Category Archives: medicine

Nanoparticle detection with whispers and bubbles

Caption: A magnified photograph of a glass Whispering Gallery Resonator. The bubble is extremely small, less than the width of a human hair. Credit: OIST (Okinawa Institute of Science and Technology Graduate University)

It was the reference to a whispering gallery which attracted my attention; a July 11, 2018 news item on Nanowerk is where I found it,

Technology created by researchers at the Okinawa Institute of Science and Technology Graduate University (OIST) [Japan] is literally shedding light on some of the smallest particles to detect their presence – and it’s made from tiny glass bubbles.

The technology has its roots in a peculiar physical phenomenon known as the “whispering gallery,” described by physicist Lord Rayleigh (John William Strutt) in 1878 and named after an acoustic effect inside the dome of St Paul’s Cathedral in London. Whispers made at one side of the circular gallery could be heard clearly at the opposite side. It happens because sound waves travel along the walls of the dome to the other side, and this effect can be replicated by light in a tiny glass sphere just a hair’s breadth wide called a Whispering Gallery Resonator (WGR).

A July 11, 2018 OIST press release by Andrew Scott (also on EurekAlert), provides more details,

When light is shined into the sphere, it bounces around and around the inner surface, creating an optical carousel. Photons bouncing along the interior of the tiny sphere can end up travelling for long distances, sometimes as far as 100 meters. But each time a photon bounces off the sphere’s surface, a small amount of light escapes. This leaking light creates a sort of aura around the sphere, known as an evanescent light field. When nanoparticles come within range of this field, they distort its wavelength, effectively changing its color. Monitoring these color changes allows scientists to use the WGRs as a sensor; previous research groups have used them to detect individual virus particles in solution, for example. But at OIST’s Light-Matter Interactions Unit, scientists saw they could improve on previous work and create even more sensitive designs. The study is published in Optica.

Today, Dr. Jonathan Ward is using WGRs to detect minute particles more efficiently than ever before. The WGRs they have made are hollow glass bubbles rather than balls, explains Dr. Ward. “We heated a small glass tube with a laser and had air blown down it – it’s a lot like traditional glass blowing”. Blowing the air down the heated glass tube creates a spherical chamber that can support the sensitive light field. The most noticeable difference between a blown glass ornament and these precision instruments is the scale: the glass bubbles can be as small as 100 microns- a fraction of a millimeter in width. Their size makes them fragile to handle, but also malleable.

Working from theoretical models, Dr. Ward showed that they could increase the size of the light field by using a thin spherical shell (a bubble, in other words) instead of a solid sphere. A bigger field would increase the range in which particles can be detected, increasing the efficacy of the sensor. “We knew we had the techniques and the materials to fabricate the resonator”, said Dr. Ward. “Next we had to demonstrate that it could outperform the current types used for particle detection”.

To prove their concept, the team came up with a relatively simple test. The new bubble design was filled with a liquid solution containing tiny particles of polystyrene, and light was shined along a glass filament to generate a light field in its liquid interior. As particles passed within range of the light field, they produced noticeable shifts in the wavelength that were much more pronounced than those seen with a standard spherical WGR.

With a more effective tool now at their disposal, the next challenge for the team is to find applications for it. Learning what changes different materials make to the light field would allow Dr Ward to identify and target them, and even control their activity.

Despite their fragility, these new versions of WGRs are easy to manufacture and can be safely transported in custom made cases. That means these sensors could be used in a wide verity of fields, such as testing for toxic molecules in water to detect pollution, or detecting blood borne viruses in extremely rural areas where healthcare may be limited.

For Dr. Ward however, there’s always room from improvement: “We’re always pushing to get even more sensitivity and find the smallest particle this sensor can detect. We want to push our detection to the physical limits.”

Here’s a link to and a citation for the paper,

Nanoparticle sensing beyond evanescent field interaction with a quasi-droplet microcavity by Jonathan M. Ward, Yong Yang, Fuchuan Lei, Xiao-Chong Yu, Yun-Feng Xiao, and Síle Nic Chormaic. Optica Vol. 5, Issue 6, pp. 674-677 (2018) https://doi.org/10.1364/OPTICA.5.000674

This paper is open access.

