Culture

HOUSTON - (Oct. 26, 2020) - A horrifying insect soap opera with vampires, mummies and infant-eating parasites is playing out on the stems and leaves of live oak trees every day, and evolutionary biologist Scott Egan found the latest character -- a new wasp species that may be a parasite of a parasite -- within walking distance of his Rice University lab.

Egan, an associate professor of biosciences at Rice, studies gall wasps, tiny insects that cast a biochemical spell on live oaks. When gall wasps lay their eggs on oak leaves or stems, they chemically program the tree to unwittingly produce a tumor-like growth, or gall, which first shelters the egg and then feeds the larval wasp that hatches from it.

Egan describes the wasps as "ecosystem engineers," because their galls are attractive morsels that harbor a supporting cast of opportunistic ne'er-do-wells, thieves and killers. It's a great setting to study how competition for resources drives evolution, and Egan and his students have spent more than a decade documenting the eerie, interspecies who's-eating-who drama.

The latest species they discovered at Rice, Allorhogas gallifolia (al-UHROH'-guhs GAHL'-ihf-ohl-eeuh), is one of four new wasp species from the genus Allorhogas that Egan and collaborators Ernesto Samaca-Saenz and Alejandro Zaldivar-Riveron at the National Autonomous University of Mexico (UNAM) in Mexico City described in a study this month in Insect Systematics and Diversity.

"They lay their egg in another wasp's gall," Egan said of A. gallifolia, which his group first hatched in 2014. "They're using the gall as a resource, and we're still not certain how, but I think they're attacking herbivorous caterpillars that are feeding on the gall tissue, and the wasp larva are eating those caterpillars after they hatch."

He said more than 50 species of Allorhogas have been found in Central America and Mexico, but only two species were previously documented in the United States, one at the University of Maryland campus in 1912 and another some years later in Arizona.

The A. gallifolia found at Rice was collected as part of an effort to describe the community of natural enemies for one species of gall wasp, Belonocnema treatae (behl-uh-NAHK'-nee-muh TREE'-tee). In that study and others like it that Egan's lab has published for other gall species, thousands of galls are collected across the southeastern United States, and everything that emerges from the galls is studied and cataloged. Egan describes the operation, which runs almost 365 days per year, as a "factory of discovery," and A. gallifolia was one of many mysterious specimens it has produced.

"It did not match any of the previously described species, so we documented that in our 2016 paper and raised the hypothesis that this might be a new species," Egan said. "A year or two went by and lead author Ernesto Samaca-Saenz contacted us and offered to collaborate on determining if this lineage was, in fact, a new species."

Samaca-Saenz is a graduate student in the UNAM lab of Zaldivar-Riveron, an expert in Allorhogas and similar predatory wasps, which can be used by farmers as biological controls for crop pests. By the time Samaca-Saenz reached out about the 2016 paper, Egan's lab had collected a number of other undescribed specimens that they also suspected were new species of Allorhogas. The email kicked off a close collaboration that has taken Rice researchers on a number of trips to Mexico to conduct field work and science outreach in remote village schools.

While the jury is still out on exactly how A. gallifolia interacts with other species on the galls of B. treatae, Egan said he, Samaca-Saenz and Zaldivar-Riveron have discussed a number of hypotheses.

"They think it could be phytophagous, meaning it's actually just eating plant material, or that it could be a gallmaker itself," Egan said. "But I'm convinced that these guys are predators of caterpillars that live inside the Belonocnema galls and eat the gall plant material. I think the larval wasp eats the caterpillar and then emerges out of the side of the gall."

Egan said it will take more research to determine whether that hypothesis is true. If it is, it would be "a whole new way of life that would be unknown to this entire genus." But it would not be the first -- or the creepiest -- interaction between species that Egan and his colleagues have found.

Take 2018's discovery, for example, that the parasitic vine Cassytha filiformis (kuh-SIHTH'-uh FIHL'-ih-form-ihs), commonly known as the love vine, targets B. treatae galls and sucks so many nutrients out of them that it mummifies the larval wasps inside. That marked the first observation of a parasitic plant attacking a gall-forming wasp, but it could not match the ghoulish weirdness of the crypt-keeper wasp they discovered in 2017.

Euderus set (yoo-DEHR'-uhs SEHT') is so diabolical that it was named for Set, the Egyptian god who trapped, murdered and dismembered his brother in a crypt. E. set -- which Egan discovered on a family vacation in Florida and later found on a tree in his front yard -- lays its egg inside the gall of the Bassettia pallida (buh-SEHT'-eeuh PAL'-ih-duh) wasp. Both eggs hatch and the larvae live side by side, maturing inside the gall. When the pair are large enough to emerge as adults, E. set manipulates its step-sibling into trying to escape before its emergence hole is finished. When B. pallida's head gets stuck in the undersized hole, E. set begins eating. Starting from the tail, it devours a tunnel through its roommate, emerging through the head to take its place in the world outside.

There are more than 1,400 known species of gall-forming wasps, and Egan said he believes there are many more species waiting to be discovered in their plant/bug-eat-bug-eat-plant corner of the world.

"We've focused on the gall former Belonocnema a lot, and that's where we initially found this first Allorhogas," he said. "When we reared out that entire community and tried to key out each of the members, A. gallifolia was one of those things where we could not narrow it down to a species. Nothing fit the description.

"Twenty-five percent of all the things we reared out of Belonocnema fit that same type of uncertainty," Egan said. "We can't find anything that's ever been described like them before. Some of those, including one I have on my desk right now, are also mostly likely new species. Considering there are 90 oak species in the United States, and I have studied only three of them, this is the tip of the biodiversity iceberg."

Researchers have developed a novel control architecture that defends complex, interconnected systems previously vulnerable to cyberattacks. Details were published in IEEE/CAA Journal of Automatica Sinica.

