Earth

Northwestern University researchers have developed a new approach to quantum device design that has produced the first gain-based long-wavelength infrared (LWIR) photodetector using band structure engineering based on a type-II superlattice material.

This new design, which demonstrated enhanced LWIR photodetection during testing, could lead to new levels of sensitivity for next-generation LWIR photodetectors and focal plane array imagers. The work could have applications in earth science and astronomy, remote sensing, night vision, optical communication, and thermal and medical imaging.

"Our design can help meet the urgent demand for ultra-sensitive photodetectors," said Manijeh Razeghi, Walter P. Murphy Professor of Electrical and Computer Engineering, who led the study. "The architecture uses a unique type-II superlattice material that optimizes LWIR photodetectors to run with low power, higher optical gain, and excellent stability."

While recent advances in semiconductor materials and devices have led to notable progress in the development of photodetectors that can capture LWIR wavelengths, state-of-the-art LWIR detection technology still suffers from shortcomings. Many photodetectors rely on mercury cadium telluride as a semiconductor, a material that can achieve excellent sensitivity and speed, but also produces low photocurrent gain and excess spectral noise.

Razeghi, who directs Northwestern's Center for Quantum Devices (CQD), designed the photodetector using a type-II superlattice, a material system known for its outstanding growth uniformity and exceptional band structure engineering -- the ability to control the band gap in a material, the space where no electron charge is present. This made it an optimal alternative semiconductor to mercury cadmium telluride for a LWIR system. Her team then applied the new material to a heterojunction phototransistor device structure, a detection system known for its high stability, but one previously limited to short-wave and near infrared detection.

During testing, the type-II superlattice allowed each part of the photodetector to be carefully tuned to use the phototransistor to achieve high optical gain, low noise, and high detectivity.

"The material's demonstrated flexibility allows for meticulous quantum mechanics-based band structure engineering for the heterostructure design, making it a versatile candidate to push the limits of infrared detection," Razeghi said.

The research builds on CQD's long history of work developing and understanding the physics of quantum semiconductor devices for novel applications, from military and earth science to medical systems. This novel artificial quantum structure opens the door toward next-generation high-gain photodetectors with potential for high-speed applications with ultra-sensitive detection capabilities for single photon detection.

RIVERSIDE, Calif. -- A team led by a biomedical scientist at the University of California, Riverside, reports a drug -- an estrogen receptor ligand called indazole chloride (IndCl) -- has the potential to improve vision in patients with multiple sclerosis, or MS.

The study, performed on mice induced with a model of MS and the first to investigate IndCl's effect on the pathology and function of the complete afferent visual pathway, is published in Brain Pathology. The afferent visual pathway includes the eyes, optic nerve, and all brain structures responsible for receiving, transmitting, and processing visual information.

In MS, a disease in which the immune system "demyelinates" or eats away at the protective covering of nerves, the initial period of inflammation and demyelination often damages the optic nerve and other parts of the visual system first. As a result, approximately 50% of patients with MS experience optic neuritis -- inflammatory demyelination of the optic nerve -- prior to showing initial symptoms. Almost all MS patients have impaired vision at some point during disease progression. Symptoms can include eye pain, blurred vision, and progressive vision loss that can lead to blindness, among other visual impairments.

The optic nerve, a heavily myelinated bundle of nerves located at the back of the eye, transfers visual information from the retina to the vision centers of the brain through electrical impulses. Myelin acts as an insulating substance that speeds the transmission of these electrical impulses. Partial myelin loss slows transmission of visual information; severe myelin loss may stop the signal altogether.

The researchers used IndCl to assess its impact on demyelinating visual pathway axons. The treatment induced remyelination and mitigated some damage to the axons that resulted in partial functional improvement in vision.

"IndCl has been previously shown in mice to reduce motor disability, increase myelination, and neuroprotection in the spinal cord and corpus callosum," said Seema Tiwari-Woodruff, a professor of biomedical sciences at the UC Riverside School of Medicine and the study's lead author. "Its effects in the visual system, however, were not evaluated until now. Our study shows the optic nerve and optic tract, which undergo significant inflammation, demyelination, and axonal damage, are able to restore some function with IndCl treatment with successful attenuation in inflammation and an increase in remyelination."

The visual pathway in mice is similar to that in humans. The mouse brain is, therefore, an excellent model for scientists to study vision impairment. In the lab, Tiwari-Woodruff and her research group first induced the mouse model of MS. They let the disease progress for about 60 days and when the disease reached a peak between 15 and 21 days, they administered IndCl to half the mice. At the end of the experiment, they performed functional assay to measure the visual electrical signal; and immunohistochemistry to examine the visual pathway. The mice that received the drug showed improvement in myelination, with visual function improving by about 50%.

For Tiwari-Woodruff, the next question is how IndCl treatment induces functional remyelination in the visual pathway. Her lab, in collaboration with the lab of co-author John A. Katzenellenbogen at the University of Illinois at Urbana-Champaign, is investigating new drugs that are analogues of IndCl.

"Measuring visual function and recovery in the presence of novel therapies can be used to screen more effective therapies that will protect axons, stimulate axon remyelination, and prevent ongoing axon damage," Tiwari-Woodruff said.

Currently approved MS drugs reduce inflammation but do not prevent neurodegeneration or initiate remyelination. Further, they only partially prevent the onset of permanent disability in patients with MS.

"We treated the MS mice with IndCl at peak disease," Tiwari-Woodruff said. "If the brain is highly diseased, some of the axons that could potentially restore visual function are too damaged and will not recover. There's a point of no return. Our paper stresses that to acquire vision improvement, treatment must start early. Early treatment can recover 75%-80% of the original function."

Tiwari-Woodruff stressed that although additional studies are required, the new findings show the dynamics of visual pathway dysfunction and disability in MS mice, along with the importance of early treatment to mitigate axon damage.

"There is a strong and urgent need to find a therapeutic candidate that restores neurological function in patients with MS," Tiwari-Woodruff said. "Therapeutics must target remyelination and prevent further axonal degeneration and neuronal loss. The good estrogens, which have neuroprotective and immunomodulatory benefits, could be candidates for MS treatment."

