Tech

The newly reported genome sequence of a water lily sheds light on the early evolution of angiosperms, the group of all flowering plants. An international team of researchers, including scientists at Penn State, used high-throughput next-generation sequencing technology to read out the water lily's (Nymphaea colorata) genome and transcriptome--the set of all genes expressed as RNAs.

The unusual high quality and depth of coverage of the sequence allowed the researchers to assemble the vast majority of the genome into 14 chromosomes and identify more than 31 thousand protein-coding genes. A paper describing the sequence and subsequent analysis appears December 18, 2019 in the journal Nature.

"Water lilies have been an inspiration to artists like Claude Monet because of their beauty and important to scientists because of their position near the base of the evolutionary tree of all flowering plants," said Hong Ma, associate dean for research and innovation, Huck Distinguished Research Professor of Plant Molecular Biology, and professor of biology at Penn State, one of the leaders of the research team. "I previously contributed to the sequencing and analysis of the genome of Amborella, which represents the earliest branch to separate from other flowering plants, but Amborella lacks big showy colorful flowers and attractive floral scent, both of which serve to attract pollinators in most groups of flowering plants. We were interested in the water lily genome to help us understand how these traits evolved."

Evolutionary comparison of the water lily genome to the genomes of Amborella, other angiosperms, and several gymnosperms--the group of seed-bearing plants that do not produce flowers--confirmed the position of Amborella, which shares some characteristics with the gymnosperms, as the earliest of currently living angiosperms to separate from other flowering plants. Water lilies were the next branch to diverge from a third branch (Austrobaileyales, which includes star anise) and a fourth very large group called the mesangiosperms, which contains over 99% of living flowering plants.

"If we make an analogy to mammalian evolution, Amborella has a similar position to that of the platypus and other egg-laying mammals," said Ma. "The platypus is a mammal because it feeds its young with milk, but it lays eggs like birds or reptiles. Amborella, like gymnosperms, has separate male and female plants, but the water lily has male and female reproductive parts within a single flower. This makes the water lily more similar to the vast majority of other flowering plants, so having the genomes of both Amborella and water lily can help us to better analyze the evolutionary transition from gymnosperms to angiosperms."

The researchers used molecular dating to estimate the separation of the family of water lilies (Nymphaeaceae) from other families of related aquatic plants at somewhere between 147 and 185 million years ago, when dinosaurs roamed the earth, with a whole-genome duplication (WGD)/polyploidy event at about the same time. Many of the key genes for flower development retained in this WGD.

The research team also analyzed genes in the water lily genome that are likely important for the generation of molecules for attractive floral scent and color, traits shared with most other angiosperms, but not found in Amborella. They identified a massive expansion in the number of genes involved in the biosynthesis of floral scent in water lilies; these genes seem to have evolved in parallel with the other angiosperms. They also analyzed the expression of genes involved in flower color between two species of water lily, identifying the key proteins responsible for blue petals.

"Having the water lily genome allows us to explore these important traits in flowering plants and especially among horticultural plants," said Ma. "It's likely that brightly colored flowers and floral scent evolved through an interaction with pollinators and such flowers are ultimately extremely important for the success of flowering plants. Identification of the key synthetic genes of blue petals has important reference value for breeding blue petal varieties."

Clusters composed of a few atoms tend to be spherical. They are usually organized in shells of atoms around a central atom. This is the case for many elements, but not for gold! Experiments and advanced computations have shown that freestanding clusters of twenty gold atoms take on a pyramidal shape. They have a triangular ground plane made up of ten neatly arranged atoms, with additional triangles of six and three atoms, topped by a single atom [see figure where a model of twenty oranges is compared with the theoretical and experimental structure].

The remarkable tetrahedral structure has now been imaged for the first time with a scanning tunnelling microscope. This high-tech microscope can visualise single atoms. It operates at extremely low temperatures (269 degrees below zero) and uses quantum tunnelling of an electrical current from a sharp scanning metallic tip through the cluster and into the support. Quantum tunnelling is a process where electrical current flows between two conductors without any physical contact between them.

