Tech

LEBANON, NH - Colorectal cancer is estimated to cause more than 53,000 deaths in the US in 2020, making it the second most common cause of cancer death. This death rate, however, has been steadily dropping, likely due to better cancer screening programs such as colonoscopy. During colonoscopies, clinicians excise colorectal polyps and visually examine them on histopathology slides for neoplasia. Detecting cancer at an early, curable stage and removing pre-invasive adenomas or serrated lesions ultimately reduces the mortality rate. Numbers and types of polyps found can also indicate future risk for malignancies and are therefore used as the basis for screening recommendations.

An artificial intelligence (AI) model for automated classification of colorectal polyps could benefit cancer screening programs by improving efficiency, reproducibility, and accuracy, as well as reducing access barriers to pathological services. In a new study out of Dartmouth's and Dartmouth-Hitchcock's Norris Cotton Cancer Center, a computer science and clinical research team led by Saeed Hassanpour, PhD, trained a deep neural network to do just that. Not only can their model distinguish the four major types of colorectal polyps at the level of practicing pathologists, as evaluated on a dataset across multiple external institutions, but also proves that a model designed using data from a single institution can achieve high accuracy on outside data.

The team found that a deep neural network, trained on colorectal polyp data from Dartmouth-Hitchcock Medical Center, still performed with the same level of sensitivity and accuracy as practicing pathologists when used on 238 slides spanning 24 different institutions in the US. These findings, "Evaluation of a Deep Neural Network for Automated Classification of Colorectal Polyps on Histopathology Slides," have been published in JAMA Network Open. "Our study is one of the first to show a deep neural network that is generalizable to data from multiple external medical centers," says Hassanpour. "A challenge in the field of deep learning for medical image analysis is collecting widespread data. Here, we have access to histopathology slides from 24 different institutions, which gave us the opportunity to evaluate and show that the AI models that we train are broadly generalizable to new data from outside."

The access to a multi-institutional dataset was made possible by Hassanpour's collaboration with Dr. Arief Suriawinata, MD, and his group from the Department of Pathology & Laboratory Medicine at Dartmouth-Hitchcock Medical Center and Dr. Elizabeth Barry, PhD, from the Department of Epidemiology at the Geisel School of Medicine at Dartmouth, as well as her colleagues from the Vitamin D/Calcium Polyp Prevention Clinical Trial.

Hassanpour's team has built a graphical user interface for showing the classifications of the neural network. They are currently working on a clinical trial to evaluate the use of their algorithm for assisting pathologists in diagnosis of colorectal polyps. "We are hoping to create a software application that can help pathologists improve their accuracy, efficiency, and consistency in diagnosing slides," he says.

A new study led by scientists at the University of Birmingham has shed fresh light on how a key front-line drug kills the tuberculosis bacterium.

The research paves the way for development of new antibiotic drugs targeted at emerging strains of TB.

Tuberculosis (TB) remains a global health challenge, responsible for around 1.5 million deaths each year, with particularly high incidences in India, China and Indonesia. There is an urgency to better understand how effective drugs work against the disease because of the emergence and spread of new strains including multi-drug resistant and extensively resistant strains.

Called ethambutol, the drug the scientists were studying has been a mainstay in the fight against TB since its discovery in 1961. Despite this, the drug's 'mode of action' - the way it kills the bacterium - has not been fully confirmed by scientists.

In this study, published in the journal Science, the research team succeeded in confirming that particular groups of proteins within the TB bacterium, called Emb proteins, are targeted by ethambutol. Although the importance of these proteins had previously been recognised, a lack of structural and biochemical data had prevented scientists from confirming precisely how the drug targets them.

The study, carried out in collaboration with scientists from ShanghaiTech, in China, and the University of Queensland in Australia, succeeds in overcoming this barrier.

Researchers used cryogenic electron microscopy and x-ray imaging to study the structures of a series of Emb proteins for the first time. They were able to show how different Emb proteins were responsible for specific physiological functions producing crucial components of the TB cell wall.

They were also able to show how ethambutol binds to and inactivates these Emb proteins.

Professor Gurdyal S. Besra, in the Institute of Microbiology and Infection and the School of Biosciences at the University of Birmingham, is a lead author of the paper. He says: "This exciting breakthrough with our colleagues from China and Australia will inform a range of medical researchers from a wide range of disciplines; from structural biologists, biochemists, chemists, and microbiologists, and most importantly, scientists in the pharmaceutical industry aiming to develop new TB antibiotics targeting this unique set of proteins for the first time".

New research has heralded a promising step for sufferers of wheat sensitivity or allergy.

A joint project between Edith Cowan University (ECU) in Australia and CSIRO has revealed key insights about the proteins causing two of the most common types of wheat sensitivity - non-coeliac wheat sensitivity and occupational asthma (baker's asthma).

With an estimated 10 per cent of people suffering from wheat sensitivity or allergy causing a raft of chronic health issues, researchers are developing tests that will help the production of low-allergen wheat varieties in the future.