Abu Dhabi, UAE, February 2, 2021: Adolescent mothers often fall through the cracks of educational programming. This is highly problematic given that globally an estimated 12 million girls between the ages of 15-19, and 777,000 girls under the age of 15, give birth each year. In populations affected by conflict and displacement, adolescent girls have an increased likelihood of becoming mothers due to various factors, such as disruptions to schooling, the loss of family members, poverty, gender-based violence, and poor access to healthcare and sexual and reproductive services and resources. There is a lack of support programs for these young mothers, and a continuing need for educational programming.

In a new paper titled A Bioecocultural Approach to Supporting Adolescent Mothers and their Young Children in Conflict Affected Contexts, published in the journal Development and Psychopathology, Global TIES for Children researchers Alice J. Wuermli and Hirokazu Yoshikawa, and affiliate Paul D. Hastings of the University of California Davis, propose a developmental, two-generational framework to guide the design of research and policies that better address the needs of adolescent mothers and their children in contexts of conflict and displacement.

The researchers draw on several bodies of research including developmental stress physiology, adolescent parenthood internationally, and developmental cultural neurobiology. They argue that neuroendocrine development during adolescence, specifically the increased sensitivity to stressful life events, poses additional risks to adolescent girls and their young children. High levels of stress influence the development of brain regions associated with cognitive, social, and emotional regulatory functioning and learning in both the mother and the unborn child with potential intergenerational consequences for health and development.

"The neurobiological effects of stress on pregnant adolescent girls have implications for prenatal development, may have detrimental effects on the adolescent mother's health and wellbeing, and affect her ability to cope and provide nurturing care," said Wuermli. "High levels of stress prenatally and the first couple of years of a baby's life can have life-long consequences. Adolescent motherhood in high-risk contexts, absent culturally grounded support systems and opportunities for peer engagement and leadership, may likely perpetuate an intergenerational cycle of poverty and poor developmental outcomes."

"Dual-generation interventions for adolescent mothers, with culturally anchored peer engagement, continued education, and child care support, have rarely, if ever, been evaluated in low-income or conflict-affected country contexts," said Yoshikawa. "Yet it is vital that we consider each of these areas. It is our hope that the framework that we've created will guide research and programming that is more specific and effective."

Many household products contain ingredients to protect them against sun damage. These UV filters are found in plastics, paints and textiles, as well as personal care products such as sunscreens and moisturizers. UV filters are entering the aquatic environment in rivers, lakes and oceans. Consider for a moment a beach goer swimming in the ocean or rain washing over plastic playground equipment and running into a stormwater drain - either directly or indirectly, UV filters end up making their way to a waterway.

UV filters are chemicals that work by either physically blocking or absorbing UV rays. There are two main types of UV filters: inorganic forms, which contain metal particles, such as titanium dioxide (TiO2) or zinc oxide (ZnO) and physically block sunrays like little mirrors; and organic chemical UV filters, such as benzophenone-3 (BP-3 or oxybenzone) and octinoxate (EHMC), which chemically absorb UV rays.

In recent years, there has been a rapid increase in public, political and scientific interest in the effect UV filters have had on coral reefs; especially organic UV filters used in sun protection products. Coral reefs are important for biodiversity and provide great economic values, such as tourism and recreation. Significant decline in the diversity and abundance of coral in recent years has been attributed to climate change and longer-duration temperature events, which are exacerbated by human activities that cause coral bleaching, like overfishing and land run-off of nutrients and chemical pollutants. The impact of organic UV filters on corals has also been scrutinized and some regulatory bodies have even banned the sale of sunscreens containing certain organic UV filters.

A recent paper in the journal of Environmental Toxicology and Chemistry (ET&C) summarizes the scientific literature assessing the impact of organic UV filters on coral ecosystems. The researchers reviewed nine laboratory coral exposure studies investigating the biological effects of organic UV filters and 12 studies that provided information on the concentration of 14 different organic UV filters in seawater near coral reefs. They concluded that while organic UV filters do occur in the environment, there is limited evidence to suggest their presence is causing significant harm to coral reefs. However, the scientists caution that based on the limited information and data currently available, it would be premature to conclude that organic UV filters do not adversely impact coral reefs. The scientists pointed to the wide variations in experimental designs used and issues of data reliability, which makes it difficult to draw conclusions. They also pointed to numerous critical data gaps in terms of reliable and relevant environmental exposure and toxicity data that need to be filled before conclusions can be drawn. In their paper, Carys Mitchelmore and colleagues outline a number of recommendations for future studies to assess the environmental risk of organic UV filters to coral reef ecosystems. Mitchelmore adds, "In addition to more field and lab studies that take reef conditions and species into account, there is a need to develop a coral environment risk assessment framework. Investigating and prioritizing stressors on corals would allow regulators, policymakers and scientists to optimize conservation and management activities."

A warmer global climate can cause mutations to have more severe consequences for the health of organisms through their detrimental effect on protein function. This may have major repercussions on organisms' ability to adapt to, and survive in, the altered habitats of the future. This is shown in a new Uppsala University research study now published in the scientific journal Proceedings of the Royal Society B.

Natural environments are being transformed at an ever faster rate, owing to ongoing climate change. This is bringing new life conditions for many species.

"In the long run, organisms will have to adapt genetically to these rapid environmental changes: otherwise, they might die out. This adaptation can take place by mutations that cause changes in the genome that are advantageous in the new surroundings. But very often mutations have negative consequences for the individual that carries them," says David Berger at Uppsala University's Department of Ecology and Genetics.

In the study, which is a collaboration with researchers at Lund University, theoretical models of how proteins function were combined with results from experiments comparing the effects of mutations across different forms of life in various habitats. The researchers experimented on beetles carrying new mutations, but also analysed results from previous, similar studies examining both unicellular microorganisms, such as yeasts, bacteria and viruses, and multicellular life forms such as thale cress (Arabidopsis thaliana), fruit fly (Drosophila melanogaster) and roundworm (Caenorhabditis elegans).

By combining all this information, the researchers were able to clarify how the organisms fared in various environments before and after the mutations were produced. Above all, the aim was to find out whether environmental conditions that imposed some kind of stress on the individual caused the mutations' detrimental effects to be expressed more or less. They manipulated the temperature to find out what effect this had.

"Individuals with and without mutations suffered just as much from the stressful environment. But when we looked at the studies where temperatures had been manipulated we found that, with higher temperatures, the effects in individuals carrying new mutations were worse than in those that lacked them," Berger says.

