Culture

On Feb 5th, Seoul National University, College of Engineering (Dean Kookheon Char) announced that Professor Sang Woo Seo's research team (Dr. Jina Yang and Mr. Yong Hee Han (graduate student)) at School of Chemical and Biological Engineering has developed a synthetic protein quality control system to enhance full-length translation in bacteria. This technology is expected to increase the efficiency of the production of biopharmaceuticals, industrial enzymes, and bio-based chemicals.

Recombinant proteins are used in various industrial fields from protein drugs such as insulin to industrial proteins such as laundry detergents. Since proteins can perform their functions only with full-length and proper 3D structure, recombinant protein production using microbial cell factories requires several protein purification steps. To enhance the yield of the production process, strain improvement techniques have been developed to increase the target protein expression level or to supplement the insufficient amino acids in a cell. However, since transcription and translation steps occur in the same place at the same time in bacteria, truncated mRNA can be served as a template for translation by ribosome resulting in the production of incomplete polypeptides.

The Protein Quality Control system (ProQC), developed by Prof. Seo's research team, is a synthetic gene expression cassette that allows ribosomes to only use intact mRNA as a template. In eukaryotic expression systems, the translation process is initiated after the transcription process is completed. By mimicking this, when the transcription process is completed, the cis-trigger element at the 3'end of mRNA can hybridize with Toehold switch at the 5'end and expose ribosome binding sites for the translation. Also, the mRNA becomes circular ensuring efficient re-initiation of ribosomes.

By applying the ProQC system to various protein expressions, the bacterial cells synthesized more full-length proteins (up to 250%). In addition, when the enzymes in the biochemical synthesis pathways were expressed under the control of the ProQC system, the target metabolite production levels were also increased more than two times.

Professor Sang Woo Seo said, "The gene expression system developed in this study allows bacteria to selectively translate intact mRNA to synthesize high-quality proteins by themselves. Also, as this technology is applied to a new level of regulation, there will be synergies when used with existing recombinant protein production strategies. It will dramatically improve the efficiency of the microbial cell factory-based recombinant protein and biochemical production."

Although SGLT-2 inhibitors are central to the treatment of diabetes, their exact mode of action was hitherto unknown. In a study conducted by a research group led by Peter Wolf, Martin Krssak and Michael Krebs from MedUni Vienna's Department of Medicine III, magnetic resonance spectroscopy (MRS) was used to show that there is a direct correlation between the elimination of glucose via the kidneys and new glucose production in the liver. A single dose of the SGLT-2 inhibitor dapagliflozin gives rise to a beneficial regulation mechanism, in which glucose loss due to drug-induced SGLT-2 inhibition is exactly balanced out by an equal increase in new glucose production in the liver. The study has been published in the leading journal Diabetes Care.

Dapagliflozin is a drug from the group of SGLT-2 inhibitors, which are standardly used in the treatment of diabetes. They increase the amount of glucose that is excreted in the urine. This reduces blood glucose levels and patients also lose weight. A beneficial impact on fatty liver, which is prevalent among diabetics, has also been described after a twelve-week course of the drug. Remarkably, this group of drugs also seems to have a protective effect on the heart and kidneys. However, the acute impact upon lipid and energy metabolism had not yet been studied in any detail.

A research group led by Peter Wolf, Martin Krssak and Michael Krebs from the Division of Endocrinology and Metabolism at the Department of Medicine III has now conducted a study using MRS, in which they observed six diabetic patients and a control group of ten healthy volunteers after they had taken dapagliflozin. It was found that, in the short term, the amount of additional glucose produced in the liver exactly matched the amount lost in the urine due to the action of the drug. This suggests that the increased elimination of glucose via the kidneys immediately triggers a series of regulation mechanisms that affect the metabolism in several organs and could therefore play a role in the beneficial effect of this drug.

The study was produced in collaboration with the Center of Excellence for High-Field MRI of MedUni Vienna's Department of Biomedical Imaging and Image-guided Therapy. Using high-resolution magnetic resonance imaging, it was possible to quantify serial measurements of glucose and fat storage in the liver in a non-invasive way. In combination with the infusion of tracers (such as a marked glucose solution, for example) it is possible to use this "virtual biopsy" to identify a change in the glucose and lipid metabolism in vivo and to study the acute, short-term impact of drugs.

Researchers at the Kobe University Graduate School of Science have revealed that when captive-bred juvenile red-spotted masu salmon are released into natural streams, very few individuals become migrants.

Red-spotted masu salmon was an important fish species for the fishing industry in the rivers of west Japan, however in recent years their numbers are declining rapidly. The results of this research offer important suggestions for stocking practices and the management of river environments.

The research group consisted of graduate school students TANAKA Tatsuya and UEDA Rui and Associate Professor SATO Takuya. The results were published in Biology Letters on January 13, 2021.

Main Points

Red-spotted masu salmon (Oncorhynchus masou ishikawae) that exceed the threshold body size by their first fall reach the smoltification (*1) stage of the salmon life cycle, and thus become migratory.

When captive-bred individuals are raised in an environment similar to that of a hatchery, they usually grow beyond the threshold size in their first fall, undergoing smoltification.

However, according to these research results, very few of the captive-bred fish released into natural streams during their first early summer exceed the threshold size by fall, with hardly any individuals becoming smolts.

