-deficits/hyperactivity disorders and being overweight or obese have also been revealed.

"Taken together, these data suggest that sugar-induced obesity may participate to the developing pathogenesis of ADHD-like symptoms in western countries. In children, high sugar consumption correlates with hyperactivity and in adults, with inattention and impulsivity.

"What has been unclear though, is whether chronic overconsumption of sucrose - starting from childhood - would have the same negative impact on our nervous system, emotions or cognition throughout adulthood as other addictive drugs.

"This study on mice goes a long way to resolving that question. Our results show for the first time that long-term consumption of sucrose leads to significant weight gain and produces persistent hyperactivity and learning impairments."

Co-lead author Dr Arnauld Belmer added that while the overall sugar consumption has dropped since the mid-1990s, obesity rates have climbed.

"This rise in obesity rates could result from a delayed effect of excess sugar, suggesting that adult obesity may be driven by high sugar intake over a life span," Dr Belmer said.

"Interestingly, our investigation with the mice found reducing the daily sucrose intake four-fold did prevent sugar-induced increase in weight gain, supporting the WHO's recommendation to restrict sugar intake by this amount would be effective. It could also limit the other negative consequences including hyperactivity and cognitive impairment."

The Amami, Okinawa region of Japan may be designated a World Heritage Site in July of 2021 based on the recent recommendation from the IUCN. The Iriomote wild cat is a symbolic species of the region, having evolved independently on the island. The area is home to many other highly endemic and unique evolutionary species. A research group comprised mostly of former students of Professor Koji Tojo's Faculty of Science lab of Shinshu University focused on the study of dragonflies, continuing from their previous study of their comparative embryogenesis. About 5,000 species of insects belonging to 26 families of the order Dragonfly are known in the world, but those with some gill-shaped protrusions on the abdomen of the larva are extremely rare. Professor Tojo's lab had been studying the Euphaea yayeyamana and the Bayadera brevicauda of the same Euphaeidae dragonfly family in Japan.

Professor Tojo considers that the abdominal gills of these dragonflies are important traits in the origin of insect wings and have studied embryology and developmental genetics targeting this area. In the process of such study, they noticed an interesting genetic feature that is the subject of this paper. Population genetics theory implies that smaller populations that are fragmented contain less genetic diversity than larger populations. They will have a higher rate of genetic fixation due to inbreeding and random genetic drift. However, the result of their genetic analysis of the mitochondrial DNA COI region revealed that E. yayeyamana (Ishigaki/Iriomote) which inhabits smaller islands, has a higher genetic diversity than E. formosa (Taiwan) which inhabits larger island.

Generally, in a small island environment, the population size remains small, so genetic diversity tends to be kept low. Ishigaki Island and Iriomote Island, which were the targets of this study, are only 1/125 and 1/155 in area, respectively, compared to Taiwan. The scale of the mountainous areas on the island is also very different, with the highest altitudes of Ishigaki Island and Iriomote Island being 469 m and 526 m, respectively, while the highest peak in Taiwan is 3,952 m. As for the habitat of Euphaea dragonflies inhabiting mountainous areas, Taiwan has more diverse environments than Ishigaki and Iriomote.

The speciation of E. yayeyamana in Yaeyama (Ishigaki / Iriomote) and E. formosa in Taiwan is estimated to be about 1.4 million years ago. In addition, this study clarified that the genetic diversity of the E. yayeyamana in Ishigaki and Iriomote is much higher than the genetic diversity of the E. formosa in Taiwan. As a result of wide-ranging and comprehensive sampling and gene analysis on both Ishigaki and Iriomote islands, dispersion was found to have occurred within Ishigaki Island and Iriomote Island, and gene flow within each island is actively occurring. On the other hand, gene flow between islands was not observed, and a large genetic differentiation was observed. In addition, it became clear that in the past, there were at least three dispersals from Ishigaki Island to Iriomote Island. The dispersion between Ishigaki Island and Iriomote Island is probably due to the westerly wind (probably Taiwan ? Iriomote ? Ishigaki). No such sign is observed for dispersion in the opposite direction. In other words, it was found that the genomes of dragonflies unique to Taiwan and the Yaeyama region are engraved with genetic information that strongly reflects the effects of geological history and meteorology.

The results of this study were very surprising. The investigation into the cause of such a genetic structure remains a mystery, but Professor Tojo believes that "in Taiwan, a phenomenon such as the "bottleneck effect" that once caused a significant reduction in population size occurred. On the other hand, on Ishigaki and Iriomote Islands, habitats such as those inhabited by E. yayeyamana have been relatively stable over a wide area of the island. In the northeastern peninsula of Ishigaki Island, the forest environment tends to be small and divided. As a result, genetic diversity is also kept low in this area. Through this research, I became keenly aware of the importance of actually analyzing data without being overwhelmed by prejudice."