The study indicates that if calculations by the Intergovernmental Panel on Climate Change (IPCC) of global warming by 2-4°C in the century ahead become a reality, the result may be a doubling of the harmful effects of new mutations in tropical species.

"Since mutations are inherited and also arise in every new generation, a marked increase in their damaging effects would have major implications both for organisms' adaptability and for the types of adaptations we can expect to see in them if global temperatures keep rising. Our results may therefore be important for understanding how future global warming may affect biodiversity," Berger says.

In the race to stop the spread of COVID-19, a three-layer cloth mask that fits well can effectively filter COVID particles, says a group of UBC researchers.

After testing several different mask styles and 41 types of fabrics, they found that a mask consisting of two layers of low-thread-count quilting cotton plus a three-ply dried baby wipe filter was as effective as a commercial non-surgical mask at stopping particles--and almost as breathable.

The cloth masks filtered out up to 80 per cent of 3-micron particles, and more than 90 per cent of 10-micron particles.

"We focused on particles larger than one micron because these are likely most important to COVID-19 transmission," explains researcher Dr. Steven Rogak, a professor of mechanical engineering who studies aerosols. "While the COVID-19 virus is only around 0.1 micron in size, it is always attached to something larger, like the droplets produced by breathing, talking and coughing, which are typically in the micron and not submicron range."

World Health Organization guidelines recommend three layers for a non-medical mask: an absorbent inner layer near the mouth, a middle filtration layer and an outer layer exposed to the external environment.

Mask materials

The team recommends specific fabrics for different parts of the mask: double-knit cotton, quilting cotton, knit nylon or polyester satin for the outer layer, and double-knit cotton, quilting cotton or simple-weave silk for the inner layer that sits closest to the skin.

Nylon and polyester repel water, keeping harmful droplets from penetrating through to the inner layers. Cotton and silk feel comfortable, breathe well, and wick away moisture. Importantly, fabric construction is important to breathability and filtration efficiency. For example, fabrics such as polyester crepe (finely woven polyester), high thread-count cotton and dupion silk are not very breathable.

Dried baby wipes, which can be swapped out, make surprisingly good filters.

"Baby wipes are typically made of spunlace and spunbond polypropylene--similar to the types of polypropylene found in medical masks and N95 respirators," said researcher Dr. Jane Wang, a clinical professor in the faculty of medicine.

"They are breathable and trap particles efficiently. They're biocompatible, containing minimal preservatives and chemicals that may otherwise cause irritation or breathing problems."

Fit is paramount

Aside from choosing efficient, breathable materials, it's important to have a good seal around the mask, say the researchers.

"Even an N95 mask is going to take in large, massive droplets with lots of viruses if it does not seal against the face. A well-fitted, well-designed cloth mask with a baby-wipe filter will be more effective at filtering 5- or 10-micron particles than a poorly fitted N95 mask," said Dr. Rogak.

He added that the highest leak rates are around the nose, chin and the cheeks, and pleated-style masks tend to leak the most.

"The mask should not sit flat against your mouth and nose, because it will be less breathable, as there's only one very tiny portion of the fabric actually exchanging air. Even if it's made of breathable material, it won't feel that way. You need to create a bit of an air pocket, with a bigger curvature in front, so that the whole mask is engaged in air exchange."

In the end, masking is an intervention aimed at risk reduction, not risk elimination, says Dr. Wang.

"For the intervention to be effective, people need to have access to the intervention and to apply the intervention correctly. An N95 mask will not be effective if people are wearing it halfway down the face. Double masking will not be effective if people cannot tolerate it because of overheating, breathability or CO2 retention problems. The focus should always be to wear a mask correctly by choosing a design that offers a good seal around the nose and mouth and to avoid cross-contamination."

New research reveals that the COVID-19 intensive care (ICU) mortality rate in Sweden was lower during the first wave of the pandemic than in many studies from other countries. And while analysis of individual underlying conditions found they were linked to mortality, an analysis looking at all these variables together found COVID-19 mortality in intensive care was not associated with underlying conditions, except for chronic lung disease. This new study did, however, find that, like previous research, mortality was driven by age, severity of COVID-19 disease and the presence and extent of organ failure.

The study is published in the European Journal of Anaesthesiology (the official journal of the European Society of Anaesthesiology and Intensive Care [ESAIC]) and is by Dr Michelle Chew, Linkoping University Hospital, Linkoping, Sweden, and colleagues.

"Coupled with what is widely perceived to be a 'relaxed' national pandemic strategy, results for ICU care in Sweden are understandably under scrutiny," explain the authors.

They analysed 1563 adult admissions to Swedish ICUs from 6 March-6 May, 2020 with laboratory confirmed COVID-19 disease, and complete 30-day follow up, and found 30-day all-cause mortality was 27%, while mortality actually within ICU was 23%, indicating the most patients who died after requiring ICU treatment actually died within ICU.

Various factors including age were associated with mortality. Being male raised the risk of death by 50%, while having severe respiratory failure (more advanced disease -present in three quarters of patients) trebled the risk of death. However, except for chronic lung disease (a 50% increased risk of death), the presence of comorbidities was not independently associated with mortality. Also of note that was that the degree of hypoxia (insufficient oxygen) was much higher in this Swedish cohort than those from other countries. Put another way, these Swedish patients were generally sicker upon entering ICU.

The ICU mortality of 23% in this Swedish study is between that found in two nationwide studies with small cohorts from Iceland and Denmark, at 15% and 37% respectively. It is lower than the mortality rate reported from a North American study (35%) and a French-Belgian-Swiss study (26-30%). These studies had nearly complete discharge data, meaning that most patients had survived and left ICU or sadly died there, with few patients still being treated at the time of the study.

In one report from Lombardy, Italy, ICU mortality was initially reported to be 26%; however this did not contain complete data as many patients were still being treated. A later study consisting of mostly the same patients and with almost complete ICU follow-up, mortality was 49%. These results are comparable to a recent meta-analysis of 20 studies worldwide (TM Cook and colleagues, Anaesthesia, 2020) that reported an ICU mortality of 42% for patients with completed ICU admissions and discharge data. Another study by Cook and colleagues, being published in Anaesthesia at the same time as this Swedish study (see separate press release) shows global ICU mortality up to October 2020 has since dropped further to 36%.

