Konzo is a severe, irreversible neurologic disease that results in paralysis. It occurs after consuming poorly processed cassava — a manioc root and essential crop for DRC and other low-income nations. Poorly processed cassava contains linamarin, a cyanogenic compound. While enzymes with glucosidase activity convert starch to simple sugars, they also break down linamarin, which then releases cyanide into the body.

“Knowing who is more at risk could result in targeted interventions to process cassava better or try to diversify the diet,” said Eric Vilain, M.D., Ph.D., director of the Center for Genetic Medicine Research at Children’s National. “An alternative intervention is to modify the microbiome to increase the level of protection. This is, however, a difficult task which may have unintended consequences and other side effects.”

The exact biological mechanisms underlying konzo disease susceptibility and severity remained poorly understood until now. This is the first study to shed light on the gut microbiome of populations that rely on toxic cassava as their primary food source.

“While the gut microbiome is not the sole cause of disease given that environment and malnourishment play a role, it is a required modulator,” said Matthew S. Bramble, Ph.D., staff scientist at Children’s National. “Simply stated, without gut microbes, linamarin and other cyanogenic glucosides would pose little to no risk to humans.”

To understand the influence of a detrimental subsistence on the gut flora and its relationship to this debilitating multifactorial neurological disease, the researchers compared the gut microbiome profiles in 180 children from the DRC using shotgun metagenomic sequencing. This approach evaluates bacterial diversity and detects the abundance of microbes and microbial genes in various environments.

The samples were collected in Kinshasa, an urban area with diversified diet and without konzo; Masi-Manimba, a rural area with predominant cassava diet and low prevalence of konzo; and Kahemba, a region with predominant cassava diet and high prevalence of konzo.

“This study overcame many challenges of doing research in low-resource settings,” said Desire Tshala-Katumbay, M.D., M.P.H., Ph.D., FANA, co-senior author and expert scientist at Institut National de Recherche Biomédicale in Kinshasa, DRC, and professor of neurology at Oregon Health & Science University. “It will open novel avenues to prevent konzo, a devastating disease for many children in Sub-Saharan Africa.”

For next steps, the researchers will study sibling pairs from konzo-prone regions of Kahemba where only one sibling is affected with the disease.

“Studying siblings will help us control for factors that cannot be controlled otherwise, such as the cassava preparation in the household,” said Neerja Vashist, Ph.D. candidate and research trainee at Children’s National. “In this work, each sample had approximately 5 million DNA reads each, so for our follow-up, we plan to increase that to greater than 40 million reads per sample and the overall study cohort size. This study design will allow us to confirm that the trends we observed hold on a larger scale, while enhancing our ability to comprehensively characterize the gut microbiome.”

Story Source:

Materials provided by Children’s National Hospital. Note: Content may be edited for style and length.

The new precision-guided sterile insect technique, or pgSIT, alters genes linked to male fertility — creating sterile offspring — and female flight in Aedes aegypti, the mosquito species responsible for spreading wide-ranging diseases including dengue fever, chikungunya and Zika.

“pgSIT is a new scalable genetic control system that uses a CRISPR-based approach to engineer deployable mosquitoes that can suppress populations,” said UC San Diego Biological Sciences Professor Omar Akbari. “Males don’t transmit diseases so the idea is that as you release more and more sterile males, you can suppress the population without relying on harmful chemicals and insecticides.”

Details of the new pgSIT are described September 10, 2021, in the journal Nature Communications.

pgSIT differs from “gene drive” systems that could suppress disease vectors by passing desired genetic alterations indefinitely from one generation to the next. Instead, pgSIT uses CRISPR to sterilize male mosquitoes and render female mosquitoes, which spread disease, as flightless. The system is self-limiting and is not predicted to persist or spread in the environment, two important safety features that should enable acceptance for this technology.

Akbari says the envisioned pgSIT system could be implemented by deploying eggs of sterile males and flightless females at target locations where mosquito-borne disease spread is occurring.

“Supported by mathematical models, we empirically demonstrate that released pgSIT males can compete, and suppress and even eliminate mosquito populations,” the researchers note in the Nature Communications paper. “This platform technology could be used in the field, and adapted to many vectors, for controlling wild populations to curtail disease in a safe, confinable and reversible manner.”

