Tech

A promising route to develop new treatments for skin cancer has been identified by University of Bath scientists, who have found a molecule that suppresses melanoma tumour growth.

Although the research is at an early stage, the team hope that their work could help develop new ways to combat melanoma and potentially other cancers too.

The team from the University of Bath's Department of Biology & Biochemistry were researching a group of 'long non-coding RNAs' (IncRNAs) with colleagues at the Ludwig Institute for Cancer Research at the University of Oxford, the Wellcome Sanger Institute and University of Lausanne, Switzerland.

IncRNAs are molecules transcribed from our DNA that don't make protein and whose functions remain largely unknown. The particular group of IncRNAs the team were interested in are thought to be involved in cancer.

From a group of 245 IncRNAs that were associated with melanomas they identified one, called _Disrupted In Renal Carcinoma 3 (DIRC3)_, which acted as a tumour suppressor to block the spread of human melanoma cells when grown in lab experiments.

By using gene-editing to switch off production of _DIRC3_, the team saw that "anchorage-independent growth" - a hallmark of malignant cancer spread - drastically increased by between two to eight times.

Furthermore the scientists showed that _DIRC3_ switches on the key tumour suppressor IGFBP5 gene, revealing that it plays a role in the complex networks governing the expression of genes important for melanoma growth and spread to other parts of the body.

The researchers used The Cancer Genome Atlas clinical data to link _DIRC3_ expression to melanoma patient outcomes. They discovered that melanoma patients who produced high levels of _DIRC3_ had statistically significant increased survival rates compared to patients who expressed low levels.

The study is published in PLOS Genetics.

Dr Keith Vance, from the University of Bath Department of Biology & Biochemistry, said: "Although it's early stages we are excited by the potential of _DIRC3_ activating drugs to become a new way to treat skin cancer. This research makes vital steps towards any future therapy development.

"Great strides have recently been made in treating melanoma. However, not all patients respond to current therapies and most skin cancers become drug resistant over time, so a new way to treat it could be another tool in combatting the disease.

"By investigating how _DIRC3_ works we can really start to understand how it blocks the spread of melanoma in detail at the molecular level, and identify druggable interfaces and specific structures that could be targets for medicine."

Black chemicals from oil pollute. Green ones from biomass don't. Or is it really so simple? Not necessarily, as demonstrated in two newly published articles about LCA in Nature Sustainability and GCB Bioenergy.

"The fact that something is 'bio' doesn't always mean that it is better. It depends primarily on modes of production conditions and energy usage at various life cycle stages. Therefore, in general, we need to think and assess the whole life cycle of the product to identify their impacts," says Ólafur Ögmundarson, Researcher at The Novo Nordisk Foundation Center for Biosustainability (DTU Biosustain).

In this study, Ólafur Ögmundarson and his colleagues investigated how LCA's can guide us towards more sustainable bio-chemical production methods. One solution is to identify problematic environmental hotspots in the production process of important bio-chemicals, which in this case are chemicals produced from renewable biomass with microbial fermentation.

Minimise solvents and black energy

In the study published in GCB Bioenergy, the researchers focused on the important bio-chemical lactic acid that is mostly used for bioplastics. Even though this bio-chemical does not come in an oil-derived version, the LCA showed some hotspots for improvement in the biomass input.

Furthermore, from the example of lactic acid, the authors saw some general tendencies. For instance, heavy usage of solvents can have a negative impact on the sustainability footprint of the biochemical. This negative impact was seen even if the solvents were being reused, because that process is often highly energy intensive.

Another general tendency is that using black energy in production can turn sustainable bio-chemicals into polluting alternatives.

One might ask whether it is worth the effort making chemicals sustainably. The answer is undoubtedly 'yes' if one wants a sustainable society that does not depend on fossil fuels. Furthermore, there is huge room for improvement, when it comes to chemicals. In 2017, consumer chemicals accounted for approximately 50 percent of the chemicals market with total revenues of approx. USD 2,100 billion. Furthermore, only about 1-2 % of all chemicals are bio-manufactured today.

"Finding alternative and sustainable production methods for black chemicals is imperative and a pressing issue," Ólafur Ögmundarson says.

Sea based biomass can become part of the solution

Today, lactic acid is produced from corn sugar by microbes. In the assessment, the researchers compared corn sugar with corn stover and macroalgae in its early stages of development. Even though macroalgae are still a hypothetical feedstock for microbes, using algae will have numerous advantages: They do not take up farmland, they are fast growing, and they are relatively easy to eat for microbes compared to hard land biomass such as leaves and tree. The main challenge with macroalgae is that they have to be dried in order to get transported to the biorefinery. And since drying is energy demanding, macro-algae ended up with a fairly bad sustainability factor in this study.

"In places with primarily black energy sources, this drying process will make the sustainable factor even worse. But if you can avoid drying macroalgae and at the same time get the microbes to feed on all of the different sugars available in this feedstock, it can become a more sustainable alternative to using sugar. But the technologies are still too immature to draw too bold conclusions," Ólafur Ögmundarson says.

We need more LCA's

The researchers stress that we need more LCA's for a lot of bio-chemicals. Without these, you are trying to fix a problem in the dark.

