Earth

A new horizon for vibrational circular dichroism spectroscopy

image: Time-step VCD measured monitoring in situ the progress of chirality amplification from microscopic to supramolecular scales.

Image: 
ROYAL SOCIETY OF CHEMISTRY

Vibrational circular dichroism (VCD) spectroscopy is an extension of circular dichroism spectroscopy into the infrared and near-infrared regions where vibrational transitions occur in the ground electronic state of a molecule. The method offers the advantage of studying the chiroptical properties of a wide range of molecules in non-crystalline states. However, due to the weakness of the signals, one measurement requires several hours to yield reliable results. Accordingly, its target was limited to a stable molecule in a solution. To overcome this difficulty, our group applied the VCD method to supramolecular systems. In this article, we report a new horizon for VCD spectroscopy. Solid state and time-step VCD methods were developed in determining the mechanism of chirality amplification from the microscopic to supramolecular scales. The VCD signals were enhanced in the following three cases: (i) chiral gels with hundreds of molecules arranged in stereoregularity, (ii) chiral metal complexes with low-lying excited states in the IR region, and (iii) a molecular pair interacting stereoselectively on a solid surface. Finally, we describe an on-going project involving the construction of a multi-dimensional VCD system.

Credit: 
Ehime University

Smart windows that self-illuminate on rainy days

image: Humidity sensor combining variable filter and solar cells.

Image: 
Junsuk Rho (POSTECH)

Smart windows that automatically change colors depending on the intensity of sunlight are gaining attention as they can reduce energy bills by blocking off sun's visible rays during summer. But what about windows that change colors depending on the humidity outside during the monsoon season or on hot days of summer?

Recently, a Korean research team has developed the source technology for smart windows that change colors according to the amount of moisture, without needing electricity.

The joint research team comprised of Professor Junsuk Rho of departments of mechanical and chemical engineering, Jaehyuck Jang and Aizhan Ismukhanova of chemical engineering department at POSTECH, and Professor Inkyu Park of KAIST's department of mechanical engineering. Together, they successfully developed a variable color filter using a metal-hydrogel-metal resonator structure using chitosan-based hydrogel, and combined it with solar cells to make a self-powering humidity sensor. These research findings were published as a cover story in the latest edition of Advanced Optical Materials, a journal specializing in nanoscience and optics.

Sensors using light are already widely used in our daily lives in measuring the ECG, air quality, or distance. The basic principle is to use light to detect changes in the surroundings and to convert them into digital signals.

Fabri-Pero interference* is one of the resonance phenomena that can be applied in optical sensors and can be materialized in the form of multilayer thin films of metal-dielectric-metal. It is known that the resonance wavelength of transmitted light can be controlled according to the thickness and refractive index of the dielectric layer. However, the existing metal-dielectric-metal resonators had a big disadvantage in not being able to control the wavelengths of transmitted light once they are manufactured, making it difficult to use them in variable sensors.

The research team found that when the chitosan hydrogel is made into the metal-hydrogel-metal structure, the resonance wavelength of light transmitted changes in real time depending on the humidity of the environment. This is because the chitosan hydrogel repeats expansion and contraction as the humidity changes around it.

Using this mechanism, the team developed a humidity sensor that can convert light's energy into electricity by combining a solar battery with a water variable wavelength filter made of metal-hydrogel-metal structured metamterial that changes resonance wavelength depending on the external humidity.

The design principle is to overlap the filter's resonance wavelength with the wavelength where the absorption of the solar cells changes rapidly. This filter is designed to change the amount of light absorption of solar cells depending on the amount of moisture, and to lead to electric changes that ultimately detect the surrounding humidity.

Unlike the conventional optical humidity sensors, these newly developed ones work regardless of the type of light, whether it be natural, LED or indoor. Also, not only does it function without external power, but it can also predict humidity according to the filter's color.

Professor Junsuk Rho who led the research commented, "This technology is a sensing technology that can be used in places like nuclear power reactors where people and electricity cannot reach." He added, "It will create even greater synergy if combined with IoT technology such as humidity sensors that activate or smart windows that change colors according to the level of external humidity."

Credit: 
Pohang University of Science & Technology (POSTECH)

SSRI antidepressants associated with increase in violent crime in some patients

Stockholm, Sweden: Scientists have found that some people being treated with selective serotonin reuptake inhibitors (SSRIs) have a greater tendency to commit violent crime. In addition, this effect seems to continue for up to 12 weeks after stopping SSRI treatment. This work is published in the peer-reviewed journal European Neuropsychopharmacology*, alongside a linked comment. The authors of both the paper and the comment note that the work indicates an association (rather than cause and effect) and urge caution in how the findings are interpreted.

First author Tyra Lagerberg at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, said:

"This work shows that SSRI (selective serotonin reuptake inhibitor) treatment appears to be associated with an increased risk for violent criminality in adults as well as adolescents, though the risk appears restricted to a small group of individuals. We don't claim that SSRIs cause the increased risk we see in our data. It is possible that the disorders that SSRIs are prescribed to treat, such as depression, are driving the association. In that case our findings may mean that SSRIs are unable to fully remove this tendency towards violent crime, which is also a potentially important insight. Previous work has found an association between SSRI use and violence in young individuals, but not in adults. Ours is a much bigger study which allows us to confirm that there is an association in adults as well".

The researchers examined the records of 785,337 people aged 15 to 60 years who were prescribed an SSRI in Sweden in 2006 through 2013. These patients were followed up for an average of around 7 years, which included periods when individuals took SSRIs and when they did not. Individuals in the study were found to have committed 6306 violent crimes while taking SSRIs, and 25,897 when not taking SSRIs. After accounting for follow-up time and variables that were associated both with the probability of getting SSRI treatment and with the risk for violence, the researchers found that the risk of committing a violent crime was on average 26% higher during periods when individuals took SSRIs compared to periods when they did not, though only a small proportion of individuals went on to commit violent crimes regardless of treatment (

The increased risk also persisted for up to 12 weeks after the estimated end of SSRI treatment, after which the risk returned to levels before start of SSRI treatment. The researchers showed that the association between SSRI treatment and violent crime existed in young adults as well as in adults aged up to 60 years (the study did not investigate the association in adults older than 60 years). However, only 2.7% of individuals in the study committed violent crimes during the study period, meaning the increased risk applied to a small subgroup of SSRI users.