Distributed systems are becoming more and more essential in everyday life. From power plants to autonomous vehicles, modular, interconnected systems, colloquially referred to as Cyber-Physical Systems (CPS), provide crucial services and capabilities while being technologically cost effective.

While well-suited for many applications, these architectures are particularly vulnerable to cyberattacks. These systems typically operate via an open communication structure, allowing the individual components to rapidly communicate with each other in order to maintain stability and precise control. Due to the nature of this network topology and the frequent connections necessary for optimal operation, CPS are particularly vulnerable to denial of service (DoS) attacks. DoS attacks can infect a portion of a CPS and through the open communication structure subsequently cascade through the entire system, degrading overall performance and even causing total failure.

Through clever implementation of a set theory-based, novel control paradigm, researchers from Italy and Canada have found a way to mitigate these particularly damaging cyberattacks by implementing a Leader-Follower approach. This approach uses one portion of the network to manage communications to the rest of the network. By assigning different roles to different portions of a CPS, the team was able to design an algorithm that can detect when and where a DoS attack occurs in the network. Upon detection, the algorithm is then able to cut off the infected portion of the network to prevent large-scale degradation while also dynamically adapting to the now-modified network structure. The algorithm can even assign new roles to different portions of the network in response to infection, increasing the robustness of the system against targeted DoS attacks.

"Organizing the distributed controllers in a Leader-Follower paradigm allows us to reduce the data exchange and provide the entire system with a modular capability so that it is possible to disconnect the attacked sub-subsystems without affecting the global operations" said Dr. Francesco Tedesco of the University of Calabria, corresponding author of the study. "Therefore, the success chance of the adversary attack can be significantly mitigated."

Tedesco goes on to say that the algorithm is not only secure; it is computationally efficient. "The required computational resources -- CPUs power, memory resources and bandwidth requirements -- are modest which clearly leads to a low economic impact."

As for what's next, the team is working to detect and apply more specific actions to counter cyberattacks based on predictive ideas, decreasing response time and further dampening the undesirable cascading effect of cyberattacks against interconnected systems.

Exposure to higher air pollution levels and greater population density during the early months of life may be associated with an increase in children's body mass index (BMI). By contrast, living in areas with greater exposure to green space and a more favourable land use mix (a measure of the variety of building types and services in an area) could be associated with the opposite effect. These are two conclusions reached by a study undertaken by the Barcelona Institute for Global Health (ISGlobal), a centre supported by the "la Caixa" Foundation, in which data from nearly 80,000 children living in urban environments in Catalonia was, for the first time, analysed to explore relationships between BMI growth trajectories and multiple urban exposures.

There is a growing body of evidence that environmental urban exposures, such as air pollution, green space and the built environment, may be linked to effects on growth and obesity in children. These effects may begin at a very early stage, during pregnancy and the first few years of life. "Urban environments are characterised by multiple exposures that may influence the BMI, but the results of research to date have been inconsistent and earlier studies did not assess simultaneous exposures," explains the first author of the study, Jeroen de Bont, researcher at ISGlobal and the IDIAPJGol Foundation.

The most notable innovation of this new large scale longitudinal study, funded by the La Marató de TV3 Foundation and published in the journal Environmental Pollution, was that multiple exposures were evaluated simultaneously. The data analysed was extracted from a database of primary care medical records in Catalonia, which included 79,992 children born between 2011 and 2012 in urban areas, who were followed up until they reached five years of age. BMI growth curves were calculated based on routine measurements of weight and height. At the same time, the authors estimated various urban exposures at the level of the census tracts where the children live. These included air pollution (nitrogen dioxides [NO2] and particulate matter [PM10 and PM2.5], green spaces and several characteristics of the built environment (population density, street connectivity, land use, and walkability).

"Our results suggest that the population density in urban areas and exposure to higher levels of air pollution may be associated with a small increase in BMI in children up to five years of age and that greater exposure to green spaces and a more favourable land use mix may be associated with a small decrease in BMI," says de Bont. "The fact that these associations were strongest during the first two months of life," he adds, "could be explained by the effects of exposure during pregnancy, which would persist over time".

According to study coordinator and ISGlobal researcher Martine Vrijheid, earlier findings indicated that the relationship between BMI and air pollution might be explained by the fact that the pollution "could affect foetal growth through various factors, such as oxidative stress and inflammation, and lead to alterations in the basal metabolism of infants, thereby increasing the risk of obesity by inducing insulin resistance and hormonal alterations".

"On the other hand," Vrijheid goes on to explain, "the possible relationship between a lower BMI and exposure to green space could be explained by the fact that such spaces are a valuable resource favouring physical activity on the part of both mother and child and result in a beneficial effect on the development of the foetus and later on that of the child".

A different hypothesis is that the association could be explained by another possible mediating factor--the lower levels of air pollution observed in the greener areas in the study.

In the case of the characteristics of the built environment, Vrijheid goes on to explain that higher population density may be associated with a higher BMI "owing to higher levels of air pollution and because traffic levels in the more populated areas in Spain may give rise to a perceived lack of safety and disincentivise active modes of travel (walking and cycling), thereby increasing childhood obesity."

While there is no clear consensus on how the land use mix affects BMI, the chief hypothesis is that a more varied land use mix decreases the distance between housing, work and services and therefore favours walking and cycling, which in turn increases levels of physical activity.

"For children, the early years of life are a time of great sensitivity; they represent a window of special vulnerability to environmental exposures that can permanently affect the structure, physiology and metabolism of the child's body. Future studies should take into account multiple exposures in the urban setting instead of analysing exposure one by one, as encouraged by the exposome concept, which studies many different exposures a person faces altogether", Vrijheid concludes.