The researchers used intense plasmas in a complex vacuum chamber setup to sputter gold atoms from a macroscopic piece of gold. "Part of the sputtered atoms grow together to small particles of a few up to a few tens of atoms, due to a process comparable with condensation of water molecules to droplets," says Zhe Li, the main author of the paper, currently at the Harbin Institute of Technology, Shenzhen. "We selected a beam of clusters consisting of exactly twenty gold atoms. We landed these species with one of the triangular facets onto a substrate covered with a very thin layer of kitchen salt (NaCl), precisely three atom layers thick."

The study also revealed the peculiar electronic structure of the small gold pyramid. Similar to noble gas atoms or aromatic molecules, the cluster only has completely filled electron orbitals, which makes them much less reactive than clusters with one or a few atoms more or less.

Gold clusters ranging from a few to several dozens of atoms in size are known to possess remarkable properties.

The new discovery helps scientists evaluate the catalytic and optical performances of these clusters, which is relevant for designing cluster-based catalyst and optical devices. Recent applications of clusters include utilisation in fuel cells and carbon capture.

A 2017 report of the discovery of a particular kind of Majorana fermion--the chiral Majorana fermion, referred to as the "angel particle"--is likely a false alarm, according to new research. Majorana fermions are enigmatic particles that act as their own antiparticle and were first hypothesized to exist in 1937. They are of immense interest to physicists because their unique properties could allow them to be used in the construction of a topological quantum computer.

A team of physicists at Penn State and the University of Wurzburg in Germany led by Cui-Zu Chang, an assistant professor of physics at Penn State studied over three dozen devices similar to the one used to produce the angel particle in the 2017 report. They found that the feature that was claimed to be the manifestation of the angel particle was unlikely to be induced by the existence of the angel particle. A paper describing the research appears on January 3, 2020 in the journal Science.

"When the Italian physicist Ettore Majorana predicted the possibility of a new fundamental particle which is its own antiparticle, little could he have envisioned the long-lasting implications of his imaginative idea," said Nitin Samarth, Downsbrough Department Head and professor of physics at Penn State. "Over 80 years after Majorana's prediction, physicists continue to actively search for signatures of the still elusive "Majorana fermion" in diverse corners of the universe."

In one such effort, particle physicists are using underground observatories that seek to prove whether the ghost-like particle known as the neutrino--a subatomic particle that rarely interacts with matter--might be a Majorana fermion. On a completely different front, condensed matter physicists are seeking to discover manifestations of Majorana physics in solid state devices that combine exotic quantum materials with superconductors. In such devices, electrons are theorized to dress themselves as Majorana fermions by stitching together a fabric constructed from core aspects of quantum mechanics, relativistic physics, and topology. This analogous version of Majorana fermions has particularly captured the attention of condensed matter physicists because it may provide a pathway for constructing a "topological quantum computer" whose qubits (quantum versions of binary 0s and 1s) are inherently protected from environmental decoherence--the loss of information that results when a quantum system is not perfectly isolated and a major hurdle in the development of quantum computers.

"An important first step toward this distant dream of creating a topological quantum computer is to demonstrate definitive experimental evidence for the existence of Majorana fermions in condensed matter," said Chang. "Over the past seven or so years, several experiments have claimed to show such evidence, but the interpretation of these experiments is still debated."

The team studied devices fashioned from a quantum material known as a "quantum anomalous Hall insulator" wherein the electrical current flows only at the edge. A recent study predicted that when the edge current is in clean contact with a superconductor, propagating chiral Majorana Fermions are created and the electrical conductance of the device should be "half-quantized" (a value of e2/2h where "e" is the electron charge and "h" is Planck constant), when subject to a precise magnetic field. The Penn State-Wurzburg team studied over three dozen devices with several different materials configurations and found that devices with a clean superconducting contact always show the half-quantized value regardless of magnetic field conditions. This occurs because the superconductor acts like an electrical short and is thus not indicative of the presence of the Majorana fermion.

"The fact that two laboratories--at Penn State and at Wurzburg--found completely consistent results using a wide variety of device configurations casts serious doubt on the validity of the theoretically proposed experimental geometry and questions the 2017 claim of observing the angel particle," said Moses Chan, Even Pugh Professor Emeritus of Physics at Penn State.

"I remain optimistic that the combination of quantum anomalous Hall insulators and superconductivity is an attractive scheme for realizing chiral Majoranas," said Morteza Kayyalha, a postdoctoral research associate at Penn State who carried out the device fabrication and measurements. "But our theorist colleagues need to rethink the device geometry."

