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The human body is composed of billions of cells, each of which is made and maintained through countless interactions among its molecular parts. But which interactions sustain health and which ones can cause disease when they go awry? The human genome project has provided us with a "parts list" for the cell, but only if we can understand how these parts go together, or interact, can we really begin to understand how the cell works and what goes wrong in disease.

To answer these questions, scientists needed a reference map of interactions--an interactome-- between gene-encoded proteins, which make up cells and do most of the work in them.

"Since the mid-1990s, our collaborative team has pushed the idea that interactome maps can illuminate fundamental aspects of life," says Marc Vidal, one team leader and Director of the Center for Cancer Systems Biology (CCSB) at Dana-Farber Cancer Institute in Boston.

"Our paper describes the first human interactome reference map, constituting a "scaffold" of information to better understand how faulty genes cause diseases such as cancer, but also how viruses such as the coronavirus that causes COVID-19 interact with their host human proteins," says Vidal.

Almost a decade in the making, the human protein map is now available thanks to a joint effort, involving over 80 researchers in the United States, Canada, Spain, Belgium, France and Israel, jointly led by Vidal, David E Hill and Michael A Calderwood, at Dana-Farber Cancer Institute, Frederick P Roth, at the University of Toronto's Donnelly Centre for Cellular and Biomolecular Research.

The largest of its kind, the Human Reference Interactome (HuRI) map charts 52,569 interactions between 8,275 human proteins, as described in a study published in Nature.

Humans have about 20,000 protein-coding genes but scientists still know remarkably little about most of the proteins they encode. Fortunately, this information can be gleaned from interaction data thanks to the "guilt by association" principle, according to which two proteins that have similar interacting partners are likely involved in similar biological processes.

"We can use our human interactome map to predict protein function," says Roth, who is also Senior Scientist at the Sinai Health System's Lunenfeld-Tanenbaum Research Institute. "People can look up their favourite protein and get clues about its function from the proteins it interacts with."

The data are already revealing important insights such as new cellular roles for human proteins and what goes wrong at the molecular level to spur on disease.

In this vein, HuRI has already revealed new functions for proteins involved in programmed cell death, release of cellular cargo and other processes.

And, by integrating protein interaction data with tissue-specific gene expression, the teams have been able to identify protein networks behind the development and maintenance of different tissues, revealing new therapeutic targets for diverse genetic diseases including cancer and potentially for infectious diseases as well.

Furthermore, using HuRI as a reference, they were also able to see how disease-causing protein variants bring about network rewiring to reveal molecular mechanisms behind those particular disorders.

"Genome sequencing can identify the variants carried by an individual that make them susceptible to disease, but it doesn't reveal how the disease is caused," says Mike Calderwood PhD, Scientific Director of the Center for Cancer Systems Biology (CCSB) at Dana-Farber Cancer Institute "Changes in the interactions of a protein is one possible mechanism of disease, and this map provides a starting point to study the impact of disease associated variants on protein-protein interactions."

The Toronto and Boston teams previously did two smaller studies mapping a total of ~14,000 protein interactions. Now HuRI has interrogated proteins encoded by nearly all human protein-coding genes and expanded the map four-fold.

To create HuRI, the researchers co-expressed in pairs almost all human proteins in yeast cells. When the two proteins interact, or bind one another, they form a molecular switch which boosts yeast cell growth--a sign that an interaction has occurred.

The team tested all possible pairwise combinations among 17,500 proteins for their ability to interact with each other in three separate versions of a yeast-based assay, each done in triplicate, amounting to a staggering three billion separate tests. The results yielded ~53,000 high-confidence binary interactions between more than 8,000 proteins, which were verified by other methods. The majority of interactions had never been detected before.

Although the largest map of its kind to date, the map remains incomplete, representing between 2-11 per cent of all human protein interactions. Roth said that one reason why many interactions were missed is probably because yeast cells lack certain human-specific molecular factors that are needed for proper protein function.

Despite these limitations, HuRI has more than tripled the number of known interactions between human proteins and will serve as an important resource for the research community. Already 15,000 people have visited the data web portal, which was built by Miles Mee, Mohamed Helmy, and Gary Bader (also in the Donnelly Centre), since HuRI was made available on bioRxiv, an open-source online publisher, in April 2019.

"We already had lots of people download the whole dataset and so I imagine we'll see the iteration of our previous paper, which has already been cited over 800 times and is less than a third of the size of HuRI," says Roth.

A team at the University of Bristol has developed a new method of dating pottery which is allowing archaeologists to date prehistoric finds from across the world with remarkable accuracy.

The exciting new method, reported in detail today in the journal Nature, is now being used to date pottery from a range of key sites up to 8,000 years old in Britain, Europe and Africa.