"In too many cases, it is not clear if the actual environmental impacts of new bio-products have been calculated before they are marketed. This can have some very negative consequences because if you find out too late if your method and product is actually more polluting than current products on the market, you do not have the time to optimise for these negative impacts," he says and continues:

"We, therefore, recommend to apply LCA in the development phase of biochemicals in a systematic way to identify environmental hotspots at early stage of development. That will give other scientists a tool to direct their research to develop truly environmentally sustainable bio-chemicals, while there is still operating space for change. This will accelerate the contribution from biotechnology to solve the world's sustainability challenges."

Money and sustainability should go hand in hand

Today, a standardised LCA does not consider the economic viability of a product, e.g. production- and investment cost, markets and prices. To correct this, researchers at The Novo Nordisk Foundation Center for Biosustainability, in collaboration with the Quantitative Sustainability Assessment research group at DTU Management, are working on combining the LCA methodology with techno-economics. A Techno-Economic Assessment (TEA) analyses the technical and economic performance of a process, product or service. This is done in order to evaluate both the environmental and economic sustainability of emerging and future bio-chemicals with a sustainable end in mind.

Ólafur Ögmundarson is today affiliated to the The Novo Nordisk Foundation Center for Biosustainability through the Horizon 2020 project MIAMi, where he investigates the sustainability potential, hotspots and opportunities in creating specific cancer drug agents in microbial production hosts instead of extracting them from rare plants.

A rapid diagnosis centre has cut waiting times for patients with non-specific symptoms who may have cancer from 84 days to 6, and costs less than current usual care if used at more than 80% of capacity, a new study by Swansea University researchers and NHS colleagues has shown.

Published in the British Journal of General Practice, the study is the first complete analysis of the cost-effectiveness of rapid diagnosis centres (RDCs).

RDCs are now being established within the NHS, building on experience in Denmark. They are aimed at the large number of patients who have vague and non-specific symptoms that could be due to cancer, but who do not meet the criteria for urgent referral.

The researchers evaluated the RDC in Swansea Bay University Health Board (SBUHB), which has been running since June 2017 at Neath Port Talbot Hospital. Patients are referred to the RDC by their GPs.

They are typically seen at the RDC within a week for a morning session where they are reviewed by a multidisciplinary team, examined and given a computerised tomography (CT) scan. They then see a clinician and a Macmillan clinical nurse specialist to discuss and act on the findings.

The research team examined the period from June 2017, when the centre opened, to May 2018. As well as the 189 patients who used the centre, the team also simulated a larger virtual group of 1000 patients, based on real-life data. They compared patients who followed the RDC route with those who were treated in the standard way.

They analysed the costs incurred but also the benefits to patients, using "quality-adjusted life years" (QALYs), the standard NHS measure combining quantity and quality of life.

The researchers found that:

The average time to a cancer or non-cancer diagnosis, or to discharge from the clinic, was reduced from 84 days in usual care to under 6 days, if the diagnosis is made at the RDC appointment.

If further investigations are arranged in the RDC, the time to diagnosis is just over 40 days.

As long as the RDC runs at 80% capacity or over, it is less costly, as well as more effective, than standard clinical practice.

If the RDC is run at full capacity of 5 patients per session, Swansea Bay University Health Board could save £157,858 and gain 9.2 quality-adjusted life years (QALYs) for every 1,000 patients attending the RDC.

Lead author Dr Bernadette Sewell, from the Swansea Centre for Health Economics at Swansea University, said:

"Our study shows that rapid diagnosis centres are beneficial for patients and the NHS. They cut waiting times, which means any treatment that people need can start earlier. The longer it takes to diagnose cancer, the worse the outcomes can be for patients and the more expensive it may be for the NHS to treat.

"The key is to ensure that the centres run at least at 80% of capacity, as the RDC in Neath Port Talbot Hospital is now doing.

"Not everyone with cancer displays 'red flag' symptoms which indicate the disease and make the patient eligible to be referred to an urgent suspected cancer pathway. As many as one in two might present with vague symptoms, or symptoms which are commonly found in a range of other conditions, such as weight loss, abdominal pain or fatigue.

These patients tend to bounce around the healthcare system, taking longer until a diagnosis can be made, with potentially worsening symptoms, anxiety and costs to the NHS. These previously underserved patients are the people that RDCs can really help by diagnosing or reassuring them quickly and cost-effectively."

Dr Heather Wilkes, GP lead of the Swansea Bay University Health Board RDC, says:

"The provision of this service, and the ongoing commitment to it by SBUHB as a diagnostic resource for primary care, has made a massive difference in trying to speedily investigate and care for some of the most difficult cases in our community. It is highly valued by patients and GPs alike and has been established as a permanent service following our evaluation."

The study was funded by Cancer Research UK.

Andy Glyde, Public Affairs Manager for Cancer Research UK in Wales said:

"This research is exciting because it shows how new ways to diagnose cancer can benefit patients and be cost effective for the NHS. It can be particularly difficult to diagnose patients with symptoms that aren't specific but still concerning, like loss of appetite or stomach pain.
There now needs to be a decision about how this pilot can be integrated into normal practice, including linking up with the Single Cancer Pathway*.