This research revealed that juvenile captive-bred salmon released into the wild are highly unlikely to become migratory individuals.

Research Background

Preserving variation within a species is vital for many reasons, including for the species' long-term existence and for the sustainability of resources for humans. Migratory behavior is one example of variation in the life cycle of a particular species which is important for its continuation.

For example, within most species of salmonid fish, there are two phenotypes: migratory and non-migratory (resident). Migratory fish travel from the rivers to the ocean and then return to the rivers to spawn, whereas non-migratory individuals live in rivers for their entire lives. However in recent years, various factors such as reduced connectivity between rivers and oceans have caused a sharp decline in the number of migratory individuals. Consequently, large numbers of salmonid fish that were bred in captivity are released into rivers across the globe with the aim of replenishing and conserving fishery resources.

It is known that these stocking practices can contribute towards an increase in migratory individuals if the released captive-bred fish have already reached the preparatory stage for migration to the sea (smolt). However, in some stocking practices, juvenile fish that have yet to undergo smoltification are released. It is not known what percentage of these juveniles become migratory in natural rivers.

Research Aims and Hypothesis

In the Oncorhynchus masou ishikawae salmonid species native to Japan both migratory and resident individuals are found.

However, the distribution of these salmon populations is sharply declining nationwide in recent years, due in part to rivers being cut off from the ocean by dams and other artificial barriers. As part of efforts to restore the numbers of migratory individuals in the wild, red-spotted masu salmon are raised in hatcheries and those with a high probability of becoming migratory are released into rivers.

Red-spotted masu salmon that exceed the threshold size upon their first fall undergo smoltification and then become migratory individuals. On the other hand, those who do not grow large enough become residents and spend their entire lives in river waters.

It has been reported that captive-bred fish experience delayed growth when they are released into rivers, due to factors such as being unable to obtain sufficient food Based on this information, the researchers predicted that, even in the case of captive-bred individuals that were highly likely to reach smoltification, juvenile fish released into natural rivers prior to smoltification would experience growth delays rendering them unable to exceed the threshold size required.

Research Methodology and Findings

In order to investigate this hypothesis, red-spotted masu salmon from two different hatcheries were released into the natural streams in the upper regions of the Arida River in Wakayama Prefecture, Japan (in 10 sections across 7 streams). The individuals had a high probability of reaching the smolt stage and were released in early summer prior to smoltification. In fall, the researchers investigated the size of the released fish and the percentage that became smolts. In an additional experiment, released fish were raised in outdoor tanks (in which they could access a similar availability of food resources to the hatchery) and the researchers investigated the percentage of smolt and threshold size required for smoltification in these groups.

The results of this stocking experiment revealed that, out of 320 fish recaptured from natural streams, only one individual (0.3%) reached the smolt stage (Figure 2). In contrast, the numbers that achieved smoltification were much higher among the group that were raised in outdoor tanks, with 64% of females and 17% of males from K- hatchery, and 75% of females and 33% of males from T-hatchery reaching the smolt stage (Figure 2).

The threshold sizes for smolt individuals in the outdoor mesocosm groups were also investigated; these were found to be 124mm for females and 162mm for males from K-hatchery, and 108mm for females and 119cm for males from T-hatchery, respectively (Figure 3a, b). On the other hand, of the juveniles that were released into natural streams, the combined total of females that exceeded the threshold size from both hatcheries was only 8 out of 304 individuals recaptured from the same section (Figure 3c, d).

These research results strongly indicate that the vast majority of released salmonids experience reduced growth in natural rivers, meaning that they are unable to exceed the threshold size necessary to become smolts.

Further Developments

This study has shown that if captive-bred salmonid fish are released into natural rivers prior to smoltification they are highly unlikely to become migratory, even if their phenotypes are expressed in a hatchery. The results thus indicate that releasing large numbers of juvenile individuals doesn't really contribute to the replenishment and conservation of migratory salmon stocks.

However, if these fish are raised in a hatchery environment that is similar to a natural river, there is a possibility that fish could be produced that can grow well even after being released. In addition, it may be possible to increase the number of migratory fish by protecting and restoring streams and their surrounding forest environments, which could improve the growth of fish in the wild.

Currently, the research group is conducting field experiments in order to improve the growth rate of captive-bred red-spotted masu salmon in rivers and to illuminate the environment required for individuals to become migratory. At the same time, they are also planning to investigate methods of reclaiming river environments that can support the growth of migratory phenotypes, without relying on stocking practices.

A study reveals the genetic factors that may expose or protect people with Down syndrome from SARS-CoV-2 infection, as well as the prognosis of COVID-19.

Their findings, which are published in the journal Scientific Reports, follow previous studies showing a tenfold mortality risk of COVID-19 for people with Down syndrome, adding further evidence to boost existing calls for priority vaccination of the medically vulnerable group.

The researchers analysed all publicly available Down syndrome transcriptomic data to uncover alterations that might affect SARS-CoV-2's infection and disease progression.

TMPRSS2, a gene that codes for an enzyme critical for aiding the entry of SARS-CoV-2 in human cells, had 60% higher levels of expression in Down syndrome. The gene is located on chromosome 21, which people with Down syndrome have three copies of.