This new study from Sweden confirms previous findings that mortality rates are significantly higher among those aged 65 years and older. Patients over 80 years of age were seven times more likely to die than those aged 50 years and under, although the authors make clear that their data "demonstrate that provision of intensive care should not be restricted on the basis of age alone". They add: "Not all over 80 year olds die in ICU, which is one reason why we cannot exclude this group of patients from ICU care based on age alone. All decisions on care must be taken on a patient-by-patient basis".

As in other studies, a majority of patients suffered from underlying conditions (comorbidities), most commonly high blood pressure, diabetes and obesity. Whilst most comorbidities were associated with death when analysed separately, their effects were not statistically significant after adjustment for other variables. Severe obesity (BMI>40) was not associated with increased mortality as suggested by other studies. The only underlying condition that was found to have an effect in Swedish patients was chronic lung disease, which was associated with a 50% increased risk of death.

The authors discuss the various aspects of the Swedish ICU policy that could be connected with the lower ICU mortality rate. They say: "We believe that process and organisational factors have likely contributed to the relatively good outcomes seen in Swedish ICUs as staffing, protective equipment, availability of drugs, medical and technical equipment were considered at an early stage at hospital and regional levels."

In the first quarter of 2020 Sweden had 5.1 ICU beds per 100,000 population, compared to 27/100,000 in the USA. The COVID-19 pandemic unleashed a coordinated response in Swedish ICUs doubling the number of beds from around 500 to more than 1100 at its peak. The proportion of occupied ICU beds in the country during the study period (the peak months of the first wave of the pandemic) never reached maximum capacity. Other factors potentially connected to lower COVID-19 ICU mortality are that anaesthesiology and intensive care are combined specialities in Sweden, and this dual competency enabled rapid diversion of resources from perioperative care to intensive care management.

However, Sweden's strategy has faced harsh criticism at home and abroad for being too relaxed and dependent on individual responsibility of citizens rather than enforced lockdowns. Sweden's King also, in late 2020, publicly criticised the country's COVID-19 strategy as a failure. New laws on public transport and gatherings were enacted in autumn 2020 to limit the rising spread of SARS-CoV-2, and in late 2020, the Swedish Government passed new laws in order to be able to enforce restrictions such as venue closures to prevent cases raging out of control. Future staffing shortages, the looming possibility of burn-out and numerous organisational challenges also remain.

The authors conclude: "Mortality rates in COVID-19 patients admitted to Swedish intensive care units are generally lower than previously reported in other countries despite more severe illness on admission among Swedish patients. Mortality appears to be driven by age, baseline disease severity, and the presence and degree of organ failure, rather than pre-existing comorbidities."

Professor Chew, who is also the deputy editor-in-chief of the European Journal of Anaesthesiology, adds: "Although Sweden chose a different pandemic strategy to its European neighbours, its population has not been immune to rising infection rates this winter. Only time will tell if the Swedish health care system can sustain the long-term burden of COVID-19 disease."

COLUMBUS, Ohio - Antarctic ice is melting, contributing massive amounts of water to the world's seas and causing them to rise - but that melt is not as linear and consistent as scientists previously thought, a new analysis of 20 years' worth of satellite data indicates.

The analysis, built on gravitational field data from a NASA satellite system, shows that Antarctica's ice melts at different rates each year, meaning the models scientists use to predict coming sea level rise might also need adjusting.

"The ice sheet is not changing with a constant rate - it's more complicated than a linear change," said Lei Wang, assistant professor of civil, environmental and geodetic engineering at The Ohio State University and lead author of the analysis. "The change is more dynamic: The velocity of the melt changes depending on the time."

The research was published in Geophysical Research Letters and presented at the American Geophysical Union's fall meeting in December.

The researchers' analysis is built on data from NASA's GRACE (Gravity Recovery and Climate Experiment), a two-satellite mission that measures changes in the world's oceans, ground water and ice sheets.

Models that predict sea-level rise are typically built around the assumption that ice is melting from the world's largest ice fields in Antarctica and Greenland at a consistent rate.

But this analysis found that, because the mass of ice on the Antarctic Ice Sheet changes depending on the season and year, those projections are not as reliable as they could be. Extreme snowfall one year, for example, might increase the amount of ice in Antarctica. Changes in the atmosphere or surrounding ocean might decrease it another year.

Overall, Wang said, the volume of ice in Antarctica is decreasing. But a chart of the decline on a line graph would have spikes and valleys depending on what happened in a given time period.

To understand those changes, Wang and the other researchers evaluated data on the gravitational field between the satellites over Antarctica and ice on the continent. Changes to the ice's mass - either increases from big snowfalls or decreases from melt - change that gravitational field.

From 2016 to 2018, for example, the ice sheet in West Antarctica actually grew a bit because of a massive snow. During that same time period, though, the ice sheet in East Antarctica shrank because of melt.

"I'm not saying Antarctica's ice melt is not an acute problem - it is still very acute," Wang said. "All of Antarctica is losing mass, very rapidly. It's just a time scale problem and a rate problem, and our models that predict sea-level change should reflect that."

Oncotarget recently published "Neuroendocrine carcinoma of uterine cervix findings shown by MRI for staging and survival analysis – Japan multicenter study" which reported that to investigate neuroendocrine carcinoma of the uterine cervix cases for MRI features and staging, as well as pathological correlations and survival.

In 50 patients who underwent a radical hysterectomy and lymphadenectomy without neoadjuvant chemotherapy, intrapelvic T staging by MRI overall accuracy was 88.0% with reference to pathology staging, while patient-based sensitivity, specificity, and accuracy for metastatic pelvic lymph node detection was 38.5%, 100%, and 83.3%, respectively.

Three-year progression-free and overall survival rates for FIGO I, II, III, and IV were 64.3% and 80.9%, 50% and 64.3%, 0% and 0%, and 0% and 0%, respectively.

Sixty-two patients with histologically surgery-proven uterine cervical NEC were enrolled.

The Oncotarget author's findings show that MRI is reliable for T staging of cervical NEC.

"The Oncotarget author's findings show that MRI is reliable for T staging of cervical NEC"

Dr. Kazuhiro Kitajima from The Department of Radiology at The Hyogo College of Medicine said, "Neuroendocrine carcinomas (NECs) of the female genital tract are aggressive uncommon tumors that usually involve the uterine cervix and ovaries, though are very rarely seen in the endometrium."