ECU Professor of Food and Agriculture Michelle Colgrave led the investigation.

"We have known for a long time that certain wheat proteins can trigger an immune response in some people, but now we have developed a way to detect and quantify these proteins," Professor Colgrave said.

"We looked a group of proteins called alpha-amylase/trypsin inhibitors (ATIs), which are known to trigger the intestinal inflammation and chronic ailments associated with wheat intolerance in some people.

"These ATI proteins are commonly found in wheat and play an important role in plant defence against pests and also act as an important nutrient for plant growth and human nutrition."

The research has resulted in a reference map of wheat ATI proteins across a diverse range of wheat varieties that represent more than 80 per cent of the genetic diversity found in commercial bread wheats.

The researchers developed an innovative new technique to specifically measure 18 of these proteins, which will help breeders to select varieties with low ATI protein levels in the future or food manufacturers to detect these proteins in food.

"This is a promising step towards future wheat breeding programs that aim to produce safe and healthy wheat varieties to meet the needs of consumers that currently rely on total wheat avoidance," Professor Colgrave said.

A new study from the University of Helsinki presents the current state of knowledge on the exposure and vulnerability of Indigenous Peoples to environmental pollution, reviewing the innumerable impacts that pollution poses on Indigenous communities from all over the world.

"While the number of studies examining the impacts of environmental pollution upon Indigenous Peoples is growing, most of this research is isolated and fragmented across disciplines and geographic regions", says Dr. Álvaro Fernández-Llamazares, from the Faculty of Biological and Environmental Sciences, who led the study. "In fact, few efforts have cut across disciplinary topics and/or regions, and until today there was no global review mapping out the worldwide impacts of environmental pollution on Indigenous Peoples".

The study reviewed more than 680 different publications to highlight broad patterns of all the documented impacts of environmental pollution among Indigenous groups from all inhabited continents. The authors found out that most pollution-related health impacts documented among Indigenous Peoples are mediated through the consumption of polluted water and food, including wild foods obtained through hunting, fishing, and gathering. Because activities associated with collecting country foods generally serve important community roles, concerns associated to pollution regarding the consumption of wild foods can also impact these practices. Pollution can result in fear of consuming traditional wild foods, and foster increased reliance on nutrient?poor and expensive market foods, often increasing the risk of malnutrition and chronic diseases.

"All the literature reviewed provides clear evidence that Indigenous Peoples are largely and heavily affected by polluting activities both through their exposure and vulnerability, and that much of this pollution is linked to broader patterns of colonization", says Fernández-Llamazares. "However, we also note that, all over the world, Indigenous Peoples are developing innovative strategies to limit, abate or stop ongoing pollution and fighting to prevent it from the outset"

The literature review documents several pathways in which Indigenous Peoples are contributing to bring pollution to levels that are not detrimental to human health and ecosystem functioning. Such strategies include social mobilization, blockades, cultural resistance camps, global policy advocacy litigation processes to hold pollutants into account or participatory monitoring, among others.

Fernández-Llamazares notes "I was particularly inspired by the numerous examples where Indigenous communities and scientists have built successful partnerships to martial global support for the defence of environmental justice. It is my hope that this review will contribute to bring visibility to the arduous efforts of the many Indigenous communities that are fighting to combat pollution all over the world."

Telehealth delivery of dementia care in the home can be as effective as face-to-face home visit services if carers and recipients take advantage of the technologies available, Australian researchers say.

Dementia affects almost 50 million people worldwide, which is predicted to increase to 131.5 million people by 2050. Every three seconds someone in the world develops dementia.

The study of 63 people living with mild to moderate dementia, and their care partners, found that telehealth services using videoconferences can save travel time - particularly in rural and remote areas - and equip families with strategies to promote independence in the person with dementia.

Giving care partners strategies to cope with, and delay, functional decline in people living with dementia is a priority, given that about 70% of people with dementia live in their own home with support from family members and friends for assistance," says lead researcher Flinders University Associate Professor Kate Laver, an ARC Discovery Early Career Research Fellow and occupational therapist.

"Giving families evidence-based information and skills can promote independence and improve quality of life and wellbeing for people with dementia," she says.

Telehealth promises to provide a more affordable alternative for older people living at home, including those with chronic health conditions.

Researchers conclude that the use of telehealth technologies to deliver non-pharmacologic interventions for people with dementia and their care partners may reduce the costs of delivering the intervention, increase accessibility, and facilitate research translation.

A new study from Tampere University in Finland found that eye contact during video calls can elicit similar psychophysiological responses than those in genuine, in-person eye contact.

Videoconferencing has become more commonplace than ever. Particularly now as the coronavirus pandemic limits social interactions, people are relying on video calls to connect with friends and family and to work from home. Though a mere video call cannot fully replace the in-person contact to which most of us are accustomed, a new study suggests that our affective responses to another's eye contact may be quite similar during video and in-person interaction.