Pottery and the dating game

Archaeological pottery has been used to date archaeological sites for more than a century, and from the Roman period onwards can offer quite precise dating. But further back in time, for example at the prehistoric sites of the earliest Neolithic farmers, accurate dating becomes more difficult because the kinds of pottery are often less distinctive and there are no coins or historical records to give context.

This is where radiocarbon dating, also known as 14C-dating, comes to the rescue. Until now, archaeologists had to radiocarbon date bones or other organic materials buried with the pots to understand their age.

But the best and most accurate way to date pots would be to date them directly, which the University of Bristol team has now introduced by dating the fatty acids left behind from food preparation.

Professor Richard Evershed from the University of Bristol's School of Chemistry led the team. He said: "Being able to directly date archaeological pots is one of the "Holy Grails" of archaeology. This new method is based on an idea I had going back more than 20 years and it is now allowing the community to better understand key archaeological sites across the world.

"We made several earlier attempts to get the method right, but it wasn't until we established our own radiocarbon facility in Bristol that we cracked it. There's a particular beauty in the way these new technologies came together to make this important work possible and now archaeological questions that are currently very difficult to resolve could be answered."

How the method works

The trick was isolating individual fat compounds from food residues, perhaps left by cooking meat or milk, protected within the pores of prehistoric cooking pots. The team brought together the latest high resolution nuclear magnetic resonance spectroscopy and mass spectrometry technologies to design a new way of isolating the fatty acids and checking they were pure enough for accurate dating.

The team then had to show that the new approach gave dates as accurate as those given by materials commonly dated in archaeology, such as bones, seeds and wood. To do this the team looked at fat extracts from ancient pottery at a range of key sites in Britain, Europe and Africa with already precise dating which were up to 8,000 years old.

From the famous Sweet Track site in Somerset and several sites in the Alsace region of France, to the World Heritage site of Çatalhöyük in central Turkey and the famous rock shelter site of Takarkori in Saharan Africa, the new method was proven to date sites incredibly accurately, even to within a human life span.

Professor Alex Bayliss, Head of Scientific Dating at Historic England, who undertook the statistical analyses, added: "It is very difficult to overstate the importance of this advance to the archaeological community. Pottery typology is the most widely used dating technique in the discipline, and so the opportunity to place different kinds of pottery in calendar time much more securely will be of great practical significance."

Using the pottery calendar to better understand London's pre-history

In London, England, the new dating method has been used on a remarkable collection of pottery found in Shoreditch, thought to be the most significant group of Early Neolithic pottery ever found in the capital. The extraordinary trove, comprising 436 fragments from at least 24 separate vessels weighing nearly 6.5 kilos in total, was discovered by archaeologists from MOLA (Museum of London Archaeology).

The site appeared to date from the time when the first farmers came to Britain but accurately dating it was difficult until the Bristol team, using their new dating method on traces of milk fats extracted from the pots, showed the pottery was 5,500 years old. The team were able to date the pottery collection to a window of just 138 years, to around 3600BC.

The results indicate that around 5600 years ago the area around what is now Shoreditch High Street was used by established farmers who ate cow, sheep or goat dairy products as a central part of their diet. These people were likely to have been linked to the migrant groups who were the first to introduce farming to Britain from Continental Europe around 4000 BC - just 400 years earlier.

Jon Cotton, a consultant prehistorian working for MOLA, said: "This remarkable collection helps to fill a critical gap in London's prehistory. Archaeological evidence for the period after farming arrived in Britain rarely survives in the capital, let alone still in-situ. This is the strongest evidence yet that people in the area later occupied by the city and its immediate hinterland were living a less mobile, farming-based lifestyle during the Early Neolithic period."

The results from this site are a prime example of where pottery survives in circumstances that other organic materials do not, so using this revolutionary new method will unlock important information about our prehistoric past.

The earliest human inhabitants of the Amazon created thousands of artificial forest islands as they tamed wild plants to grow food, a new study shows.

The discovery of the mounds is the latest evidence to show the extensive impact people had on the area. From their arrival 10,000 years ago they transformed the landscape when they began cultivating manioc and squash.

This led to the creation of 4,700 of the forest islands in what is now Llanos de Moxos in northern Bolivia, the team has found. This savannah area floods from December to March and is extremely dry from July to October, but the mounds remain above the water level during the rainy season allowing trees to grow on them. The mounds promoted landscape diversity, and show that small-scale communities began to shape the Amazon 8,000 years earlier than previously thought.

The research confirms this part of the Amazon is one of the earliest centres of plant domestication in the world. Using microscopic plant silica bodies, called phytoliths, found well preserved in tropical forests, experts have documented the earliest evidence found in the Amazon of manioc -10,350 years ago, squash - 10,250 years ago, and maize - 6,850 years ago. The plants grown on the forest islands were chosen because they were carbohydrate-rich and easy to cook, and they probably provided a considerable part of the calories consumed by the first inhabitants of the region, supplemented by fish and some meat.