We know that diagnosing cancer at an early stage improves survival, so it is important that the Welsh Government and NHS Wales continue to improve the way we test and diagnose cancers in Wales. This needs to include ensuring we have the right number of specialists to run cancer tests"

Cancer-promoting genes MYC and TWIST1 co-opt immune system cells to enable cancer cells to spread, but blocking a key step in this process can help prevent the disease from developing.

These findings, published today in eLife, may help clinicians to identify cancer patients at risk of metastasis, a process where cancer cells spread to other parts of the body. They may also inform the development of new strategies to prevent or treat metastasis.

"Most cancer-related deaths are caused by metastasis, but there are currently no treatments available to stop it," explains lead author Renumathy Dhanasekaran, a PhD student in the Division of Gastroenterology and Hepatology at Stanford University, California, US. "The main goal of our research is to understand how cancer-causing genes enable metastasis and use that information to identify targeted therapies that may prevent it."

Dhanasekaran and her colleagues genetically engineered mice to express both MYC and TWIST1 and found that these two major cancer-promoting genes led to metastases. They also saw that the cancer cells produced inflammation-promoting molecules Ccl2 and Il13, which attract immune cells called macrophages and make them more tumour-cell friendly. This makes it easier for the cancer cells to migrate to new areas of the body.

The team next showed that exposing mice with liver cancer caused by MYC alone to Ccl2 and Il13 causes metastasis. But blocking this specific combination of cytokines appeared to hinder the process.

To see if the two genes also contributed to metastases in humans, the scientists analysed 10,000 samples of tumours collected from humans with 33 different types of cancer. They found that patients with MYC and TWIST1 were less likely to survive, produced more Ccl2 and Il13, and had more macrophages in their tumours.

"Interestingly, MYC and TWIST1 have previously been shown to cooperate in a positive way to modulate inflammation during embryonic development," says senior author Dean Felsher, PhD, Professor in the Division of Oncology at Stanford University. "These microenvironment changes are needed to enable mesodermal cells to migrate to their destination. But in multiple human cancers, both MYC and TWIST1 are over-expressed, and we suggest that they in turn cause tumour invasion by 'hijacking' this embryonic cell migration program."

Finally, the team monitored Ccl2 and Il13 levels in 25 patients with liver cancer and 10 control patients with cirrhosis. They found that only the patients with liver cancer had elevated levels of the two molecules and, of this group, those with higher levels of Il13 were more likely to have aggressive tumours.

"These results suggest that patients with more aggressive cancers will likely have higher levels of Ccl2 and Il13 cytokines in their blood," Felsher concludes. "Testing for these molecules in future could help identify those who may benefit from combination therapies that target them."

New Rochelle, NY, January 14, 2020--A new coliphage - a bacteriophage that infects and can destroy Escherichia coli -- is presented and characterized in PHAGE: Therapy, Applications, and Research, a new peer-reviewed journal from Mary Ann Liebert, Inc., publishers launching in early 2020. Click here to read the full-text article free on the PHAGE website through February 14, 2020.

The article entitled "Genome Sequence and Characterization of Coliphage vB_Eco_SLUR29." was coauthored by Andrew Millard, University of Leicester, and colleagues from the University of Leicester, University of Warwick (Coventry), and University of Nottingham (Sutton Bonington), U.K. Coliphage have potential therapeutic applications, and more than 600 unique coliphage have been isolated and their genomes sequenced to date. The researchers isolated vB_Eco_SLUR29 from cattle slurry collected from a farm in rural England. They analyzed the ability of this novel coliphage to lyse E. coli and they sequenced its genome. They used transmission electron microscopy to identify the phase as a member of the Siphoviridae family, and they used physogenetic analysis and comparative genomics to identify it as part of a new genus within the subfamily Tunavirinae.

"In an increasing era of finding new phages that infect bacterial pathogens, it will be to our advantage as much as possible to systematically catalogue genomic and biological data collected on new phages," said Martha Clokie, PhD, Editor-in-Chief of PHAGE and Professor of Microbiology, University of Leicester (U.K.). "To present newly isolated and characterized phages, we suggest they are written up as 'phage introductions.' I am very pleased that Andy Millard -- who coined this concept -- has written a key exemplar paper to showcase our first 'introduction.' Please meet coliphage vB_Eco_SLUR29!"

WASHINGTON, January 14, 2020 -- Most robotic gripping mechanisms to date have relied on humanlike fingers or appendages, which sometimes struggle to provide the fine touch, flexibility or cost-effectiveness needed in some circumstances to hold onto objects. Recent work looks to provide a path forward for gripping robots from an unlikely source -- the doughnut-shaped sea anemone.

Researchers at the Southwest University of Science and Technology and Tsinghua University in China demonstrated a robotic gripping mechanism that mimics how a sea anemone catches its prey. The bionic torus captures and releases objects by crimping its skin. The grasper not only is relatively cheap and easy to produce but also can grab a variety of objects of different sizes, shapes, weights and materials. They discuss their work in this week's Applied Physics Letters, from AIP Publishing.