Researchers from Kumamoto University, Japan have proposed that cellular senescence variations during the aging process could lead to control of health and onset of age-related diseases. Based on the characteristics of the secretion of inflammatory cytokines released by aged cells, they hypothesize that there are at least four distinct states of cellular senescence, and that these four states arise from coordinated metabolic and epigenomic changes. Characterizing and categorizing qualitatively different states of cellular senescence could provide a new understanding of the aging and senescence process.

The world's population is aging at an accelerated rate, especially in developed countries. Since the elderly population is expected to increase in the future, it especially important to maintain healthy life spans. Many of the cells that make up the body eventually decline in function and stop growing after repeated divisions in a process called "cellular senescence," an important factor in health and longevity. Premature senescence occurs when genomic DNA is damaged by stressors such as radiation, ultraviolet light, or drugs, but its mechanisms are not yet fully understood. It can be good, like when cells become cancerous, cellular senescence works to prevent the development of malignancy, but it also increases the likelihood of many age-related diseases. It is therefore important for medical science to try to understand and control it.

Although senescent cells lose their ability to proliferate, recent research has shown that they secrete various proteins that act on surrounding cells and promote chronic inflammation and cancer cell growth. This is called the senescence-associated secretory phenotype (SASP). Cellular senescence is thought to be the cause of aging in the entire body. Senescent cells have been shown to accumulate in the bodies of aged mice, and removal of these cells may suppress whole-body aging. In other words, if cellular senescence is controlled, it may become possible to regulate the aging process of the whole body.

Professor Mitsuyoshi Nakao's research group at Kumamoto University is studying the mechanisms of cellular aging from the viewpoint of epigenetics--a research field that investigates the activities of the approximately 25,000 protein-coding genes on the human genome, related to life phenomena, health & disease conditions, and aging in the human body. To date, the researchers have screened a wide range of factors involved in the aging of human fibroblasts (a cell type present in all tissues and organs) and found that SETD8 methyltransferase, NSD2 methyltransferase, and other proteins play a role in preventing cellular senescence. So far, no biomarker specific to senescent cells has been discovered. It is now a question of how can we understand the cellular senescence process. Thus, the researchers reviewed cellular senescence over time and in terms of the characteristics of protein-secreting SASPs.

They realized that there are at least four phenotypic variations (states) in cellular senescence: 1. initiation (proliferation arrest), 2. early (anti-inflammation), 3. full (increased inflammation and metabolism), and 4. late (decreased inflammation and metabolism). Focusing on the molecular level changes for each period, they showed that variations in cellular senescence may be shaped by a "senescent program" in which the change of intracellular metabolism and epigenomics (gene ON/OFF control) takes place in a coordinated manner.

The researchers then focused on transcriptional and epigenomic factors that regulate the expression of genes that play important functions in the process of cellular senescence. During the initiation state, genes that promote cell proliferation are suppressed, while genes that block proliferation are activated. It is known that the tumor suppressor proteins p53 and retinoblastoma (Rb) play a major role in this process. In the early state, cell morphology changes significantly and cytokines with anti-inflammatory properties are activated. This may be a defense against the later inflammatory action. Then, in the full state, the genes of pro-inflammatory cytokines become highly expressed and produce a strong inflammatory response. At the same time, the expression of metabolic genes, such as mitochondria, and genes that synthesize proteins are increased via the aforementioned Rb (previously reported by this research group). Here, it is thought that metabolic reactions produce the energy needed to synthesize and secrete proteins. Finally, in the late state, the inflammatory response and metabolism decline, but interferon is produced and secreted in response to the cytoplasmic DNA fragments of the nuclear genome and mitochondrial DNA. At present, the mechanisms and significance of these processes are still unidentified, but it is now understood that cellular senescence results in a qualitatively different inflammatory response.

"We hope that our work will provide an opportunity for the scientific community to consider a new understanding of the mechanisms of cellular senescence and body aging," said Professor Mitsuyoshi Nakao. "We believe that phenotypic variation in cellular senescence can lead to new methods to promote healthy longevity and the control and prevention age-related diseases."

Researchers have revealed the key factors that can improve outcomes in children with ADHD, a disorder that costs Australia US$13 billion a year in social and economic losses.

Research, led by the Murdoch Children's Research Institute (MCRI) and published in Pediatrics, highlighted the importance of identifying academic, behavioural and social functioning difficulties in the first years of school and empowering teachers and parents to intervene early.

The Journal of Attention Disorders study, led by the Australian ADHD Professionals Association (AAPDA) and Deloitte Access Economics in collaboration with MCRI researchers, revealed for the first time the true social and economic cost of ADHD to the Australian community.

The financial and non-financial costs of ADHD in Australia reached US$12.75 billion or US$14,575 per person during the 2018/2019 financial year.

MCRI Associate Professor Daryl Efron said little quality evidence had existed on the factors that influence changes in ADHD symptoms and impairments over time.

The Pediatrics study followed 477 children at age seven from the Children's Attention Project over three years, and tracked their performance across a range of areas compared to children without ADHD. Only a minority of participants had been treated with medication.

The study found that children with ADHD who had a poor working memory (a limited capacity to hold information temporarily) at age seven tended to have poorer academic performance at age 10 year whereas ADHD symptom severity was linked to their emotional-behavioral outcomes. Children with ADHD who also had autism spectrum disorder symptoms at seven had poorer emotional and social functioning at 10 years of age.

Associate Professor Efron said given children with ADHD go on to experience persisting problems, early identification and treatment may help improve outcomes.

"The predictors for those who had worse outcomes were significant irrespective of whether children meet diagnostic ADHD criteria, suggesting clinicians should monitor children with symptoms even when they fall below the diagnostic threshold," he said.