The study, in the journal Nature, was conducted by Umberto Lombardo and Heinz Veit from the University of Bern, Jose Iriarte and Lautaro Hilbert from the University of Exeter, Javier Ruiz-Pérez from Pompeu Fabra University and José Capriles from Pennsylvania State University.

The study involved an unprecedented large scale regional analysis of 61 archaeological sites, identified by remote sensing, now patches of forest surrounded by savannah. Samples were retrieved from 30 forest islands and archaeological excavations carried out in four of them.

Dr Lombardo said: "Archaeologists, geographers, and biologists have argued for many years that southwestern Amazonia was a probable centre of early plant domestication because many important cultivars like manioc, squash, peanuts and some varieties of chili pepper and beans are genetically very close to wild plants living here. However, until this recent study, scientist had neither searched for, nor excavated, old archaeological sites in this region that might document the pre-Columbian domestication of these globally important crops."

Professor Iriarte said: "Genetic and archaeological evidence suggests there were at least four areas of the world where humans domesticated plants around 11,000 years ago, two in the Old World and two in the New World. This research helps us to prove South West Amazonia is likely the fifth.

"The evidence we have found shows the earliest inhabitants of the area were not just tropical hunter-gatherers, but colonizers who cultivated plants. This opens the door to suggest that they already ate a mixed diet when they arrived in the region."

Javier Ruiz-Pérez said: "Through an extensive archaeological survey including excavations and after analysing dozens of radiocarbon dates and phytolith samples, we demonstrated that pre-Columbian peoples adapted to and modified the seasonally flooded savannahs of south-western Amazonia by building thousands of mounds where to settle and by cultivating and even domesticating plants since the beginning of the Holocene."

A new prognostic tool predicts how long someone diagnosed with chronic lymphocytic leukemia (CLL) will be able to wait before starting cancer treatment. Researchers describe what they hope will become a point-of-care resource to help improve clinical decision making in a study published today in the journal Blood.

The tool, which is based on the results from three common and widely available tests, could help alleviate the frustration patients feel when told that they have cancer but should 'watch and wait' rather than starting treatment immediately - the strategy medical guidelines recommend for patients with early-stage CLL who don't have disease symptoms. Such patients comprise about 70-80% of those diagnosed with CLL each year. It is estimated that more than 400,000 patients in the United States and Europe currently fall into this category.

In addition to offering patients a better sense of how they might need to adjust work, travel, and other activities to plan for cancer treatment, the prognostic tool can help doctors determine how frequently to monitor each patient. Most existing prognostic tools for CLL focus on assessing a patient's chance of survival once the disease has progressed to the point that treatment is necessary. The new tool, called IPS-E, is the first validated prognostic score specifically tailored to forecast the need for treatment.

"While some patients display a milder disease never requiring therapy, others present active disease shortly after diagnosis and require intervention," said lead study author Davide Rossi, MD, Institute of Oncology Research in Bellinzona, Switzerland. "The IPS-E is a simple and a robust prognostic tool based on routine clinical and laboratory variables. The simplicity of IPS-E should facilitate its translation to the clinic."

CLL is a cancer of the white blood cells that causes the body to produce too many lymphocytes, a type of immune cell. The disease typically progresses more slowly than other forms of leukemia and many patients have no symptoms. As CLL gets worse, it can cause fatigue, swollen lymph nodes and frequent infections and increase the risk of other types of cancer and immune system problems.

Previous studies have shown there is no survival benefit to starting available therapies until a patient's white blood cell counts and symptoms reach a certain threshold. Among all CLL patients, roughly one-third never require treatment, a third will need treatment only after many years without symptoms, and a third require therapy within the first few months or years. However, until now doctors have lacked evidence-based tools for predicting which patients will fall into which category, said Dr. Rossi. Most patients are advised to visit their doctor every 3-12 months to check for signs of disease progression.

This research drew data from 4,933 patients with asymptomatic early-stage CLL who had participated in 11 international cohort studies. Starting with a training cohort of 333 patients, researchers found that three factors consistently and independently correlated with a shorter time to first treatment: unmutated immunoglobulin heavy chain variable region (IGHV) genes, high absolute lymphocyte counts, and palpable lymph nodes.

They used this information to develop a prognostic score with each factor counting as one point. Patients with zero factors are considered to have a low risk of needing treatment within five years of their diagnosis. Patients with one factor are considered to face an intermediate risk and patients with two or three factors are considered high risk.

Validating the scoring system using data from 10 other cohorts, the researchers found that about 30% of patients were categorized as low risk, 35% were at intermediate risk and 35% were at high risk. The scores correlated closely with actual outcomes; of those in the low-risk category, 8.4% required treatment within five years, compared to 28.4% in the intermediate group and 61.2% in the high-risk group.