Tyra Lagerberg commented:

"Previous studies have shown that depression itself is associated with a 3-fold increase in the risk for violent crime, and of course many SSRIs are prescribed for depression; so it may be the underlying depression that causes the association with violent crime, rather than any effect of the SSRI. More work is needed to uncover the causes of this association.

Our results suggest there may be a need for clinical awareness of the risk for violence during and possibly after SSRI treatment across age groups. However, a large majority of SSRI-users, around 97% in our sample, will not experience the outcome of violent crime, so our work needs to be understood in this context. Our findings do not affect the vast majority of people taking antidepressants and should not be used as basis for individuals to stop their SSRI treatment, nor for prescribers to withhold treatment from individuals who might benefit from it. Nevertheless, clinicians should be attentive when prescribing SSRIs to individuals with aggressive tendencies. More work is necessary to identify what further individual characteristics might give someone a higher risk of committing violent crimes during SSRI treatment, regardless of whether the risk is increased because of the SSRI or because of the underlying disorder that indicates an individual for treatment with these medications".

An associated commentary, explores possible explanations for the increase. Lead author, Professor Eduard Vieta (University of Barcelona) said:

"This observational study presents a firm basis for further investigations on SSRI use and criminality. However, as the authors themselves say, we need to emphasise that the study shows an association between violent crime and SSRI use in a small subset of patients, it doesn't show that one causes the other. The study also shows that past offenders were more likely to commit a violent crime during SSRI treatment: this in itself is an interesting finding, which could be the main focus of future research on the topic".

Credit: 
European College of Neuropsychopharmacology

Well begun is half done? Skoltech researchers study the recipe for efficient protein synthesis

image: An outline of the Escherichia coli experiment

Image: 
Pavel Odinev / Skoltech

Skoltech scientists and their colleagues have studied more than 30 thousand variants of genetic sequences encoding two fluorescent proteins in order to determine which characteristics of mRNA and of the first dozen or so codons in it can increase the efficiency of translation. Among other things, they found that rare codons at the beginning of the sequence do not seem to enhance translation, contrary to some hypotheses.

Translation is one of the fundamental processes in any cell: decoding a newly minted messenger RNA (produced from DNA during transcription), a ribosome builds an amino acid chain that then folds into a protein, which goes on to perform various vital functions in the cell. Each amino acid is represented by a codon, a triplet of nucleotides in the mRNA chain. There are 61 codons for amino acids but only 20 amino acids that a ribosome can make, which means that some codons are, in effect, synonymous -- they encode the same amino acid.

After decades of research, scientists still aren't sure what makes the work of a cellular "protein plant" more or less efficient. For instance, there is evidence suggesting that some particular secondary structures of mRNA, i.e. how the coding sequence is folded spatially at its start, can prevent the ribosome from binding to the mRNA and doing its job. Another factor might have to do with those synonymous codons: earlier research hinted at the possibility that codons that are statistically used more rarely can enhance the efficiency of translation if placed at the beginning of an open reading frame. These codons make the ribosome move slower along the mRNA at its beginning so that ribosome queues do not form downstream.

This is not an idle line of inquiry. Studying the efficiency of translation will help us understand gene expression better and aid biotechnology by making sure our protein-producing workhorses are at their best. That is why Ilya Osterman and Zoe Chervontseva of Petr Sergiev, Olga Dontsova and Mikhail Gelfand groups at Skoltech and Lomonosov MSU and their colleagues decided to run a competition of sorts: they tested more than 30,000 variants of mRNA encoding the same protein to see which ones will lead to a more efficient translation. The researchers were interested in the role of codons number 2 to 11 (the first codon is always the ATG start codon, much like the first line of code in some programming languages that tells the computer that a program will follow).

They used Escherichia coli and plasmids -- rings of DNA encoding what's called a dual fluorescent protein reporter (the "duo" are RFP and CER, two fluorescent proteins). The randomized 30-nucleotide sequences were inserted right after the start codon so that they would become codons number 2 to 11 in an mRNA. After growing the modified E. coli to make the CER and RFP proteins and sorting the cells by how efficient they were at it, scientists used the so-called flowseq method to determine which coding sequences turned out to be better for efficient protein production.

"Flowseq is a combination of flow cytometry, a technique where physical and chemical characteristics of cells are measured via the scattering of light from a laser beam, with sequencing of the separated fractions. This method allows to assess the efficiency of protein synthesis in a massively parallel setup, analyzing thousands of variants at a time," Ilya Osterman, principal research scientist at Skoltech, comments.

While the secondary structure of mRNA did indeed inhibit translation, the researchers were unable to show that rare codons at the beginning of a coding sequence affected it in a positive way. However, they found that additional start codons are beneficial for translation, while additional Shine-Dalgarno boxes --sequences that help recruit the ribosome to the mRNA -- are inhibitory.

Among other things, researchers believe their results will help design more efficient artificial gene constructs that can be used to turn common bacteria such as E. coli into potent biotechnological instruments.

Credit: 
Skolkovo Institute of Science and Technology (Skoltech)

Study finds surge in hydroxychloroquine/chloroquine prescriptions during COVID-19

A new study by investigators from Brigham and Women's Hospital examines changes in prescription patterns in the United States during the COVID-19 pandemic.

In an exploratory analysis of data from GoodRx used to generate national estimates, Brigham investigators found prescriptions of the anti-malarial drug chloroquine and its analogue hydroxychloroquine dramatically surged during the week of March 15, likely due to off-label prescriptions for COVID-19. Results of the study are published in JAMA.