"This is an excellent illustration of how science should work," said Samarth. "Extraordinary claims of discovery need to be carefully examined and reproduced. All of our postdocs and students worked really hard to make sure they carried out very rigorous tests of the past claims. We are also making sure that all of our data and methods are shared transparently with the community so that our results can be critically evaluated by interested colleagues."

Building and maintaining soil health is essential to agricultural sustainability, long-term productivity, and economic viability. Soil health is defined as the continued capacity of soil to function as a vital living system that supports biological productivity, to maintain environmental quality, and to promote plant, animal, and human health.

Understanding how to maintain soil health is especially important, as agricultural production tends to degrade soil over time. The potential harm caused by soil degradation is particularly high for potato production systems, as a result of short rotations, intensive tillage, and lack of crop residues. Additionally, as tubers maintain direct contact with soil, changes in soil health can more immediately affect potato crops.

In the webcast "Basics of Soil Health in Potato Production," Robert Larkin discusses the issues that arise as a result of poor soil health, including increased erosion, reduced root growth, and soil compaction. Improved soil health can result in better potato growth, quality, and yield and reduce the risk of yield losses during periods of stress.

Larkin introduces soil management strategies and practices, including crop rotations, cover crops and green manures, and conservation tillage and draws on a 14-year crop management strategy study to show how these practices have major impacts. He concludes that potatoes thrive best under a 3-year rotation with reduced/conservation tillage. He recommends planting a disease-suppressive rotation crop prior to the potato crop, an alternative cash crop after the potato crop, and a cover crop such as winter rye or ryegrass. Larkin discusses crop rotation in additional detail in the webcast "Crop Rotation and Soil Health in Potato Production Systems."

Some of the effects of air pollution on health are well documented -lung cancer, stroke, respiratory diseases, and a long etcetera- but for others there is less scientific evidence. Such is the case of bone health: there are only a few studies and results are inconclusive. Now, a study in India led by the Barcelona Institute for Global Health (ISGlobal), an institution supported by "la Caixa", has found an association between exposure to air pollution and poor bone health.

Osteoporosis is a disease in which the density and quality of the bone is reduced. Globally, it is responsible for a substantial burden of disease and its prevalence is expected to increase due to aging of the population.

The new study performed by the CHAI Project, led by ISGlobal and published in Jama Network Open, analysed the association between air pollution and bone health in over 3,700 people from 28 villages outside the city of Hyberabad, in southern India.

The authors used a locally-developed model to estimate outdoor exposure at residence to air pollution by fine particulate matter (suspended particles with a diameter of 2.5 μm or less) and black carbon. The participants also filled a questionnaire on the type of fuel used for cooking. The authors linked this information with bone health assessed using a special type of radiography that measures bone density, called dual-energy x-ray absorptiometry, and measured bone mass at the lumbar spine and the left hip.

The results showed that exposure to ambient air pollution, particularly to fine particles, was associated with lower levels of bone mass. No correlation was found with use of biomass fuel for cooking.

"This study contributes to the limited and inconclusive literature on air pollution and bone health," explains Otavio T. Ranzani, ISGlobal researcher and first author of the study. Regarding the possible mechanisms underlying this association, he says "inhalation of polluting particles could lead to bone mass loss through the oxidative stress and inflammation caused by air pollution".

Annual average exposure to ambient PM2.5 was 32.8 μg/m3, far above the maximum levels recommended by the World Health Organisation (10 μg/m3). 58% of participants used biomass fuel for cooking.

"Our findings add to a growing body of evidence that indicates that particulate air pollution is relevant for bone health across a wide range of air pollution levels, including levels found in high income and low-and medium income countries" says Cathryn Tonne, coordinator of the study and of the CHAI project. "

The research was supported by a Russian Science Foundation's grant under the title "Synthesis and research of a new class of nanocomposite ceramics with degenerate dielectric permeability for opto-plasmonic applications."

A metalens described in the article is a thin composite metal-dielectric film placed on a dielectric substrate; the width is several dozen nanometers.

"The light has a wave nature, so there is a diffraction limit which confines the resolution of traditional optical microscopy," explains Kharintsev. "Our metalens is an optical device capable of surpassing that diffraction limit. Such a solution paves way for using optical technologies in nanoscale integral circuits and sensors."