According to the World Health Organization classification, neuroendocrine tumors in the uterine cervix are categorized into 4 categories; typical carcinoid, atypical carcinoid, small cell neuroendocrine carcinoma, and large cell neuroendocrine carcinoma.

Cervical NEC has a higher frequency of lymphovascular invasion, lymphatic and distal metastasis, and recurrence as compared to other subtypes of uterine cervical malignancies, e. g., squamous cell carcinoma and adenocarcinoma.

However, findings obtained in smear and cervical biopsy analyses are insensitive and inconclusive for diagnosis of cervical NEC in some patients, due to limited sample size or tumor heterogeneity.

To the best of these researcher's knowledge, 2 different reports have been presented that include discussion of MRI characteristics of uterine cervical SCNEC, with a small number of patients in each, while no known reports discussing MRI findings of cervical LCNEC are available.

The aim of this study was to identify the distinct features and staging accuracy of uterine cervical NEC, including SCNEC and LCNEC, using MRI, as well as pathological correlations.

The Kitajima Research Team concluded in their Oncotarget Research Paper that NEC of the uterine cervix is rare and affected patients have a poor prognosis, especially advanced stage cases.

A definitive diagnosis based on preoperative MRI results seems to be difficult. Nevertheless, the present as well as other previous findings indicate that a homogeneous lesion texture with an obvious restricted diffusion throughout the tumor are suggestive of uterine cervical NEC.

Furthermore, they found pelvic MRI to provide reliable imaging findings for T staging in these patients.

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DOI - https://doi.org/10.18632/oncotarget.27613

Full text - https://www.oncotarget.com/article/27613/text/

Correspondence to - Kazuhiro Kitajima - ka-kitajima@hyo-med.ac.jp

Keywords -
cervical cancer,
neuroendocrine carcinoma,
small cell carcinoma,
large cell carcinoma,
MRI

About Oncotarget

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DOI

10.18632/oncotarget.27613

Michelle O'Malley(link is external) has long been inspired by gut microbes. Since she began studying the herbivore digestive tract, the UC Santa Barbara chemical engineering professor has guided several students to their doctoral degrees, won early and mid-career awards (including a recognition from President Obama), attained tenure and advanced to the position of full professor. She even had three children along the way. A constant through it all: goat poop.

"This has been the longest single effort in my lab," said O'Malley, who with her research team way back in 2015 first embarked on an ambitious project to characterize gut microbes in large herbivores. The purpose? To understand how these animals manage, via their microbiomes, to extract energy from plant material, particularly the fibrous, non-food parts, where sugars are locked behind tough plant cell walls. Understanding this process could reveal methods for extracting the raw materials necessary for a wide variety of the chemicals required for modern life -- from biofuels to pharmaceuticals -- all from abundant, renewable, plant parts. This, in turn, could decrease or even eliminate our reliance on more finite resources for these materials.

Now, O'Malley has reached another milestone. In a paper(link is external) in the journal Nature Microbiology, she and her team report the results of more than 400 parallel anaerobic enrichment experiments, which include more than 700 previously unknown microbial genomes and thousands of new enzymes, as well as a possible mechanism for much of the methane often blamed on cows and goats.

Microbial Roll Call

"One of the things we wanted to do with this study was to ask ourselves if we could learn the bioprocessing lessons that the goat digestive tract has to offer," O'Malley said. Like all ruminants, goats have gut microbiomes that have evolved over millions of years to secrete powerful enzymes that break down tough plant parts, allowing the animals access to nutrition from a variety of vegetation.

"The aim of the study is really to learn about the microbes, and, importantly, the teams of microbes that do those difficult jobs," she said.

Of particular interest to the researchers were the non-bacteria denizens of the goat gut microbiome -- "minor players" like anaerobic fungi that constitute a tiny fraction of the bacteria-dominated population. Not only are these members of the community few and far between, they are difficult to culture, O'Malley said. So while gut microbiome research has been going on for a long time, most studies ignore the contributions of rare members of the microbiome.

"Nobody had really looked at the effects of these rare members," she said.

Over roughly 400 parallel enrichment experiments on fecal matter contributed by Elway, a San Clemente Island Goat named who lives at the Santa Barbara Zoo, the researchers teased out populations of biomass-degrading microbes with different biomass substrates. They further sculpted some of these populations using antibiotics to inhibit the growth of bacteria, leaving rarer microbes such as fungi and methanogens (single-celled organisms from the domain Archaea) to dominate.

"And then we sequenced all of those cultures," O'Malley said. "We put the fragmented DNA sequences back together again to reconstruct high-quality genomes, and that gave us a collective picture of who was there. Then we scanned these genomes for enzymes and pathways that gave us a clue as to what each microbe was doing in the microbiome." The O'Malley lab researchers sequenced these samples at the Department of Energy Joint Genome Institute (JGI(link is external)) as part of the JGI Community Science Program(link is external); they collaborated with JGI experts in metagenome sequencing and fungal genomics for this study.

In the process, the team uncovered more than 700 novel microbial genomes "unique at the species level," according to the study. Also present were rare fungi they had previously isolated from large herbivores.

"But this was the first time we had really seen them in action, in their normal community," O'Malley said.

Heavy Hitters

For their small population, fungi, it turns out, play a disproportionately large role in biomass degradation.

"They produce the lion's share of the biomass degrading enzymes that the community relies on to function," O'Malley noted. Additionally, according to the paper, fungi have other strategies, such the ability to physically penetrate plant cell walls, exposing surfaces for these enzymes to act on.

The researchers also found that along with the increased rate of biomass degradation came an increase in methane production in the fungal-dominated consortia. While both gut bacteria and gut fungi form cross-domain partnerships with methanogens, essentially passing carbon to the archaeans that ferment it into natural gas, fungi seem to be more efficient at it.

"We think the fungi are more effective at shunting carbon to methane," O'Malley said. "In other words, fungi are not producing a bunch of side products like bacteria would. Bacteria produce additional short-chain fatty acids and other chemical products, in addition to some methane. But, the fungi may have a more direct route passing materials to the methanogens." This, according to the paper, suggests that "fungi play a larger role in methane release than previously recognized."