"There have been indications that hydroxychloroquine prescribing had increased and shortages had been reported, but this study puts a spotlight on the extent to which excess hydroxychloroquine/chloroquine prescriptions were filled nationally," said corresponding author Haider Warraich, MD, an associate physician in the Division of Cardiovascular Medicine at the Brigham. "This analysis doesn't include patients who were prescribed HCQ in a hospital setting -- this means that patients could have been taking the drugs at home, without supervision or monitoring for side effects."

Chloroquine is an anti-malarial drug and its analogue, hydroxychloroquine, is used to treat autoimmune diseases such as lupus or rheumatoid arthritis. Both drugs are considered safe and effective for these indications. Laboratory testing has suggested that the drugs may also have antiviral effects, and, given their relatively low cost, there has been much interest in their potential effectiveness against COVID-19. However, a study published last week by Brigham researchers and collaborators found that, in an observational analysis, COVID-19 patients who were given either drug (with or without an antibiotic) did not show an improvement in survival rates and were at increased risk for ventricular arrhythmias.

For the current analysis, Warraich and colleagues looked at prescribing patterns for hydroxychloroquine/chloroquine as well as many other commonly prescribed drugs. These included angiotensin-converting-enzyme-inhibitors (ACEi) and angiotensin-receptor blockers (ARBs), both of which are prescribed for patients with hypertension or heart failure, as well as the antibiotic azithromycin, and the top 10 drug prescriptions filled in 2019. The team compared the number of filled prescriptions for each drug to the number of prescriptions filled last year over a 10-week period from Feb. 16 to April 25.

The team found that fills for all drugs, except the antibiotic amoxicillin and the pain reliever combination of hydrocodone/acetaminophen, peaked during the week of March 15 to March 21, 2020, followed by subsequent declines. During this week, hydroxychloroquine/chloroquine fills for 28 tablets increased from 2,208 prescriptions in 2019 to 45,858 prescriptions in 2020 (an increase of more than 2,000 percent). Over the full 10 weeks, there were close to half a million excess fills of hydroxychloroquine/chloroquine in 2020 compared to the year before.

In contrast, prescriptions for antibiotics such as amoxicillin and azithromycin and for hydrocodone/acetaminophen declined. Prescriptions for heart therapies remained stable or declined slightly.
After the surge in prescriptions, the authors observed a reduction in longer-term prescription fills for hydroxychloroquine/chloroquine, which could indicate decreased availability of the drug for patients with systemic lupus erythematosus and rheumatoid arthritis. The United States Food and Drug Administration reported a drug shortage of hydroxychloroquine starting March 31.
The surge in prescriptions occurred between March 15 and March 21, within days of the World Health Organization declaring a global coronavirus pandemic on March 11, the U.S. declaring a national emergency on March 13, the publishing of a pre-print about hydroxychloroquine on March 17, and President Trump's announced support of hydroxychloroquine on March 19.

"During this pandemic, there has been both good information and misinformation about benefits and potential harms of common medications like hydroxychloroquine, and there had been conjecture that proven medications for heart failure may be harmful in this patient population," said Warraich. "One positive finding is that we didn't see a stark reduction in prescription fills for routine, chronic care, but our findings for HCQ are concerning."

Credit: 
Brigham and Women's Hospital

Sea snakes have been adapting to see underwater for 15 million years

video: An olive sea snake (Aipysurus laevis) surfacing to have a breath in Western Australia.

Image: 
Bruno Simoes, University of Plymouth

Sea snakes first entered the marine environment 15 million years ago and have been evolving ever since to survive in its changing light conditions, according to a new study.

Research led by the University of Plymouth (UK) has for the first time provided evidence of where, when and how frequently species have adapted their ability to see in colour.

It suggests sea snakes' vision has been modifying genetically over millions of generations, enabling them to adapt to new environments and meaning they can continue to see prey - and predators - deep below the sea surface.

In an unexpected twist, the study published in Current Biology also suggests that diving sea snakes actually share their adaptive properties not with other snakes or marine mammals, but with some fruit-eating primates.

The research was led by Dr Bruno Simões, Lecturer in Animal Biology at the University of Plymouth, and involved scientists from the UK, Australia, Denmark, Bangladesh and Canada.

Dr Simões, formerly a Marie Sk?odowska-Curie Global Fellow at the University of Bristol (UK) and University of Adelaide (Australia), said: "In the natural world, species obviously have to adapt as the environment around them changes. But to see such a rapid change in the sea snakes' vision over less than 15 million years is truly astonishing. The pace of diversification among sea snakes, compared to their terrestrial and amphibious relatives, is perhaps a demonstration of the immensely challenging environment they live in and the need for them to continue to adapt in order to survive.

"Our study also shows that snake and mammal vision has evolved very differently in the transition from land to sea. Sea snakes have retained or expanded their colour vision compared to their terrestrial relatives, whereas pinnipeds and cetaceans underwent a further reduction in the dimensions of their colour vision. This contrast is further evidence of the remarkable evolutionary diversity of snake eyesight."

In the study, scientists say that despite being descended from highly visual lizards, snakes have limited (often two-tone) colour vision, attributed to the dim-light lifestyle of their early snake ancestors.

However, the living species of front-fanged and venomous elapids are ecologically very diverse, with around 300 terrestrial species (such as cobras, coral snakes and taipans) and 63 fully marine sea snakes.

To try and establish how this diversity occurred, scientists analysed various species of terrestrial and sea snakes from sources including fieldwork in Asia and Australia and historical museum collections.

They investigated the evolution of spectral sensitivity in elapids by analysing their opsin genes (which produce visual pigments that are responsible for sensitivity to ultra-violet and visible light), retinal photoreceptors and eye lenses.

Their results showed that sea snakes had undergone rapid adaptive diversification of their visual pigments when compared with their terrestrial and amphibious relatives.