"Our results suggest that a broad clinical approach is needed to manage ADHD which includes not only symptom management, but also identification and management of other conditions which often coexist with ADHD."

Associate Professor Efron said the research showed children with ADHD who had academic delays could be identified by teachers without the need for formal assessment, which could speed up intervention.

Prior to the Journal of Attention Disorders paper no international studies have comprehensively mapped the social and economic costs of ADHD across multiple areas and included both children and adults.

AADPA president Professor Mark Bellgrove said the data would help to shine a light on ADHD as a serious mental health condition in Australia and would hopefully improve public policy.

The study found the total financial costs associated with ADHD in Australia were about US$7.45 billion. The financial total includes productivity losses (mostly due to absenteeism, presenteeism and reduced employment) of US$6 billion, health system costs of US$321.1 million, educational costs of US$74.1 million, crime and the justice system costs US$215 million and deadweight losses arising from the need to levy taxes to fund government expenditure on services and programs and reduced taxation revenue was US$790.9 million.

The non-financial costs of lost wellbeing associated with reduced quality of life and premature deaths linked to ADHD amounted to US$5.31 billion.

MCRI and Deakin University Associate Professor Emma Sciberras said the considerable socioeconomic impact and burden of ADHD should drive investment and policy decisions to improve ADHD identification and treatment.

"This data points to the considerable public health significance of ADHD and the need for expansion of clinical services for the condition, as well as increased research investment," she said.

In Australia 3.2 per cent (814,500) of people and one in 20 children have ADHD.

MCRI and University of Melbourne Professor David Coghill said the many structural challenges facing ADHD services should be rapidly addressed.

"One particular barrier to care facing young people with ADHD is the high risk of discontinuity of treatment when transitioning from paediatric to youth and/or adult services," he said.

"The complex reasons for this include poor transition planning, lack of available services and trained professionals in the area, other life transitions occurring at the same time, and the shift during adolescence towards increased independence.

"There is also a need to improve screening approaches that can identify those at risk of ADHD early in life, which will go a long way to reducing the associated costs and burdens."

Professor Coghill said with 81 per cent of the financial costs due to lost productivity, more workplace support was needed to help those with ADHD.

"Medication is likely to result in multiple functional benefits and additionally adjustments in the workplace can be considered, however, further research is needed to demonstrate the real world effectiveness and cost-effectiveness of such approaches," he said.

Researchers from the University of Melbourne, The Royal Children's Hospital, Monash University, La Trobe University, National Institute for Health Research Applied Research Collaboration in the UK, The University of Sydney, Joondalup Child Development Centre, University of Western Australia, Deloitte Access Economics, Metro North Mental Health Service, Brisbane, QIMRB Research Institute Herston, Queensland Centre for Mental Health Research, University of Queensland, Children's Health Queensland Hospital and Health Service, Vrije Universiteit Amsterdam, Children's Hospital at Westmead and the Hollywood Specialist Centre, Western Australia, also contributed to one or both studies.

Industrial oil-producing microalgae can use light energy to convert carbon dioxide and water into oils on a large scale. Therefore, it is a potential solution for the sustainable supply of food, nutrition and fuel for human society.

To promote resource sharing and research cooperation for the synthetic biology and molecular breeding of industrial oil-producing microalgae, an international team led by Single-Cell Center (SCC), Qingdao Institute of Bioenergy and Bioprocess Technology (QIBEBT) of the Chinese Academy of Sciences (CAS), has released the "NanDeSyn Database" (http://www.nandesyn.org). This work was published in The Plant Journal on Oct. 25.

Nannochloropsis spp. is industrial microalgae that can be grown outdoors in a large scale for producing oils. They have highly attractive features as "photosynthetic yeast", such as a haploid nuclear genome of ~30M base pairs, simple and reliable DNA transformation, high genome-editing efficiency, and flexible gene expression regulation techniques.

The global Nannochloropsis research community has accumulated a large amount of functional genomics data, as well as genetic resources such as plasmids and mutant strains.

The "NanDeSyn Database", developed by GONG Yanhai, et al., from SCC, and Nam Kyu Kang, et al., from Korea Advanced Institute of Science and Technology (KAIST), systematically collects and integrates functional genomics and epigenetics data including the latest genome sequences, gene annotations, transcriptomes, proteomes, and small RNAs of all Nannochloropsis species.

At the same time, online data mining tools such as gene search, genome comparison, collinearity analysis, gene enrichment analysis, metabolic pathway analysis, and genome browser are provided through the website.
In addition, combined with literature research, the present research status of each gene, as well as the corresponding vectors and mutant strains, are displayed, so as to promote the free sharing of these research materials.

Dr Cefa Karabag and Dr Constantino Carlos Reyes-Aldasoro have collaborated with the Francis Crick Institute in preparing and analysing HeLa cells as part of a research project, documented in the October edition of the PLoS ONE journal: Semantic segmentation of HeLa cells: An objective comparison between one traditional algorithm and four deep-learning architectures.

The HeLa cell line was developed in the 1950s from a particularly aggressive strain of cervical cancer cells taken during a routine biopsy from a 30-year-old African-American mother of five named Henrietta Lacks.

She was treated for the disease by Dr George Gey in the segregated, coloured ward, of The Johns Hopkins Hospital in Baltimore, USA.

The City/Francis Crick Institute team prepared and observed the HeLa cell line using Electron Microscopy (EM), which can acquire tens of thousands of data sets that can easily exceed several gigabytes of data per month.

Part of the team's research requires the identification of the nuclei of these cells, which is a complicated task that can take an expert around a week to accomplish.

Dr Cefa Karabag and Dr Constantino Carlos Reyes-Aldasoro developed a computational approach that solves this task in minutes, and with minimal effort, using an algorithm. It consists of several steps of processing in which features are highlighted and used to ultimately identify the nucleus of the cell and the membrane surrounding it.