The recently published study investigated physical reactions to eye contact in various situations. The researchers compared the reactions caused by seeing another person's direct and averted gaze in three situations: in-person interaction, a video call and just watching a video. In these situations, they measured the participants' skin conductance and activation of facial muscles. Changes in skin conductance reflect the activation of the autonomic nervous system, which is an indicator of affect, whereas the activation of facial muscles reflects the positivity or negativity of the affect.

Corroborating previous studies, in-person eye contact was found to elicit a heightened autonomic arousal response. More importantly, this eye contact effect was also observed when the other person was seen over a bidirectional video call. When the other person was only seen on video, direct gaze, in contrast, did not similarly activate the autonomic nervous system. In addition, direct gaze was found to induce facial reactions associated with positive emotion in all three situations. In other words, the mere perception of direct gaze activated the zygomatic or "smile" muscles and relaxed the corrugator or "frown" muscles.

"Our results imply that the autonomic arousal response to eye contact requires the perception of being seen by another. Another person's physical presence is not required for this effect," says Jonne Hietanen, the first author of the study.

"Unexpectedly, we also found that even when the other person was presented just on video, seeing direct gaze elicited the subtle facial reactions of smiling. This suggests that these facial reactions are highly automated responses to eye contact," Hietanen continues.

The results have implications for the use of video calls in everyday situations, even though the researchers caution against too far-reaching conclusions.

"Most present-day applications do not permit direct eye contact as the other person is usually seen with a slightly averted gaze. Therefore, it is not clear whether these affective similarities between in-person and video call interactions extend to the use of applications such as Skype," Hietanen adds.

Antioxidants are one of the most interesting and widely investigated compounds in life sciences due to their key role in the protection of living systems from the negative effects of free radicals. A great variety of antioxidants and discoveries of new ones give opportunities to better understand their pathways and mechanisms of action. Furthermore, evaluation of the ratios of antioxidants in different samples (foods, herbs, pharmaceuticals, biological fluids, etc.) helps quality control and predicting of possible health effects. Guzel Ziyatdinova and her colleagues at Kazan Federal University have been working on this topic for nearly 20 years.

Among a wide range of antioxidants, synthetic phenolic antioxidants and, in particular, sterically hindered phenols are of much practical interest. They are used as a food antioxidant additives for oily and fatty products in order to prevent oxidative rancidity. The most common preserving additives of this type are tert-butylhydroquinone (TBHQ), butylated hydroxyanisole (BHA) and butylated hydroxytoluene. Nevertheless, their quantity in food is strictly regulated because high concentrations lead to negative health effects like chronic neurotoxicity, vision impairment, carcinogenesis, and underdevelopment of the reproductive system. Mixtures of additives are applied as well, and their ratios in products are varied. Therefore, sensitive and selective methods for the simultaneous determination of these antioxidants are required.

The presence of phenolic fragment in the structure of compounds under investigation makes them oxidizable under different conditions, including electrochemical oxidation. Therefore, methods of electroanalysis can be applied for the determination of sterically hindered phenols. The main advantages of electroanalysis over other analytical tools are high sensitivity and selectivity, rapid response, simplicity and cost-efficiency, as well as capacity for miniaturization.

Due to their structural similarity, TBHQ and BHA are usually oxidized at close potentials, rendering it impossible to determine them simultaneously. In this research, a novel amperometric sensor has been developed for this purpose. It is based on glassy carbon electrode covered with multi-walled carbon nanotubes and electropolymerized carminic acid as the sensitive layer. Carminic acid - a natural dye - was used as a monomer for the first time. Poly(carminic acid) was obtained by electrochemical potential cycling. Attention was paid to the conditions of electro-polymerization (monomer concentration, supporting electrolyte pH, number of cycles and electrolysis parameters) that strongly affect the properties of polymeric coverage and, consequently, the voltammetric response of target compounds.

Both TBHQ and BHA are oxidized on the sensor surface at relatively low anodic potentials, which reduces the interference effect from other electroactive compounds. The combination of electrode surface modifiers (carbon nanotubes and polymeric layer) provides improvements in the voltammetric response of TBHQ and BHA and good resolution of their oxidation peaks in simultaneous presence, as far as oxidation of the phenols proceeds independently, in contrast to strong overlapping of the oxidation peaks occurring at the unmodified glassy carbon electrode. The sensor is selective to TBHQ and BHA in the presence of inorganic ions, ascorbic acid, and α-tocopherol.

Sensor characteristics are significantly improved or comparable with those reported earlier for another modified electrodes. The advantages of this sensor are also the simplicity and rapidity of its preparation, as well as higher selectivity of TBHQ and BHA quantification in comparison to other amperometric sensors.

The sensor has been successfully tested on linseed oils. TBHQ and BHA have been extracted by ultrasonic-assisted extraction with ethanol. The recovery values confirm high accuracy of the TBHQ and BHA determination, the absence of the matrix effects, and the applicability of the sensor to real samples.