In one specific example, a particular lineage of sea snake had expanded its UV-Blue sensitivity. Sea snakes forage on the sea floor in depths exceeding 80metres, yet must swim to the surface to breathe at least once every few hours. This expanded UV-Blue sensitivity helps the snakes to see in the variable light conditions of the ocean water column.

Also, most vertebrates have pairs of chromosomes resulting in two copies of the same genes. In some fruit-eating primates, the two copies might be slightly different (alleles) resulting in visual pigments with different spectral properties, expanding their colour vision. This study suggests that some sea snakes used the same mechanism to expand their underwater vision with both UV sensitive and blue-sensitive alleles.

Dr Kate Sanders, Associate Professor of the University of Adelaide and senior author, said: "Different alleles of the same gene can be used by organisms to adapt new environmental conditions. The ABO blood types in primates are a result of different alleles of the same gene. However, despite being very important for the adaptation of species this mechanism is still poorly reported. For vision, it has been only reported on the long-wavelength opsin of some primates but our study suggests an intriguing parallel with diving sea snakes."

Credit: 
University of Plymouth

Antarctic ice sheets capable of retreating up to 50 meters per day

image: Bathymetric data of the grounding-zone wedge complex, derived from an AUV-deployed multibeam echo sounder.

Image: 
Julian Dowdeswell

The ice shelves surrounding the Antarctic coastline retreated at speeds of up to 50 metres per day at the end of the last Ice Age, far more rapid than the satellite-derived retreat rates observed today, new research has found.

The study, led by the Scott Polar Research Institute at the University of Cambridge, used patterns of delicate wave-like ridges on the Antarctic seafloor to calculate how quickly the ice retreated roughly 12,000 years ago during regional deglaciation.

The ridges were produced where the ice sheet began to float, and were caused by the ice squeezing the sediment on the seafloor as it moved up and down with the movement of the tides. The images of these landforms are at unprecedented sub-metre resolution and were acquired from an autonomous underwater vehicle (AUV) operating about 60 metres above the seabed. The results are reported in the journal Science.

While modern satellites are able to gather detailed information about the retreat and thinning rates of the ice around Antarctica, the data only goes back a few decades. Calculating the maximum speed at which an ice sheet can retreat, using sets of these seafloor ridges, reveals historic retreat rates that are almost ten times faster than the maximum observed rates of retreat today.

"By examining the past footprint of the ice sheet and looking at sets of ridges on the seafloor, we were able to obtain new evidence on maximum past ice retreat rates, which are very much faster than those observed in even the most sensitive parts of Antarctica today," said lead author Professor Julian Dowdeswell, Director of the Scott Polar Research Institute.

The study was carried out as part of the Weddell Sea Expedition, which set out in early 2019 to undertake a science programme and to find Sir Ernest Shackleton's doomed ship Endurance. Although sea ice conditions at the time prevented the team from acquiring imagery of the legendary wreck, they were able to continue with their scientific work, including mapping of the seafloor close to the Larsen Ice Shelf, east of the Antarctic Peninsula.

Using drones, satellites and AUVs, the researchers were able to study ice conditions in the Weddell Sea in unprecedented detail.

Their goals were to investigate the present and past form and flow of the ice shelves, the massive floating sections of ice that skirt about 75% of the Antarctic coastline, where they act as a buttress against ice flow from inland.

Like much of the rest of the ice in the polar regions, these buttresses are weakening in some parts of Antarctica, as witnessed most dramatically at the Larsen A and B ice shelves, which collapsed rapidly in 1998 and 2002, when roughly 1250 square miles of ice fragmented and collapsed in little over a month.

The ice shelves are thinning because relatively warm water currents are eating away at them from below, but they're also melting from the top as summer air temperatures rise. Both these effects thin and weaken the ice shelves and, as they do, the glaciers they are holding back flow faster to the sea and their margins retreat.

Using AUVs, the team were able to gather data on historic ice shelf fluctuations from the geological record on the Antarctic continental shelf.

"By examining landforms on the seafloor, we were able to make determinations about how the ice behaved in the past," said Dowdeswell, who was chief scientist on the Weddell Sea Expedition. "We knew these features were there, but we've never been able to examine them in such great detail before."

The team identified a series of delicate wave-like ridges on the seafloor, each only about one metre high and spaced 20 to 25 metres apart, dating to the end of the last great deglaciation of the Antarctic continental shelf, roughly 12,000 years ago. The researchers have interpreted these ridges as formed at what was formerly the grounding line - the zone where grounded ice sheet begins to float as an ice shelf.

The researchers inferred that these small ridges were caused by the ice moving up and down with the tides, squeezing the sediment into well-preserved geological patterns, looking a little like the rungs of a ladder, as the ice retreated. Assuming a standard 12-hour cycle between high and low tide, and measuring the distance between the ridges, the researchers were then able to determine how fast the ice was retreating at the end of the last Ice Age.

They calculated that the ice was retreating as much as 40 to 50 metres per day during this period, a rate that equates to more than 10 kilometres per year. In comparison, modern satellite images show that even the fastest-retreating grounding lines in Antarctica today, for example in Pine Island Bay, are much slower than these geological observations, at only about 1.6 kilometres per year.

"The deep marine environment is actually quite quiet offshore of Antarctica, allowing features such as these to be well-preserved through time on the seafloor," said Dowdeswell. "We now know that the ice is capable of retreating at speeds far higher than what we see today. Should climate change continue to weaken the ice shelves in the coming decades, we could see similar rates of retreat, with profound implications for global sea level rise."

Credit: 
University of Cambridge

Imaging reveals unexpected contractions in the human placenta

image: This figure shows the information on blood oxygen and speed of blood movement within the placenta for both a healthy pregnancy (top) and a preeclamptic pregnancy (bottom).