The ultra-high resolution is based on an unusual behavior of the metalens in optical and infrared ranges.

"The material part of the dielectric constant oscillates near zero. This property can be used to enhance stimulated Raman scattering of light in a spatially limited medium illuminated by low-intensity continuous laser light. For most materials found in nature, nonlinear effects are weak, and to observe them it is necessary to increase the length of the medium (for example, using optical fibers) and / or to increase the laser pump power (using high-power pulsed lasers).

"We used a 50 nm thick titanium oxy nitride (TiON) film as a disordered nonlinear medium. The film was synthesized by magnetron sputtering and subsequent oxidation in air. As a result of a two-stage procedure, metal (TiN) and dielectric (TiO2) nanoparticles were formed in the film. An increase in the amplitude of the Stokes wave in a TiN / TiO2 film occurs due to the enhancement of the cubic susceptibility because of localized plasmon resonance and a small refractive index of the effective medium. Such metal-insulator nanocomposite films having several epsilon-near-zero frequencies in the visible and infrared ramges have found application in creating broadband metal technologies providing resolution beyond the limits of light diffraction," adds the author.

Kazan University employees have succeeded in visualizing 40 nm multiwall carbon nanotubes scattered along the surface of the metalens created by them, and the resolution was below 100 nm.

"Nanocomposite epsilon-near-zero film works as a surface-enhanced Raman scattering substrate, and it helps not only enhance the scattered signal, but also achieve beyond-diffraction resolutions. Metalenses and ENZ films can be used to create broadband absorbers for solar panels," concludes Dr. Kharintsev.

Knockin (KI) animals carrying exogenous sequences integrated at specific genomic loci are invaluable tools for biomedical research. To understand the role of lethal genes in post-embryonic functions, it is usual to use KI animals carrying two loxP insertions at interested genomic loci to generate conditional gene knockout (CKO) animals. The zebrafish (Danio rerio) is a vertebrate animal model excellent for in vivo imaging of biological events. However, to knockin two loxP sites in the zebrafish genome is still a big challenge due to the unavailability of gene targeting techniques for zebrafish embryonic stem cells and the low efficiency of homologous recombination (HR) in fast-developing fertilized zebrafish eggs. Du's lab previously developed a non-HR-mediated efficient KI strategy without destroying targeted genes, in which a Cas9 target is selected in an intron and the donor plasmid is integrated into the targeted intron. This strategy has been used to efficiently make KI zebrafish and mouse.

"We develop a novel method for making zebrafish CKO and KI switch (zCKOIS) in one step based on our previously reported non-HR-mediated intron targeting. We showed that the zCKOIS cassette can be targeted into the last intron of hey2 with a high efficiency via CRIPSR/Cas9 mediated non-HR insertion." said Dr Jia Li, the co-first author for this work. A floxed and invertible gene-trap cassette with an RNA slice acceptor is inserted in the intron sequence of the donor plasmid. Without Cre, the zCKOIS cassette will not be inverted and a KI reporter with green fluorescence will be transcripted under the control of the endogenous promoter of the targeted gene. In the present of Cre, the cassette will be inverse, and the targeted gene will be destroyed, associated with the expression of a KO reporter with red fluorescence. "Using this strategy, we generated a hey2zCKOIS fish line and observed green fluorescence (i.e., KI reporter) in various cell types, including glial cells, endothelial cells (ECs) and haematopoietic stem cells (HSCs), similar to the expression pattern of the endogenous hey2 in zebrafish and mouse." said Dr Jia Li. By injecting Cre mRNA, they validated that the inverted hey2zCKOIS (hey2zCKOIS-inv) coupled with red fluorescence (i.e., KO reporter) is a non-functional KO allele. Finally, they achieved EC-specific KO of hey2 by crossing the hey2zCKOIS with the KI line Ki(flk1-P2A-Cre), in which Cre expression is driven by the EC-specific promoter flk1.

This method realizes the generation of CKO and KI reporter line in one step via efficient non-HR-mediated insertion. The simplification and combination of CKO and KI make the zCKOIS strategy an applicable approach for zebrafish and even other organisms.

A new expert review confirms that diet significantly influences mental health and wellbeing, but cautions that the evidence for many diets is comparatively weak. This, the most up to date overview of the new field of Nutritional Psychiatry, is produced, by the Nutrition Network of the ECNP and is published in the peer-reviewed journal European Neuropsychopharmacology (see download details below).