Although molecular genetic engineering tools are new, farmers have been sterilizing male insects to protect their crops since at least the 1930s. United States growers in the 1950s began using radiation to sterilize pest species such as the New World Screwworm fly, which is known to destroy livestock. Similar radiation-based methods continue today, along with the use of insecticides. pgSIT is designed as a much more precise and scalable technology since it uses CRISPR — not radiation or chemicals — to alter key mosquito genes. The system is based on a method that was announced by UC San Diego in 2019 by Akbari and his colleagues in the fruit fly Drosophila.

As envisioned, Akbari says pgSIT eggs can be shipped to a location threatened by mosquito-borne disease or developed at an on-site facility that could produce the eggs for nearby deployment. Once the pgSIT eggs are released in the wild, typically at a peak rate of 100-200 pgSIT eggs per Aedes aegypti adult, sterile pgSIT males will emerge and eventually mate with females, driving down the wild population as needed.

Beyond Aedes aegypti, the researchers believe the pgSIT technology could be directed to other species that spread disease.

“… This study suggests pgSIT may be an efficient technology for mosquito population control and the first example of one suited for real-world release,” the researchers say. “Going forward, pgSIT may provide an efficient, safe, scalable, and environmentally friendly alternative next-generation technology for wild population control of mosquitoes resulting in wide-scale prevention of human disease transmission.”

The complete list of paper co-authors: Ming Li, Ting Yang, Michelle Bui, Stephanie Gamez, Tyler Wise, Nikolay Kandul, Junru Liu, Lenissa Alcantara, Haena Lee, Jyotheeswara Edula, Robyn Raban, Yinpeng Zhan, Yijin Wang, Nick DeBeaubien, Jieyan Chen, Hector Sanchez C., Jared Bennett, Igor Antoshechkin, Craig Montell, John Marshall and Omar Akbari.

Funding for the research was provided by a DARPA Safe Genes Program Grant (HR0011-17-2-0047); the National Institutes of Health (R01AI151004 and R56-AI153334); the U.S. Army Research Office (cooperative agreement W911NF-19-2-0026 for the Institute for Collaborative Biotechnologies); and the Innovative Genomics Institute.

The brachiopod Discinisca tenuis lives on the west coast of Africa.I It has a mineral-rich shell that protects it from harmful environmental influences. Bathing the shell in water leads to a structural change in the material: The flat, hard shell becomes so flexible that it can even be folded up without breaking. With the help of the Swiss Light Source SLS, the researchers have deciphered exactly how this transformation takes place.

The phenomenon was discovered by chance a few years ago by Fabio Nudelman, a materials chemist currently at the School of Chemistry, University of Edinburgh in Scotland. Maggie Cusack, who was recently appointed president of Munster Technological University in Ireland, had provided Nudelman with shells of the brachiopod Discinisca tenuis, which originally came from Namibia. When he wanted to wash the hard object, it suddenly became soft and flexible in contact with water. The shell had absorbed liquid and thereby changed its structure. The process was reversible: When the shell dried, it became hard and brittle again.

Together with colleagues from six countries, Nudelman set out to discover what exactly takes place during this unexpected transformation. “In its composition, the shell resembles bone,” he explains. “But bone doesn’t change its structure when it gets wet.” The same goes for clams: If the animals need to adapt the properties of their shell to different environmental conditions, they normally have to rework the material in a lengthy and energetically costly process, by resorbing and redistributing minerals. It doesn’t work simply through the absorption of water.

Hybrid material with a special trick

It was so-called cryo-tomography, performed at the Swiss Light Source SLS, that “opened the door to reveal the secret,” says Johannes Ihli, a PSI researcher at SLS. With this technique, the researchers examined the material as if under a very high-resolution microscope, and in fact at extremely low temperatures. “At room temperature it would not have been possible, since the high-energy X-ray light would immediately alter the sensitive shell structure,” Ihli explains.

The brachiopod’s shell, which is no more than half a millimetre thick, consists of a hybrid material: mainly inorganic mineral in which organic polymers made from proteins and sugars are embedded. Bones, clam shells, and teeth are structured in a similar way out of a mixture of organic and inorganic material. The mineral that constitutes the main component of the shell is a type of fluoroapatite — similar to the material that makes up the enamel of our teeth.