Nanotechnology tackles nail fungus

I never thought I’d be highlighting nail fungus here but sometimes life throws you a twist and a turn. Researchers at George Washington University (GWU; Washington, DC, US) announce their latest nanotechnology-enabled approach to nail fungus in a July 11, 2018 news item on ScienceDaily,

Onychomycosis, a nail fungus that causes nail disfigurement, pain, and increased risk of soft tissue infection, impacts millions of people worldwide. There are several topical antifungal treatments currently available; however, treatment failure remains high due to a number of factors.

The most recent treatment, a broad spectrum triazole called efinaconazole, is designed to improve nail penetration. It boasts the highest cure rates among other topical antifungals, but the cost for a bottle is more than $600, and full treatment calls for multiple bottles.

A July 11, 2018 GWU news release (also on EurekAlert), which originated the news item, provides more details,

Adam Friedman, MD (link is external), professor of dermatology at the George Washington University School of Medicine and Health Sciences, and his team investigated the use of nanotechnology to improve efinaconazole treatment and make it more cost effective. They observed that when nitric oxide-releasing nanoparticles are combined with the efinaconazole, it achieves the same antifungal effects, but at a fraction of the amount of the medication alone needed to impart the same effect.

“Nanotechnology is being studied and employed in many areas of medicine and surgery to better deliver established imaging and therapeutic agents to ultimately improve patient outcomes,” said Friedman. “A quickly emerging roadblock in patient care is, unfortunately, access to medications due to rising cost and poor insurance coverage.”

The study, published in the Journal of Drugs in Dermatology, found that, when combined, the nanoparticles and the medication are more effective than both alone, opening the door to potentially better and more tolerable treatment regimens. An additional benefit is the ability of nanoparticles to access infections in difficult to reach locations, as penetration and retaining activity across the nail plate is a common impediment for many antifungals.

“What we found was that we could impart the same antifungal activity at the highest concentrations tested of either alone by combining them at a fraction of these concentrations,” Friedman explained. “The impact of this combo, which we visualized using electron microscopy as compared to either product alone, highlighted their synergistic damaging effects at concentrations that would be completely safe to human cells.”

Given these results, the authors note that it is worth further researching the synergy of nitric oxide-releasing nanoparticles and efinaconazole against onychomycosis to determine the efficacy of the treatment in a clinical setting.

Here’s a link to and a citation for the paper,

Nitric Oxide Releasing Nanoparticles as a Strategy to Improve Current Onychomycosis Treatments by Caroline B. Costa-Orlandi, Breanne Mordorski, Ludmila M. Baltazar, Maria José S. Mendes-Giannini, Joel M. Friedman, Joshua D. Nosanchuk, Adam J. Friedman. Journal of Drugs in Dermatology, 2018; 17 (7): 717-720 July 2018 Copyright © 2018  http://jddonline.com/articles/dermatology/S1545961618P0717X/1

This paper is behind a paywall.

Cellulose and natural nanofibres

Specifically, the researchers are describing these as cellulose nanofibrils. On the left of the image, the seed look mores like an egg waiting to be fried for breakfast but the image on the right is definitely fibrous-looking,

Through contact with water, the seed of Neopallasia pectinata from the family of composite plants forms a slimy sheath. The white cellulose fibres anchor it to the seed surface. Courtesy: Kiel University (CAU)

A December 18, 2018 news item on Nanowerk describes the research into seeds and cellulose,

The seeds of some plants such as basil, watercress or plantain form a mucous envelope as soon as they come into contact with water. This cover consists of cellulose in particular, which is an important structural component of the primary cell wall of green plants, and swelling pectins, plant polysaccharides.

In order to be able to investigate its physical properties, a research team from the Zoological Institute at Kiel University (CAU) used a special drying method, which gently removes the water from the cellulosic mucous sheath. The team discovered that this method can produce extremely strong nanofibres from natural cellulose. In future, they could be especially interesting for applications in biomedicine.