Thus, poly(carminic acid) based sensors can be used for the control of the quality and safety of edible oils.

The investigation confirmed that electrodes modified with electropolymerized dyes can be used for the determination of structurally similar compounds, including antioxidants. Further findings can be focused of the enlargement of the dyes forming non-conductive polymers in combination with conductive nano materials as electrode surface modifiers. On the other hand, the study of another types of structurally similar antioxidants used in food industry or being a part of daily human diet is also of practical interest. This problem in electroanalysis can be solved using the aforementioned approaches. In general, such kind of investigations will enlarge the application area of electrochemical methods in the routine practice of sample screening as a good alternative to other analytical methods, including chromatography.

Laboratory of Novice Magnet Materials working in collaboration with Spanish scientists (the University of Oviedo, Spain) tested the Preisach model using interfacing Fe-based microwires. This research was made to check whether it is applicable for FORC-analysis and how real-life conditions affect it.

Soft magnetic ferromagnetic microwires are used for magnetic field sensors, as well as for encoding and reading information. Such microwires are used, for example, for the implementation of 3D geolocation in gadgets, as well as for tagging commercial fish, etc.

The sensors mainly consist of a system containing several closely spaced microwires. This research issue is relevant, and several world scientific groups from different countries (Spain, Slovakia, Brazil, Russia) are engaged in these studies.

MA Student at "Functional nanomaterials and modern applications", Valeria Kolesinkova:

"The FORC-analysis is one of the most well-known ways of magnet interaction analysis, based on the Preisach model, where the idea of a bistable microwire is introduced. To study various properties of magnetic (and not only) materials, we mainly use the well-known characterization methods, however, each method has its own applicability limits and this work shows the applicability limits of the method for analyzing magnetic interactions for ideal magnetic samples with bistable hysteresis loop. The study emphasizes the problems that can be encountered when working with this method in the framework of the Preisach model".

Efforts to contain the spread of the Covid-19 pandemic are now the top priority of governments across the globe. As they make these life-saving decisions, it is particularly crucial for policymakers to accurately predict how the spread of the virus will change over time. Through research published in EPJ Plus, Ignazio Ciufolini at the University of Salento, and Antonio Paolozzi at Sapienza University of Rome, identify a clear mathematical trend in the evolution of daily new cases and death numbers in China, and use the same curve to predict how a similar slowdown will unfold in Italy.

By aligning their strategies with predictions made by the curve, policymakers could be better equipped to draw out scientifically robust plans and timescales for their containment measures. Ciufolini and Paolozzi based their approach around a function commonly used in statistics to track changes in the total values of specific quantities over time. After fine-tuning the parameters defining the shape of their curve, they found that it closely approximated the evolution of daily new cases and deaths in official data from China, where Covid-19 has now been largely contained.

The researchers then used the same approach to predict the evolution of the two values in Italy, by fitting the initial part of their curve to the official data available as of March 29th. This allowed them to make informed predictions of when numbers of daily new cases and deaths will peak, and then begin to fall significantly. Furthermore, the duo strengthened the reliability of these predictions by incorporating their mathematics into Monte Carlo computer simulations, which they ran 150 times.

Ciufolini and Paolozzi acknowledge that their approach cannot account for real-world factors like numbers of daily nasopharyngeal swabs, social distancing, or the fact that real case numbers are likely far higher than those reported. They are now improving their algorithm's predictions by considering how the number of individuals tested by swabs is now far higher in Italy than at the beginning of the infection. If the necessary precautions are taken by governments, and curve parameters tailored to specific nations, they hope that it could become an important part of monumental global efforts to reduce the human cost of the global pandemic.

B-cell acute lymphoblastic leukemia (B-ALL) is characterized by the accumulation of abnormal immature B-cell precursors (BCP) in the bone marrow (BM) and is the most common pediatric cancer. Among the different subtypes known in B-ALL, the most common one is characterized by the presence of a higher number of chromosomes than in healthy cells and is called High hyperdiploid B-ALL (HyperD-ALL). This genetic abnormality is an initiating oncogenic event affiliated to childhood B-ALL, and it remains poorly characterized.

HyperD-ALL comprises 30% of pediatric B-ALL and usually has a favorable clinical outcome, with 90% of survival in patients with this hematologic cancer. Despite this, until date, there was very little knowledge on how hyperdiploidy occurs in HyperD-ALL, as an initiating oncogenic event in B-ALL and which secondary alterations are necessary for leukemic B-ALL cells accumulation in the bone marrow, impeding the growth of healthy cells and leading to the clinical leukemia complications.

A precise knowledge of the physiopathogenic mechanisms underlying HyperD- ALL was necessary because the morbidity/mortality associated with HyperD-ALL still represents a clinical challenge due to the high number of patients suffering from this type of B-ALL. For this reason, Oscar Molina, researcher of the Group of Stem Cells, Developmental Biology, and Immunotherapy of the Josep Carreras Leukaemia Research Institute, has led research on the mechanisms underlying HyperD-ALL, unveiling how and why it happens, published in Blood Journal this April 2020.