The researchers also found higher expression levels for CXCL10, a gene that can trigger a cascade of events resulting in out-of-control inflammation where the body's immune system attacks its own lung cells. This phenomenon, known as a cytokine storm, is one of the main causes of patient hospitalization and death. The authors hypothesize this may lead individuals with Down syndrome to be more susceptible to late onset complication such as lung fibrosis.

People with Down syndrome may also be susceptible to subsequent bacterial infections following COVID-19. The researchers found that trisomic cells have lower expression of the NLRP3 gene, which is critical for the maintenance of homeostasis against pathogenic infections.

However, the researchers also found signs that people with Down syndrome have an overactivated interferon response, an important innate defence that shuts down viral replication within cells. Two of the genes linked to an interferon response - IFNAR1 and IFNAR2 - are found on chromosome 21.

One of the limitations of the study is that the datasets studied cannot be used to assess the risk of COVID-19 across different ages. A recent survey from the international Trisomy 21 Research Society highlights a substantial increased risk of mortality for people with Down syndrome above the age of 40.

Another recently published study in the Annals of Internal Medicine reported that people with Down syndrome affected by COVID-19 in the United Kingdom are five times more likely to be hospitalised and ten times more likely to die.

"Previous studies have shown an association between Down syndrome and higher COVID-19 mortality. These studies have not shown a direct causal interpretation but can inform policy and motivate further investigation,"
says Dr. Mara Dierssen, Group Leader at the Cellular & Systems Neurobiology lab at the Centre for Genomic Regulation (CRG) and author of the study.

"On balance, we consider that individuals with Down syndrome who are older than 40 or have significant comorbidities are highly medically vulnerable, both at the stage of infection and for the prognosis once the cytokine storms begins," says Dr. Dierssen, who is also the former President of the Trisomy 21 Research Society. "This is why people with Down syndrome should be prioritized immediately for early vaccination against COVID-19 worldwide."

According to Ilario de Toma, a postdoc at the CRG and co-author of the study, "we need further research to study transcriptomic alterations within lung tissue during the different stages of the infection, possibly stratifying by age."

The team will further validate their results in future studies, initiating new studies using mouse models for Down syndrome that target some of the candidates found in this study. This may provide important insights to boost the immune response and increase future efficacy of vaccinating people with Down syndrome.

In humans, differences in personalities have been evident since the ancient times. Personality in animals has long been ignored, but recently this question has received increasing research interest as it has been realized that personality has evolutionary and ecological significance. An international team of behavioral biologists from Austria, Brazil and the Netherlands, with Vedrana Å lipogor from the University of Vienna as leading author of the study, designed a set of tasks to assess personality of common marmosets. These results have just been published in American Journal of Primatology.

Marmosets are small highly social New World monkeys that parallel humans in their social organization, as they live in cohesive family units, where parents act as breeders and their offspring help them raise the young. The researchers showed that captive monkeys living in Austria as well as those monkeys living under natural conditions in semi-arid Caatinga forests of Northeastern Brazil show consistent differences in their personalities, similarly to humans.

In the personality tasks, the monkeys could explore and engage with a familiar environment, new foods, new objects, and situations mimicking a predatory situation (e.g. encountering a plastic toy snake or a strange-looking object). The researchers carefully observed these monkeys' reactions in the tasks, for instance when trying a piece of jackfruit or engaging with a colorful rattle shaped toy. Some individuals were fast to approach any novelty, while others were more careful; hereby showing a similar pattern to humans: for instance, some humans enjoy trying out new restaurants, whereas others prefer to eat in their favorite restaurant. What is more interesting, when comparing personality traits of monkeys in Austria across four years, the authors found that these monkeys are quite consistent in their personality traits (e.g., those that are explorative when they are younger, stay similarly explorative four years afterwards). The only exception to this rule were monkeys who changed their breeding status in the family units.

"We have found that those monkeys who became breeders, that is, dominant individuals in the group, also became bolder", says Vedrana Šlipogor, a postdoctoral fellow at the University of Vienna. "In humans and other non-human animals we see a similar pattern. People effective in leading positions often show higher levels of extraversion, as well as some other traits (e.g., high agreeableness and conscientiousness and low neuroticism). In homing pigeons, it has been shown that bolder individuals have a higher rank in the hierarchy and are likely to influence direction of collective movement, and subordinate field crickets who change their status to dominant, also show an increase in boldness, exploration and activity."

It is especially interesting that this is the first time that researchers captured personality in wild marmoset monkeys. "We adapted our test battery from the well-controlled captive setting to the unpredictable conditions in the wild. In the wild, monkeys have plenty of things to do in their day-to-day lives, however, and in exchange for some bananas, they decided to participate in these tasks. We were pleased to discover that wild monkeys show a very similar personality structure as those in captivity", says Thomas Bugnyar, Professor of Cognitive Ethology at the University of Vienna and senior author of the study. "This gives further support that consistent variation in individuals can be reliably assessed with our personality test battery, both in captive and wild settings. It also gives us more confidence that we provide the best possible conditions to our monkeys in Austria, as they show such striking similarity to the marmosets in Brazil".