A December 18, 2018 Kiel University press release, which originated the news item, offers further details about the work,

Thanks to their slippery mucous sheath, seeds can slide through the digestive tract of birds undigested. They are excreted unharmed, and can be dispersed in this way. It is presumed that the mucous layer provides protection. “In order to find out more about the function of the mucilage, we first wanted to study the structure and the physical properties of this seed envelope material,” said Zoology Professor Stanislav N. Gorb, head of the “Functional Morphology and Biomechanics” working group at the CAU. In doing so they discovered that its properties depend on the alignment of the fibres that anchor them to the seed surface

Diverse properties: From slippery to sticky

The pectins in the shell of the seeds can absorb a large quantity of water, and thus form a gel-like capsule around the seed in a few minutes. It is anchored firmly to the surface of the seed by fine cellulose fibres with a diameter of just up to 100 nanometres, similar to the microscopic adhesive elements on the surface of highly-adhesive gecko feet. So in a sense, the fibres form the stabilising backbone of the mucous sheath.

The properties of the mucous change, depending on the water concentration. “The mucous actually makes the seeds very slippery. However, if we reduce the water content, it becomes sticky and begins to stick,” said Stanislav Gorb, summarising a result from previous studies together with Dr Agnieszka Kreitschitz. The adhesive strength is also increased by the forces acting between the individual vertically-arranged nanofibres of the seed and the adhesive surface.

Specially dried

In order to be able to investigate the mucous sheath under a scanning electron microscope, the Kiel research team used a particularly gentle method, so-called critical-point drying (CPD). They dehydrated the mucous sheath of various seeds step-by-step with liquid carbon dioxide – instead of the normal method using ethanol. The advantage of this method is that evaporation of liquid carbon dioxide can be controlled under certain pressure and temperature conditions, without surface tension developing within the sheath. As a result, the research team was able to precisely remove water from the mucous, without drying out the surface of the sheath and thereby destroying the original cell structure. Through the highly-precise drying, the structural arrangement of the individual cellulose fibres remained intact.

Almost as strongly-adhesive as carbon nanotubes

The research team tested the dried cellulose fibres regarding their friction and adhesion properties, and compared them with those of synthetically-produced carbon nanotubes. Due to their outstanding properties, such as their tensile strength, electrical conductivity or their friction, these microscopic structures are interesting for numerous industrial applications of the future.

“Our tests showed that the frictional and adhesive forces of the cellulose fibres are almost as strong as with vertically-arranged carbon nanotubes,” said Dr Clemens Schaber, first author of the study. The structural dimensions of the cellulose nanofibers are similar to the vertically aligned carbon nanotubes. Through the special drying method, they can also vary the adhesive strength in a targeted manner. In Gorb’s working group, the zoologist and biomechanic examines the functioning of biological nanofibres, and the potential to imitate them with technical means. “As a natural raw material, cellulose fibres have distinct advantages over carbon nanotubes, whose health effects have not yet been fully investigated,” continued Schaber. Nanocellulose is primarily found in biodegradable polymer composites, which are used in biomedicine, cosmetics or the food industry.

Here’s a link to and a citation for the paper,

Friction-Active Surfaces Based on Free-Standing Anchored Cellulose Nanofibrils by Clemens F. Schaber, Agnieszka Kreitschitz, and Stanislav N. Gorb. ACS Appl. Mater. Interfaces, 2018, 10 (43), pp 37566–37574 DOI: 10.1021/acsami.8b05972 Publication Date (Web): September 19, 2018

Copyright © 2018 American Chemical Society

This paper is behind a paywall.

Terahertz imagers at your fingertips

It seems to me that I stumbled across quite a few carbon nanotube (CNT) stories in 2018. This one comes courtesy of Japan (from a June 28, 2018 news item on Nanowerk),

Researchers at Tokyo Tech have developed flexible terahertz imagers based on chemically “tunable” carbon nanotube materials. The findings expand the scope of terahertz applications to include wrap-around, wearable technologies as well as large-area photonic devices.

Here’s a peek at an imager,

Figure 1. The CNT-based flexible THz imager (a) Resting on a fingertip, the CNT THz imager can easily wrap around curved surfaces. (b) Just by inserting and rotating a flexible THz imager attached to the fingertip, damage to a pipe was clearly detected. Courtesy Tokyo Tech

A June 28, 2018 Tokyo Tech Institute press release (also on Eurekalert), which originated the news item, provides more detail,

Carbon nanotubes (CNTs) are beginning to take the electronics world by storm, and now their use in terahertz (THz) technologies has taken a big step forward.