Molina and the co-authors of the study hypothesized that the origin of the pathogenic mechanisms associated with hyperdiploidy in B-ALL could be in the moment of the cell's division, known as mitosis, which is a highly orchestrated cellular process that controls the equal distribution of the genetic material, already duplicated and compacted in chromosomes, in two "newborn" cells.

"We knew already that HyperD-ALL arises in a BCP in utero. However, the causal molecular mechanisms of hyperdiploidy in BCPs remained elusive. As faithful chromosome segregation is essential for maintaining the genomic integrity of cells, and deficient chromosome segregation leads to aneuploidy and cancer, we wanted to observe and deepen on what is happening in chromosomes' segregation in HyperD-ALL, because we suspected that by studying cell division in these cells we would find an explanation to this oncogenic process."

Molina was right. Researchers used a large cohort of primary pediatric B-ALL samples, 54. What Molina and his colleagues discovered was that three key processes and actors for correct mitosis or cell division and chromosome segregation were misfunctioning in hyperdiploid cells; that artificial disruption of these processes in blood cells with normal chromosome numbers generated hyperdiploid cells resembling those in B-ALL samples. Therefore, shedding light on the cellular and molecular mechanisms involved in HyperD-ALL origin and progression.

The main proteins and processes leading to fatal error were a malfunctioning of the Condensin complex, a multiprotein complex responsible for helping condense the genetic material correctly into chromosomes; the protein Aurora B kinase, that is responsible for a correct chromosome attachment to the spindle poles, thus ensuring proper chromosome segregation; and the mitotic checkpoint, or Spindle Assembly Checkpoint (SAC), the cell machinery involved in controlling that chromosomes are correctly separated to each pole of the cell that is dividing.

With these findings, Molina et al. have unveiled the molecular mechanisms that are altered in this frequent type of pediatric blood cancer.

"Next steps would be to study whether other subtypes of B-ALL with abnormal chromosome numbers, such as hypodiploid B-ALL, a very aggressive subtype of pediatric blood cancer characterized by lower numbers of chromosomes, share a common molecular mechanism. These studies will allow generating the first in vivo models of leukemias with abnormal chromosome numbers in mice that will be crucial to understand its origin and development, thus facilitating the development of more targeted and less toxic therapies for these pediatric blood cancers" stated Oscar Molina.

Air pollution from just the City of Boston contributes to nearly as many deaths across the wider region as car crashes do, as well as non-fatal cardiovascular and respiratory disease and days of missed work.

With much of the City of Boston shut down by COVID-19, the region is enjoying better air quality than it has seen in decades, a preview of the reduced emissions that will come as part of the city's ambitious "Carbon Free Boston" goals.

But what if Boston eliminated all emissions--and not just because of a pandemic, but for good? That is the question asked by a new Boston University School of Public Health (BUSPH) study published in the journal Environmental Research Letters.

The study estimates that a zero-emissions Boston would mean over 200 deaths avoided in the city (and the rest of Suffolk County) each year, with reductions in fatal and non-fatal cardiovascular and respiratory illness extending all the way from Worcester to Barnstable and into southern New Hampshire and northern Rhode Island, with 6 deaths avoided per 100,000 people in the whole region--which the researchers note is roughly equivalent to the Massachusetts motor vehicle crash fatality rate.

"Public health and climate policymaking are intertwined," says study lead author Matthew Raifman, a doctoral student in environmental health at BUSPH. "While Boston's climate policies are focused on reducing greenhouse gas emissions, these actions will also likely reduce deaths and improve the quality of life of residents of Boston and the surrounding region."

The researchers also estimated that the resulting decrease in medical costs and lost/reduced work could save $1.7 billion in Suffolk County, and $2.4 billion for the entire 75-square-mile zone modeled in the study.

"In showing the substantial health and economic benefits that clean air can bring to Boston area residents, this study demonstrates that climate action isn't just about saving the planet; it's also about making us healthier," says study senior author Dr. Patrick Kinney, Beverly Brown Professor of Urban Health and professor of environmental health at BUSPH.

Raifman, Kinney, and colleagues used the US Environmental Protection Agency's Community Multiscale Air Quality model to estimate the 2011 emissions and air quality status quo for Boston and the surrounding 75 square miles, focusing on air pollutants known to harm health: PM2.5 (particulates with a diameter of less than 2.5 micrometers, or 3 percent of the diameter of a human hair) and O3 (ozone). They then set the model's human-made emissions--including motor vehicles, generators, rail, industry, all oil- and gas-burning, shipping and boating, and residential wood fire--from within Boston's city limits to zero.