The three tests required to establish a patient's prognostic score are widely available. Lymphocyte counts and lymph node status are already assessed as part of routine CLL diagnosis. The genetic test to determine IGHV status is typically performed when a patient is preparing to start treatment. Performing this test at the time of diagnosis would allow doctors and patients to benefit from the prognostic tool and the test would not need to be repeated later if the patient begins treatment.

In addition to its importance for patients and doctors, the prognostic tool can also inform the design of clinical trials, for example to assess monitoring and early intervention strategies for patients who face the highest risk of disease progression.

"The IPS-E can be regarded as a building block to which newly discovered independent outcome predictors for patients with early stage CLL could be added," said Dr. Rossi. "A prospective study would help to further assess and eventually strengthen this prognostic tool."

What The Study Did: Describes testing for and treatment of children with coronavirus disease 2019 (COVID-19) in Madrid.

Authors: Alfredo Tagarro, Ph.D., M.D., of the Hospital Infanta Sofía de San Sebastián de los Reyes in Madrid, Spain,  is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamapediatrics.2020.1346)

Editor's Note: The article includes conflict of interest disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflicts of interest and financial disclosures, and funding and support.

Fungi play an important role for mankind. In the soil, they decompose dead organic material, making it accessible to plants as a nutrient. In industrial biotechnological plants, fungi produce vast quantities of chemicals and food every day. In addition, fungi produce very complex active ingredients that could have potential for medical applications.

On the other hand, there are fungi that damage crops or make people sick. For example, infections caused by the fungus Aspergillus fumigatus can be fatal - especially people with a severely weakened immune system, for example after stem cell or organ transplantation, are affected.

Despite this great importance, far less is known about fungi than about other organisms. "New findings in fungal biology also require that as many researchers as possible have access to state-of-the-art analytical methods," says Dr. Ulrich Terpitz from the Biocenter at Julius-Maximilians-Universität (JMU) Würzburg in Bavaria, Germany.

Successful with expansion microscopy

Terpitz's team has developed such a method in collaboration with three other research groups: For the first time, fungi can now be visualised using expansion microscopy (ExM). This method makes cellular structures visible with a resolution of less than 60 nanometres - using a conventional confocal fluorescence microscope.

"Although this is less than can be achieved with high-tech super-resolution fluorescence microscopes, access to such facilities is often limited, especially for fungal researchers. In contrast, standard fluorescence microscopes are widely used and expansion microscopy can be carried out in any biological laboratory," said Terpitz.

The JMU working groups of Professor Markus Sauer (Biocenter) and Dr. Johannes Wagener (Institute of Hygiene and Microbiology) and the group "Molecular Genetics of Fungal Pathogenicity" headed by Professor Antonio Di Pietro from the University of Cordoba in Spain contributed to the development.

Method used for three fungal species

The ExM procedure is quite simple: the stained fungus sample is embedded in a polyacrylamide hydrogel and the fluorescent dyes are anchored in the hydrogel. After water is added, the polymer expands like a gummy bear in a glass of water. It also expands the fluorescent dyes in a uniform manner.

However, there is a problem to be solved first: Fungi have a cell wall that must be removed before expansion. The researchers use cell wall dissolving enzymes for this purpose. "The result is an easy-to-handle protocol for the ExM of fungi that can be used for different fungus species, including the clinically relevant Aspergillus fumigatus," said Terpitz. The researchers also applied their method to the pathogens of corn blight (Ustilago) and tomato wilt (Fusarium oxysporum).

Funding by the German Research Foundation

These results were developed within the framework of the transregional collaborative research centre 124 FungiNet (Jena/Würzburg), which is funded by the German Research Foundation (DFG). Next, the JMU researchers want to use expansion microscopy to show the immune system's reaction to invading fungi. For this purpose, they will bring fungi in cell cultures into contact with immune cells.

To this end, the team identified several thousand proteins, determined their respective amounts in mutant and reference lines and combined the findings with measurements of photosynthetic performance. Their findings were published in the journal Nature Communications on 3 April 2020.

Mutations cause defects

For their joint research, the team headed by Dr. Julia Grimmer from MLU and Professor Sacha Baginsky, Head at the Chair for Plant Biochemistry at RUB, used Arabidopsis thaliana as model organism. "This plant has been studied in detail and there are many known mutations," explains Julia Grimmer. Two of these mutations were of particular interest to the research group and were pivotal for the discoveries that have now been described.

One of the mutations is characterised by a defect in protein import into the chloroplasts. Chloroplasts are dependent on importing a large proportion of their proteins from the cytoplasm. "A defect in the import prevents the production of sufficient chlorophyll - the plants are not green, they are albino mutants," explains lead author Julia Grimmer. The other mutation affects the function of the so-called proteasome, a protein complex responsible for degrading proteins in the cytoplasm. In the mutant, the functionality of the proteasome is altered.