The main contributions of the team's work can be summarised as follows:

The objective comparison of five semantic segmentation strategies - one traditional image processing and four deep learning.

These strategies were compared through the semantic segmentation of the nucleus, nuclear envelope, cell and background of three hundred slices of a HeLa cell observed with electron microscopy.

The open source code for all the segmentation strategies, has been made available through GitHub. All the programming was performed in Matlab® (The Mathworks™, Natick, USA).

The four-class ground truth for 300 slices has been created and made available through Zenodo. The EM data is available through EMPIAR.

Maths - it's the subject some kids love to hate, yet despite its lack of popularity, mathematics is critical for a STEM-capable workforce and vital for Australia's current and future productivity.

In a new study by the University of South Australia in collaboration with the Australian Council for Educational Research, researchers have been exploring the impact of anxiety on learning maths, finding that boosting student confidence, is pivotal to greater engagement with the subject.

Maths anxiety, or 'mathemaphobia', is the sense of fear, worry and nervousness that students may experience when participating in mathematical tasks.

In Australia a quarter to a third of Australian secondary students report feeling tense, nervous or helpless when doing maths, and it's this reaction that's influencing their decisions to study maths.

Lead researcher, Dr Florence Gabriel says maths anxiety is one of the biggest barriers to students choosing to study it, especially at senior school and tertiary levels.

"Many of us would have felt some sort of maths anxiety in the past - a sense of panic or worry, feelings of failure, or even a faster heart rate - all of which are associated with stress," Dr Gabriel says.

"Maths anxiety is essentially an emotional reaction, but it's just like stress in other situations.

"When students experience maths anxiety, they'll tend to hurry through maths questions, lose focus, or simply give up when it all seems too hard. Not surprisingly, these reactions compound and lead to poor maths achievement - and later a reluctance to engage with the subject at all.

"To break this cycle, our research shows that we need to build and grow student confidence in maths, especially before starting a new maths concept.

"This draws on the notion of self-regulated learning ¬- where students have the ability to understand, track and control their own learning.

"By drawing a student's attention to instances where they've previously overcome a difficult maths challenge, or to a significant maths success, we're essentially building their confidence and belief in their own abilities, and it's this that will start to counteract negative emotions."

The study assessed the responses of 4295 Australian 15-year-old students that participated in the 2012 cycle of the OECD's Program for International Student Assessment (PISA).

It focussed on the psychological factors of maths learning: motivation (the belief that maths is important and useful for their future); maths self-concept (the belief in their ability to do maths); maths anxiety (self-feelings when doing maths); perseverance (their willingness to continue to work on difficult problems); maths self-efficacy (their self-belief that they can successfully solve maths problems); and maths literacy (the ability to apply maths to the real world).

"Importantly, our research shows the domino effect that these variables have on one another," Dr Gabriel says.

"Through structural equation modelling, our data shows that low motivation and self-concept will lead to maths anxiety, which in turn affects perseverance, self-efficacy and, ultimately, maths achievement.

"By developing a student's ability to reflect on past successes - before maths anxiety sets in - we can break through some of the negative and emotional beliefs about maths and, hopefully, pave the way for students to accept and engage with maths in the future."

A test to diagnose two very serious diseases such as ALS and FTD when the pathologies have not yet appeared, thereby providing doctors and patients with essential information tools to tackle them early and develop new treatments. A team of researchers at SISSA in association with different clinical and Italian research institutes have made a first promising step in this direction. The protagonist of the study, published in the journal Brain Communication, is the protein TDP-43 which accumulates in brain cells in 97% of cases of ALS and in approximately 45% of those with frontotemporal dementia. This protein is therefore a possible biomarker for the diseases. In their work, the scientists developed a technique able to detect TDP-43 even when it is present in the body in minute quantities and in the earlier stages of disease, potentially in individuals who are still asymptomatic. The researchers explain that since there are currently no treatments that can interfere with the course of the two diseases, very early detection made thanks to the presence of this protein could be of great help to develop useful drugs to stop their progression and understand their dynamics.

What is the secret behind the technique? Produce many copies of the same protein

"Many neurodegenerative diseases, such as Alzheimer's or Parkinson, and the diseases caused by prions are characterised by the uncontrolled accumulation of specific proteins in the nerve cells" explain Carlo Scialò and Giuseppe Legname of SISSA, respectively first and last author of the publication. "A test called RT-QuIC (Real Time Quaking Induced Conversion Reaction) had already been developed for early identification of the proteins involved in several of these diseases. We thought of using it for the first time for two other diseases, ALS and frontotemporal dementia, where the protein that accumulates is the same: TDP-43". However, identifying it in the early stages of the disease means that the pathological forms of this protein may be present in minute quantities. How to detect them? "The sense of this technology is precisely this: minimum quantities of the pathological protein or fragments of the same are captured and multiplied in many identical copies, until sufficient quantities are obtained to be detected by the instrumentation. The presence of these pathological forms of the protein are an indicator of its accumulation in the central nervous system".

Research that involves more than 10 institutes in Italy

Besides SISSA, the research has involved the San Martino of Genoa, the University of Turin, the Carlo Besta of Milan, the Italian Auxological Institute, the University of Milan, the University of Brescia and the Institute Centro San Giovanni di Dio Fatebenefratelli of Brescia and three other institutes of Trieste: the University of Trieste, Elettra Sincrotrone and the ICGEB. "We have collaborated with all these institutes at various levels," explain Scialò and Legname. "Many of them were essential in the recruitment of patients who took part in the research". A sample of cerebrospinal fluid, the substance that surrounds the central nervous system, was taken from all of them and in which, the researchers deduced, it is likely to find the protein TDP-43, albeit in small quantities. The samples were then tested to identify the protein. "The patients involved were all carriers of a particular genetic mutation which we know leads to the accumulation of TDP-43 in the brain. With our system, we identified it in 94% of them, which is an excellent result".