They found that a zero-emissions Boston would halve PM2.5 concentrations in the city itself, and slightly decrease concentrations for the rest of the modeled zone. Concentrations of ozone would also decrease across much of zone, although Boston and areas west of the city would actually see an increase in ozone during warmer months--which the researchers explain is because of the reduction in nitrogen oxide emissions that would normally transform ozone into other compounds.

The researchers then used the EPA's Environmental Benefits Mapping and Analysis Program (BenMAP) Community Edition v1.5 to estimate how these changes in PM2.5 and ozone would affect health at the county level. The health benefits from the decrease in PM2.5 would mainly override the health harms of increased ozone, resulting in 288 fewer deaths per year across the 75-square-mile area, mainly in Boston and the Greater Boston area. A zero-emissions Boston would also prevent 116 non-fatal heart attacks, 46 cardiovascular hospitalizations, 117 cases of chronic bronchitis, and over 17,000 asthma attacks across the zone, again mainly in Boston. However, the high ozone levels would increase emergency room visits for asthma and respiratory hospitalizations.

Looking at the effects by race and ethnicity, the researchers found that the greatest reduction in deaths and non-fatal health issues relative to population size would be in black residents, who the researchers note currently bear the greatest burden of environmental injustice and are more likely to live in Boston than any other area in the larger modeled zone.

The researchers estimated that the decrease in deaths, hospitalizations, days of missed work, and other benefits of a zero-emission Boston would translate to savings of $1.7 billion for Suffolk County, $182 million for Norfolk County, $159 million for Middlesex County, and tens of millions of dollars in savings for other surrounding counties in eastern Massachusetts and bordering states.

"In this study, we focused only on the City of Boston's climate action plan, but it's important to note that Boston's actions will not occur in a vacuum," Raifman says. "Many cities across the region are pursuing similar climate goals. The sum may be different from the parts."

UNIVERSITY PARK, Pa. -- Whiteflies are among the most important agricultural pests in the world, yet they have been difficult to genetically manipulate and control, in part, because of their small size. An international team of researchers has overcome this roadblock by developing a CRISPR/Cas9 gene-editing protocol that could lead to novel control methods for this devastating pest.

According to Jason Rasgon, professor of entomology and disease epidemiology, Penn State, whiteflies (Bemisia tabaci) feed on many types of crop plants, damaging them directly through feeding and indirectly by promoting the growth of fungi and by spreading viral diseases.

"We found a way to genetically modify these insects, and our technique paves the way not only for basic biological studies of this insect, but also for the development of potential genetic control strategies," he said.

The team's results appeared on April 21 in The CRISPR Journal.

The CRISPR/Cas9 system comprises a Cas9 enzyme, which acts as a pair of 'molecular scissors' that cuts DNA at a specific location on the genome so bits of DNA can be added or removed, and a guide RNA, that directs the Cas9 to the right part of the genome.

"Gene editing by CRISPR/Cas9 is usually performed by injecting the gene-editing complex into insect embryos, but the exceedingly small size of whitefly embryos and the high mortality of injected eggs makes this technically challenging," said Rasgon. "ReMOT Control (Receptor-Mediated Ovary Transduction of Cargo), a specific type of CRISPR/Cas9 technique developed in my lab, circumvents the need to inject embryos. Instead, you inject the gene-editing complex which is fused to a small ovary-targeting molecule called BtKV, into adult females and the BtKV guides the complex into the ovaries."

To explore the use of ReMOT Control in whiteflies, the team targeted the "white" gene, which is involved in eye color. When this gene is functioning normally, whiteflies have brown eyes, but when it is non-functional due to mutations, the insects is supposed to have white eyes. The team found that ReMOT Control generated mutations that resulted in juvenile insects with white eyes that turned red as they developed into adults.

"Tangentially, we learned a bit about eye color development," said Rasgon. "We expected the eyes to remain white and were surprised when they turned red. Importantly, however, we found that the mutations we generated using ReMOT Control were passed on to offspring, which means that a change can be made that is inherited to future generations."

Rasgon said the team hopes its proof-of-principle study will allow scientists to investigate the same strategy using genes that affect the ability for the insects to transmit viral pathogens of crop plants to help control the insects and protect crops.

"This technique can be used for any application where you want to delete any gene in whiteflies, for basic biology studies or for the development of potential genetic control strategies," he said.

WESTMINSTER, Colorado - April 23, 2020 - Cover crops have a well-documented role to play in suppressing troublesome weeds. But what happens as those cover crops degrade?

A new study featured in the journal Weed Science explores whether cover-crop residues help to suppress summer annual weeds and promote greater crop yields. Researchers planted single cover-crop treatments of cereal rye, hairy vetch, crimson clover and forage radish in the fall, as well as two-way and three-way mixtures. Each was followed by corn and soybean crops.

The team tracked the biomass of each cover crop and the residual components produced - uncovering several key trends. They found that cover-crop biomass and the ratio of carbon to nitrogen influenced weed suppression and its duration. For example, a 9 to 1 ratio of carbon to nitrogen suppressed pigweed by 50 percent at four weeks after treatment, while a 20 to 1 ratio delivered the same level of control eight weeks after treatment.