Not only is the evolutionary history but the morphological traits are unique to this area, and the group is planning to continue to analyze the genetic structure using various molecular markers in addition to pursuing the relationship between morphogenesis and the genetic basis. While adding the analysis of nuclear DNA, the group have analyzed another region of mitochondrial DNA and would like to re-evaluate the gene flow scale using more sensitive gene markers.

A long-standing basic question in biology relates to how life satisfies the fundamental constraints put on it by physics and chemistry. Darwin's warm pond hypothesis for the origin of primordial cells is a familiar one. Advances have been made in mapping out the organic molecules that likely existed on the early Earth, and recently candidate prototypic pathways in early cells have been formulated. But how did these candidates' early biochemistry actually function as a system, on which subsequent cellular life is based?

A team of bioengineers at the Novo Nordisk Foundation Center for Biosustainability, DTU, has now defined ten overarching classes of constraints on early metabolic networks dictated by basic chemistry and physics. These constraints concern fundamental aspects of chemical processes, such as thermodynamics, electroneutrality, osmotic pressure, and pH. These are abiotic constraints (called ABCs given their fundamental nature) that all living systems have to abide by.

The challenge has been to simultaneously reconcile all these complex constraints to define allowable operating conditions for living cells. This problem is a challenge in computational biology, a challenge that the team has resolved, the results of which have been published in Nature Communications.

"The computations are challenging because of the nonlinearity of governing equations and nonconvexity of solution spaces, which required special optimization techniques tailored to the geometric structure of the problem", says Dr. Amir Akbari, the lead author of the study and adds:

"We worked hard on the formulation of the algorithms that eventually gave the solution and thus the conditions under which fundamental biochemical processes can operate."

The investigators analysed how these constraints operate on basic energy metabolism in bacteria. The results demonstrated, among other things, the fundamental role of thermodynamic constraints in the evolution of alternative transport systems.

"The computations are consistent with published metabolomic data", says Bernhard Palsson, CEO and Professor at The Novo Nordisk Foundation Center for Biosustainability at Technical University of Denmark.

He continues:

"The study also revealed how basic stress response mechanisms, such as those for osmotic pressure and reactive oxygen species (ROS) have to work and be regulated. Remarkably, the behavior of modern bacteria reflects the computational predictions."

Overall, this advancement helps to understand systems biology at a fundamental level and how the basis for the process of life shapes possible early evolutionary trajectories. The next step for the scientists is to apply this computational framework to gain insight into candidate abiotic organic chemical processes and the possible forms of initial metabolic networks.

"These processes have to form homeostatic states that are sufficiently stable to provide the environment for the evolution of more complex cellular functions.", says Professor Palsson.

The fluorescence dyes were dominant species of the near-infrared (NIR) dyes, but the energy gap of the NIR dyes between S1 state and S0 state is generally small to induce the ultrafast internal conversion dynamics to quench the NIR emission of the fluorescence dyes. Therefore, the quantum yield of the fluorescence NIR dyes is usually low. On the other hand, the organic dyes with room-temperature phosphorescence (RTP) in the NIR region could prevent the ultrafast internal conversion dynamics quenching because of the T1 state and S0 state the organic molecules are spin forbidden.

Recently, scientists in China reported a new assumption to construct efficient NIR materials based on the energy gap law on the National Science Review. In addition, a series of metal-free RTP films with NIR emission was constructed based on the assumption, and the first phosphorescence-based half-subtractor operation was also developed based on the stimuli-responsive properties of the dyes.

It could be an available strategy to construct efficient metal-free NIR materials by controlling the external environments of the organic molecules with red-light fluorescence to inhibit the non-radiation decay of the light-emitting molecules. The short lifetimes of the triplet state of the NIR RTP molecules could benefit their NIR emission because the other non-radiation decay processes of the long-lifetime triplet state of the NIR RTP molecules could offset the spin forbidden benefit factor of the IC to quench the NIR emission. This assumption could lower the threshold of the construction of the metal-free NIR materials. Therefore, phenolsulfonphthalein dyes with red-light emission (BR, BPB, TBPB) were chosen as NIR emitters in this research to demonstrate this assumption and polyvinyl alcohol (PVA) were chosen as rigid matrixes to inhibit the non-radiation relaxation process. In conclusion, all phenolsulfonphthalein dyes emitted moderate NIR RTP in the PVA matrix, where TBPB@PVA films shown the best performance (ΦRTP = 3.0%, λp = 819 nm). This research preliminary proved that the spin forbidden IC process of the T state and the ground state of the organic molecules could be favorable to construct effective NIR dyes, and this assumption might provide a new train of thought for the development of the organic materials with NIR emission.