These and other insights from the research take us closer to developing technologies using microbes to create industrially important chemicals from cellulose, the most abundant organic compound on the planet. O'Malley and her group are focused on understanding the roles of and interactions between members of these complex ruminal communities, and they're looking to a future where designed microbial communities can create value-added chemicals.

"Can we build a bio-reactor that houses not just one type of microbe, but a few, or dozens? Can we do really complex chemistry the way nature does? That's kind of the ultimate goal here," O'Malley said.

Oncotarget published "The pro-apoptotic actions of 2-methoxyestradiol against ovarian cancer involve catalytic activation of PKCδ signaling" which reported that the authors have previously shown that a flaxseed-supplemented diet decreases both the incidence and severity of ovarian cancer in laying hens, also induces CYP1A1 expression in liver.

Recently, they have shown that as a biologically derived active component of flax diet, 2MeOE2 induces apoptosis in ovarian cancer cells which is partially dependent on p38 MAPK.

The objective of this Oncotarget study was to elucidate the molecular mechanism of actions of 2MeOE2, a known microtubule disrupting agent, in inducing apoptosis in ovarian tumors.

The objective of this Oncotarget study was to elucidate the molecular mechanism of actions of 2MeOE2, a known microtubule disrupting agent, in inducing apoptosis in ovarian tumors

2MeOE2 induces γH2Ax expression and apoptotic histone modifications in ovarian cancer cells, which are predicted downstream targets of protein kinase Cδ during apoptosis.

Overexpressing full length PKCδ alone does not induce apoptosis but potentiates 2MeOE2-mediated apoptosis.

Dr. Dale Buchanan Hales from The Southern Illinois University said, "With an estimated 22,530 cases reported and 13,980 estimated deaths in the year 2019, ovarian cancer is the deadliest gynecological disease accounting for more deaths than any other cancer in the female reproductive tract."

With an estimated 22,530 cases reported and 13,980 estimated deaths in the year 2019, ovarian cancer is the deadliest gynecological disease accounting for more deaths than any other cancer in the female reproductive tract.

Their laboratory studies epithelial ovarian cancer in laying hens, the only known natural animal model that spontaneously develops the disease over its lifespan.

The research has shown that dietary ingestion of flaxseed reduces the onset and severity of ovarian cancer in laying hens.

Recently they have shown that 2MeOE2 induces apoptosis in human ovarian cancer cells.

The objective of this study was to investigate the epigenetic modifications exerted by 2MeOE2 and assess the role of PKCδ in 2MeOE2 actions in order to gain an in-depth mechanistic understanding of its molecular and cellular pro-apoptotic actions.

The Hales Research Team concluded in their Oncotarget Research Paper, "Our findings indicate that 2MeOE2 -mediated anti-tumor actions involve the catalytic activation of PKCδ in the pro-apoptotic pathway. The catalytic fragment of PKCδ is responsible for the apoptotic histone modifications and acceleration of the apoptotic cascade through p38 MAPK pathway. Dietary flaxseed supplementation activates PKCδ secondary to increasing endogenous production of 2MeOE2 which drives apoptosis in ovarian cancer cells (Figure 7). This study offers new insight into the molecular underpinnings of dietary flaxseed's chemopreventative actions in ovarian cancer."

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DOI - https://doi.org/10.18632/oncotarget.27760

Full text - https://www.oncotarget.com/article/27760/text/

Correspondence to - Dale Buchanan Hales - dhales@siumed.edu

Keywords -
2-methoxyestradiol,
ovarian cancer,
protein kinase Cδ,
p38 MAPK,
apoptosis

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Journal

Oncotarget

DOI

10.18632/oncotarget.27760

Each year, billions of tons of goods are transported globally using cargo containers. Currently, there are concerns that this immense volume of traffic could be exploited to transport illicit nuclear materials, with little chance of detection. One promising approach to combating this issue is to measure how goods interact with charged particles named muons - which form naturally as cosmic rays interact with Earth's atmosphere. Studies worldwide have now explored how this technique, named 'muon tomography,' can be achieved through a variety of detection technologies and reconstruction algorithms. In this article of EPJ Plus, a team headed by Francesco Riggi at the University of Catania, Italy, build on these results to develop a full-scale muon tomograph prototype.

The technology is particularly advantageous since cosmic muons are available worldwide; display well-known properties at sea level; and can penetrate far deeper into heavy materials than x-rays. As they interact with heavy elements such as nuclear materials, muons are scattered at characteristic angles. Therefore, by comparing the trajectories of muons entering and exiting a material being inspected, researchers can identify these elements, even if they are hidden within large containers. However, since cosmic muons are relatively rare, this technique requires long scanning times to produce suitable levels of sensitivity and image resolution - limiting its use in large-scale monitoring. Many previous studies have now addressed this issue using advanced muon detection techniques, alongside image reconstruction algorithms.

In this article, Riggi and colleagues used the insights gained through these studies to build a full-scale muon tomograph prototype, with a sensing area of 18m2 – large enough to inspect a standard cargo container. Their study involved placing light-emitting muon detectors above and below a small lead block. A specialised algorithm then used the data they gathered to estimate the closest approach between nuclei with high atomic numbers within the block, and the muons which were scattered by them - enabling the researchers to determine the position of the block in 3D. The outcomes of the study pave the way for practical detectors with low sensing times and high image resolutions. Through further improvements, the prototype could soon lead to sophisticated monitoring systems, suitable for use in cargo-handling facilities worldwide.

A key thread that holds together the delicate balance of a complex biological system is the transmembrane ion channel. These are supramolecular, or multi-molecule, ion and molecule exchange routes embedded within cell membranes to ensure essential chemical transport to and from the cell and facilitate cell signaling.

In recent years, synthetic biomolecules that mimic the structures and functions of natural ion channels have garnered much interest among molecular biology researchers as models for studying the fundamentals of these channels and perhaps, even creating drug alternatives or developing advanced biosensors.

However, although several good synthetic ion channels have been developed, most of them are activated via only a single stimulus and none are what scientists call "anisotropic dual-stimuli-responsive", or ones that can be activated and controlled by two specific kinds of stimuli dependent on the biased orientation of the structure within the membrane. This has limited research scope in the field.