Lead author, Professor Suzanne Dickson (University of Gothenburg, Sweden) said:

"We have found that there is increasing evidence of a link between a poor diet and the worsening of mood disorders, including anxiety and depression. However, many common beliefs about the health effects of certain foods are not supported by solid evidence".

The researchers found that there are some areas where this link between diet and mental health is firmly established, such as the ability of a high fat and low carbohydrate diet (a ketogenic diet) to help children with epilepsy, and the effect of vitamin B12 deficiency on fatigue, poor memory, and depression.

They also found that there is good evidence that a Mediterranean diet, rich in vegetables and olive oil, shows mental health benefits, such as giving some protection against depression and anxiety. However, for many foods or supplements, the evidence is inconclusive, as for example with the use of vitamin D supplements, or with foods believed to be associated with ADHD or autism.

"With individual conditions, we often found very mixed evidence", said Suzanne Dickson. "With ADHD for example, we can see an increase in the quantity of refined sugar in the diet seems to increase ADHD and hyperactivity, whereas eating more fresh fruit and vegetables seems to protect against these conditions. But there are comparatively few studies, and many of them don't last long enough to show long-term effects".

The study confirms that while certain foods can be associated with a mental health condition, this tells us little about why the food causes this effect. It concludes that the need to link mental health effects with provable dietary causes needs to be the main focus of future research in nutritional psychiatry.

Professor Dickson continued:

"There is a general belief that dietary advice for mental health is based on solid scientific evidence. In reality, it is very difficult to prove that specific diets or specific dietary components contribute to mental health.

The scientists confirmed that some foods had readily provable links to mental health, for example, that nutrition in the womb and in early life can have significant effects on brain function in later life. Proving the effect of diet on mental health in the general population was more difficult.

Suzanne Dickson said "In healthy adults dietary effects on mental health are fairly small, and that makes detecting these effects difficult: it may be that dietary supplementation only works if there are deficiencies due to a poor diet. We also need to consider genetics: subtle differences in metabolism may mean that some people respond better to changes in diet that others.

There are also practical difficulties which need to be overcome in testing diets. A food is not a drug, so it needs to be tested differently to a drug. We can give someone a dummy pill to see if there is an improvement due to the placebo effect, but you can't easily give people dummy food. Nutritional psychiatry is a new field. The message of this paper is that the effects of diet on mental health are real, but that we need to be careful about jumping to conclusions on the base of provisional evidence. We need more studies on the long-term effects of everyday diets".

Commenting, the Chair of the ECNP Scientific Programme Committee, Professor Andreas Reif (University Hospital, Frankfurt am Main) said:

"The interface between gut and the brain on the one side and diet and mental health on the other side is one of the most debated issues in biological psychiatry at the moment, and is an exciting development which has gained momentum in the last decade. Many high-quality findings (mainly from animal studies) have been published in top notch journals in recent years, but this contrasts with the comparative shortage of hard evidence on how nutrition and mental health are connected in humans. This leaves room for speculation and flawed science. This comprehensive review is therefore much-needed as it sheds light on hypes and hopes, facts and fiction in the new field of Nutritional Psychiatry. As the potential societal impact of this rapidly developing field is enormous, we must be scientifically sound in making our recommendations. This review is an important and scholarly contribution".

This is an independent comment; Professor Reif was not involved in this work.

In a newly published series appearing in Environmental Toxicology and Chemistry, researchers describe the current state of the science, the challenges, and science-based best practices for modeling the influence of water chemistry on the toxicity of metals, which is a critical step in calculating protective metal concentrations in water for the protection of aquatic life.

Metals are abundant in the environment. They occur naturally and as a result of human activity. Metal levels in freshwater bodies, such as rivers and lakes, are often controlled to protect aquatic life, such as algae, zooplankton, and fish. Regulatory agencies manage metal levels by establishing numeric threshold concentrations considered acceptable to aquatic life, which can be referred to generically as protective values for aquatic life (PVALs).

There have been a number of models designed to explain the toxicity of metals to aquatic organisms by describing and predicting the conditions that influence metals toxicity, and ultimately calculate PVALs. Chris Schlekat, guest editor on the series, notes that "the scientific community agrees that bioavailability-based aquatic toxicity models are recommended for use in environmental management." Unfortunately, the development of these models has outpaced their incorporation into regulation and application for some metals, which has left some water quality regulations outdated.