Similarly, a cover-crop biomass of 2,800 kg per hectare was needed for 50 percent suppression four weeks after treatment, while a biomass of 6,610 kg per hectare was needed for the same level of suppression at eight weeks after treatment.

In fields where the cover crop was the only weed control measure used, corn and soybean yields increased as both cover crop biomass and carbon to nitrogen ratios increased.

Researchers found that most mixtures of cover crops produced more biomass than individual cover crops alone. Carbon to nitrogen ratios produced by cereal rye and a cereal rye-forage radish mixture were 36 to 1 - greater than all the other cover crop treatments. Hairy vetch and crimson clover had ratios of 12 to 1 and 17 to 1, which were the lowest ratios produced by any of the cover crops.

"Our study shows that the biomass of the cover crop isn't all that matters," says Kara Pittman of Virginia Tech, lead researcher for the study. "The composition of the residues the cover crop leaves behind are also important to weed control."

Susanne Hellmuth and Olaf Stemmann from the Chair of Genetics at the University of Bayreuth have discovered a natural protective mechanism that leads to the programmed death of potentially diseased cells. It protects from cancer that can develop as a result of irregular distribution of genetic information to daughter cells. The enzyme separase plays a central role in these processes. The findings published in "Nature" offer promising approaches for cancer therapy.

With this study, the Bayreuth researchers are following up on their contribution to the regulation of separase recently published in "Nature". The strict regulation of this enzyme during cell division is a prerequisite for healthy daughter cells to develop. If the separase is activated too early, there is a risk of cellular transformation into malignant cancer cells.

Re-purposed proteins cause the death of diseased cells

In their follow-up study, the Bayreuth geneticists have now discovered a previously unknown protective mechanism of the cell. It is the separase itself that prevents the threatening consequences of its premature activity: it induces the dividing cell to undergo suicide, a process known as apoptosis. This happens because the separase re-purposes two proteins that usually have the task of counteracting apoptosis. These are the proteins MCL1 and BCL-XL. In a healthy cell they prevent the protein BAK from causing the cell to die. Yet, when separase becomes active too early, it cuts these two proteins. As a result, they can no longer fulfil their cell-protecting function and BAK is free to induce apoptosis. Moreover, separase-dependent processing transforms MCL1 and BCL-XL from anti-apoptotic factors into pro-apoptotic protein fragments. In other words, guardians who are supposed to keep the cell alive become agents of death.

An emergency mechanism protecting against genetic malfunction

Based on these findings, Hellmuth and Stemmann have discovered another important mechanism in the process of cell division. It ensures that the separase spares healthy cells and actually only attacks the proteins MCL1 and BCL-XL in the case of an imminent pathological cell development.

The separase is prepared for this attack as soon as the two proteins have been modified by phosphate groups. The enzyme NEK2A is responsible for this labelling, or phosphorylation, of the proteins. The point is that NEK2A is degraded relatively early in the course of cell development. Before the cell begins to divide, the enzyme has disappeared - provided that the spindle assembly checkpoint is functional and can ensure that cell division proceeds in orderly manner. In this case, the separase fulfils its functions at the right time, without being able to identify and attack the no longer phosphorylated MCL1 and BCL-XL. However, if the spindle assembly checkpoint is defective, the process of cell division is accelerated: And while NEK2A is still present in the cell, the separase becomes active. Now it recognizes the two proteins, and apoptosis is initiated immediately.

Hellmuth and Stemmann refer to this interaction of the two enzymes they have discovered as the "Minimal Duration of Early Mitosis Checkpoint", or "DMC" for short. It is an emergency mechanism that comes into effect as soon as a defective spindle assembly checkpoint causes chromosome mis-segregation associated with the risk of carcinogenesis.

A new approach to cancer therapy

The research results published in "Nature" offer several starting points for new cancer therapies. For example, it has been appreciated for quite some time that MCL1 and BCL-XL are often highly over-produced in cancer cells. In these cases, however, the two proteins protect the wrong cells. They prevent cancer cells from apoptosis, which would have to be induced by proteins such as BAK. "Therefore, a promising approach in the fight against cancer could now be to encourage separase-dependent transformation of MCL1 and BCL-XL into pro-apoptotic factors because this would be especially harmful to diseased cells. We intend to continue pursuing this approach with various research groups in the future, for example from clinical oncology and drug development. It is possible that this approach will enable us to selectively destroy cancer cells with the very proteins that are used by healthy cells for their own self-protection," says Stemmann.

New perovskite-based detectors can sense X-rays over a broad energy range.

Getting an X-ray at the dentist or the doctor is at best a little inconvenient and at worst a little risky, as radiation exposure has been linked to an increased risk of cancer. But researchers may have discovered a new way to generate precise X-ray images with a lower amount of exposure, thanks to an exciting set of materials that is generating a lot of interest.