Researchers from the Institute of Environmental Science and Technology of the Universitat Autònoma de Barcelona (ICTA-UAB) warn of the impact the current tourism model in the Mediterranean islands has on the production of marine litter on beaches, and recommend taking advantage of the situation generated by the Covid19 pandemic to rethink a new more sustainable model. The research, recently published in the journal Scientific Reports, shows that the recreational use of Mediterranean island beaches during the summer is responsible for up to 80% of the marine litter accumulating on those beaches, and generates huge amounts of microplastics through the fragmentation of larger plastic items.

The international study led by ICTA-UAB researchers has analysed the effects of waste generated by tourism on eight Mediterranean islands over the past four years. The marine litter, including microplastics, can be defined as any persistent, manufactured or processed solid material discarded, disposed of or abandoned in the marine and coastal environment. It results from human activity and can be found in all the world's oceans and seas. "This environmental issue is threatening the good health of marine ecosystems and can lead to the loss of biodiversity. It can have as well huge economic impacts for coastal communities that depend on ecosystem services by increasing expenditure on beach cleaning, public health or waste disposal", says Dr. Michaël Grelaud, ICTA-UAB researcher and author of the article.

The Mediterranean region welcomes about one-third of the world's tourism every year and is particularly affected by environmental pollution related to this sector. Due to their attractiveness, Mediterranean islands multiply their population by up to 20 during the high season. This represents a challenge for coastal municipalities, which depend on this sector but must adapt and cope with the increase of waste generated, including on the beaches, by the seasonal inflow of tourists. Coastal tourism is indeed expected to be one of the main land-based sources of marine litter.

The amount and type of waste collected was characterized during 147 marine litter surveys conducted during both the low and high tourist season of 2017, on 24 beaches from 8 different Mediterranean islands. The results show that the vast majority of the items collected are made of plastic, as they represent more than 94% of the marine litter.

During the summer, on average 330 items accumulate per 1000m2 of beach per day on the highly popular tourist beaches, 5.7 times more than during the low season. This represents one item every three steps. The number of items most likely left on beaches by the visitors, such as cigarette butts, straws or drink cans, represent more than 65% of the amount of marine litter accumulating on the beaches most popular with tourists. This can increase up to 80% if the large microplastics are included as suggested by the results: during the summer, plastic items left on the beach will undergo fragmentation under the combined effects of solar irradiance and friction with the sand, accelerated by the high volume of visitors. Extrapolated to all the islands of the Mediterranean Sea, the results show that the visitors could be responsible for the accumulation of more than 40 million items per day during the high tourist peak in July and August.

In 2019, and after the implementation of citizen awareness campaigns, the results showed a decrease of more than 50% of the items associated with visitors.

"These very encouraging results probably benefit from the growing attention of the public to the plastic pollution in the oceans or to the measures adopted by the European Commission to reduce marine litter, such as the single-use plastic directive", says Dr. Patrizia Ziveri, ICREA Research Professor at the ICTA-UAB.

In addition, they recall that "the confinement by the COVID19 and the related temporary drastic reduction of tourism offers an opportunity to rethink the fundamental importance of sustainable tourism to ensure a healthy future for the environment and, therefore, also for people", Dr. Patrizia Ziveri concludes.

A German-Chinese research team has found a new synthetic route to produce biofuel from biomass. The chemists converted the substance 5-hydroxymethylfurfural (HMF) produced from biomass into 2,5-dimethylfuran (DMF), which could be suitable as a biofuel. Compared to previous methods, they achieved a higher yield and selectivity under milder reaction conditions. The team led by Dr. Baoxiang Peng and Professor Martin Muhler from the Laboratory of Industrial Chemistry at Ruhr-Universität Bochum (RUB) and the group led by Professor Christof Hättig from the RUB Chair for Theoretical Chemistry described the method together with colleagues from Changzhou, China, in the journal Angewandte Chemie. The final version of the article has been online since 22 January 2021.

The work was part of the German-Chinese research cooperation "Novel Functional Materials for Sustainable Chemistry", which is supported by the German Research Foundation.

Better fuel than ethanol

"DMF would be well-suited as a biofuel, as it has a higher octane number than ethanol, a better energy intensity and an ideal boiling point of 92 to 94 degree Celsius," explains Baoxiang Peng. Although the conversion from HMF into DMF has been researched intensively, there are several hurdles. DMF production requires relatively harsh reaction conditions, such as high hydrogen pressure, and often only creates a small quantity of the desired product, while also forming unwanted by-products. Researchers are thus looking for new ways to efficiently trigger the reaction under milder conditions. This was achieved in the current work.

Formic acid as the key to success

The team carried out the reaction in the presence of formic acid and hydrogen. Palladium nanoparticles were used as a catalyst. In doing so, the chemists achieved a five-times larger reaction rate than those reported with previous methods. The addition of formic acid, in particular, played a crucial role in creating favourable reaction conditions, as shown by the researchers in their detailed investigations.

They performed the reaction with various additives and compared the yield and selectivity, which were best in the presence of formic acid. The substance facilitates a faster reaction pathway and also prevents the occurrence of unwanted side reactions.

The molecular details of how SARS-CoV-2 enters cells and infects them are still not clear. Researchers at Uppsala University have tested the bioinformatic predictions made by another research group and have identified receptors that could be important players in the process. The results are presented in the journal Science Signaling and at the AAAS Annual Meeting held this week.