The series goes on to detail considerations for model selection and model application, which will be useful for environmental professionals, managers and regulators. The models are at a state of maturity that supports their use to inform management decisions, and that will go a long way toward improving ecosystem protection.

A recently published study indicates that oral infections seem to have no association with the risk of stem cell transplantation patients dying of or getting a serious infection within six months of the procedure.

A study collaboratively conducted by the University of Helsinki, the Helsinki University Hospital, the University of Basel and the University Hospital Basel investigated whether oral infections are associated with the mortality rate and infectious complications post-stem cell transplantation.

Haematopoietic stem cell transplantation is used to treat cancers as well as severe blood and autoimmune diseases. Due to the long period of recovery for the immune system after a stem cell transplantation procedure, the patients have a heightened risk of infection.

The study, published in the PLOS ONE journal, involved patients treated at the University Hospital Basel, of whom 341 had received an allogeneic stem cell transplantation and 125 an autologous stem cell transplantation. The procedures were carried out between 2008 and 2016.

Before carrying out the transplantation procedure, all patients underwent a clinical and radiological dental examination to identify any potential foci of infection as well as the number of missing and filled teeth.

A total of 51 stem cell transplant patients died within six months of the procedure. The foci of infection, the number of missing or filled teeth and the cases of periodontitis identified in the examinations completed before the transplantation were not associated with the survival of patients.

Furthermore, the oral foci of infection and oral infections were not associated with infections requiring hospitalisation or bacteraemia identified by blood culture occurring within six months of the transplantation.

"Contrary to our assumptions, untreated oral infections had no connection with post-stem cell transplantation survival during the six-month follow-up period. Another surprise was that they had no link with any serious infectious complications occurring during the follow-up period," Professor Tuomas Waltimo, who headed the study, sums up.

Dental infections always require treatment - Cooperation between physicians and dentists essential

Most likely, the long-term and broad-spectrum antimicrobial therapy administered during treatment was, in this study, able to prevent the spread of chronic infections of dental origin. However, Waltimo stresses that the antibiotic resistance level of oral microbes must be monitored, and dental infections should always be treated as soon as possible, either conservatively or surgically.

"Even though the cause of dental infections must always be eliminated, our study demonstrates that teeth need not be extracted just before a stem cell transplantation procedure due to chronic but asymptomatic dental infections. However, the patient's health permitting, and if the wound has enough time to heal before chemotherapy, the radical treatment of such infections is justified. Other than that, conservative, non-radical treatment that eliminates the infection carried out by a dentist familiar with the case appears to be the lowest-risk option in terms of infectious and bleeding complications."

Waltimo points out that the findings cannot be applied to any other patient groups, especially not to patients suffering from cancer in the region of the head and neck, or the treatment of patients with a heart valve or a prosthetic joint. In such cases, the treatment of the oral foci of infections in good time is always well grounded.

"Based on our results, it seems that radical and extensive procedures to treat oral infections are not necessary before stem cell transplantations. Instead, such treatment can be postponed until after the transplantation," notes Matti Mauramo, LicMed and DDM, a physician specialising in pathology and the principal author of the article.

For the sake of the patient's quality of life and treatment costs, dental infections should be prevented or treated as soon as possible. Antibiotic therapy given when immune defences are impaired appears to make it possible to delay dental treatment by as much as several months after a stem cell transplantation procedure.

The researchers emphasise that the significance of cooperation between physicians and dentists must not be underestimated, neither in terms of the patient's quality of life nor in terms of infectious complications.

A first-of-its-kind study on molecular interactions by biomedical engineers in the University of Minnesota's College of Science and Engineering will make it easier and more efficient for scientists to develop new medicines and other therapies for diseases such as cancer, HIV and autoimmune diseases.

The study resulted in a mathematical framework that simulates the effects of the key parameters that control interactions between molecules that have multiple binding sites, as is the case for many medicines. Researchers plan to use this computational model to develop a web-based app that other researchers can use to speed the development of new therapies for diseases.

The research is published in the Proceedings of the National Academy of Sciences (PNAS), one of the world's most-cited and comprehensive multidisciplinary scientific journals.