Image: 
Penny Gowland

High-resolution imaging of the human placenta provides new insights into blood circulation patterns that are crucial for fetal development, according to a study publishing May, 28 2020 in the open-access journal PLOS Biology by Penny Gowland of the University of Nottingham, and colleagues. These findings improve our understanding of the functioning of this understudied organ, both in healthy pregnancies and in serious medical conditions such as pre-eclampsia.

Blood circulation in the human placenta is critical for fetal development. A technique called magnetic resonance imaging (MRI) is increasingly used to study fetal growth and development. In the new study, Gowland and colleagues used MRI to shed light on the movement and oxygenation of blood in the human placenta.

The researchers observed relatively uniform, high oxygenation levels across the whole placenta, and a decrease in the velocity of blood flow as it enters the placenta. These findings suggest that oxygen is delivered efficiently from the mother to the fetus. The researchers also observed rapid draining from veins in the placenta, a feature that is crucial for proper circulation but has largely been neglected in past studies.

Moreover, they discovered a new physiological phenomenon, named the utero-placental pump, by which the placenta and underlying uterine wall contract independently of the rest of the uterus. Such contractions facilitate better blood flow through the placenta and the fetus.

Finally, the researchers characterized altered patterns of blood movement associated with pre-eclamptic pregnancies, which are characterized by the onset of high blood pressure and often a significant amount of protein in the urine, increasing the risk for poor outcomes for both the mother and the baby. According to the authors, their results can be used to improve placental models and to optimize MRI protocols to provide more specific information about placental abnormalities.

Credit: 
PLOS

Scientists analyze spatio-temporal differentiation of spring phenology in China from 1979 to 2018

image: Fifteen temporal patterns of first bloom date (FBD) over 40 years and spatial delineation in China.

Image: 
©Science China Press

Spatial and temporal differentiations are important features in the study of phenology of ecosystems. Plant phenology studies the life circle phases in plants driven by environmental factors and the study of its long-term patterns and dynamics is significant to reveal the responses of vegetation in different regions of China to global changes. By partitioning data elements into groups and considering them at an abstract level, clustering is one of the most widely used methods to study the spatio-temporal differentiation of phenology. However, differentiations identified by only using spatial clustering are incapable to illustrate the time-varying behavior in the phenology and vice versa. A recent research used co-clustering analysis to explore spatio-temporal differentiation of spring phenology in China.

The recently published paper in SCIENCE CHINA Earth Sciences, "Spatio-temporal differentiation of spring phenology in China driven by temperatures and photoperiod from 1979 to 2018", were written by Professor Cheng Changxiu, Professor Song Changqing and Dr. Wu Xiaojing of Beijing Normal University. The researchers analyzed the long-term first bloom dates (FBD) dataset in China using Bregman block average co-clustering algorithm with I-divergence (BBAC_I) and Extended spring indices (SIx), and the result revealed the spatio-temporal differentiation of spring phenology in China of the recent 40 years (1979~2018).

The results first resulted in three spatial patterns of FBD in China: Spatial patterns 1~3 represent three typical patterns of FBD during the movement from the South to North of China. Their temporal dynamics for 40 years (1979~2018) can be divided into 3 time periods (Figure 1): (1) Early stage (1978~1996): spatial patterns of FBD in China vary between Spatial pattern1 and Spatial pattern2, in which areas located in Jiangxi, northern Xinjiang and middle Inner Mongolia experienced the trend of fluctuant increasing spring onsets; (2) Middle stage (1996~2012): spatial patterns of FBD in China vary between Spatial pattern2 and Spatial pattern3, in which areas located in Fujian, Hunan and eastern Heilongjiang exhibited the trend of fluctuant increasing spring onsets; (3) Late stage (2013~2018): spatial patterns of FBD in China stayed at Spatial pattern3.

The research also displayed 15 temporal patterns of spring phenology over the study period and their spatial delineation in China (Figure 2). These temporal patterns can be divided into five categories according to the changing state of FBD: stable, first stable and then fluctuant, first fluctuant and then stable, frequently fluctuant and drastic fluctuant. According to the spatial delineation, most areas in China belong to the stable state (green region), while northern Guizhou, Hunan, southern Hubei (blue region) belong to the state of first stable in 1979~1997 and then fluctuant; areas of eastern Sichuan, southeastern Hunan and northern Jiangxi (orange region) belong to the state of first fluctuant in 1979~1997 and then stable.

Results of this research revealed the spatio-temporal differentiation of spring phenology in China for the recent 40 years by displaying the spatial patterns of FBD and their temporal dynamics, temporal patterns of FBD and their spatial delineation. Furthermore, the results have certain directive significance on the design of existing observational sites in Chinese Phenological Network.

Credit: 
Science China Press

Exploiting viruses to attack cancer cells

image: The AdARET killed cancer cells (A549, H1299, and C33A) in a
dose-dependent manner while normal cells (BJ and WI38) were largely
unaffected particularly with small doses of AdARET. Living cells were
stained blue. MOI indicates the number of virus particles per cell.
(Yohei Mikawa et al., Cancers, May 11, 2020)

Image: 
Yohei Mikawa et al., Cancers, May 11, 2020

An adenovirus is now better able to target and kill cancer cells due to the addition of an RNA stabilizing element.

Hokkaido University scientists have made an adenovirus that specifically replicates inside and kills cancer cells by employing special RNA-stabilizing elements. The details of the research were published in the journal Cancers.

Much research in recent years has investigated genetically modifying adenoviruses to kill cancers, with some currently being tested in clinical trials. When injected, these adenoviruses replicate inside cancer cells and kill them. Scientists are trying to design more efficient viruses, which are better able to target cancer cells while leaving normal cells alone.

Hokkaido University molecular oncologist Fumihiro Higashino led a team of scientists to make two new adenoviruses that specifically target cancer cells. To do this, they used 'adenylate-uridylate-rich elements' (AREs), which are signals in RNA molecules known to enhance the rapid decay of messenger RNAs (mRNAs) in human cells. "AREs make sure that mRNAs don't continue to code for proteins unnecessarily in cells," explains Higashino. "Genes required for cell growth and proliferation tend to have AREs."