The spike protein of SARS-CoV-2 binds the protein ACE2 on the outside of the human cell. This triggers a series of events that leads to invasion of the cell by the virus. The molecular details of this process have remained obscure despite much research on SARS-CoV-2 and other coronaviruses. Moreover, ACE2 is not present in human lung cells, which would suggest that different players are involved when the virus infects these cells.

A recent study by researchers at Uppsala University sheds some new light on the issues. The study was published back-to-back with a study by an international team led by Dr Toby Gibson at the European Molecular Biology Laboratory (EMBL) in Heidelberg. The Gibson study predicted potential interactions that could be of importance for the entry of Sars-CoV-2 into the cell.

The researchers at Uppsala University tested the bioinformatic predictions in vitro and could show that ACE2 and the potential co-receptor integrin beta3 interact with important players involved in endocytosis and autophagy - cellular processes of uptake and disposal of substances. This means that these processes might be hijacked by the virus during infection.

"The Gibson team is world leading in terms of the bioinformatic analysis of these types of interactions, and we were excited to follow up on their predictions," says Professor Ylva Ivarsson, who headed the Uppsala study. "Our results also helped them to improve their analysis. It was an easy decision to engage in this project, as our lab has a strong interest in host-pathogen protein-protein interactions."

Femtosecond direct laser writing as a 3D printing technology has been one of the key building blocks for miniaturization in modern times. It has transformed the field of complex microoptics since the early 2000s. Especially medical engineering and consumer electronics as vastly growing fields benefit from these developments. It is now possible to create robust, monolithic and nearly perfectly aligned freeform optical systems on almost arbitrary substrates such as image sensors or optical fibers.

Simultaneously, the miniaturisation of spectroscopic measurement devices has been advanced, for instance based on quantum dot or nanowire technology. These are based on computational approaches, which have the drawback of being calibration sensitive and require complex reconstruction algorithms.

In a new paper published in Light: Advanced Manufacturing, a team of scientists, led by Professor Alois Herkommer from the Institute of Applied Optics and Professor Giessen from the 4th Physics Institute, University of Stuttgart, Germany, have demonstrated an angle-insensitive 3D-printed miniature spectrometer with a direct separated spatial-spectral response. It has a volume of less than 100 × 100 × 300 μm³.

The design is based on a classical grating spectrometer and was fabricated via two-photon direct laser writing combined with a super-fine inkjet process. Its tailored and chirped high-frequency grating enables strongly dispersive behavior. The miniature spectrometer features a wavelength range in the visible from 490 nm to 690 nm. It has a spectral resolution of 9.2 ± 1.1 nm at 532 nm and 17.8 nm ± 1.7 nm at a wavelength of 633 nm. Leading author Andrea Toulouse assesses the potential as:

"With its volume of less than 100 × 100 × 300 μm³ we explore a whole new size range for direct spectrometers. An order of magnitude this small could only be realised by computational approaches until now. In contrast, we translate the spectrum directly into a spatially encoded intensity signal which can be read out with a commercial monochromatic image sensor."

"For 3D-printed microoptics, the complexity of the optical design marks an innovation. Refractive, diffractive and spatially filtering elements have never been combined in such a small volume to create a complex and monolithic measurement system."

"Our spectrometer could be fabricated directly on a miniature image sensor as the tip of a distal chip endoscope. This way, regions in the human body could be examined with extremely high bending radii that were not accessible before" the scientists forecast. "It could also be an interesting approach for hyperspectral imaging where the spectrometer would be used as a unit cell (macro pixel). The redistribution of spectral energy instead of high-loss Fabry-Perot-filtering could thus enable highly efficient hyperspectral imaging sensors. The ever-growing world population could benefit from such a camera if it was used for spectral mapping in precision farming, for instance."

In diagnostic medicine, biopsies, where a sample of tissue is extracted for analysis, is a common tool for the detection of many conditions. But this approach has several drawbacks - it can be painful, doesn't always extract the diseased tissue, and can only be used in a sufficiently advanced disease stage, making it, in some cases, too late for intervention. These concerns have encouraged researchers to find less invasive and more accurate options for diagnoses.

Professor Nir Friedman and Dr. Ronen Sadeh of the Life Sciences Institute and School of Computer Engineering have published a study in Nature Biotechnology that shows how a wide range of diseases can be detected through a simple blood test. The test allows lab technicians to identify and determine the state of the dead cells throughout the body and thus diagnose various diseases including cancers and diseases of the heart and liver. The test is even able to identify specific markers that may differ between patients suffering from the same types of tumorous growths, a feature that has the potential to help physicians develop personalized treatments for individual patients.

The test relies on a natural process whereby every day millions of cells in our body die and are replaced by new cells. When cells die, their DNA is fragmented and some of these DNA fragments reach the blood and can be detected by DNA sequencing methods. However, all our cells have the same DNA sequence, and thus simply sequencing the DNA cannot identify from which cells it originated. While the DNA sequence is identical between cells, the way the DNA is organized in the cell is substantially different. The DNA is packaged into nucleosomes, small repeating structures that contain specialized proteins called histones. On the histone proteins, the cells write a unique chemical code that can tell us the identity of the cell and even the biological and pathological processes that are going on within it. In recent years, numerous studies have successfully developed a process where this information can be identified and thus reveal abnormal cell activity.