Due to their excellent conductivity and unique physical properties, CNTs are an attractive option for next-generation electronic devices. One of the most promising developments is their application in THz devices. Increasingly, THz imagers are emerging as a safe and viable alternative to conventional imaging systems across a wide range of applications, from airport security, food inspection and art authentication to medical and environmental sensing technologies.

The demand for THz detectors that can deliver real-time imaging for a broad range of industrial applications has spurred research into low-cost, flexible THz imaging systems. Yukio Kawano of the Laboratory for Future Interdisciplinary Research of Science and Technology, Tokyo Tech, is a world-renowned expert in this field. In 2016, for example, he announced the development of wearable terahertz technologies based on multiarrayed carbon nanotubes.

Kawano and his team have since been investigating THz detection performance for various types of CNT materials, in recognition of the fact that there is plenty of room for improvement to meet the needs of industrial-scale applications.

Now, they report the development of flexible THz imagers for CNT films that can be fine-tuned to maximize THz detector performance.

Publishing their findings in ACS Applied Nano Materials, the new THz imagers are based on chemically adjustable semiconducting CNT films.

By making use of a technology known as ionic liquid gating1, the researchers demonstrated that they could obtain a high degree of control over key factors related to THz detector performance for a CNT film with a thickness of 30 micrometers. This level of thickness was important to ensure that the imagers would maintain their free-standing shape and flexibility, as shown in Figure 1 [see above].

“Additionally,” the team says, “we developed gate-free Fermi-level2 tuning based on variable-concentration dopant solutions and fabricated a Fermi-level-tuned p-n junction3 CNT THz imager.” In experiments using this new type of imager, the researchers achieved successful visualization of a metal paper clip inside a standard envelope (see Figure 2.)

Non-contact, non-destructive visualization

Figure 2. Non-contact, non-destructive visualization

The CNT THz imager enabled clear, non-destructive visualization of a metal paper clip inside an envelope.

The bendability of the new THz imager and the possibility of even further fine-tuning will expand the range of CNT-based devices that could be developed in the near future.

Moreover, low-cost fabrication methods such as inkjet coating could make large-area THz imaging devices more readily available.

1 Ionic liquid gating

A technique used to modulate a material’s charge carrier properties.

2 Fermi level

A measure of the electrochemical potential for electrons, which is important for determining the electrical and thermal properties of solids. The term is named after the Italian–American physicist Enrico Fermi.

3 p-n junction

Refers to the interface between positive (p-type) and negative (n-type) semiconducting materials. These junctions form the basis of semiconductor electronic devices.

Here’s a link to and a citation for the paper,

Fermi-Level-Controlled Semiconducting-Separated Carbon Nanotube Films for Flexible Terahertz Imagers by Daichi Suzuki, Yuki Ochiai, Yota Nakagawa, Yuki Kuwahara, Takeshi Saito, and Yukio Kawano. ACS Appl. Nano Mater., 2018, 1 (6), pp 2469–2475 DOI: 10.1021/acsanm.8b00421 Publication Date (Web): June 6, 2018

Copyright © 2018 American Chemical Society

This paper is behind a paywall.

Call for abstracts: Seventh annual conference on governance of emerging technologies & science (GETS)

The conference itself will be held from May 22 – 24, 2019 at Arizona State University (ASU) and the deadline for abstracts is January 31, 2019. Here’s the news straight from the January 8, 2019 email announcement,

The Seventh Annual Conference on Governance of Emerging Technologies & Science (GETS)

May 22-24, 2019 / ASU / Sandra Day O’Connor College of Law
111 E. Taylor St., Phoenix, AZ
 
The conference will consist of plenary and session presentations and discussions on regulatory, governance, legal, policy, social and ethical aspects of emerging technologies, including nanotechnology, synthetic biology, gene editing, biotechnology, genomics, personalized medicine, digital health, human enhancement, artificial intelligence, virtual reality, internet of things (IoT), blockchain and much, much more!
 