The next steps to take

The researchers conclude: "In this phase we have developed the test and verified that it works well to identify TDP-43. Now further steps will be needed to fine-tune the methodology and the protocol, for example increasing the number of patients to be analysed. "Only" 36 were involved in this first test, but we are still at an early stage. It will also be necessary to understand in how many cases the detection of the protein at an early stage actually leads to the development of the disease. Therefore further investigations will be necessary before this test can be used safely and reliably for experimental diagnostic purposes, for example for enrolling subjects in clinical trials". But, they assure, the initial results are truly encouraging.

One of the most important and puzzling events in the evolution of life has been the origin of the first complex eukaryotic cells. Almost all lifeforms that we can perceive with the naked eye, such as algae, plants, animals and fungi, are made up of complex cells known as 'eukaryotes'. A collaborative study between the groups of Toni Gabaldón, ICREA researcher at the Institute for Research in Biomedicine (IRB Barcelona) and the Barcelona Supercomputing Center (BSC-CNS), and Berend Snel at the University of Utrecht, has concluded that the first cell to incorporate a mitochondrion (considered the key step to the increased complexity of eukaryotic cells) already presented eukaryote-like complexity in structure and functions. This scenario serves as a bridge between the signs of complexity observed in some archaeal genomes and the proposed role of mitochondria in triggering eukaryogenesis.

"The acquisition of mitochondria was considered either to be the crucial first step or the last step in the development of eukaryotic cell complexity," explains Gabaldón, "our findings show that it was indeed a crucial event, but that it happened in a scenario where cell complexity had already increased."

Complexity as a prelude to the diversity of life

For roughly the first half of the history of life on Earth, the only forms of life were the relatively simple cells of bacteria. "Eukaryotic cells are larger, contain more DNA and are made up of compartments, each with their own task," explains first author Julian Vosseberg. "In that sense, you could compare bacterial cells with a tent, while eukaryotic cells are more like houses with several rooms."

How and when organisms traded the tent for a house is still a mystery, as there are no intermediate forms. One important moment in evolution was the origin of mitochondria, a component of eukaryotic cells that function as their 'power plants'. Mitochondria were once free-living bacteria, but during evolution, they were absorbed by the ancestors of today's eukaryotic cells. As gene duplication probably drove the increase in cell complexity, the researchers attempted to reconstruct the evolutionary events based on these genetic changes.

Bioinformatics for evolutionary path reconstruction

"We can use the DNA of contemporary species to reconstruct evolutionary events. Our genes were formed over aeons of evolution. They have changed dramatically over that time, but they still hold echoes of a distant past." Vosseberg adds, "We have a vast quantity of genetic material available, from a variety of organisms, and we can use computers to reconstruct the evolution of thousands of genes, including ancient gene duplications. These reconstructions have enabled us to uncover the timing of important intermediate steps."

The co-corresponding author, Berend Snel, from the University of Utrecht, says, "Scientists did not have a timeline of these events. But now we've managed to reconstruct a rough timeline." To achieve this, the researchers adapted an existing method developed at Gabaldon's lab to create a new protocol, which has resulted in novel insights. These indicate that a lot of complex cellular machinery had evolved even before the symbiosis with mitochondria, including the development of transport within the cell and the cytoskeleton. "The symbiosis wasn't an event that served as the catalyst for everything else. We observed a peak in gene duplications much earlier in time, indicating that cell complexity had already increased before that moment," says Snel.

"Our study suggests that the ancestral host that acquired the mitochondrial endosymbiont had already developed some complexity in terms of a dynamic cytoskeleton and membrane trafficking" says Gabaldón "this might have favoured the establishment of symbiotic associations with other microorganisms, including the mitochondrial ancestor, which eventually became integrated".

(Jena, Germany) It still sounds unlikely today, but declines in insect numbers could well make it a frequent occurrence in the future: fields full of flowers, but not a bee in sight.

A research group of the University of Jena (Germany) and the German Centre for Integrative Biodiversity Research Halle-Jena-Leipzig (iDiv) has discovered that insects have a decisive influence on the biodiversity and flowering phases of plants. If there is a lack of insects where the plants are growing, their flowering behaviour changes. This can result in the lifecycles of the insects and the flowering periods of the plants no longer coinciding. If the insects seek nectar at the wrong time, some plants will no longer be pollinated.

Innovative research method in iDiv Ecotron

Ecosystems are changing around the world, in particular due to global warming and altered land use. Insect species are dying out and the insect biomass is decreasing. Researchers have therefore studied how the biodiversity of plants is changing in the context of climate change. For this purpose, various climate scenarios have been simulated, using different temperatures and precipitation.

In a new study reported in the specialist journal Frontiers in Plant Science, the Working Group Biodiversity of Plants of the University of Jena, led by Prof. Christine Römermann, presents a different research approach. In cooperation with scientists from iDiv, led by Prof. Nico Eisenhauer, the researchers are focusing on the influence of invertebrates, such as insects, on the biodiversity and flowering behaviour of plants.

"We know that the insect biomass is decreasing," says Josephine Ulrich, a doctoral candidate from Römermann's team, referring to a study from 2017 which detected that insects had declined by 75 per cent over the previous 30 years.

The Jena research group has now studied in detail for the first time the extent to which decreasing insect density influences plant development. Whereas previous studies had only carried out field experiments, the research team used the "Ecotron", an iDiv research facility where identical climatic situations can be simulated in artificial ecosystems and observed with cameras.