Double defect improves performance

"The combination of these two mutations has resulted in a new phenotype of the plant," explains Sacha Baginsky. "The plants are greener than the albino mutant and they carry out more photosynthesis. This surprised us, because it is contra-intuitive. If a second defect is added to the first, the function improves." The researchers interpret this result as follows: the reduced degradation of proteins due to the proteasome mutation means that more chloroplast proteins are available in the cytoplasm. Even though transport is disrupted due to the import mutation, some proteins can still be transported into the chloroplasts, where more chlorophyll can thus be formed than in albino plants. The new double mutant also has more thylakoid stacks: this is where the functional photosynthetic complexes are located.

Studies of wild-type Arabidopsis plants showed that the improvement in photosynthetic performance due to the proteasome mutation also occurs independently of the import mutation. "We assume that the proteasome is constantly degrading chloroplast proteins in the cytoplasm, which in turn protects the plant from potential damage caused by too much photosynthesis," says Sacha Baginsky. This means the plant wastes energy that could be used to build up biomass in order to protect itself. Due to the proteasome mutation, which interferes with the degradation of proteins in the cytoplasm, this limiting factor is reduced and photosynthesis is rendered more efficient. "Since all photosynthetic organisms protect themselves through similar mechanisms, we assume that this effect can also be transferred to higher plants," reckons the biologist. This could potentially help to render the conversion of carbon dioxide into biomass by plants more efficient.

Complex proteome analysis

The research team has based its findings on complex analyses of the entirety of plant proteins, the so-called proteome. Several thousand proteins were both identified and their respective amounts in the different mutants were quantitatively determined. "Only very few research groups are able to do this in this level of detail. This has enabled us to document the effects and to understand them," concludes Sacha Baginsky.

WASHINGTON, April 8, 2020 — Crooner Bing Crosby knew a thing or two about sound. In 1947, recognizing that recorded music sounded better on magnetic reel-to-reel tape than on vinyl records, he invested in a company to develop equipment to record his radio shows. Soon, reel-to-reel tapes and recording and playback machines were a household craze. Now, as reel-to-reel tapes make a comeback among audio buffs, scientists are unraveling the secret of why some decades-old tapes are unplayable, while others retain their original superb audio fidelity.

The researchers are presenting their results through the American Chemical Society (ACS) SciMeetings online platform.

“It is a mystery why some tapes hold up and others don’t,” says Andrew R. Davis, Ph.D. “I talked to audio technicians to ask what they do to remedy unplayable tapes. They knew that heating degraded tapes worked, and they used everything from toaster ovens to hair dryers. But no one knew exactly why heat worked, and sometimes the tapes reverted quickly to being unplayable. We are trying to find out why.”

The project is of special interest to Davis, a polymer chemist at the Library of Congress (LC), which has nearly 200,000 reels of audio tapes spanning recordings of popular musicians, National Public Radio (NPR) broadcast archives and the American Folklife Center. The collections are used by scholars and documentary producers around the world. Universities, private citizens and museums also have aging reel-to-reel tapes, and Davis emphasizes that his work could help them preserve recordings in their collections, as well.

Reel-to-reel tapes are generally comprised of a multilayer polyester-urethane polymer containing various additives and lubricants. Tapes that degrade often have “sticky-shed syndrome,” which is created by the deterioration of binders in a magnetic tape that hold the iron oxide magnetizable coating to its plastic carrier or that hold the thinner back-coating on the outside of the tape. Sticky-shed syndrome leaves a residue that can damage the tape and playback equipment.

The sweet spot for thermal treatment of tapes appears to be around 130 F, Davis says. In his studies, Davis used sample tapes from LC’s analytical lab that are representative of the library’s valuable collections. On most of the tapes he studied, he observed that residues on the surface of the binder layer were crystalline and polyester-like. He also found that these residues melted back into the bulk polymer layer upon heating, turning an unplayable tape into a playable one. It turns out that the crystals re-appear, or bloom, on the tape surface when they become unplayable again. His studies of thermal transitions in the magnetic layer and polyethylene terephthalate support film indicate that a single component does not account for tape degradation and that the detrimental residues are not isolated to the tape binder layer.

“This research also confirmed what we heard from audio technicians, that thermally treated tapes that were wound on reels reverted to a visibly deteriorated condition within a few weeks,” Davis says. “Surprisingly, we found that when our small unwound test samples of tape were thermally treated, they appeared to be optically fine even after weeks. Clearly being wound has some effect on the tapes.”

“One explanation is that when you bake and melt the tape residues, they transfer to the backside of the adjacent, nonmagnetic layer of tape. As it cools down, it retransfers to the oxide layer if the tape is tightly wound,” Davis says. “Or perhaps the pressure of winding the reel has something to do with the melting and recrystallization process.” Davis and his colleagues are studying those possibilities now.