"In industries, multi-fingered dexterous hands are widely used to perform grabbing tasks. However, these end-effectors consist of a large number of components, like joints and sensors, which are difficult to control," said author Weifeng Yuan.

The thermoplastic rubber skin that lines the exterior of the liquid-filled ring rolls inward when the inner skin of the gripper experiences a pulling force, sucking in whatever target being grabbed.

Researchers can adjust various features of the torus, such as the rolling direction and length of the skin, to control whether items are engulfed, swallowed or released.

"We found that sea anemones can capture sea creatures with different shapes and sizes, so we decided to investigate the mechanism of the predation strategy, and we believed that the study would be helpful to the design of adaptive soft graspers," Yuan said.

The group demonstrated the device by latching onto objects, ranging from a piece of cloth to a cellphone to a glass beaker filled with liquid.

Yuan said a flexible gripper has the potential to grasp fragile objects in narrow spaces or extreme, high-pressure environments, such as collecting samples of deep-sea organisms or conveying pipes. What's more, the grasper can also be built on the nanoscale to manipulate individual cells. Yuan sees potential in developing surgical instruments.

"Our grasper can grasp a steel bar from a table one minute and an egg from a basket the next without resetting control parameters," Yuan said.

The group hopes to continue fleshing out the potential for such a unique device, such as increasing the strength-to-weight ratio by using air instead of liquids.

A nanopore is a tiny hole in a thin membrane with a diameter of around a billionth of a meter, or about the width of a single DNA molecule. The potential applications of these nanopores are so diverse - from medicine to information technology (IT) - that they could have a major impact on our daily lives. Now a team of researchers at the University of Ottawa is democratizing entry into the field of nanopore research by offering up a unique tool to accelerate the development of new applications and discoveries.

The innovative T.-Cossa Lab, which studies applied single-molecule biophysics, came up with the idea to provide the research community with the protocols, hardware designs, and software required to fabricate solid-state nanopores in a fast, low cost, and completely automated fashion. This method is now available in the online journal Nature Protocols.

The move is a boon for researchers developing diagnostic and sequencing applications in health, life sciences, and IT, where being able to detect and identify single biological molecules like proteins or DNA with the exacting precision of a nanopore is needed.

"For the first time, we are making our unique nanopore fabrication tool freely available," explained Vincent Tabard-Cossa, professor in the Department of Physics and Director of the Laboratory for Applied Single-Molecule Biophysics at the University of Ottawa. "We opted to offer our patented nanopore fabrication technology to the research community for free, to help disseminate it and expand the field of nanopore research."

Solid-state nanopores are now well established as single-biomolecule sensors which hold enormous promise for fast and low-cost sensing and sequencing applications, including rapid identification of pathogens, biomarker quantification for precision medicine, metagenomics, microbiome analysis, and cancer research. However, until recently, this promise had been stifled by the expensive, labor intensive, and low-yield methods by which pores were fabricated. To address this problem, Professor Tabard-Cossa and his team pioneered a cheap and scalable solid-state nanopore fabrication method in 2012 called controlled breakdown (CBD), which has since become the method of choice by which solid-state nanopores are fabricated by research groups around the world.

"To foster accessible innovation, we set out to make an instrument and workflow that could be operated successfully by someone who had never even heard of a nanopore," said Matthew Waugh, lab manager of the T.-Cossa Lab. "We've already had some amazing successes through a local scientific outreach program where high school students have been able to independently produce nanopores and detect individual DNA molecules in a single afternoon using our tools."

CBD pore fabrication replaces expensive, manually operated electron microscopes with low cost, easy-to-use, small benchtop instruments that automatically fabricate nanopores to a given size at the click of a button. According to Dr. Tabard-Cossa, researchers can now focus their attention on developing different real-world nanopore applications in various fields.

"One such application tackles the growing need to store and archive huge amounts of digital information for very long timescales," said Kyle Briggs, postdoctoral fellow in the T.-Cossa lab. "Nature solved this problem a long time ago with DNA, and a similar approach will work for us, in which the information is stored as the sequence of a synthetic polymer, reducing server farms down to the size of a fridge and saving billions of dollars in energy costs and fried hard drives. Solid-state nanopores could enable the next major breakthrough in data storage since they can be used as the element that reads the information off the polymers," he added.

Video: https://www.youtube.com/watch?v=s98--BRCCWY&feature=emb_logo

The cover for issue 2 of Oncotarget features Figure 5, "MASPIN can prevent the formation of UPA - UPA-receptor complex by a single step, and thus decrease the possibility of the abnormal degradation of the ECM, the development metastasis and angiogenesis," by Fodor, et al.

In the present study, the research team investigated AEZS-108 induced cytotoxicity and the altered mRNA expression profile of regulatory factors related to angiogenesis and metastasis in LHRH receptor-positive OCM3 cells.

Their results show that AEZS-108 upregulates the expression of MASPIN/SERPINB5 tumor suppressor gene, which is downregulated in the normal uvea and UM specimens independently from the LHRH receptor-ligand interaction.