As Australia officially enters winter, UniSA ecologists are urging coastal communities to embrace all that the season brings, including the sometimes-unwelcome deposits of brown seaweed that can accumulate on the southern shores.

While tidal seaweed (or sea wrack) may seem unsightly - especially at beach-side tourist destinations - new research from the University of South Australia shows that it plays a vital role for many migratory seabirds and should be protected.

In the first study of its kind, UniSA researchers show that beach-cast seaweed provides shelter, and a range of microclimates, in addition to food, that ensure the survival of many shore-bird species.

Specifically, sea wrack acts like a reverse-cycle air conditioner creating cooler conditions when the weather is hot and warmer conditions when it is cold, helping seabirds regulate their body temperatures.

UniSA researchers, Tim Davis and Associate Professor Gunnar Keppel, say that councils, residents and tourists must be educated about the ecological role of sea wrack and how removing it from beaches can have a significant impact on the environment and the survival of bird species.

"Australian beaches are renowned for stretches of golden sand - it's one of the main drawcards for tourists - so it's not altogether surprising that beachside destinations tend to favour a seaweed-free coastline," Davis says.

"The challenge is, however, that while people may see beach-cast sea wrack as an eye-sore, it actually has an ecological role to fulfill, particularly for migratory shorebirds.

"Our research shows that sea wrack provides important microclimates to help seabirds regulate their body temperatures - they mostly forage, rest and roost in the older, dryer wrack, which is warm throughout most of the day. However, they also seek refuge among fresh wrack in the early mornings when it is the warmest habitat available.

"Shore birds move between the different wrack types depending on the prevalent weather conditions. This helps them conserve and build sufficient energy stores for successful migration and reproduction in overseas breeding grounds.

"When sea wrack is removed, then so too are the habitats of these sea birds, and this can have a devastating impact on their populations."

Globally, beach-cast wrack is removed from many beaches worldwide, either for aesthetic reasons to increase tourism, for fertilisers, or to extract alginate for applications in the food and beverage industry, and the biomedical and bioengineering fields.

Currently, Australian has no guidelines for harvesting wrack.

"Sustainable management of all aspects of coastal environments is essential if we are to conserve the livelihoods of the species that rely upon them," Davis says.

"Until a code of practice is established, our coastal ecosystems will remain under threat."

Travellers abroad may pick up bacteria and other vectors containing genes conferring antimicrobial resistance which remain in the gut when returning to their home country, according to a study published in Genome Medicine.

A team of researchers at Washington University, USA and Maastricht University, Netherlands investigated the presence of antimicrobial resistance (AMR) genes in the human gut microbiome by analysing the faecal samples of 190 Dutch travellers before and after travel to destinations in Northern Africa, Eastern Africa, Southern Asia and Southeastern Asia. The gut microbiome includes bacteria and other organisms that live in the digestive tracts of humans. The participants and their samples were taken from a subset of data from the larger COMBAT study also investigating AMR. AMR genes have naturally developed in bacteria over millennia when they were exposed to antibiotics naturally produced by a few environmental bacteria, but overuse and misuse of antibiotics in human medicine and animal agriculture is accelerating the process. Antimicrobial resistant bacteria do not respond to treatment with antibiotics to which they have developed resistance.

The authors found an increase in the amount and diversity of AMR genes in faecal samples from travellers who had returned from abroad, including high-risk AMR genes that are resistant to common and last resort antibiotics (antibiotics which are used when other antibiotics do not work).

The authors used metagenome sequencing of the faecal microbiomes to identify AMR genes in the samples by matching them to a database of known AMR genes. They also identified new AMR genes by testing whether genes from the samples, when added to an E. coli host, would allow those E. coli to gain new resistance to antibiotics.

Diversity of AMR genes in the microbiome significantly increased in individuals travelling back from all destinations, with evidence for 56 different AMR genes acquired during travel. This diversity was highest in those who went to Southeastern Asia. AMR genetic diversity was lower between travellers who went to the same destination, meaning they had more AMR genes in common with each other than with travellers from different destinations. This indicates that travellers picked up destination-specific AMR genes.

An in-depth genetic analysis identified high-risk AMR genes which are resistant to common and last resort antibiotics. Six of the ten high-risk genes identified were present after travel but not before, which indicates that they were acquired during travel. For example, the mcr-1 gene, which confers resistance to colistin, a last resort treatment for infections such as pneumonia and meningitis, was found only in samples after travel. The gene was found predominantly in the microbiome of travellers to Southeastern Asia; 18 of 52 (34.6%) travellers included in the study who travelled to destinations in the region carried the gene upon returning. The finding indicates that travellers may have acquired the gene at their destinations.