Despite the ongoing mystery, Davis has advice for people who love their stashes of reel-to-reel tapes and want to know how to store or restore their old tapes. “The best bet is to buy a good technical oven to control the temperature of restoration and good playback equipment, rather than highly specific environmental controls,” he says. “You probably wouldn’t want to store your tapes in a sauna, but normal seasonal changes in temperature and humidity seem to bode well for tape storage.”

What The Study Did: The case of a patient with coronavirus disease 2019 (COVID-19) whose main symptom was a loss of smell without nasal obstruction is reported in this article.

Authors: Michael Eliezer, M.D, of Lariboisière University Hospital in Paris, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamaoto.2020.0832)

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, conflicts of interest and financial disclosures, and funding and support.

New data from a landmark study done by Monash University researchers in Australia raises significant concerns that even short-term exposure to low level air pollution can affect gene expression, leaving us at risk of other diseases such as cancer, cardiovascular and respiratory diseases.

It has long been known that exposure to air pollution, including the widespread smoke events in the US and Europe, can lead to short term health problems such as respiratory distress. It is also known that, longer term, exposure to air pollutants leads to oxidative stress and issues like an increased risk of cardiovascular disease.

Research, published in the journal Environment International, provides the first evidence that exposure to even very low levels of air pollution can change gene expression that are the hallmark of diseases such as cancer.

Research from Associate Professor Yuming Guo from the Monash School of Public Health and Preventive Medicine, and colleagues at Nagasaki University in Japan and Cambridge University in the UK, studied blood samples from 266 pairs of twins (192 identical and 74 non identical) as well as 165 parents in Brisbane over periods from 2005 to 2010. The volunteers are part of the Brisbane System Genetics Study.

The periods when the blood samples were taken were matched to data from seven air quality monitoring stations around Brisbane at that time, to measure the levels of exposure to PM2.5 (the main particulate matter in smoke) and sulphur dioxide (the main gaseous pollutant).

The researchers studied expression in six genes associated with oxidative stress and inflammation, which have long been considered important features of disease processes initiated by pollutants.

The researchers found that even the low levels of air pollution experienced in Brisbane over the decade of the study led to change of gene expression associated with morbidity and mortality in the longer term.

The latest study is further evidence that exposure to air pollutants, even at low levels, has long term health consequences, which has real life implications for the current COVID pandemic. according to Associate Professor Guo. "This is the first evidence as to how exactly exposure to low level of air pollution actually alters our gene expression which in turn impacts out health," he said.

"Combined with the global consequences of COVID 19 and its impact on respiratory health there is even a greater need to be conscious of limiting our exposure to air pollution."

The rate of pregnant women with opioid use disorder, or OUD, when giving birth more than quadrupled from 1999 to 2014, according to the Centers for Disease Control and Prevention. This indicates a significant public health concern related to adverse health outcomes for both mother and child. Impacts may range from preterm labor or neonatal abstinence syndrome, to adverse child welfare outcomes and early foster care placement.

n response to this growing concern, Oregon-based health care organizations and substance treatment centers collaborated in 2014 to develop Project Nurture, a novel intervention model that combines maternity care, substance use treatment and social services coordination for women who struggle with addiction.

A new study published in the April issue of the journal Health Affairs says that, since its inception, Project Nurture has helped to reduce the necessary placement of children in foster care by more than 8 percentage points. The rate of reported maltreatment within the child's first year of life also declined by approximately 7 percentage points.

"These outcomes are significant," says the study's lead investigator John McConnell, Ph.D., director of the Oregon Health & Science University Center for Health Systems Effectiveness. "They point to Project Nurture's positive outcomes for mothers and children as well its potential to reduce the burden on the foster care system."

McConnell and a team of researchers at OHSU, Kaiser Permanente Northwest and Portland's Central City Concern evaluated more than 1,500 Medicaid enrollees across the state of Oregon who had hospital births and concurrent OUD diagnoses between the years 2012 - 2017, comparing outcomes for women giving birth in the county served by Project Nurture to outcomes for similar women in Oregon counties not served by Project Nurture.

In addition to the positive outcomes related to child welfare, the analysis suggests that Project Nurture also helped increase the number of prenatal visits, as well as hospital length-of-stay, for new mothers diagnosed with OUD.

"The effectiveness of Project Nurture is promising; however, additional challenges such as long-term financing, secure data sharing and expanded treatment options for a broader set of substance abuse disorders must be met in order to ensure the program maintains its success and influence in integrating health care and human services in the years ahead," says McConnell.

New research has uncovered the risk factors for Fijians carrying a pneumonia-causing bacteria.