Tiny nanocrystals of this material are arranged in layers. Nudelman compares it to brick walls: “In this analogy, the bricks are the nanocrystals, and the mortar between the bricks consists of organic molecules such as chitin and proteins.” As the researchers observed, this “mortar” can absorb large amounts of water, causing it to swell up. Through the storage of water, it changes its structure: It becomes soft, and the bricks become movable with respect to each other. “Then water acts like a lubricant between the individual nanocrystals,” Ihli explains. “The crystals can then slip against each other.” Through this movement, the shell becomes flexible. The researchers found a network of pores in the shell that was especially effective in guiding water inside and rapidly distributing it throughout the material.

Evolutionary advantage

Discinisca tenuis lives in large clusters in tidal zones on the coast where, depending on the tide, the animals are exposed to strong waves or calm waters. The researchers speculate that it is probably advantageous if the animals can quickly adapt the softness or hardness of their shell to the respective situation: “This could prevent damage to the shell and thus be a key to the animals’ survival,” they write in the study. The phenomenon may even be more widespread than suspected: “We don’t know how many other animal species there might be that have this kind of property,” says Nudelman.

Aside from biology and evolution, the newly gained insights are also of interest for materials science: The development of a hard, brittle material whose stiffness can be controlled could hold promise for many applications. Sports clothing or helmets, for example, might be able to flexibly adapt to movements and always offer the protection required depending on the impact. Harnessing this phenomenon could also prove useful in developing bone-replacement materials.

Story Source:

Materials provided by Paul Scherrer Institute. Original written by Brigitte Osterath. Note: Content may be edited for style and length.

Type 2 diabetes is one the most common lifestyle diseases worldwide, and its onset is usually preceded by impaired insulin sensitivity, i.e. insulin resistance. This refers to a state in which the body does not react to insulin normally, and the blood glucose levels rise.

Lifestyle has a strong impact on insulin resistance and the development of type 2 diabetes, and regular physical activity is known to have an important role in the prevention of these issues. However, so far, little is known about the impact of sedentary behaviour, breaks in sitting, and standing on insulin resistance.

In a study of Turku PET Centre and UKK institute, the researchers investigated the associations between insulin resistance and sedentary behaviour, physical activity and fitness in inactive working-age adults with an increased risk of developing type 2 diabetes and cardiovascular diseases. In the study published in Journal of Science and Medicine in Sport, the researchers observed that standing is associated with better insulin sensitivity independently of the amount of daily physical activity or sitting time, fitness level, or overweight.

“This association has not been shown before. These findings further encourage replacing a part of daily sitting time with standing, especially if physical activity recommendations are not met,” says Doctoral Candidate Taru Garthwaite from the University of Turku.

Body Composition Strongly Associated with Insulin Sensitivity

The study also emphasises the importance of healthy body composition on metabolic health. The results show that increased body fat percentage was a more important factor in terms of insulin sensitivity than physical activity, fitness, or the amount of time spent sitting. Standing, on the other hand, was associated with insulin sensitivity independently, irrespective of body composition.

“Regular exercise is well known to be beneficial for health. It seems that physical activity, fitness, and sedentary behaviour are also connected to insulin metabolism, but indirectly, through their effect on body composition,” Taru Garthwaite explains.

Causal effects cannot yet be predicted based on this study, but according to Garthwaite, the results suggest that increasing daily standing time may help in prevention of lifestyle diseases if physical activity recommendations are not met.

Next, the researchers aim to investigate how changes in daily activity and sedentariness impact cardiovascular and metabolic disease risk factors and metabolism by comparing two groups in an intervention study of a longer duration.

“Our aim is to study if reducing daily sitting time by an hour has an impact on energy metabolism and fat accumulation in liver and the whole body, for example, in addition to insulin sensitivity and blood sugar regulation,” says Garthwaite.

Story Source:

Materials provided by University of Turku. Note: Content may be edited for style and length.