In their experiment, the researchers studied how plant composition and plant development change if the number of insects falls by three-quarters.

Mismatch between plant and animal worlds

Ulrich and her colleagues discovered that the reduced insect biomass brings about a change in plant species. It is especially the dominant plant species, such as red clover, which become more prevalent. The development of the flowering period also changes as insect density declines. Some of the plants studied flowered earlier and others later.

"These changes can lead to mismatches between plant and animal species, which lead to adverse consequences for the ecosystem," says Ulrich, the lead author of the study. Examples are the food supply of insects and pollination success. This deterioration in the ecosystem function could entail further losses of insect and plant species. An additional consequence could be that plants become increasingly infested with pests. Due to the falling numbers of insects that feed on aphids, for example, these pests could spread unchecked.

This study proposes a systematic method, which first integrates both the evenness and the overall status of all goals, to distinguish the ideal development pathways from the uneven ones. The results suggest that, despite the remarkable progress, a bottleneck has been reached in China since 2013 due to the stagnant developments in some SDGs. However, many far-reaching policies in China have been targeting these deficiencies since then, providing a perspective on how a country approaches sustainable development by promoting evenness among all SDGs.

At the regional level, all provinces had increased evenness score and sustainable development score from 2000 to 2015 (Fig. 1). Notably, regions with the slowest progress are those developed provinces, owing to the persistent uneven status of all goals. The effective development scores were further used to quantify the progress of 31 provinces towards SDGs from 2000 to 2015 through assessing the developing pathway (Fig. 2). Four of the top five economically developed regions had nearly no improvement from 2000 to 2015 (namely, Shanghai, Beijing, Tianjin, and Jiangsu). The bottleneck for economically developed regions in approaching SDGs is mainly ascribed to the resource and environmental constraints derived from their high population density along with urbanization.

Moreover, the 31 provinces were divided into four categories in terms of their relative status towards sustainable development in 2015 (Fig. 3). According to their current status, the relatively underdeveloped and uneven regions may collaborate in a complementary way towards SDGs, particularly beneficial for economically developed regions (mostly uneven). For instance, the stagnant progress in SDG 15 (life on land) in Beijing may be improved by collaborating with its surrounding regions (e.g., Hebei, which has much lower GDP per capita than Beijing) on ecological conservation. A feasible ecological compensation for Hebei province and the industrial relocation from Beijing to Hebei should help with the conservation and restoration of natural habitats in Beijing and its surrounding areas, and also help Hebei achieve economic development. Regional integration and cooperation might be effective in holistically achieving SDGs across regions.

By integrating all these findings, evenness expands the implications of sustainable development assessment and helps the government to match adaptive strategies to places. Moreover, the methods proposed in the present study can be applied to the rest of the world since they generally follow the widely adopted methods in data selection, normalization, and calculation of SDG scores. Overall, the study provides a new perspective on how a country approaches sustainable development by promoting evenness among all SDGs.

PHILADELPHIA -- Administering radiation therapy to multiple myeloma patients waiting for CAR T cells to be manufactured was found to be safe and undisruptive to CAR T therapy, according to a new study from researchers in the Abramson Cancer Center at the University of Pennsylvania to be presented Tuesday, October 27, at the virtual American Society for Radiation Oncology Annual Meeting (Abstract #35562) .

The study found patients who received radiation 34 days or fewer before their infusion with CART-BCMA (B cell maturation antigen) cells did not have worse rates of severe cytokine release syndrome (CRS) or neurotoxicity, two common side effects of the cellular therapy, and hematologic toxicities than patients who did not have so-called bridging care.

Radiation for relapsed/refractory multiple myeloma is often used to palliate bone pain associated with the disease; however, what effect it may have on patients and CAR T cell therapy hasn't been fully understood. The new findings suggest it appears to be a safe option for patients before they receive their CAR T cell infusions, lending more support for future studies that combine radiation with cellular therapy.

"The most important takeaway here is that bridging radiation doesn't appear to increase the risk of CRS or neurotoxicity," said lead author Shwetha Manjunath, MD, a resident in Radiation Oncology in Penn's Perelman School of Medicine. "These patients safely received bridge radiation without it affecting the efficacy of CAR T cells or the rates of toxicity."

Chimeric antigen receptor T cell therapy, known as CAR T, is an investigational treatment pioneered by researchers at Penn that modifies patients' own immune T cells, which are collected and reprogrammed to seek and destroy the patients' cancer cells. After being infused back into patients' bodies, these newly built "hunter" cells both multiply and attack. The Penn-developed CART-BCMA targets cells that express BCMA, which is highly expressed in myeloma.

This study, which is a retrospective analysis of a collaboration project with Novartis, evaluated the medical records of 25 patients who received CART-BCMA and categorized them into three groups. One group received radiation after their cells were collected for CAR T manufacturing but before their infusion, a period of 34 days or less. A second group of patients had received radiation within one year prior to CAR T infusion. A third group received either no radiation at all or no radiation within the year preceding CAR T infusion.

None of the four patients who received radiation while awaiting manufacturing experienced CRS, gastrointestinal, infectious, liver-related, or neurologic toxicities higher than a grade 3. CRS is a toxicity that includes varying degrees of flu-like symptoms, with high fevers, nausea, and muscle pain, and can require ICU-level care. Those patients also had lower rates of grade 4 hematologic toxicities. Of the eight patients who had a prior history of radiation, three experienced grade 3 or higher CRS. Among the 13 patients who did not receive any radiotherapy, five experienced Grade 3 or higher CRS. Radiation status was not associated with a decrease in overall survival or progression free survival.

In 2019, Penn researchers presented findings at ASTRO that found radiation did not interfere with the efficacy of CAR T cell therapy in non-Hodgkin lymphoma and had the potential to lower side effects in these patients.