Now, finally, a group of scientists from Tokyo Tech and the University of Tokyo, Japan, have successfully synthesized a biomolecule that resembles a natural anisotropic dual-stimuli-responsive channel: transient receptor potential melastatin 8 (TRPM8), which underlies signal transmissions in neurons. Their channel is called VF and their breakthrough is published in Journal of the American Chemical Society.

VF is a multiblock amphiphilic (it has both water loving (hydrophilic) and fat loving (lipophilic) properties) molecule that can assemble to form supramolecular channels. Each unit in a block comprises an organic lipophilic/hydrophobic moiety with six fluoride atoms that position it within the lipid bilayer of the cell membrane and lend it an electrical polarity; a phosphate ester group which ensures that the structure is biased in its orientation (with the phosphate side towards the extracellular space); and flexible ethylene glycol hydrophilic chains between hydrophobic units and on the ends that contribute to the stimuli-responsiveness.

The scientists' studies of this structure showed that by manipulating the polarities and amplitudes of applied voltages, the channel could be activated. Prof. Kazushi Kinbara, lead scientist in the team, explains: "Without the application of a voltage, the hydrophobic units of VF repel each other so that they would be spatially separated from each other and would not form clear and functional transmembrane ion channels. When a voltage with the electric field vector antiparallel to the electrical polarity of the VF is applied, a displacement of electron distribution within VF occurs, weakening the repulsion between hydrophobic units and enhancing their face-to-face stacking. This causes conformational changes throughout the molecule which leads to the formation of supramolecular channels that can efficiently transport ions across the membrane."

The scientists found that the second stimulus had to do with the binding of ligand (R)-propranolol at the connection between the phosphate esters and the hydrophobic units. As Prof. Kinbara explains, "(R)-propranolol is an antiarrhythmic agent known to block voltage-gated sodium channels. Moreover, our previous studies indicated that it interacts with phosphate ester groups and aromatic units to localize inside the channel pore and block ion transport. That is why we chose it for our study." Their nuclear magnetic resonance spectroscopy revealed its binding at the phosphate sites, and that it completely inhibits the current flow and thus the ion channel activity of VF. Its removal via the addition of β-cyclodextrin reactivates the channel. "Reversible ligand binding such as this is key to maintaining homeostasis within the body via the regulation of transmembrane ion channels. The highly regulated orientation of VF allowed for this anisotropic response to this ligand molecule," Prof. Kinbara says. "With our success in this study, there is now great potential for sensing and manipulating various biologically important events."

Indeed, with the synthesis of VF, suited to the variable cellular environments ubiquitous in biological systems, perhaps, new possibilities for research emerge in the field of molecular biology.

The virtual conferencing that has replaced large, in-person gatherings in the age of COVID-19 represents a drastic reduction in carbon emissions, but those online meetings still come with their own environmental costs, new research from the University of Michigan shows.

The research offers a framework for analyzing and tallying the carbon emissions of an online conference based on factors that include everything from energy used by servers and monitors to the resources used to manufacture and distribute the computers involved.

It also includes a case study showing that a May 2020 virtual conference held by the AirMiners carbon removal networking community produced 66 times less greenhouse gas emissions that an in-person gathering in San Francisco would have.

And it highlights steps that online meeting hosts and attendees can take to further reduce associated emissions.

Grant Faber, a research assistant with the Global CO2 Initiative at the U-M College of Engineering, said the method he developed shows that virtual conferencing's environmental impacts remain significant, particularly in light of increasing internet connectivity and use of video conferencing.

"There are projections that say by 2030, information and communications technologies may use more than 20% of the global electricity supply," he said. "And as time goes on and more and more people become connected to the internet for more energy intensive activities, such as Bitcoin mining, they're only going to use more and more electricity.

"It's important to know the true cost of our online behaviors and, by quantifying it, we can take action. As an example, our AirMiners conference was able to estimate our impact and purchase carbon removal offsets to make the event carbon negative."

Faber's system for gauging the energy usage from a virtual conference looks at:

Life cycle emissions: The raw materials and resources needed to build and distribute the computers used, as well the electricity needed to run them

Network data transfer: Energy computers use for uploading and downloading data

Server energy usage

Monitor energy usage

Room lighting

Additional online meetings necessary for conference planning

Emissions from conference-related website visits and search engine queries

Computer and monitor emissions are estimated by tallying total life cycle emissions based on the number of hours they were used for the conference. Emissions from network data transfer and server use were calculated using their respective energy consumption during the conference.

Faber offers steps for both industry and individuals to lessen the environmental impact of virtual conferencing. Industry could start by improving the energy efficiency of the hardware and software involved in conferencing. That could have a trickle down effect.

Platforms such as Zoom may be able to decrease data rates while preserving quality simply by updating their software and servers. And powering computers, network infrastructure and data centers with renewable energy can reduce emissions of virtual activities in a substantial way.

Individuals could skip features like gallery view, disable HD video and repair instead of replace computers to extend their useful lifetimes.

"In order to address climate change, we need to develop an awareness of the CO2 emissions associated with specific actions we take in our daily lives-- similar to how we have learned to watch calories to maintain a healthy weight. Grant's work quantifies this for the growing relevance of video conferences," said Volker Sick, an Arthur F. Thurnau Professor in Mechanical Engineering, the DTE Energy Professor of Advanced Energy Research and director of the Global CO2 Initiative.

A paper by a multidisciplinary team of scientists affiliated with various Brazilian institutions, including the University of São Paulo (USP) and the National Cancer Institute (INCA), shows that people of African descent are less likely to find a donor in the National Register of Voluntary Bone Marrow Donors (REDOME) than people with predominantly European ancestry. The paper is published in Frontiers in Immunology.

REDOME is the world’s third-largest bone marrow bank, with more than 5 million registered voluntary donors.

According to the study, having mainly African genetic ancestry can reduce a person’s chances of finding a donor by up to 60%, and having African copies of HLA genes, which must be compatible with the donor’s to make a transplant possible, can reduce them by 75%.

As the degree of African ancestry increases, the likelihood of finding a match on REDOME decreases, according to the study, which also discusses what the authors argue is a weak correlation between self-identification in accordance with the categories used by IBGE, the national census bureau, and actual genetic ancestry. IBGE’s classification “explains only a small amount” of people’s ancestry, they write.