In order to investigate the mechanism of the induction of MASPIN by AEZS-108, OCM3 cells were treated with free DOX, D-Lys6 LHRH analog, or AEZS-108.

Dr. Gabor Halmos from the University of Debrecen, Department of Biopharmacy, in Debrece, Hungary as well as the Veterans Affairs Medical Center, Endocrine, Polypeptide and Cancer Institute, in Miami, FL, USA said, "Although uveal melanoma (UM) is a rare disease, it is the most prevalent lethal ophthalmological tumor."

The discovery of specific receptors for peptide hormones on cancer cells has led to the development of cytotoxic or radiolabeled hormone analogs that are appropriate for tumor localization and targeted therapy.

AEZS-108 guides the chemotherapeutic agent specifically to those tumors that express LHRH-receptors, which could result in targeted cytotoxicity and less damage to healthy tissues.

The authors reported that previously OCM3 UM cell line expresses the receptor of LHRH localized on the cell membrane and in the cytoplasm, rendering them susceptible to AEZS-108 uptake and the detection of the LHRH receptor in OCM3 cells has led to the use of AEZS-108 for targeted therapy of the tumor.

Moreover, that the OCM3 UM cell line expresses the LHRH receptor and LHRH rendering them susceptible to AEZS-108 uptake.

The Halmos Research Team concluded, "In summary, our data confirmed previous results showing LHRH receptor expression in OCM3 cells, a UM in vitro model. Furthermore, we report for the first time that AEZS-108 causes changes in the expression of genes that are involved in angiogenesis and ECM degradation and which might inhibit cell proliferation and induce apoptosis in OCM3 cells.

These findings suggest that AEZS-108 plays a pivotal role in the regulation of angiogenesis and tumor suppression. Taken together, targeted cytotoxic LHRH analogs, such as AEZS-108, might serve as an effective treatment for patients with LHRH receptor-positive uveal melanoma."

Journal

Oncotarget

DOI

10.18632/oncotarget.27431

Graphene-based heterostructures of the van der Waals class could be used to design ultra-compact and low-energy electronic devices and magnetic memories. This is what a paper published in the latest issue of the Nature Materials journal suggests. The results have shown that it is possible to perform an efficient and tunable spin-charge conversion in these structures and, for the first time, even at room temperature.

The work has been led by ICREA Prof. Sergio O. Valenzuela, head of the ICN2 Physics and Engineering of Nanodevices Group. The first authors are L. Antonio Benítez and Williams Savero Torres, of the same group. Members of the ICN2 Theoretical and Computational Nanoscience Group, as its head, ICREA Prof. Stephan Roche, also signed the paper. This study has been developed within the framework of the Graphene Flagship, a broad European Project in which researchers of the Catalan Institute of Nanoscience and Nanotechnology (ICN2), at the Universitat Autònoma de Barcelona campus, play a leadership role. The results complement recent researches carried out within this same initiative, such as the one published in 2019 in NanoLetters by scientists from the University of Groningen (RUG).

The electronics that use spin - a property of electrons - to store, manipulate and transfer information, called spintronics, are driving important markets, such as those of motion sensors and information storage technologies. However, the development of efficient and versatile spin-based technologies requires high-quality materials that allow long-distance spin transfer, as well as methods to generate and manipulate spin currents, i.e. electron movements with their spin oriented in a given direction.

The spin currents are usually produced and detected using ferromagnetic materials. As an alternative, spin-orbit interactions allow the generation and control of spin currents exclusively through electric fields, providing a much more versatile tool for the implementation of large-scale spin devices.

Graphene is a unique material for long distance spin transport. The present work demonstrates that this transport can be manipulated in graphene by proximity effects. To induce these effects, transition metal dichalcogenides have been used, which are two-dimensional materials as graphene. Researchers have demonstrated a good efficiency of spin-charge interconversion at room temperature, which is comparable to the best performance of traditional materials.

These advances are the result of a joint effort by experimental and theoretical researchers, who worked side by side in the framework of the Graphene Flagship. The outcomes of this study are of great relevance for the communities of spintronics and two-dimensional materials, as they provide relevant information on the fundamental physics of the phenomena involved and open the door to new applications.

Excessive activity of an immune system gene previously linked to schizophrenia reproduces neural and behavioral aspects of the disease in mice, according to a new study publishing on January 14 in the open-access journal PLOS Biology by Ashley Comer and Alberto Cruz-Martín of Boston University and colleagues. The finding provides mechanistic support for the importance of the gene in the development of schizophrenia, and may offer a new avenue for therapy development.

Genetics variants that increase the activity of the C4 gene, which encodes part of the immune system's so-called "complement" cascade, have previously been shown to increase risk for schizophrenia in large genome-wide association studies. However, the mechanism through which such variants might contribute to the emergence of schizophrenia have not been clear because C4 has not previously been experimentally overexpressed.

During normal brain development, it's known that complement sticks to neuronal synapses and attracts microglia (immune cells in the brain), which engulf synaptic material in the process known as "synaptic pruning." When mis-regulated, this process can lead to abnormal connectivity in the brain.