Submit Your Abstract Here: 2019 Abstract
or
Conference Website
 
Call for abstracts:
 
The co-sponsors invite submission of abstracts for proposed presentations. Submitters of abstracts need not provide a written paper, although provision will be made for posting and possible post-conference publication of papers for those who are interested. 
Abstracts are invited for any aspect or topic relating to the governance of emerging technologies, including any of the technologies listed above.
 
·         Abstracts should not exceed 500 words and must contain your name and email address.
·         Abstracts must be submitted by January 31, 2019 to be considered. 
·         The sponsors will pay for the conference registration (including all conference meals and events) for one presenter for each accepted abstract. In addition, we will have limited funds available for travel subsidies (application included in submission form).
For more informationcontact our Executive Director Josh Abbott at Josh.Abbott@asu.edu.

Good luck on your submission!

Neurons and graphene carpets

I don’t entirely grasp the carpet analogy. Actually, I have no why they used a carpet analogy but here’s the June 12, 2018 ScienceDaily news item about the research,

A work led by SISSA [Scuola Internazionale Superiore di Studi Avanzati] and published on Nature Nanotechnology reports for the first time experimentally the phenomenon of ion ‘trapping’ by graphene carpets and its effect on the communication between neurons. The researchers have observed an increase in the activity of nerve cells grown on a single layer of graphene. Combining theoretical and experimental approaches they have shown that the phenomenon is due to the ability of the material to ‘trap’ several ions present in the surrounding environment on its surface, modulating its composition. Graphene is the thinnest bi-dimensional material available today, characterised by incredible properties of conductivity, flexibility and transparency. Although there are great expectations for its applications in the biomedical field, only very few works have analysed its interactions with neuronal tissue.

A June 12, 2018 SISSA press release (also on EurekAlert), which originated the news item, provides more detail,

A study conducted by SISSA – Scuola Internazionale Superiore di Studi Avanzati, in association with the University of Antwerp (Belgium), the University of Trieste and the Institute of Science and Technology of Barcelona (Spain), has analysed the behaviour of neurons grown on a single layer of graphene, observing a strengthening in their activity. Through theoretical and experimental approaches the researchers have shown that such behaviour is due to reduced ion mobility, in particular of potassium, to the neuron-graphene interface. This phenomenon is commonly called ‘ion trapping’, already known at theoretical level, but observed experimentally for the first time only now. “It is as if graphene behaves as an ultra-thin magnet on whose surface some of the potassium ions present in the extra cellular solution between the cells and the graphene remain trapped. It is this small variation that determines the increase in neuronal excitability” comments Denis Scaini, researcher at SISSA who has led the research alongside Laura Ballerini.

The study has also shown that this strengthening occurs when the graphene itself is supported by an insulator, like glass, or suspended in solution, while it disappears when lying on a conductor. “Graphene is a highly conductive material which could potentially be used to coat any surface. Understanding how its behaviour varies according to the substratum on which it is laid is essential for its future applications, above all in the neurological field” continues Scaini, “considering the unique properties of graphene it is natural to think for example about the development of innovative electrodes of cerebral stimulation or visual devices”.

It is a study with a double outcome. Laura Ballerini comments as follows: “This ‘ion trap’ effect was described only in theory. Studying the impact of the ‘technology of materials’ on biological systems, we have documented a mechanism to regulate membrane excitability, but at the same time we have also experimentally described a property of the material through the biology of neurons.”

Dexter Johnson in a June 13, 2018 posting, on his Nanoclast blog (on the IEEE [Institute of Electrical and Electronics Engineers] website), provides more context for the work (Note: Links have been removed),

While graphene has been tapped to deliver on everything from electronics to optoelectronics, it’s a bit harder to picture how it may offer a key tool for addressing neurological damage and disorders. But that’s exactly what researchers have been looking at lately because of the wonder material’s conductivity and transparency.

In the most recent development, a team from Europe has offered a deeper understanding of how graphene can be combined with neurological tissue and, in so doing, may have not only given us an additional tool for neurological medicine, but also provided a tool for gaining insights into other biological processes.