Under certain stress conditions, however, ARE-containing mRNAs can become temporarily stabilized allowing the maintenance of some necessary cell processes. ARE-mRNAs are also stabilized in cancer cells, supporting their continuous proliferation.

Higashino and his team inserted AREs from two human genes into an adenovirus replicating gene, making the new adenoviruses: AdARET and AdAREF. "The idea behind the insertion is that the AREs will stabilize the killer adenoviruses, allowing them to replicate only inside cancer cells but not in normal healthy ones," says Higashino.

Indeed, AdARET and AdAREF were both found to replicate inside and kill cancer cells in the laboratory, while they hardly affected normal cells. Tests confirmed that the specific replication in cancer cells was due to stabilization of the viral genes with AREs, which did not happen in the healthy cells.

The scientists then injected human cancer cells under the skin of nude mice, which then developed into tumors. When AdARET and AdAREF were injected into the tumors, they resulted in a significant reduction in tumor size.

This wasn't the first time for the team to test the use of AREs in adenoviruses. In a previous study, another scientist used an ARE belonging to a different gene and found this adenovirus worked specifically in cancers containing a mutation in a gene called RAS. AdARET and AdAREF, on the other hand, were found to be effective against cancer cells without a mutated RAS gene, making the viruses applicable to a wider range of cancer cells.

"Since ARE-mRNA stability has also been reported in diseases other than cancer, we think the viruses we engineered could also have potential for treating diseases related to inflammations, viral infection, hypoxia, and ultraviolet irradiation," says Higashino.

Credit: 
Hokkaido University

Beyond the garnish: Will a new type of produce get the microgreen light?

image: Sarah Ardanuy Johnson with microgreens

Image: 
Colorado State University

Microgreens. They're leafy green vegetables that are relatively new to the dining room, but a study by a Colorado State University team indicates that they will be welcome company at the table.

"You've probably heard of sprouts and baby greens," said lead researcher and registered dietitian nutritionist Sarah Ardanuy Johnson, an assistant professor and director of the Functional Foods & Human Health Laboratory in CSU's Department of Food Science and Human Nutrition. "These are somewhere in the middle."

Microgreens are young and tender leafy greens of most vegetables, grains, herbs and flowers that are harvested when their first leaves appear. Their rapid maturity of a few weeks and affinity for controlled-environment agriculture (also known as indoor farming) means they use very little water and can be harvested quickly. It makes them a model of sustainability: They can be grown indoors, year-round, in cities and rural communities, in greenhouses, warehouses, vertical farms and even homes.

"I came across microgreens and had never heard of them before," said Johnson, who initially studied environmental science and ecology as an undergraduate before realizing her true academic passion was in nutrition and food science. "The need for our food to be more sustainable is greater than ever. I love the idea that they can be grown in an urban environment, indoors in big cities and smaller towns. We can't just grow everything in the soil outside anymore, and we need to conserve what natural resources we still have."

NUTRITIONAL BENEFITS

Johnson described them as leafy greens that pack a punch. They carry fewer food safety concerns than sprouts because they are grown in an environment with less moisture and, unlike sprouts, the roots of microgreens are removed during harvest. Nutritionally, they have been shown to have higher concentrations of phytochemicals and nutrients like beta-carotene (which can be converted to Vitamin A) than mature plants.

"Vitamin A deficiency is the leading cause of blindness worldwide," Johnson said, explaining that microgreens may become a key food source for preventing nutrient deficiencies and promoting global health and environmental sustainability. "That potential is pretty cool."

But she and her fellow researchers wanted to find out if microgreens are acceptable to consumers, and possible factors in how much consumers like or dislike them. They sought to understand if microgreens' appearance, taste and other considerations make them an appealing addition to people's plates. The answer? Signs point to more and more people exhibiting a microgreen palate.

Results of the study were published in March in the Journal of Food Science. Johnson's team surveyed 99 people about their reactions to six different types of microgreens: arugula, broccoli, bull's blood beet, red cabbage, red garnet amaranth and tendril pea. The microgreens were grown in the CSU Horticulture Center. The participants, who didn't know in advance what they would be trying, answered a variety of questions about things like flavor, aroma, texture and appearance.

'FUNFETTI'

"Some people call them 'vegetable confetti' or 'funfetti' because they're small, colorful and flavorful," Johnson said, adding that they have historically been used as a garnish or topping in restaurants.

The red-colored ones -- beet, cabbage and amaranth -- received top marks for appearance, but broccoli, red cabbage, and tendril pea got the highest grades overall. Arugula was ranked lowest, on average, likely due to its somewhat spicy and bitter flavor, although many people did like the taste. Overall, microgreens that rated highly for appearance, flavor and texture also scored lower on factors like astringency, bitterness, heat and sourness. Food neophobia, or the fear of trying new foods, was found to also be an important factor driving consumer acceptability.

"But they were all liked well enough that people said they would consume them and purchase them," Johnson said. "I feel like they should be used more as a vegetable and not just a garnish. That's part of the reason why I wanted to do this study."

INCREASING DEMAND

In fact, that was one of her key goals in launching the research: Can the appeal of microgreens lead to more popularity, more demand, more production and more grocery stores carrying them? Such products can be expensive due to markup and packaging.

"But people's mindsets are changing," Johnson said. "People don't want to buy something that's going to just end up in the landfill. They are looking for something that can benefit their health and the environment."

Participants said factors they would consider in buying microgreens included familiarity and knowledge, cost, access/availability and freshness/shelf-life.

For the research project, Johnson teamed up with Steven Newman, a professor and greenhouse crops specialist in CSU's Department of Horticulture and Landscape Architecture. Johnson found him online in her quest to find a collaborator with expertise in greenhouse crops; Newman has provided leafy greens grown in the Horticulture Center to campus dining halls. Newman's team grew the microgreens used in the study with help from Johnson's team, in a classic example of the type of cross-disciplinary research that's on the rise at CSU.