Loss of synapses in the prefrontal cortex is a hallmark of schizophrenia, which led the authors to ask whether an overactive C4 gene might contribute to development of schizophrenia through mis-regulation of complement-mediated synaptic pruning by microglia. When they overexpressed complement C4 in the mouse prefrontal cortex, they found an increase in the level of microglial engulfment of synapses, reduced functional connectivity between neurons, and alterations in the properties of neuronal membranes.

Schizophrenia is characterized by deficits in social cognition and social interactions, effects that often precede the development of psychosis. The authors found that juvenile mice with too much complement C4 reduced the time they spent seeking out their mothers compared to control mice, and that adult mice spent less time than control mice interacting with new cage mates.

Together, these results suggest that the genetic association found between increased C4 gene activity and schizophrenia may be due at least in part to an inappropriate increase in synaptic pruning during brain development. "This critical developmental window may provide an opportunity to intervene to alter the developmental trajectory of schizophrenia," Cruz-Martín, the senior investigator, said. While there are currently few approved drugs that can block the complement system, it is an area of intense pharmaceutical research, and these findings are likely to spur even further interest in this approach.

Adverse outcomes from childhood exposures to lead and mercury are on the decline in the United States, likely due to decades of restrictions on the use of heavy metals, a new study finds.

Despite decreasing levels, exposure to these and other toxic chemicals, especially flame retardants and pesticides, still resulted in more than a million cases of intellectual disability in the United States between 2001 and 2016. Furthermore, as the target of significantly fewer restrictions, experts say, flame retardants and pesticides now represent the bulk of that cognitive loss.

NYU Grossman School of Medicine researchers found that IQ loss from the toxic chemicals analyzed in their study dropped from 27 million IQ points in 2001 and 2002 to 9 million IQ points in 2015 and 2016.

While this overall decline is promising, the researchers say, their findings also identify a concerning shift in which chemicals represent the greatest risk. Among toxin-exposed children, the researchers found that the proportion of cognitive loss that results from exposure to chemicals used in flame retardants, called polybrominated diphenyl ethers (PDBEs), and organophosphate pesticides increased from 67 percent to 81 percent during the same study period.

"Our findings suggest that our efforts to reduce exposure to heavy metals are paying off, but that toxic exposures in general continue to represent a formidable risk to Americans' physical, mental, and economic health," says lead study investigator Abigail Gaylord, MPH, a doctoral candidate in the Department of Population Health at NYU Langone. "Unfortunately, the minimal policies in place to eliminate pesticides and flame retardants are clearly not enough."

The substances analyzed are found in household products from furniture upholstery to tuna fish, and can build up in the body to damage organs, researchers say. Heavy metals, lead and mercury in particular, are known to disrupt brain and kidney function. In addition, they, along with flame retardants and pesticides, can interfere with the thyroid, which secretes brain-developing hormones. Experts say exposure at a young age to any of these toxins can cause learning disabilities, autism, and behavioral issues.

In their investigation, the researchers found that everyday contact with these substances during the 16-year study period resulted in roughly 1,190,230 children affected with some form of intellectual disability. Overall childhood exposures cost the nation $7.5 trillion in lost economic productivity and other societal costs.

"Although people argue against costly regulations, unrestricted use of these chemicals is far more expensive in the long run, with American children bearing the largest burden," says senior study author Leonardo Trasande, MD, MPP, the Jim G. Hendrick, MD Professor at NYU Langone Health.

Publishing online Jan. 14 in the journal Molecular and Cellular Endocrinology, the new study is the only long-term neurological and economic investigation of its kind, the authors say. The investigators analyzed PBDE, organophosphate, lead, and methylmercury exposures in blood samples from women of childbearing age and 5-year-olds. Data on women and children was obtained from the National Health and Nutrition Examination Survey.

The researchers used results from several previous environmental health studies to estimate the annual number of IQ points lost per unit of exposure to each of the four main chemicals in the study. Then, they estimated the lost productivity and medical costs over the course of the children's lives linked to long-term intellectual disability using a second algorithm, which valued each lost IQ point at $22,268 and each case of intellectual disability at $1,272,470.

While exposure to these chemicals persists despite tightened regulations, experts say Americans can help limit some of the effects by avoiding the use of household products or foods that contain them.

"Frequently opening windows to let persistent chemicals found in furniture, electronics, and carpeting escape, and eating certified organic produce can reduce exposure to these toxins," says Trasande, who also serves as chief of environmental pediatrics in the Department of Pediatrics at NYU Langone.

Trasande notes that the impact of these chemicals may be worse than their study can capture since there are far more hazards that affect brain development than the four highlighted in the investigation, and other potential consequences beyond IQ loss. "All the more reason we need closer federal monitoring of these substances," she says.

The study authors say they plan to explore the cost of exposure to endocrine-disrupting chemicals in other countries.

BEER-SHEVA, Israel - January 14, 2020 - Ben-Gurion University of the Negev (BGU) researchers have developed a new nitrate sensor that will provide real-time and continuous measurement in soil to better detect water pollution and measure conditions for higher agricultural productivity.

Natural nitrate levels in groundwater are generally very low. However, excess application of fertilizers in agriculture often results in leaching of nitrate from the soil to water resources. Increased levels of nitrate in water is one of the main reasons for disqualification of drinking water, causing a worldwide environmental problem.