A new approach advanced by Hebrew University researchers, Professor Friedman and Dr. Ronen Sadeh is able to precisely read this information from DNA in the blood and use it to determine the nature of the disease or tumor, exactly where in the body it's found and even how far developed it is.

The approach relies on analysis of epigenetic information within the cell, a method which has been increasingly fine-tuned in recent years. "As a result of these scientific advancements, we understood that if this information is maintained within the DNA structure in the blood, we could use that data to determine the tissue source of dead cells and the genes that were active in those very cells. Based on those findings, we can uncover key details about the patient's health," Professor Friedman explains. "We are able to better understand why the cells died, whether it's an infection or cancer and based on that be better positioned to determine how the disease is developing."

Along with the clear diagnostic benefits of this process, the test is also non-invasive and far less expensive than traditional biopsies. Dr. Ronen Sadeh said, "We hope that this approach will allow for earlier diagnosis of disease and help physicians to treat patients more effectively.
Recognizing the potential of this approach and how this technology can be so beneficial for diagnostic and therapeutic purposes, we set up the company Senseera which will be involved with clinical testing in partnership with major pharmaceutical companies with the goal of making this innovative approach available to patients."

A study has described genetic changes in patients with the most common form of hereditary kidney disease that affects an estimated 12.5 million people worldwide. The research, which focussed on Polycystic Kidney Disease (PKD) in Ireland, provides insights into PKD that will assist doctors and patients in the management of this of inherited condition.

The study, led by researchers from the RCSI University of Medicine and Health Sciences, is published in the European Journal of Human Genetics.

In the research, a cohort of 169 patients with PKD in Ireland were analysed. The genetic changes were identified in up to 83% of cases. It is the first time that the diversity of genetic causes of PKD in Ireland have been described. The results will better assist doctors in identifying patients who may require transplantation or dialysis. The findings also have important implications for people who have a family history of PKD and are planning a family or considering kidney donation.

"This study is hugely important in providing us with an insight into the genetic landscape of Polycystic Kidney Disease, the most common form of inherited kidney disease in the world," said first author on the study Dr Katherine Benson, School of Pharmacy and Biomolecular Sciences, RCSI.

"Our findings have implications for the prognosis of patients by helping us to further identify why the disease may progress more rapidly in some cases and how we can reduce the burden of inherited kidney disease in future."

Results from a new study which draws on survey data collected during the peak of the first wave of the pandemic suggests that being forced to slow down life, as a consequence of lockdown, has had significant, positive impacts for many people and their families.

The research, recently published in the British Journal of Psychiatry from a team at the University of Bath with international colleagues, analysed survey results from 385 caregivers of children aged 6-16 both in the UK and Portugal. Individuals completed an online questionnaire between 1 May 2020 and 27 June 2020.

This cohort had experienced considerable adversity because of COVID-19. 70% were working exclusively from home, almost half reported a reduction in income and nearly all children (93%) were being home schooled at the time. In addition, one in five identified at least one family member who was suspected or had been infected with COVID-19.

Yet despite all this, when asked the question - "Do you think there are any positive to come out of this pandemic and of the social distancing restrictions?" - 88% of respondents said 'yes'.

Their responses fell into four key areas, which the researchers describe collectively as examples of 'post-traumatic growth' - whereby individuals experience positive effects following stressful or traumatic events:

48% described a growth in family relationships. One participant explained how the lockdown had brought "closer relationships and a better understanding of each other." Carers also positively reported spending more time together as a family, had more involvement in their children's lives, and felt closer, whilst also feeling more connected to other family members.

22% described feeling a greater appreciation for life, involving the re-assessment of their personal values and priorities and the opportunity to 'reconsider what's really important'. This included increased appreciation and gratitude for the simpler things in life, with opportunities for 'reconnection with small pleasures' and less consumerism and reliance on material things. It also involved the adoption of a healthier lifestyle (22%) because 'life has slowed down', resulting in less stress and 'an opportunity to enjoy the garden and the quiet of the day.'

16% described spiritual growth, which involved a greater engagement with fundamental, existential issues. This included a greater appreciation for others (in particular health and essential workers), a 'stronger sense of community' and an 'acknowledgement of inequalities' (in particular outdoor space). It also included environmental benefits through 'less car use' creating less air pollution, which was 'better for the environment'.

11% described discovering and embracing new opportunities and possibilities, which was reflected in comments about changes in working practice, involving positive 'changes in attitudes to home working' and the adoption of a 'better work/life balance'. It was also reflected through opportunities to learn or develop new skills, particularly 'acquiring new technology-related competencies.' These were highlighted as particularly important by carers as they increasingly relied on technology for work, educating their children and socialising. Others described the positive opportunity to home educate their children, with one carer reporting: "I have always wanted to home school but cannot afford to...this has been a wonderful experience."

Lead researcher, Professor Paul Stallard of the University of Bath's Department for Health, explains: "Of course, the pandemic has affected all our lives in significant ways, most obviously the understandable and substantial negative impact it has placed on our mental health which we know has been acute for very many.

"But that is not the full story. Many respondents in our study emphasised what we had heard anecdotally about some of the positive effects people have derived from leading their lives in quieter, slower ways because of lockdowns.