"The big advance with this study is that usually researchers use a trial-and-error experimental method in the lab for studying these kinds of molecular interactions, but here we developed a mathematical model where we know the parameters so we can make accurate predictions using a computer," said Casim Sarkar, a University of Minnesota biomedical engineering associate professor and senior author of the study. "This computational model will make research much more efficient and could accelerate the creation of new therapies for many kinds of diseases."

The research team studied three main parameters of molecular interactions--binding strength of each site, rigidity of the linkages between the sites, and the size of the linkage arrays. They looked at how these three parameters can be "dialed up" or "dialed down" to control how molecule chains with two or three binding sites interact with one another. The team then confirmed their model predictions in lab experiments.

"At a fundamental level, many diseases can be traced to a molecule not binding correctly," said Wesley Errington, a University of Minnesota biomedical engineering postdoctoral researcher and lead author of the study. "By understanding how we can manipulate these 'dials' that control molecular behavior, we have developed a new programming language that can be used to predict how molecules will bind."

The need for a mathematical framework to decode this programming language is highlighted by the researchers' finding that, even when the interacting molecule chains have just three binding sites each, there are a total of 78 unique binding configurations, most of which cannot be experimentally observed. By dialing the parameters in this new mathematical model, researchers can quickly understand how these different binding configurations are affected, and tune them for a wide range of biological and medical applications.

"We think we've hit on rules that are fundamental to all molecules, such as proteins, DNA, and medicines, and can be scaled up for more complex interactions," said Errington "It's really a molecular signature that we can use to study and to engineer molecular systems. The sky is the limit with this approach."

Increasing abundance of plastic waste has alarmed the society, but the environmental fate of microplastics has been difficult to trace. A research group led by the University of Jyväskylä used carbon isotope labelling to follow the fate of polyethylene in the food chain. For the surprise of the researchers, plastic carbon was transformed even to beneficial fatty acids, omega-3 and omega-6, by the microbes originating from humic lakes. The research was published in Scientific Reports -series at the end of December 2019.

In the recently published study, Dr. Sami Taipale and his co-workers studied biodegradation of polyethylene, which is one of the most used plastics. Polyethylene was labelled with 13C-isotope, which enables the most sensitive technology for studying the fate of slowly degrading materials.

"We analyzed produced gases and microbial fatty acids using stable isotope mass spectrometry", says Taipale, who just received a 4-year project from Kone Foundation to continue his studies on microplastic degradation.

"We wanted to study whether microbes that have the ability to decompose complex humic compounds would also use recalcitrant microplastic polymers, continues Taipale. -And indeed, microplastic degradation was more pronounced by microbes originating from the humic lakes than from the clear water lakes.

"Fatty acids profiles also helped to identify the bacterial groups that were responsible for the decomposition", says the co-author, professor Marja Tiirola, who leads a new Academy of Finland project for discovering decomposers of recalcitrant materials.

"The lack of labelled material limits the microplastic studies, so we welcome partners to synthesize other labelled plastic types."

Showing direct utilization of polyethylene carbon and its upgrading in the upper food chain is a methodological breakthrough. The method was sensitive enough to show that microplastic carbon was incorporated into essential fatty acids, omega-3 and omega-6, of flagellated eukaryotic species. In the further study, these essential fatty acids supported the growth and became integrated to the cell membranes of herbivorous zooplankton, next level in the aquatic food chain.

Previous studies have suggested that high concentrations of microplastics can inhibit the growth of algae and zooplankton. However, this study showed that growth-inhibition observed in high polyethylene concentrations (30 mg L-1) was fully neutralized by microbial decomposers.

"The plastic surface was covered by microbes, which utilized released chemicals or prevented physical contact to algae and zooplankton", says one of the co-authors professor Jussi Kukkonen specialized in ecotoxicology. Since microbes can cease the potential toxicity of microplastics in aquatic environments, ecorealistic testing should be performed in the presence of natural microbiomes.

(Boston)--Immune checkpoints are surface proteins that cancer cells use to evade immune response. These surface proteins are critical for cancer cell growth and drugs targeting these proteins have revolutionized the management of patients with a wide array of cancers. Finding a mechanism to degrade these immune checkpoints may allow the immune system to kill cancer cells.