“The classification is coarse in terms of predicting the genes that matter for transplants, which are the immune function genes, but it’s used by REDOME. Donors have to choose one of these categories when they fill out the registration form. A person can be of African or European ancestry in terms of immune function genes, but the identifiers ‘black’, ‘brown’ and ‘white’ don’t really line up with those categories,” said Diogo Meyer, a professor at USP who specializes in population genetics and was the principal investigator for the study.

The study concludes that people who self-identify as “preto” (black) or “pardo” (brown, i.e. mixed) are up to 57% less likely to find donors than those who self-identify as “branco” (white).

HLA (human leukocyte antigen) immune function genes bind to antigens, including potentially toxic residues of cellular metabolism or fragments of an invading pathogen. T-cells, an important part of the immune system, can distinguish between antigens produced by the organism and invaders. When HLA molecules bind to antigens that are not recognized, immune responses are triggered. A perfect match between recipient and donor is therefore critical to avoid rejection and assure the success of a stem cell transplant.

There are several reasons for the difficulty of finding a match for Brazilians of African descent, Meyer explained. They are not proportionally represented in REDOME, which anyway uses imprecise ethnic categories. They are more diverse and heterogeneous genetically than the rest of the population, and two unrelated Africans are unlikely to have identical HLAs because human migration began in Africa. The people who made the journey carried only part of the existing variability.

The paper, whose first author is biologist Kelly Nunes, a postdoctoral fellow at USP, associates the 75% reduction in the odds of finding a donor with having an MHC region of exclusively African ancestry. MHC stands for major histocompatibility complex, a group of genes that help the immune system recognize foreign substances. It includes the HLAs.

“Self-identification as ‘preto’ is a predictor that the person has African genetic ancestry in their genome. That includes immune function genes, which are the ones that matter in the case of a transplant,” Meyer said. “This is a rule of thumb, however, and there are exceptions, especially in a highly admixed population like Brazil’s, where it’s not unusual for a person who self-identifies as ‘preto’ to have European HLA genes. Indeed, donors for African patients in REDOME may self-identify as ‘branco’. However, the more genetically African individuals we found in a population sample, the larger the proportion of black donors.”

The results do not mean black people have no chance of finding a donor in REDOME, Meyer stressed. “We compared the probabilities of matches for different ancestries. In an actual transplant case, HLA typing has to be done to a high degree of precision, and the donor must be in good health and have a carefully analyzed genotype to make sure they’re genuinely compatible. Each step reduces the chances of a transplant occurring,” he said.

The study was supported by FAPESP via a Regular Research Grant and a postdoctoral fellowship in Brazil.

Combinations of chromosomes

Many questions remain unanswered, according to Meyer. “One thing we haven’t addressed so far is whether what makes it hard for Brazilians with African ancestry to find donors is having African chromosomes or having an admixture of African and European genes,” he said. “The European and African parts are presumably represented in REDOME, but the two combined may be rare, and thousands of these combinations may be possible.”

According to Meyer, the team cannot yet answer the question regarding the degree to which admixture and the percentage of African ancestry hinder a match. “These two things are a little different. What we know is that on average people with African HLA genes tend to have more difficulty than people with European ancestry,” he said. “It remains to be seen if there are combinations of European and African chromosomes that can also reduce the probability of a match.”

In Brazil, moreover, the term “African” can refer to people from various different parts or regions of Africa. “We may be dealing with genotypes that only exist in Brazil – a mixture of ancestries associated with different parts of the African continent,” Meyer said. “All this depends on what’s represented in REDOME since we didn’t characterize the repository from the genetic standpoint. We just had the labels ‘preto’, ‘branco’ and ‘pardo’.”

Methodology and sampling

The group, which comprised scientists in the areas of human health, biology, statistics, and computation, used two Brazilian cohorts as samples: Recipient Epidemiology and Donor Evaluation – Brazil Sickle Cell Disease (REDS-III Brazil SCD); and EPIGEN-Brazil, part of a Latin America-wide population genomics and genetic epidemiology initiative.

From the former they selected 2,703 individuals with sickle cell disease recruited from four institutions: three blood banks (Fundação Hemominas in Belo Horizonte, Juiz de Fora and Montes Claros; Fundação Hemope in Recife; and Fundação Hemorio in Rio de Janeiro); and the Children’s Institute of Hospital das Clínicas, the teaching and general hospital run by the University of São Paulo’s Medical School (FM-USP).

In the case of the EPIGEN-Brazil cohort, 5,334 individuals from Salvador (Bahia State), Bambuí (Minas Gerais State), and Pelotas (Rio Grande do Sul State) were included in the study sample.

“The sample wasn’t made up of people on the waiting list for a bone marrow transplant,” Meyer said. “It was a convenience sample comprising individuals with known ancestry.” With regard to those with sickle cell disease, however, the results may anticipate future situations. “Most people with the disease are of African descent and there’s a prospect of treatment by marrow transplant, so these are people who may benefit from this type of intervention in future.”

Laboratory analysis of the genotypes of more than 8,000 individuals would have been too costly, so the researchers used a technique called SNP-based HLA imputation. “The structure of our genome lets us make predictions. A mutation in one position in the genome can predict another since we pass on our genetic material in the form of bits of chromosomes. These bits are recombined, but not fused as if in a blender: there’s a certain logic, enabling statisticians and geneticists to develop an algorithm to predict a person’s HLAs from the mutations in their physical vicinity,” Meyer explained.

The software used to infer genetic ancestry was fed with data for the frequency with which genetic variants occur in the ethnic groups comprised in the Brazilian population.

Next steps

According to the researchers, the results support the idea that if REDOME wished to be representative and assure equitable access to people of African descent, it would have to have more donors with African ancestry. “However, for people of African descent to have as many matches as people of European descent, it would probably be necessary for the proportion of the former in REDOME to be larger than the proportion in the total population, since they’re more ‘demanding’ in terms of sampling.”

The researchers now plan to find out whether it is difficult for Brazilians of African descent to find a donor because African chromosomes are rare in REDOME or because the admixture with European chromosomes creates hard-to-locate combinations. “We also want to conduct an evolutionary quantitative study to investigate kinship in terms of MHC in different parts of the world – in other words, to find out how much more closely related two Europeans are on average than two Africans,” Meyer said.