"These are important findings. Not only do we identify what some of these positive experiences have been, but we also show that those people who have been able to find those positives had better mental wellbeing than those who did not. And it gives us clues about how we might build back happier and healthier by embracing aspects of a quieter life and those small, positives that have emerged from this period."

Co-author, Dr Ana Isabel Pereira of the University of Lisbon added: "This study also suggests strategies that families returning to a more restrictive lockdown in several countries can use. It is important, especially in these moments of high adversity, to find meaning and purpose in these experiences.

"In each moment, we can find new ways to connect and build stronger connections with our children, partner or friends; to choose how we can make the best use of this time of confinement and to help others in the community experiencing more adversity or with fewer resources navigate this period."

Cells, like humans, cast votes to make decisions as a group. But how do they know what to vote for? Researchers at the Francis Crick Institute and King's College London have uncovered how cells actively seek information in order to make faster and better collective decisions to coordinate the growth of new blood vessels. This provides a new basis for understanding intelligence in cells.

The process of how cells precisely and quickly coordinate action when they create new tissue is complex. They must collectively decide which cells should take on specific jobs and ensure that not too many or too few cells are fulfilling each role.

In their study, published in Philosophical Transactions of the Royal Society B, the researchers found that when growing new blood vessels, cells make collective decisions using a process of active perception. This is where moving around to better sense the environment helps inform a decision.

The researchers compare this to entering a dark, unfamiliar room and extending your arms to feel around the wall for a light switch. In the case of the cells, they reach out long 'fingers' and feel their way in the environment. This allows them to quickly choose the cell that senses the most signal from the surroundings to become their leader. This leader, called a tip cell, drives the new blood vessel forward.

Katie Bentley, senior author and group leader of the Cellular Adaptive Behaviour Laboratory at the Crick and senior lecturer at King's College London says: "In most biology textbooks, processes are set out step by step in a certain order. Molecule A binds to receptor B and causes movement C. In the case of this important collective cell decision, steps happen alongside each other rather than consecutively, as cells simultaneously move about while 'deciding' how to form new tissue.

"This ability to use feedback from moving through the world while making a choice is something we usually associate with 'higher-organisms' so recognising how these processes also play a role in more basic living systems could reveal fundamental aspects of biological function driving them to behave as they do.

"And in cases where this process has gone wrong, it could even unlock new therapies and treatments that impact these feedback processes."

In their proof of concept work, the researchers focussed on blood vessel formation, which is vital to healthy tissue development and repair, and is often dysregulated in disease.

At the start of this process, some endothelial cells along the outside of an existing blood vessel turn into tip cells. These tip cells have long finger-like protrusions on their surface, called filopodia, and are the first to move out from the existing vessel to form the head of the new, sprouting vessel.

Many aspects of the timing and cell interactions involved in this process, including how the endothelial cells decide which of them should become tip cells, are not yet understood.

Using computer simulations and studies of zebrafish embryos, the researchers found that the filopodia start forming on the cell surface before it has committed to becoming a tip cell. The filopodia then extend out into the surrounding tissue and detect signals which can either trigger the cell to become a tip cell or inhibit it. This process of filopodia movement and sensing constitutes an active perception feedback loop.

Importantly, to stop all the cells becoming tip cells, neighbouring cells send signals to each other so that only every other cell specialises.

Bahti Zakirov, author and researcher at the Crick and King's College London says: "It was exciting to find that the creation of filopodia was taking place before the cells had fully become tip cells. Until now these protrusions have been considered as merely the end product of the cell decision making process. We've flipped this on its head and shown that the cells use filopodia to better sense their environment and inform their decision - highlighting the feedback between movement and sensing as an important player in the decision-making process."

When the researchers disrupted the filopodia in their computer models and in zebrafish embryos, fewer tip cells were selected and this selection happened more slowly. This delayed process has previously been shown to lead to the formation of less dense blood vessel networks.

Zakirov continues: "If tip cell selection goes wrong or is slowed down this can lead to poorly branched or abnormal vessel networks, limiting blood flow. This in turn, can contribute to diseases such as cancer, retinopathy and HHT- hereditary haemorrhagic telangiectasia. A greater understanding of how to speed up or alter the branching tempo could therefore lead to new therapies which can regulate blood vessel density. This could also help in the creation of artificial organs or tissues as these also need dense blood vessel networks."

Bentley adds: "This work has not only given us a a fresh perspective on the tip cell selection process, revealing a hidden, yet vital time-keeping role for filopodia, but also opened the door to a myriad of new and exciting research directions. We will be exploring some of these important questions in future work, with a view to better interpreting and understanding cell behaviour."

Goal 7 of the Sustainable Development Goals (SDGs) aims to ensure access to affordable, reliable, sustainable and modern energy for all by 2030. Yet according to new research by Copenhagen Business School the poor planning and execution of decarbonisation strategies in emerging markets challenges the aims of Goal 7.

"In the effort to produce renewable energy and decarbonise their economies, emerging countries have neglected the effect on marginalised populations, which could ultimately prove unsustainable for all," says Assistant Professor Jacobo Ramirez from the Department of Management, Society and Communication at CBS.