The new optical nitrate sensor is based on absorption spectroscopy. It enables continuous, real-time measurement of nitrate and can detect nitrate concentrations in the range of tens to hundreds of parts per million (ppm), which is the range relevant to growing crops. Its ability to continuously monitor soil nitrate levels produces a highly detailed portrayal of the rapidly changing concentrations of nitrate in the soil solution. The new sensor is also highly resistant to harsh chemical and physical soil conditions.

The invention was developed by Prof. Ofer Dahan of the BGU Zuckerberg Institute for Water Research, Prof. Shlomi Arnon of the Department of Electrical and Computer Engineering, and Elad Yeshno, Ph.D. student at the Zuckerberg Institute.

"Current methods for measuring soil nitrate are cumbersome, labor-intensive and do not provide real-time indication on the actual concentration of nutrients in the soil," says Prof. Dahan.

"Our invention, which enables real-time monitoring of soil nitrate levels, can supply farmers with valuable data on the amount of nutrient availability for crops," Prof. Arnon says. "It also optimizes fertilizer application, thus preventing over-fertilization, economizes irrigation and reduces water resources pollution."

According to Shirley Sheffer Hoffman, senior vice president of business development for water, energy and agriculture at BGN Technologies, BGU's technology-transfer company, "This is another example of the cutting-edge multidisciplinary research preformed at the BGU Jacob Blaustein Institutes for Desert Research, in collaboration with BGU's engineering faculty. This promising project received funding from the Israel Innovation Authority, and now BGN Technologies is seeking an industry partner for its further development and commercialization."

Researchers have developed a new process that could make it much cheaper to produce biofuels such as ethanol from plant waste and reduce reliance on fossil fuels.

Their approach, featuring an ammonia-salt based solvent that rapidly turns plant fibers into sugars needed to make ethanol, works well at close to room temperature, unlike conventional processes, according to a Rutgers-led study in the journal Green Chemistry.

"Our pretreatment system can slash - by up to 50-fold - the use of enzymes to turn solvent-treated cellulose (plant fiber) into glucose (a sugar) used to make bioproducts like ethanol," said lead author Shishir P. S. Chundawat, an assistant professor in the Department of Chemical and Biochemical Engineering in the School of Engineering at Rutgers University-New Brunswick. "Similar processes could greatly reduce the cost of producing biofuels from waste biomass like corn stalks and leaves."

The solvent can also extract more than 80 percent of the lignin in plant waste. Lignin, which binds to and fortifies plant fibers, could be used to help upgrade valuable aromatic chemicals in the future, according to Chundawat. The research benefited from collaborative efforts and access to a high-tech Bio-SANS instrument at Oak Ridge National Laboratory for analysis of how complex biological systems like plant waste respond during processing to better understand how cellulose is dissolved at a molecular level.

Corn stalks, leaves and other residue (called corn stover) and switchgrass, for example, have tightly packed cellulose microfibrils, which are tiny strands thinner than fibers. Microfibrils are difficult to break down using enzymes or microbes, making it hard to turn many plant-based materials in biomass into biofuels or biochemicals. Biomass includes microbial, plant or animal-derived materials used for renewable energy production and industrial processes.

Speeding up the conversion of cellulose into sugars like glucose with enzymes requires suitable solvents or heat- and/or chemical-based pretreatments. In the last 150 years, several solvents that can break down cellulose fibers have been explored. But most solvents remain costly or require extreme ranges of operating pressures or temperatures to be effective.

The ammonia-salt based solvent system quickens the conversion of cellulose into sugars using enzymes. It can greatly reduce the cost of biofuels production because enzymes can account for about 15 percent to 20 percent of the cost of making biofuels like ethanol from biomass.

Next steps will be to optimize the pretreatment process for biomass like corn stover, municipal solid wastes and bioenergy crops like switchgrass and poplar that could be turned into fuels, while also developing more robust enzymes to further reduce costs, according to Chundawat.

In a time of aging infrastructure and increasingly smart control of buildings, the ability to predict how buildings use energy--and how much energy they use--has remained elusive, until now.

Researchers from Saudi Arabia, China and the United States collaborated to develop a smarter way to predict energy use through a method that involved artificial systems, computational experiments and parallel computing. They published their results in IEEE/CAA Journal of Automatica Sinica.

"Generally, it is challenging to predict building energy consumption precisely due to many influential environmental factors correlated to energy-consuming such as outdoor temperature, humidity, the day of the week, and special events," said Abdulaziz Almalaq, paper author and assistant professor in the Department of Electrical Engineering in University of Hail's Engineering College in Saudi Arabia.

"While environmental parameters are useful resources for energy consumption prediction, prediction using a large number of a building's operational parameters, such as room temperature, major appliances and heating, ventilation, and air-conditioning (HVAC) system parameters, is a quite complicated problem, compared with prediction using only historical data."

According to Almalaq, the environmental parameters are useful but limited. For example, two identical buildings in identical settings may have very different energy consumptions based on how the buildings are used. Even if both buildings are maintained at the same temperature, one building's HVAC system will need to use more energy if that building is holding an event with a few hundred people.