"This has been a fun project with fruitful outcomes," Newman said. "This is how transdisciplinary research is supposed to work."

OTHER PARTNERS

Study co-author Marisa Bunning, a food science professor and Extension food safety specialist, has become a microgreens fan and now grows them at home. Laura Bellows, an associate professor with expertise in public health and health behaviors, helped assess factors contributing to consumer acceptability, such as food neophobia.

Other members of Johnson's team included Hanan Isweiri, Newman's former postdoctoral fellow; first author Kiri Michell, one of Johnson's graduate students; graduate student Michelle Dinges; undergraduate Lauren Grabos; Associate Professors Michelle Foster and Tiffany Weir of the Department of Food Science and Human Nutrition; Assistant Professors Adam Heuberger and Mark Uchanski, Associate Professor Jessica Prenni, and Professor Henry Thompson of the Department of Horticulture and Landscape Architecture; and Assistant Professor Sangeeta Rao of the Department of Clinical Sciences.

Experts say that by 2050, there will be more than 10 billion people in the world to feed, making it more important than ever to think about ways to produce and grow nutritious food, as well as diversify the food supply in a sustainable way.

'Small but mighty'

"This was a very exciting, interdisciplinary study, and I am glad I was able to take part and help lead it," Michell said. "I look forward to more research regarding these small but mighty greens and their role in our food supply and on human health."

"I don't know that we could have done the advanced interdisciplinary research without Kiri's hard work and leadership," Johnson said. "But this was truly a team effort."

Michell noted that The Foundry dining hall on the CSU campus has started using microgreens in some of its dishes, and even has a viewing window where students can see them being grown.

The large collaboration aims to advance research on microgreens, and to increase knowledge of microgreens and their integration into the global food system. The group is conducting additional research, such as examining the feasibility, tolerability and potential health impacts of daily microgreen consumption at a higher dose (two cups per day, which is a typical serving size for leafy green vegetables), and comparing the nutritional value of microgreens to that of their more mature counterparts.

Credit: 
Colorado State University

Tackling airborne transmission of COVID-19 indoors

Preventing airborne transmission of Covid-19 should be the next front of the battle against the virus, argue experts from the University of Surrey.

In a study published by the City and Environment Interaction journal, scientists from Surrey's Global Centre for Clean Air Research (GCARE), together with partners from Australia's Queensland University and Technology, argue that the lack of adequate ventilation in many indoor environments - from the workplace to the home - increases the risk of airborne transmission of Covid-19.

Covid-19, like many viruses, is less than 100mn in size but expiratory droplets (from people who have coughed or sneezed) contain water, salts and other organic material, along with the virus itself. Experts from GCARE and Australia note that as the water content from the droplets evaporate, the microscopic matter becomes small and light enough to stay suspended in the air and over time the concentration of the virus will build up, increasing the risk of infection - particularly if the air is stagnant like in many indoor environments.

The study highlights improving building ventilation as a possible route to tackling indoor transmission of Covid-19.

Professor Prashant Kumar, lead author and the Director of the GCARE at the University of Surrey, said: "These past months, living through the Covid-19 crisis, has been truly unprecedented, but we must turn this global tragedy into an opportunity to better prepare for similar threats. An improved indoor ventilation is an important step that can be taken to reduce the risk of infection. However, more must be done to recognise and understand airborne transmission of Covid-19 and similar viruses, to minimise the build-up of virus-laden air in places typically containing high densities of people."

Credit: 
University of Surrey

Combination therapy well-tolerated and highly effective for patients with IDH1-mutated AML

image: This is Curtis Lachowiez, M.D.

Image: 
The University of Texas MD Anderson Cancer Center

HOUSTON - A combination therapy of ivosenidib (IVO) plus venetoclax (VEN) with or without azacitidine (AZA) was found to be effective against a specific genetic subtype of acute myeloid leukemia (AML) in a Phase Ib/II trial led by researchers at The University of Texas MD Anderson Cancer Center. The results of this trial may support a novel course of action for patients with AML harboring an IDH1 mutation who have historically had few treatment options.

Across all treatment groups, the composite complete remission rate was 78% overall and 100% for treatment-naïve patients. Half of the patients who achieved complete remission also were negative for minimal residual disease (MRD). The results were presented at the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting by lead author Curtis Lachowiez, M.D., hematology fellow.

"This trial is the manifestation of remarkable basic and translational work that is resulting in improved clinical outcomes for patients," said Lachowiez. "The triplet combination may ultimately result in a new, effective therapeutic regimen. As the median age at AML diagnosis is 68, these findings are particularly important for older AML patients who may not be fit enough to receive the aggressive cytotoxic chemotherapy regimens historically used to treat AML."

Mutations in the IDH1 gene lead to myeloid differentiation arrest and subsequent induction of leukemia. IVO, as an IDH1 inhibitor, is a well-tolerated oral therapy that aims to interrupt this leukemogenic process.

The combination of VEN and AZA was previously established to be well-tolerated and effective against newly diagnosed AML, and IVO is approved as a single agent for relapsed IDH1-mutated AML. This trial sought to evaluate the safety, tolerability, and response rate of adding this targeted therapy, IVO, to either venetoclax alone as an oral doublet, or to the AZA and VEN combination to treat this subset of AML patients with a specific genetic mutation.

"To our knowledge, AZA plus VEN and AZA plus IVO 'doublets' are effective but not curative for newly diagnosed IDH1-mutated AML patients, and patients still ultimately relapse. This triplet combination trial aims to determine whether this regimen leads to deeper responses and even curative therapy in some patients," said Courtney DiNardo, M.D., associate professor of Leukemia and the study's senior author. "Additionally, this trial evaluates the oral IVO plus VEN doublet for the first time, and we hope patients will benefit from this outpatient regimen."