Both half reactions of water electrolysis — hydrogen and oxygen evolution — are unfortunately slow and require a lot of power. Catalytically effective electrodes, particularly those based on precious metals, can accelerate the electrochemical processes and improve their energy efficiency. However, their large-scale use is impeded by high costs, limited abundance, and low stability. Alternatives based on abundant, inexpensive metals usually do not work satisfactorily for both half reactions.

A team led by Shuyan Gao (Henan Normal University, China) and Xiong Wen (David) Lou (Nanyang Technological University, Singapore) has now developed a novel, inexpensive, multifunctional electrode material based on cobalt (Co) and nickel (Ni) for efficient electrocatalytic hydrogen production. To make the material, nanospheres made of cobalt-nickel-glycerate are subjected to combined hydrothermal sulfidation and gas-phase phosphorization. This forms objects called yolk-shell nanoparticles made of phosphorus-doped cobalt-nickel-sulfide (P-CoNi₂S₄). These are tiny spheres with a compact core and a porous shell with a space in between — much like an egg whose yolk is surrounded by the egg white and so does not touch the shell.

Phosphorus doping increases the proportion of Ni³⁺ relative to Ni²⁺ in the hollow particles and allows for faster charge transfer, causing the electrocatalytic reactions to run faster. The material can be used as either an anode or a cathode, and demonstrates high activity and stability in the production of hydrogen and oxygen in the electrolysis of water.

To reduce the overall voltage of the electrolysis cell, hybrid electrolysis concepts are also being researched. For example, instead of being coupled to the production of oxygen, hydrogen production could be coupled to the oxidation of urea, which requires significantly less energy. Sources of urea could include waste streams from industrial syntheses as well as sanitary sewage. The new nanoparticles are also very useful for this half reaction.

Both water and urea electrolysis require comparatively low cell voltage (1.544 V or 1.402 V, respectively, at 10 mA cm^-2 over 100 hours). This makes the new bimetallic yolk-shell particles superior to most known nickel-sulfide- and even precious-metal-based electrocatalysts. They present a promising approach for electrochemical hydrogen production, as well as for the treatment of urea-containing wastewater.

Story Source:

Materials provided by Wiley. Note: Content may be edited for style and length.

“Metasurfaces are ultrathin and compact optical elements that can be used to manipulate the amplitude, phase and polarization of light,” said research team leader Jiafang Li from the Beijing Institute of Technology in China. “Although most metasurfaces are static and passive, we created metasurfaces that mechanically deform in response to electrostatic forces.”

In The Optical Society (OSA) journal Optics Express, the researchers describe how they created the new metasurfaces using nanoscale techniques inspired by kirigami, a variation of origami that includes cutting as well as folding. This allowed them to create tinyunits that transform from 2D designs into 3D structures when a voltage is applied.

“We were able to create a dynamic holographic display using our reconfigurable metasurface,” said Li. “These optical elements could lead to new types of devices with optical multitasking and rewritable functionalities. They might also be used in real-time 3D displays and high-resolution projectors, for example.”

Spiral patterns that transform from 2D to 3D

To create the new metasurfaces, the researchers designed a repeating 2D pattern of two combined spirals that are etched into a gold nanofilm and suspended above silicon dioxide pillars. The units are arranged in a square lattice with just two microns of space between each one. When a voltage is applied, the spirals deform due to electrostatic forces. This transformation, which is reversable and repeatable, can be used to dynamically modulate the optical properties of the metasurface.

The researchers used their new approach to make two types of metasurfaces for controlling light on a pixel-by-pixel basis. One metasurface used the same voltage to deform each unit but featured spirals with structural patterns that varied to create different deformation heights. The second metasurface used different voltages applied to each unit to achieve different deformation heights for units with identical structural patterns.

As a proof-of-concept demonstration, the researchers used these metasurfaces to demonstrate beam control and to make a holographic display. “We were able to reconstruct images from the metasurface by merely controlling the voltage bias, proving the feasibility of our scheme for effective light modulation,” said Li.

The researchers plan to explore strategies that can be used to achieve pixelated voltage control, such as the multi-line addressing method used to drive several rows simultaneously in commercial OLED displays. To make the technology more practical, they are also working to improve the signal-to-noise ratio and modulation quality of the reconfiguration system.

Story Source:

Materials provided by The Optical Society. Note: Content may be edited for style and length.