The collaborative study, led by the Murdoch Children's Research Institute (MCRI) and the Fiji Ministry of Health and Medical Services, will help determine further public health interventions to prevent people carrying and transmitting the bacteria.

MCRI's Eleanor Neal said Streptococcus pneumoniae was a leading cause of childhood illness and death around the world.

An estimated 9.18 million cases of illness and 318,000 deaths in children under five years in 2016 were caused by pneumococcal disease, an infection caused by Streptococcus pneumoniae.

Ms Neal said because carrying pneumococci could progress to a serious infection, reducing community transmission was crucial.

"Mostly, people carry the bacteria around harmlessly at the back of the nose without any symptoms. But it has the real potential to cause disease by invading the bloodstream, resulting in severe infections such as meningitis and bloodstream infection (sepsis), and can cause pneumonia," Ms Neal said.

"Control of pneumococcal carriage is considered a key aspect of controlling disease, as it is the means of transmission and a prerequisite of disease."

The study of 8,109 participants analysed data from four annual (2012-2015) Fijian cross-sectional surveys, before and after the introduction of the ten-valent pneumococcal conjugate vaccine (PCV10) in October 2012.

Ms Neal said before this study it was largely unknown what the impact of PCV10 was on the risk factors for pneumococcal carriage in low and middle income countries in the Asia-Pacific region.

Senior researcher on the study, MCRI's Professor Fiona Russell, said the study found PCV10 helped to reduce overall and PCV10 pneumococcal carriage in Fiji.

But she said iTaukei ethnicity, which made up 56.8 per cent of the Fijian population, young age, urban residence, living with two or more children under five years, low family income, and upper respiratory tract infection symptoms were still associated with pneumococcal carriage.

The study found toddlers and children aged 2-6 years, and symptoms of upper respiratory tract infections were also positively linked to a higher burden of pneumococcal bacteria.

Research findings suggest gut microbes can effect allergic immune responses. Tasuku Ogita who has recently joined Shinshu University is an expert on teas and their effects on gut bacteria. In this study, his team looked at green tea and the abundance of Flavonifractor plautii (FP) bacteria found in the gut. FP has been reported to be a part of the catechin metabolism in the intestines. Catechin is an antioxidant found in a variety of foods including green tea, of which 30 to 42% of its dry weight is catechin.

Tasuku Ogita and his team including supervisor Takeshi Shimosato has found that oral administration of FP strongly suppresses the Th2 immune response to food allergies in vivo. The food we eat effects the complex cocktail of different strains of bacteria in the gut. Drinking green tea increases the abundance of FP (Flavonifractor plautii) which suppresses the Th2 immune response. FP is a strain of the Clostridia family of bacteria, which is known to have effects on the immune system, notably inhibiting inflammation. Some Clostridia strains show promise of lowering blood pressure and some are known to be abundant in lean people and not in heavier people, leading researchers to believe they can be used to regulate weight.

Dr. Ogita has successfully cultured FP which took 6 months to accomplish. It is not easy to grow bacteria that grows inside the intestines out of its environment. Dr. Ogita was delighted when he was able to see the "face" of this FP strain under a microscope. A photo of the FP bacteria did not exist because research into its study is in its infancy. Dr. Ogita believes this is the first photo of FP.

Shinshu University is located in Nagano prefecture, known throughout Japan for having a variety of fermented food items with positive health outcomes. Nagano is unusual in that it does not have direct access to an ocean, so the food culture that has developed here has been unique. Due to its mountainous terrain, residents have had to survive long winters without access to the outside world, cultivating a rich food culture of natural preserves including miso and lacto-fermented pickles.

Nowadays, its residents have the best health and highest longevity in Japan, meaning it is likely a great contender for the area with some of the best health lifestyles in the world. Nagano manages to do this with some of the lowest costs for medical care for the elderly in Japan, meaning people live long but are also healthier longer. Researchers at Shinshu University continue to work to study unique foods indigenous to Nagano and Japan, and metabolic processes in the body scientifically to share this knowledge with others around the world with the hope that they too, can benefit from this culture.

There is potential for the FP strains of bacteria to follow in the steps of lactic acid bacteria and bifidobacterium in being added to foods for their desired functionality. At this point more studies are needed to look into the safety of FP before it can be used as an anti-allergy probiotic.

Researchers at Lund University in Sweden have succeeded in restoring mobility and sensation of touch in stroke-afflicted rats by reprogramming human skin cells to become nerve cells, which were then transplanted into the rats' brains. The study has now been published in the research journal PNAS.

"Six months after the transplantation, we could see how the new cells had repaired the damage that a stroke had caused in the rats' brains", says Professor Zaal Kokaia, who together with senior professor Olle Lindvall and researcher Sara Palma-Tortosa at the Division of Neurology is behind the study.