Faecal samples of the microbiome taken before travel also contained some AMR genes and the authors acknowledge that it is possible that the travellers also spread AMR genes to the destinations they visited. The authors lacked samples from the contacts travellers interacted with, so cannot be certain how the travellers acquired the AMR genes.

Alaric D'Souza, the lead author, said: "These findings provide strong support that international travel risks spreading antimicrobial resistance globally. Upon returning, travellers' microbiomes had acquired a significant amount of AMR genes. Many of these genes were high-risk AMR genes, since they confer resistance to commonly used antibiotics."

The authors conclude that understanding how AMR genes spread from country to country will help target public health measures to prevent further spread. Future research could investigate the contacts travellers interact with during their visits to understand how AMR genes are transmitted.

D'Souza said: "It is vital that we address AMR in lower income countries with high resistance rates and low public health funds. This global approach may not only help the respective countries, but it could also benefit others by reducing the international spread of resistance genes."

In football, chance is defined as actions or situations occurring during the game that cannot be planned and are therefore difficult to train for. Take for instance deflected shots, balls that rebound off the post only to be kicked straight into the goal or goals that are unintentionally assisted by a defender. The primary focus of most researchers has been on analysing success factors, to enable the coach to build these systematically into the training programme. But they have often neglected to include the pure chance factor at play. This is because of the difficulty of integrating such random chance factors into training routines and game patterns.

A recent study led by Prof. Dr. Daniel Memmert, Executive Head of the Institute of Exercise Training and Sports Informatics at the German Sport University Cologne shows that such factors still warrant closer examination. The research team analysed a total of 7,263 goals scored in the English Premier League in the 2012/13 to 2018/19 seasons, leading to the publication in the Journal of Sports Sciences of the largest Big Data study to date, on chance as a factor in professional football. In order to be able to quantify randomness in football by identifying chance and its influence in the goal-scoring process, six basic variables were selected, including goals following a rebound, long-range shots, deflected shots or goals created by defensive errors like, for instance, own goals. In addition, the study takes into account nine further situational variables, which include season, matchday, match location, match situation, goal number or team strength. All 7,263 goals were then evaluated for the presence of the variables mentioned.

The researchers' findings turn up surprising results: in almost every second goal scored (46%), some form of random influence has been identified. Furthermore, there is a pronounced increase in the proportion of chance goals scored by weaker teams, but also for goals scored when the current scoreline is a draw. Moreover, the occurrence of chance goals is dependent on the match situation (open play, free kick, corner, penalty kick). Sport scientist Fabian Wunderlich, first author of the recently published paper sums up the findings: "The results clearly highlight the essential role of chance in football, as almost every second goal benefits from random influence." Wunderlich goes on to note: "Another interesting finding is that the proportion of chance goals has dropped from 50 per cent to 44 per cent over the seven seasons. This might be caused by the fact that match preparation is becoming increasingly professional and data-based driven, or that players are becoming better trained technically as well as tactically."

Within the evaluated data set of 2,451 matches, more than 60 per cent of all matches ended either in a draw or with a goal difference of one goal. "A single random goal can therefore be enough to significantly change the outcome of a match. Thus, chance is not only highly relevant in the case of that particular goal. Chance also plays a significant role in deciding the final score of the match," concludes co-author, Prof. Dr. Memmert.

The research team is convinced that a better understanding of random influences in football can have important implications for research and practice. Coaches and match analysts should bring chance into the equation as a decisive factor while taking much greater cognizance of the difference between performance and success. Memmert suggests, "Coaches could even consider deliberately creating uncontrollable situations to provoke random influences in the goal-scoring process".

Indeed, the relevance of chance seems to be diminishing, at least according to this study. However, pure chance and good luck are still likely to continue throwing up one or two surprises in football.

Carbon loss in Canadian peatland is projected to increase by 103 per cent under a high emission scenario, according to new research led by scientists from the University of Waterloo.

The results of the study, which was published today in Nature's Communications Earth & Environment journal, reinforces the urgent need for a comprehensive understanding of peatlands as evolving sources of atmospheric CO2 in a warming world.

Peatlands, which are a type of wetland, are some of the most valuable ecosystems globally. In addition to their role in preserving biodiversity and minimizing flood risk, they store approximately one-third of the world's terrestrial organic carbon, despite only covering an estimated three per cent of the continents.