"Our work is hypothesis generating, hinting at a potential synergism between radiation and CART-BCMA therapy, which has been reported by others in the literature," Manjunath said. "Future prospective trials that combine radiation with CART-BCMA may further optimize safety and long-term efficacy of this novel cell therapy."

Upper limb forequarter amputations which involve the removal of the entire arm and scapula require highly customized prosthetic devices that are expensive but yet, usually underutilized due to their high maintenance and low comfort levels. At the same time, while cosmetic prostheses - artificial limbs which provide patients the appearance of a pre-amputated body part - have a higher rate of continuous use, they have limitations in functional use.

Combining both technical and clinical expertise, the Singapore University of Technology and Design's (SUTD) Medical Engineering and Design Laboratory collaborated with Tan Tock Seng Hospital's (TTSH) Foot Care and Limb Design Centre, the largest provider of prosthetic services in Singapore, on a patient-specific upper limb prosthesis. This cosmetic prosthesis with a self-locking function was found to be more comfortable and around 20 percent cheaper compared to similar prostheses available in the industry.

To reduce the underutilization and delivery time, while taking improved fit, function and comfort into consideration, the research team turned to 3D printing due to its versatility and ability to cater to the device's geometrical and functional complexity.

The team also adopted a user-centered design approach, involving the patient throughout the customized design and development process. They then meticulously captured and documented the design process so that it can serve as a blueprint for other device applications or be replicated for other patients with limb amputations, thus reducing the over reliance on a prosthetist's judgement, skills and experience for an optimal fit.

Based on regular consultations with the patient and prosthetist at TTSH, including the shadowing of the patient to better understand his daily activities and functional needs, it was concluded that the new prosthesis needed to be lightweight, capable of dissipating heat, locking at 90° of flexion, comfortable to wear and void of metal components that would be detectable by airport scanners.

The research team used a digital scanner to capture residuum and contralateral arm geometries to replicate the patient's arm with high precision. They then designed different parts of the prosthesis from the captured geometries, 3D printed and verified these for fit, comfort, and function (refer to image). Their research paper was published in the Prosthetics and Orthotics International Journal.

The patient's satisfaction for the 3D printed prosthesis over his conventionally made prosthesis rated higher for its overall effectiveness, accurate size, symmetrical appearance and ease of use. Even though the new prosthesis weighed 100 grams more than the current prosthesis, the patient preferred it due to its improved suspension contributing to the feel of a lighter arm during use. However, the prosthesis was perceived to be less durable due to the patient's unfamiliarity with the quality of 3D printing, his concerns of the elbow locking mechanism breaking, and the appearance of the mesh structure compared to his current prosthesis.

"Digitalization and 3D printing have been transforming the design and manufacture of complex medical devices, surgery planning, medical education, and care delivery. Even though 3D printing technology has been around for more than three decades since the early 90's, it wasn't until recently that people really began to appreciate and trust it for end-use fabrication. In this work, 3D printing freed us from the manufacturing constraints and enabled us to optimize the design to suit the patient's needs. More importantly, this work sets the groundwork for future patient-specific end-use 3D printed parts for prosthetic needs," said principal investigator, Assistant Professor Subburaj Karupppasamy from SUTD's Engineering Product Development pillar.

Trevor Binedell, Principal Prosthetist at the Foot Care and Limb Design Centre, TTSH, and PhD student from SUTD, added, "The collaboration between TTSH and SUTD has led to a great outcome for this patient. User-design and the digitalization techniques have elevated the levels of patient-specific care to create individual designs that truly meet the needs of the user. This process has the potential to improve unique designs for many of our patients and enhance their quality of lives."

Shortly after the lockdown began, a huge number of volunteers signed up to help people in coronavirus risk groups - primarily via online platforms. A study by the University of Basel has found that websites such as these can have a positive impact with regard to the mobilization, willingness and satisfaction of volunteers, including in the longer term.

Right at the start of the COVID-19 pandemic, the importance of volunteer work became abundantly clear: thousands and thousands of people signed up spontaneously - and generally outside of formal structures - to buy groceries for others or to help in another way, such as by supporting the public health system. Unlike in previous crises, everyone involved faced the same risk of becoming infected. Their efforts were therefore generally organized through various online platforms that matched up volunteers with people in need.

Offers of help significantly exceeded demand

On all of the platforms, the offers of help far exceeded demand. Now, researchers from the Center for Philanthropy Studies CEPS at the University of Basel have worked with colleagues from the University of Freiburg and the ZHAW in Winterthur to study the importance of online platforms when it comes to the motivation and willingness of volunteers. They have reported their findings in the journal Nonprofit and Voluntary Sector Quarterly.

The researchers' survey of a sample of 565 volunteers from a major platform reveals that online placement can help channel the oversupply of volunteers and thus reduce unrealistic expectations. By providing information on safety and health matters during participation in voluntary work, the coronavirus platforms also had a positive impact on volunteer satisfaction.

Moreover, the satisfaction of active volunteers was higher the more afraid they were of catching the virus. According to the researchers, one possible explanation for this is that volunteer work boosted the volunteers' self-confidence -even more so when they believed themselves to be at greater risk.

Willingness to commit in the long term

"Greater satisfaction gained from spontaneous volunteering means people are more willing to commit to long-term volunteering opportunities at a later stage," says Professor Georg von Schnurbein, associate professor of foundation management at the University of Basel and co-author of the study. "Volunteer work is immensely important for our society - not only in times of crisis."

He highlights the importance of long-term commitment in many areas of society, such as in health and social services, as well as in cultural activities and youth work. According to the most recent survey, 665 million hours of volunteer work were completed in Switzerland in 2013, while paid work in the entire health and social services sector amounted to 853 million hours.