“The results demonstrate that, depending on how the interface with [single-layer graphene] is engineered, the material may tune neuronal activities by altering the ion mobility, in particular potassium, at the cell/substrate interface,” said Laura Ballerini, a researcher in neurons and nanomaterials at SISSA.

Ballerini provided some context for this most recent development by explaining that graphene-based nanomaterials have come to represent potential tools in neurology and neurosurgery.

“These materials are increasingly engineered as components of a variety of applications such as biosensors, interfaces, or drug-delivery platforms,” said Ballerini. “In particular, in neural electrode or interfaces, a precise requirement is the stable device/neuronal electrical coupling, which requires governing the interactions between the electrode surface and the cell membrane.”

This neuro-electrode hybrid is at the core of numerous studies, she explained, and graphene, thanks to its electrical properties, transparency, and flexibility represents an ideal material candidate.

In all of this work, the real challenge has been to investigate the ability of a single atomic layer to tune neuronal excitability and to demonstrate unequivocally that graphene selectively modifies membrane-associated neuronal functions.

I encourage you to read Dexter’s posting as it clarifies the work described in the SISSA press release for those of us (me) who may fail to grasp the implications.

Here’s a link to and a citation for the paper,

Single-layer graphene modulates neuronal communication and augments membrane ion currents by Niccolò Paolo Pampaloni, Martin Lottner, Michele Giugliano, Alessia Matruglio, Francesco D’Amico, Maurizio Prato, Josè Antonio Garrido, Laura Ballerini, & Denis Scaini. Nature Nanotechnology (2018) DOI: https://doi.org/10.1038/s41565-018-0163-6 Published online June 13, 2018

This paper is behind a paywall.

All this brings to mind a prediction made about the Graphene Flagship and the Human Brain Project shortly after the European Commission announced in January 2013 that each project had won funding of 1B Euros to be paid out over a period of 10 years. The prediction was that scientists would work on graphene/human brain research.

The secret lives of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-Cas (CRISPR-associated) proteins

This research isn’t quite as exciting as the title promises but it is important as it attempts to answer some fundamental questions about Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR-Associated (Cas).proteins. From a June 13, 2018 news item on phys.org,

Recently published research from the University of Georgia and UConn Health [University of Connecticu Health Center] provides new insight about the basic biological mechanisms of the RNA-based viral immune system known as CRISPR-Cas.

CRISPR-Cas, short for Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated, is a defense mechanism that has evolved in bacteria and archaea that these single celled organisms use to ward off attacks from viruses and other invaders. When a bacterium is attacked by a virus, it makes a record of the virus’s DNA by chopping it up into pieces and incorporating a small segment of the invader’s DNA into its own genome. It then uses this DNA to make RNAs that bind with a bacterial protein that then kills the viral DNA.

The system has been studied worldwide in hopes that it can be used to edit genes that predispose humans to countless diseases, such as diabetes and cancer. However, to reach this end goal, scientists must gain further understanding of the basic biological process that leads to successful immunity against the invading virus.

A June 12, 2018 University of Georgia news release by Jessica Luton and Jessica McBride, which originated the news item, provides more detail,

Distinguished Research Professor of Biochemistry and Molecular Biology in UGA’s Franklin College of Arts and Sciences and principal investigator for the project Michael Terns and UGA postdoctoral fellow Masami Shiimori collaborated with Brenton Graveley and Sandra Garrett at UConn Health to sequence millions of genomes to learn more about the process. Graveley is professor and chair of the Department of Genetics and Genome Sciences and associate director of the Institute for Systems Genomics at UConn Health, and Garrett is a postdoctoral fellow in his laboratory.

“This research is more fundamental and basic than studies that are trying to determine how to use CRISPR for therapeutic or biomedical application,” said Terns. “Our study is about the unique first step in the process, known as adaptation, where fragments of DNA are recognized and integrated into the host genome and provide immunity for future generations.”

Previously, researchers did not understand how the cell recognized the virus as an invader, nor which bacterial proteins were necessary for successful integration and immunity.

“In this project we were able to determine how the bacterial immune system creates a molecular memory to remove harmful viral DNA sequences and how this is passed down to the bacterial progeny,” said Graveley.