The research, published in the Journal of International Business Policy, calls for policymakers and business to re-evaluate large-scale renewable energy investments in emerging markets to mitigate climate change and meet the SDGs.

Energy decarbonisation

Energy is a dominant contributor to climate change. According to the UN, it accounts for around 60% of global greenhouse gas emissions. Yet 770 million people still lack access to electricity, while a further 2.6 billion, mainly living in emerging markets, continue to rely on solid biomass such as firewood for fuel.

The study investigated the impact of wind investment on the lives of indigenous people from the Isthmus of Tehuantepec in Oaxaca, Southern Mexico. This region has some of the most powerful wind resources in the world, making it a hot spot for investment in wind energy.

But instead of bringing jobs, development and modern energy to the region, Mexico's current approach to energy decarbonisation has focused on large-scale investments that have benefitted multinational enterprises but left indigenous people behind. This has divided local communities and caused social conflict between opponents and supporters of wind energy.

While wind investments outwardly appear to be paving the way for a sustainable future, the research found that failings in Mexico - corruption, poor accountability, and limited access to information about energy and the environment - have led to public consultation processes that do not meet Mexican regulations or international conventions.

"Conflicts in the Isthmus could prevent decarbonisation, access to renewable energy, and democratic decision-making in the energy transition. To achieve Goal 7, we need to achieve governance in energy democracy in emerging economies like Mexico, with transparent decision-making processes that allow public participation in energy systems and investments," adds Ramirez.

Energy democracy

The study introduces a novel way of thinking about how governance can help - or hinder - the success of renewable energy ventures in emerging markets. To achieve governance in energy democracy, public policies should allow both collectives and individuals to challenge existing energy systems and shift resources towards new investment models, such as decentralised or community-owned renewable energy (CRE) systems. Indeed, CRE models are associated with increased local participation, acceptance, and benefit (both economically and environmentally) from renewable energy.

The research points to examples in countries like Denmark and the UK, where energy democracy has been implemented through decentralised CRE. "Decentralised CRE models ensure communities benefit from renewable energy, and empower them to control the energy system, from production to distribution. This can be encouraged by government, such as through regulation and financial incentives," adds Ramirez.

European models could be a source of inspiration for those investing in renewable energy in emerging economies to address poor governance and facilitate the transition to a decarbonised society. Nevertheless, this research highlights the need for strong institutions, as stated in Goal 16, for redesigning laws and conventions and engaging with marginalised communities.

"Indigenous people aspire to actively participate in renewable energy investments, beyond 'unfair' and 'unjust' public consultation processes. If other emerging markets do not learn from the mistakes made in Mexico, it may endanger the Sustainable Development Goals and undermine global efforts to mitigate climate change," concludes Ramirez.

BUFFALO, N.Y. -- In cells, numerous important biochemical functions take place within spherical chambers made from proteins and RNA.

These compartments are akin to specialized rooms inside a house, but their architecture is radically different: They don't have walls. Instead, they take the form of liquid droplets that don't have a membrane, forming spontaneously, similar to oil droplets in water. Sometimes, the droplets are found alone. Other times, one droplet can be found nested inside of another. And these varying assemblies can regulate the functions the droplets perform.

A study published on Feb. 8 in Nature Communications explores how these compartments, also known as membraneless organelles (MLOs) or biomolecular condensates, form and organize themselves. The research lays out physical rules controlling the arrangement of various types of synthetic MLOs created using just three kinds of building materials: RNA and two different proteins, a prion-like polypeptide (PLP) and an arginine-rich polypeptide (RRP).

The project brought together a team from the University at Buffalo and Iowa State University.

"Different condensates can coexist inside the cells," says first author Taranpreet Kaur, a PhD student in physics in the UB College of Arts and Sciences. "They can be detached, attached to another condensate, or completely embedded within one another. So how is the cell controlling this? We found two different mechanisms that allowed us to control the architecture of synthetic membraneless organelles formed inside a test tube. First, the amount of RNA in the mixture helps to regulate the morphology of the organelles. The other factor is the amino acid sequence of the proteins involved."

"These two factors impact how sticky the surfaces of the condensates are, changing how they interact with other droplets," says Priya Banerjee, PhD, UB assistant professor of physics, and one of two senior authors of the paper. "In all, we have shown using a simple system of three components that we can create different kinds of organelles and control their arrangement in a predictive manner. We suspect that such mechanisms may be employed by cells to arrange different MLOs for optimizing their functional output."

Davit Potoyan, PhD, assistant professor of chemistry at Iowa State University, is the study's other senior author.

Addressing questions in cell biology

The experiments were done on model systems made from RNA and proteins floating in a buffer solution. But the next step in the research -- already underway -- is to conduct similar studies inside a living cell.

"Going back to our motivations in researching MLOs, the big questions that started the field were questions in cell biology: How do cells organize their internal space?" Banerjee says. "The principles we uncover here contribute to the knowledge base that will improve understanding in this area."

Research on MLOs could lead to advancements in fields such as synthetic cell research or new materials for drug delivery.

"We are in the process of learning the biomolecular grammar that may be a universal language used by cells for taming their inner cellular complexity. We hope one day to utilize this knowledge to engineer artificial protocells with custom-designed functionalities inspired by nature," Potoyan says.