Patients with AML or high-risk myelodysplastic syndrome (MDS) were assigned one of three cohorts, either receiving IVO + VEN 400 mg, IVO + VEN 800mg or IVO + VEN 400mg + AZA.

The median time to best response was two months. Of the 18 evaluable patients, nine remain enrolled in the study, and three proceeded to receive a stem cell transplant following complete remission.

"This study is exciting because it displays that we are able to tailor therapy for AML patients based on their molecular profile," said Lachowiez. "While some mutations have traditionally been associated with poor outcomes, we can now identify certain subgroups of patients with genetic mutations who are more likely to respond to a specific therapy, and then we can design a treatment and follow-up plan to best suit them."

Based on a patient's molecular profile, their care team may be able to decide on options like closer monitoring or earlier transition to transplant for high-risk patients. Further, as in the case of patients with molecular mutations associated with favorable responses, the care team may be able to prescribe tailored therapeutic combinations, leading to durable remissions and potential cures.

Study accrual is continuing, and the research team is conducting additional follow-up to elucidate the biomarkers and potential duration of response.

Credit: 
University of Texas M. D. Anderson Cancer Center

Cancer doctors call for more training in palliative care and delivery of 'bad news'

Oncologists who practice and teach at the Johns Hopkins Kimmel Cancer Center are calling on medical oncology training programs to invest substantially more time educating physicians about palliative care and how to talk to patients about "bad news."

In a commentary published on April 9, 2020, in the Journal of Clinical Oncology, the physicians noted studies showing that cancer doctors deliver bad news to patients an average of 35 times a month. "However, few have training in how best to do so," says Ramy Sedhom, M.D., a medical oncology fellow at the Johns Hopkins University School of Medicine and lead author.

According to the researchers, oncology fellows -- those who have embarked on lengthy post-doctoral training programs specializing in cancer care -- report getting more coaching on how to perform technical procedures such as bone marrow biopsies than how to conduct a meeting with patients and families facing difficult or limited choices in care and disease outcomes. At the same time, Sedhom says, research suggests that how doctors frame difficult conversations can influence and direct patient preferences for treatment or palliative care.

As advances in treatment have increased in number and complexity in recent years, many oncologists have moved from practicing general medical oncology to focusing on just one or two cancers, says Thomas J. Smith, M.D., professor of oncology and director of palliative medicine at the Johns Hopkins University School of Medicine.

"As a consequence," he says, "the abilities of these doctors to predict patient outcomes becomes even more complicated and highlights the need for palliative care training."

Smith, Sedhom and colleagues previously surveyed accredited oncology training programs in the United States, finding none that offered a combined or integrated medical oncology and hospice/palliative care medicine program. Seventy-three institutions, including Johns Hopkins Medicine, offer the training in separate programs.

Smith and Sedhom say their commentary finds that training in the science of communication can help oncologists effectively address patient emotions and in turn, help patients and their families make more informed decisions about treatment choices.

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Johns Hopkins Medicine

Reintroduction of wolves tied to return of tall willows in Yellowstone National Park

image: In Yellowstone's Lamar Valley, bison congregate in the summer and graze not only on grass but also on willow, cottonwood, and aspen. These bison are eating willows in the foreground, while in the background some emerging willow thickets are visible.

Image: 
Luke Painter, Oregon State University

CORVALLIS, Ore. - The reintroduction of wolves into Yellowstone National Park is tied to the recovery of tall willows in the park, according to a new Oregon State University-led study.

Wolves were reintroduced to the park in 1995. The new study shows their predation on elk is a major reason for an increase in the height of willows in northern Yellowstone, said Luke Painter, a wildlife ecologist at Oregon State University and lead author on the study.

There's been a debate among scientists over the degree to which willows may have recovered from decades of suppression by elk following the restoration of wolves and subsequent reductions in elk numbers, Painter said.

"Our results demonstrate that the reduction of elk browsing over the last two decades in northern Yellowstone has allowed willows to grow taller in many places, despite a warming and drying climate," Painter said, adding that willows aren't recovering in some areas due to continued browsing by increased numbers of bison.

Following wolf restoration in the 1990s, elk numbers decreased, and some researchers reported willows growing taller with reductions in elk browsing, evidence of a shift toward willow recovery.

The new study compared data from three time periods: 1988-1993, when elk densities were high and most willows very short; 2001-04, when willows may have begun to recover; and 2016-18.

The researchers confirmed that willows have indeed increased in height and cover in response to a reduction in browsing by elk.

The study is published in the journal Ecosphere.

Elk numbers in northern Yellowstone have declined from a high of nearly 20,000 in 1995 - the year wolves were restored to the park - to 4,149 counted over two days in March 2019 by biologists with Montana Fish, Wildlife, and Parks; U.S. Forest Service and U.S. Geological Survey.

Painter and co-author Michael Tercek of Walking Shadow Ecology in Montana found a strong contrast between sites along streams compared to wet meadows. Willows in meadow sites did not increase in height, but willows in stream sites increased significantly, exceeding 200 centimeters, or 6 feet - a height accessible to elk - in the summers of 2001-04 and in the spring of 2016.

They also found a significant change in willow thickets at least 200 centimeters in height along streams, with thickets occupying about 80% of willow patches in some sites, but as little as 22% in others. Tall willow thickets are an important habitat feature and an indicator of willow recovery, Painter said.

Thus, passive restoration through the return of predators has begun to reverse the loss of willows, something active culling of elk in the past was unable to accomplish, he said.

"Wolves didn't do it all by themselves," Painter said. "Other predators and hunters also affected elk, but this would not have happened without the wolves.

"This does not mean a wider expanse of willow habitat has been restored as existed in the early days of the park when beavers created large wetland expanses. This may eventually happen as beavers return but could take a long time to develop."

This is the latest OSU study led by Painter that examines the effects of wolf reintroduction to Yellowstone on trees. In 2018, he published a study that showed that aspen is recovering in areas around the park, as well as inside the park boundary.

Credit: 
Oregon State University