Several previous studies from the Lund team and others have shown that it is possible to transplant nerve cells derived from human stem cells or from reprogrammed cells into brains of rats afflicted by stroke. However, it was not known whether the transplanted cells can form connections correctly in the rat brain in a way that restores normal movement and feeling.

"We have used tracking techniques, electron microscopy and other methods, such as light to switch off activity in the transplanted cells, as a way to show that they really have connected correctly in the damaged nerve circuits. We have been able to see that the fibres from the transplanted cells have grown to the other side of the brain, the side where we did not transplant any cells, and created connections. No previous study has shown this", says Zaal Kokaia, who, even though he and colleague Olle Lindvall have studied the brain for several decades, is surprised by the results.

"It is remarkable to find that it is actually possible to repair a stroke-damaged brain and recreate nerve connections that have been lost. The study kindles hope that in the future it could be possible to replace dead nerve cells with new healthy nerve cells also in stroke patients, even though there is a long way to go before achieving that", says Olle Lindvall.

The researchers have used human skin cells that have been reprogrammed in the laboratory to become nerve cells. They were then transplanted into the cerebral cortex of rats, in the part of the brain that is most often damaged after a stroke. Now the researchers will undertake further studies.

"We want to know more about how the transplanted cells affect the opposite hemisphere of the brain. We also want to take a closer look at how a transplant affects intellectual functions such as memory. In addition, we will study possible side effects. Safety is, of course, extremely important for cell transplantation if it is going to be used clinically in the future", says Zaal Kokaia.

A European Union (EU) programme aimed at reducing carbon dioxide (CO2) emissions has made significant progress despite low prices in carbon markets, according to a study at the Universities of Strathclyde and Pittsburgh.

Under the EU's Emissions Trading System (ETS), introduced in 2005 in response to the Kyoto Protocol, governments set a cap on an allowable total amount of emissions over a certain period. They also issue tradable emission permits, which allow for one ton of CO2.

It is widely considered that carbon markets require high prices to reduce emissions but many observers believe they often set prices which are considered too low. However, the study by Strathclyde and Pittsburgh has found that the EU ETS saved around 1.2 billion tons of CO2 between 2008 and 2016, nearly half of what governments pledged to reduce in their Kyoto Protocol commitments.

The study has been published in the journal PNAS (Proceedings of the National Academy of Sciences of the United States of America). Strathclyde's home city, Glasgow, is due to host the next United Nations Climate Change Conference.

Dr Patrick Bayer, a Chancellor's Fellow in Strathclyde's School of Government & Public Policy and lead author of the study, said: "The ETS was set up to cover some of the most polluting industries"It has focused on very carbon-intensive energy production and manufacturing but there is evidence in other research suggesting that these industries have started to diversify their business models and to look into adopting carbon-neutral technologies or, at least, are interested in thinking about how to change their operations.

"Firms got an initial endowment of permits free but if they had emissions in excess of what they were allowed, they needed to buy more. If firms are to change their behaviour in the long run, prices of permits should be as high as possible to incentivise them to change away from carbon-intensive production.

"It turned out prices in carbon markets were fairly low, which then caused major concerns for environmentalists and policy-makers, because they felt they might not provide sufficient incentives.

"It depends on the sector or size of firm but we argue that, if firms think of carbon regulation as a long-term project, then they do need to start to change their behaviour."

The study used emissions in sectors not covered by the EU ETS to estimate what emissions would have been in those sectors the system does cover. It found that emissions in covered sectors decreased by between 8.1% and 11.5%, compared to expected emission levels without the EU ETS. This translates to a decrease of around 3.8%, compared with the EU's total emissions during 2008 to 2016.

Dr Bayer said: "In the energy and electricity markets, we have seen even big players thinking about how they can run their operations when becoming less dependent on fossil fuels. But there can be a threat that, whenever prices in those markets go up, an industry or business becomes exposed to high costs.

"The appeal of carbon markets is that, once they are established with the right rules, you can connect them to other markets. Climate is not concerned about whether emissions are reduced in the UK or Germany or China; so long as they are reduced, that helps to address the problem. If you have carbon markets scattered across the world, you might be able to trade across those markets.

"The UK's future place in the ETS is still up for discussion but all options are on the table. Whether any UK carbon market would be connected to the European market isn't clear and would probably depend on negotiations with the EU and how trade will be regulated in future relations. Assuming there were agreement on this and some strong economic integration between the two countries, it would probably make a lot of sense to connect those markets. The UK has been successful in decarbonising its economy in the past decade or so and has a strong role to play in continuing to advocate for future decarbonisation"

"The period our study covered, from 2008 to 2016, included the financial crisis and economic downturn, when demand for the permits reduced. We used a statistical model to account for the effect of the crisis. The emission reductions that we measure are in addition to lower demand for permits due to the economic crisis, energy efficiency targets and climate policies that try to address carbon emissions."