Scientists at the U.S. Department of Energy’s (DOE) Argonne National Laboratory and Los Alamos National Laboratory have identified a new class of X-ray detectors based on layered perovskites, a semiconducting material also used in some other types of applications such as solar cells and light-emitting diodes. The detector with the new material is 100 times more sensitive than conventional, silicon-based X-ray detectors.

“This new material for detecting X-rays could soon find its way into a variety of different everyday environments, from the doctor’s office to airport security lines to research labs,” said Argonne X-ray physicist Joseph Strzalka, who helped to characterize the perovskite material at Argonne’s Advanced Photon Source (APS), a DOE Office of Science User Facility.

The perovskite materials work because they are deposited as a sprayed-on thin film, a production method that helps to reduce cost compared to having to grow a large silicon single crystal.

“This new material for detecting X-rays could soon find its way into a variety of different everyday environments, from the doctor’s office to airport security lines to research labs.” — Argonne physicist Joseph Strzalka

The new perovskite detectors can also detect X-rays over a broad energy range, especially at higher energies. This is because the perovskite contains heavy elements, such as lead and iodine, which tend to absorb these X-rays more readily than silicon. The potential even exists for the perovskite technology to be used as a gamma-ray detector, provided the films are made a little bit thicker and a small external voltage is applied.

“The perovskite material at the heart of our detector prototype can be produced with low-cost solution process fabrication techniques,” said Hsinhan (Dave) Tsai, an Oppenheimer postdoctoral fellow at Los Alamos National Laboratory. “The result is a cost-effective, highly sensitive and self-powered detector that could radically improve existing X-ray detectors, and potentially lead to a host of unforeseen applications.”

The development and analysis of the perovskite material was a close collaboration between Argonne APS (beamline 8-ID-E) and a Los Alamos team lead by device physicist Wanyi Nie. The material and thin film was created at Los Alamos and brought to Argonne to perform grazing incidence wide-angle X-ray scattering, which gives information about the crystallinity of the thin film. According to Strzalka, the technique shows how the crystal is oriented in the thin film, which relates to the performance of the detector.

Strzalka and Nie were also interested in how the charge transport properties of the film related to the crystal structure and temperature. By using a special stage that allowed the researchers to change the temperature of the sample and make electrical contacts during the measurement, they were able to understand the current generation and transport processes induced in the sample by the X-ray exposure.

“Our instrument at the beamline provides a versatile platform for different kinds of in-situ measurements, including keeping the sample in a vacuum environment while maintaining its temperature and also performing charge transport measurements,” Strzalka said.

According to Strzalka, perovskites may continue to offer important breakthroughs. “The perovskite area is really hot right now, and users come to us to say ‘can we do this and can we do that,’ and it’s really pushing us to develop our capabilities,” he said.

A paper based on the research, “Highly sensitive and robust thin film X-ray detector using 2D layered perovskite diodes,” was published in Science Advances on April 10.

The research was funded by the Los Alamos National Laboratory’s Laboratory Directed Research and Development (LDRD) funding and DOE’s Office of Science.

About the Advanced Photon Source

The U. S. Department of Energy Office of Science’s Advanced Photon Source (APS) at Argonne National Laboratory is one of the world’s most productive X-ray light source facilities. The APS provides high-brightness X-ray beams to a diverse community of researchers in materials science, chemistry, condensed matter physics, the life and environmental sciences, and applied research. These X-rays are ideally suited for explorations of materials and biological structures; elemental distribution; chemical, magnetic, electronic states; and a wide range of technologically important engineering systems from batteries to fuel injector sprays, all of which are the foundations of our nation’s economic, technological, and physical well-being. Each year, more than 5,000 researchers use the APS to produce over 2,000 publications detailing impactful discoveries, and solve more vital biological protein structures than users of any other X-ray light source research facility. APS scientists and engineers innovate technology that is at the heart of advancing accelerator and light-source operations. This includes the insertion devices that produce extreme-brightness X-rays prized by researchers, lenses that focus the X-rays down to a few nanometers, instrumentation that maximizes the way the X-rays interact with samples being studied, and software that gathers and manages the massive quantity of data resulting from discovery research at the APS.

This research used resources of the Advanced Photon Source, a U.S. DOE Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357.

Argonne National Laboratory seeks solutions to pressing national problems in science and technology. The nation’s first national laboratory, Argonne conducts leading-edge basic and applied scientific research in virtually every scientific discipline. Argonne researchers work closely with researchers from hundreds of companies, universities, and federal, state and municipal agencies to help them solve their specific problems, advance America’s scientific leadership and prepare the nation for a better future. With employees from more than 60 nations, Argonne is managed by UChicago Argonne, LLC for the U.S. Department of Energy’s Office of Science.

The U.S. Department of Energy’s Office of Science is the single largest supporter of basic research in the physical sciences in the United States and is working to address some of the most pressing challenges of our time. For more information, visit https://energy.gov/science.