Researchers from Boston University School of Medicine (BUSM) have discovered the protein c-Cbl has the ability to degrade checkpoint protein PD-1, a protein found on T cells that helps keep them from attacking other cells in the body. Manipulating c-Cbl's ability to regulate expression of PD-1 may be beneficial in the treatment of certain cancers including melanoma, bladder, kidney, breast and non-small lung cancers.

Cancer cells often increase their expression to "trick" the immune system and avoiding being detected as foreign or harmful and thus avoid being attacked or destroyed. Manipulating c-Cbl's ability to regulate expression of PD-1 may be incredibly beneficial in the treatment of these cancers.

Researchers examined the effect of c-Cbl on immune cells on experimental models lacking one copy of the c-Cbl gene. Tumor cells were implanted in these models and growth of the tumors was compared between models lacking the gene and unmodified models which served as controls. The researchers found that tumor growth was greater in the genetically the modified model.

According to the researchers, it may be possible in the near future to develop therapies that will inhibit tumor growth by activating c-Cbl protein. "While drugs targeting PD-1 are currently available for clinical use and such agents command a global market cap of more than $3 billion, only a small fraction of cancer patients respond to them. This trend suggests a need for agents that work simultaneously on more than one cancer-causing mechanism. Activating c-Cbl will degrade several proteins that contribute to tumor formation allowing the effects of its actions to go above and beyond PD-1 medications alone," explained corresponding author Vipul Chitalia, MD, PhD, associate professor of medicine at BUSM.

These findings appear online in the journal Scientific Reports.

The 170,000-year-old charred remains of starchy plant parts from Border Cave, South Africa provides the earliest direct evidence for the collecting and cooking of carbohydrate-rich rhizomes, a new study reports. The findings suggest that palatable rhizomes from Hypoxis sp.– a genus of small flowering plants – ay have been a reliable and transportable staple food for Middle Stone Age humans at the site and perhaps a familiar source of food for early human populations traveling throughout Africa and beyond. Hunting strategies and animal-based diets of early humans are well recognized and widely studied as the bones and stone tools left behind from these activities are often preserved far better in archaeological sites than the perishable evidence of plant diets. However, plants rich in carbohydrates were almost certainly eaten throughout the long history of our earliest ancestors and likely contributed substantially to ancient nutrition. Some plants called geophytes – onions, potatoes and ginger, for example – store carbohydrates by growing starchy roots beneath the ground. In more modern times, many of these plants have become an important source of food, but because of their ephemeral nature in the archaeological record, it remains unclear when humans first began eating them. Sifting through the ashes from ancient cooking fires from Border Cave in South Africa, Lyn Wadley and colleagues discovered the charred remains of ancient rhizomes roasted up to 170 thousand years ago. According to Wadley et al., the rhizome specimens – likely only preserved because they were burnt – are suggestive of Hypoxis genus plants, which are commonly known as the star lily or the African Potato and found growing throughout southern Africa. Hypoxis rhizomes are highly nutritious carbohydrate-rich and, while edible raw, are far less tough once cooked, the authors say.

Color-changing fibers and mathematical theory combine to disclose the simple rules that govern the strength and stability of commonly used knots, researchers report. The new study addresses a centuries-old mystery - what makes knots work? Fibers tied into knots and tangles remain one of humanity's most ancient and enduring technologies and play a ubiquitous, fundamental role in our daily lives. From ships' sails and shoes to micro-sutures and turbulent quantum liquids, it's well known that some knots are better suited than others for specific purposes - a fact that's given rise to a great variety of knotted structures. It's known that the subtle interaction between topology (how a knot is tied), elasticity and friction give knots their inherent mechanical properties and strength. However, there remains no comprehensive mathematical theory capable of fully explaining how knots "work." Thus, the ability to understand why some knots hold fast while others easily slip currently evades explanation. To address these long-enduring questions, Vishal Patil and colleagues developed an experimental and theoretical analysis that reveals the key rules underlying the mechanical stability of "bend knots," which are commonly used in both sailing and climbing activities. Combining optomechanical experiments using recently developed color-changing photonic fibers, which show stress differences in different parts of a knot and theoretical knot modeling, Patil et al. were able to quantifiably predict the strain distribution in a knotted structure and reveal several key topological factors that determine a knot's stability. According to the authors, the framework could be used to design and explore new classes of knots with specific behaviors.