The researchers believe the study, which had Faculty of Engineering student Arash Rafat as lead author, has implications for future climate policy. Even under the lowest radiative forcing scenario, peatlands will act as a source of CO2 during the non-growing season (NGS) throughout the remainder of the 21st century. This reinforces the hypothesis that climate warming has the potential to increase peatland CO2 emissions during the NGS across various northern regions from around the world.

"Our research offers important insights into how Canada's northern peatlands will react to climate warming, especially during the non-growing season," said Fereidoun Rezanezhad, a professor in Waterloo's Department of Earth and Environmental Sciences. "As the climate warms, it is important to understand to what degree this will impact peatland ecosystems and their release of CO2 emissions - especially in areas of greatest warming, which include peatlands in northern regions and during the NGS."

To improve our ability to predict NGS CO2 emissions from northern peatlands under current and future climate change, a team of Waterloo's Water Institute researchers led by Ecohydrology Research Group professors Rezanezhad and Philippe Van Cappellen worked with professor William Quinton of Wilfrid Laurier University, professor Elyn Humphreys of Carleton University, and research scientist Dr. Kara Webster from the Canadian Forest Service Great Lakes Forestry Centre.

The team developed a machine-learning model to determine that changes in soil temperature and photosynthesis are the primary drivers of changes in net carbon flux. To predict future NGS CO2 emissions, the team developed the model using a continuous 13-year dataset of eddy covariance flux measurements from a peatland site located in Ottawa, Canada called the Mer Bleue Bog.

"The projected 103 per cent increase in peatland carbon loss by 2100 under a high radiative forcing scenario will constitute a strong positive climate feedback loop," said Rafat, who engaged in the research during his co-op term in the Waterloo's Faculty of Science. "In this climate feedback loop as the climate warms, peatlands release greenhouse gases, which in turn contributes to further climate warming."

For years, psychology researchers have treated peer rejection and social network isolation as being somewhat interchangeable when it comes to early adolescence; it was thought that if kids fell into one of those two groups, they fell into the other. A recent study finds there is actually little overlap between the groups - and socially isolated kids face different risks.

"Broadly speaking, there are two types of socially marginalized groups in early adolescence," says Kate Norwalk, lead author of the study and an assistant professor of psychology at North Carolina State University. "There are kids who face peer rejection, meaning they are disliked by other kids; and there are kids who are experiencing social network isolation, meaning they don't have a group of friends. Historically, I think researchers have treated these two groups as being the same.

"What I wanted to explore with this study is whether these two groups are actually distinct from each other, and what that means for the well-being of these kids. We know a lot about rejected kids - there's decades of research on them. But we really haven't paid any attention to isolated kids. And, as it turns out, they are very different."

For their study, Norwalk and her collaborators drew on data from 1,075 students in 5th, 6th and 7th grade. The students were surveyed twice a year for two years. Peer rejection was measured by asking the students who they "liked least" in their class. Social network isolation was measured by asking kids to describe who in their class "hangs out together;" kids who were not named were considered isolated, because they were not identified as being part of any peer group. Students were also asked which students in their classes exhibited a range of specific behaviors. Lastly, students were asked whether they thought peers would help them if they were being bullied.

Simply put, the researchers found that there were clear distinctions between kids who were rejected and kids who were isolated.

"There was very little overlap between the two groups," Norwalk says. "Most of the kids who were liked least in a class still had some sort of peer group; and the kids who didn't have a peer group weren't especially disliked."

In fact, one of the only things the two groups had in common was that being in either the rejected group or the isolated group was associated with an increased risk of victimization - meaning that students in either group were more likely than other kids to be picked on or bullied.

But while each group was also associated with other behavioral challenges, the nature of those challenges varied significantly.

Students in the rejected group were more likely than other kids to exhibit aggressive behavior, such as bullying and disrupting class. They were also less likely to exhibit prosocial behavior, such as being kind and doing well in the classroom.

This was not the case with students in the isolated group, who were more likely to exhibit internalizing behaviors, such as being shy and withdrawn. Kids in the isolated group were also the only ones who generally reported that they would not expect support from their peers if they were bullied.

"This study shows that students facing peer rejection and students dealing with social isolation have different profiles and face different risks," Norwalk says. "What's more, isolated kids may be more likely to fly under the radar precisely because they're not causing problems in class or bullying other kids.

"But children grappling with social isolation clearly need support. The internalization behaviors we see associated with isolated kids in this study are often early symptoms of mental health challenges. And because they are isolated, teachers and parents may be less likely to identify them as victims of bullying - even as they struggle with less peer support against bullying," Norwalk says.

"I think we - parents, teachers, counselors, researchers - need to find ways to better identify and support those kids."