"The accurate prediction of energy consumption at a specific time under many outside and inside conditions becomes an essential step to improve energy efficiency and management in a smart building," Almalaq said.

Almalaq and his team used hybrid deep learning algorithms, coupled with artificial systems, computational experiments and parallel computing theory based on complex, but generic, systems. When tested using real building at the University of Colorado Denver, the method significantly helped improve energy management.

"The analysis performed in this paper showed that the hybrid deep learning model is a powerful artificial intelligence tool for modeling multivariable complex systems," Almalaq said. "It has the potential to be applied in different areas, such as the smart office, the smart home and the smart city."

It is well-known that LEDs and transistors should not be connected in parallel as slight differences in resistance can lead to imbalanced current flow. This effect gets even stronger if the devices heat up as their resistance changes with temperature. For organic LEDs (OLEDs), this is a big issue: Every large-area OLED lighting panel can be understood as a parallel connection of numerous individual tiny OLEDs. As a consequence, these devices show inhomogeneous light emission if they heat up. A phenomenon that has been observed by researchers as well as industrial companies in the last couple of years, is a saturation of brightness that occurs even though the total applied current is continuously increased. Now a team of researchers from TU Dresden (Chair of organic semiconductors at IAPP/cfaed, Prof. Sebastian Reineke) and the Weierstrass Institute Berlin (WIAS, deputy head of research group Partial Differential Equations, Dr. Annegret Glitzky) experimentally prove that OLEDs do not only saturate, they even show regions that are switched-back in brightness: Suddenly the OLED gets darker in a certain area although the total applied current is increased - clearly a counter-intuitive result. This so-called "switched-back" effect is directly related to the presence of a strong nonlinear electrothermal feedback in OLEDs that takes place upon heating up and which in turn induces negative differential resistance that makes the device prone to unstable operation.

The results have a strong impact on understanding long-term stability in applications with high brightness e.g. as they are found in the automotive sector. Here, OLEDs are now considered to replace LED technology for tail lights, signal lights, or brake lights due to their new design possibilities. One problem OLEDs are still facing are sudden-death phenomena. They are rarely described in literature due to their unpredictable and seemingly random occurrence. However, it is likely that the now proven switched-back regions are strongly related to such sudden-death phenomena. A better understanding of the OLED as a complex electrothermal system will, therefore, be essential to forecast device breakdown and to develop new strategies for better brightness uniformity and device stability. In the future, novel applications with ultra-high light intensity such as organic lasers will also benefit from exact knowledge about self-heating effects.

The cooperation between the two groups at IAPP and WIAS dates back to 2011. Since then, several joint publications about electrothermal feedback in organic semiconductor devices have been published. "The prediction of the switched-back regions actually goes back to 2014 when we got some first hints by a rather rudimentary simulation," said Dr. Axel Fischer who is the corresponding author of this work and continues with "We then focused on creating an improved setup that would allow us to measure the effect for our lab-scale samples.". The term "switched-back" is actually related to the current density that locally decreases in the OLED in contrast to the total current that still increases. As it is difficult to measure the local current density, a camera was used to detect the emission that corresponds to the local current flow. If there would be a decreasing brightness before the OLED degrades, it would be the proof of switched-back regions. Indeed, the experimentalists suddenly observed a decreasing luminance in the expected region of the active area just after the first negative differential resistance occurred. These experiments have been carried out and evaluated by Anton Kirch, who is currently a Ph.D. student at IAPP: "First, a region of negative differential resistance occurs and propagates through the device for increasing the supply current. At a certain point, they switch back regions that are distant to the electrodes and which do not have a sufficiently high power dissipation. One can imagine that these switched-back regions only 'see' the decreasing voltage of the OLED parts operating in the regime of negative differential resistance and do not know that the externally applied voltage still increases."

To confirm the experimental results, the complex interplay between current and heat flow was studied numerically in a highly nonlinear system, taking the different layers of the OLED into account. Therefore, the mathematicians from the Weierstrass Institute Berlin created a simulation tool for solving the derived system of partial differential equations. "We had to introduce an advanced path following algorithm", explains Dr. Matthias Liero, "to capture the behavior of the device within the bistable regime, i.e. when parts of the OLED operate in the regime of negative differential resistance". After this was implemented, the numerical simulation was able to reproduce the experimental finding based on reasonable assumptions and parameters. Liero further outlines: "Frankly, we have been astonished about the qualitative and the quantitative agreement between simulation and experiment. The shape and occurrence of the switched-back region were calculated as found in the experiment.". The group is now looking for further partners from science as well as from industry to transfer the results from lab-scale OLEDs to larger thin-film lighting panels and more complicated geometries.

Both groups want to continue their joint work on electrothermal feedback. The next challenges are to create new strategies to prevent switched-back regions in order to homogenize the luminance even upon self-heating. It will be the aim to create non-trivial solutions that explicitly take the non-linear nature of the problem into account. Furthermore, in-depth studies exploring the interdependency between the appearance of switched-back regions and sudden-death scenarios have been started.