By looking at patterns in the data, the researchers discovered several new findings about how two previously poorly characterized Cas4 proteins function in tandem with Cas1 and Cas2 proteins found in all CRISPR-Cas systems.

In this initial adaptation phase, one of two different Cas4 proteins recognizes a signaling placeholder in the sequence that occurs adjacent to the snippet of DNA that is excised.

When the Cas1 and Cas2 proteins are present in the cell with either of two Cas4 protein nucleases, Cas4-1 and Cas4-2, they act like the generals of this army-based immune system, communicating uniform sized clipped DNA fragments, directions on where to go next and ultimately instructions that destroy the lethal DNA fragment.

In order for a cell to successfully recognize and excise strands of DNA, incorporate them into its own genome and achieve immunity, the Cas4 proteins must be present in conjunction with the Cas1 and Cas2 proteins.

“Cas4 is present in many CRISPR-Cas systems, but the roles of the proteins were mysterious,” said Terns. “In our system, there are two Cas4 proteins that are essential for governing this process so that functional RNAs are made and immunity is conferred”

To achieve these findings, the research team from the University of Georgia created strains of archaeal organisms with key genetic deletions.

Hundreds of millions of DNA fragments captured in the CRISPR loci were sent to the Graveley lab in Farmington, Connecticut, where they were sequenced with the Illumina MiSeq system. The researchers then used supercomputing for bioinformatics analysis and data interpretation.

While there is still much to learn about the biological mechanisms involved in CRISPR-Cas systems, this research tells scientists more about the way these proteins work together to save the cell and achieve immunity.

“The data are so clear. We sequenced millions and millions of DNA fragments captured in CRISPR loci in different genetic strains and found the same results consistently,” he said.

Here’s a link to and a citation for the paper,

Cas4 Nucleases Define the PAM, Length, and Orientation of DNA Fragments Integrated at CRISPR Loci by Masami Shiimori, Sandra C. Garrett, Brenton R. Graveley, Michael P. Terns.Molecular Cell Volume 70, Issue 5, p814–824.e6, 7 June 2018 DOI: https://doi.org/10.1016/j.molcel.2018.05.002

This paper is behind a paywall.

Shape-conforming hydrogel and the body’s own healing mechanisms

A June 11, 2018 news item on ScienceDaily announces a development of interest to people with diabetes or those who treat them,

A simple scrape or sore might not cause alarm for most people. But for diabetic patients, an untreated scratch can turn into an open wound that could potentially lead to a limb amputation or even death.

A Northwestern University team has developed a new device, called a regenerative bandage, that quickly heals these painful, hard-to-treat sores without using drugs. During head-to-head tests, Northwestern’s bandage healed diabetic wounds 33 percent faster than one of the most popular bandages currently on the market.

A June 11, 2018 Northwestern University news release by Amanda Morris, which originated the news item, provides more detail,

“The novelty is that we identified a segment of a protein in skin that is important to wound healing, made the segment and incorporated it into an antioxidant molecule that self-aggregates at body temperature to create a scaffold that facilitates the body’s ability to regenerate tissue at the wound site,” said Northwestern’s Guillermo Ameer, who led the study. “With this newer approach, we’re not releasing drugs or outside factors to accelerate healing. And it works very well.”

Because the bandage leverages the body’s own healing power without releasing drugs or biologics, it faces fewer regulatory hurdles. This means patients could see it on the market much sooner.

The research was published today, June 11 [2018], in the Proceedings of the National Academy of Sciences. Although Ameer’s laboratory is specifically interested in diabetes applications, the bandage can be used to heal all types of open wounds.

An expert in biomaterials and regenerative engineering, Ameer is the Daniel Hale Williams Professor of Biomedical Engineering in the McCormick School of Engineering, professor of surgery in the Feinberg School of Medicine and director of Northwestern’s new Center for Advanced Regenerative Engineering (CARE).

The difference between a sore in a physically healthy person versus a diabetic patient? Diabetes can cause nerve damage that leads to numbness in the extremities. People with diabetes, therefore, might experience something as simple as a blister or small scratch that goes unnoticed and untreated because they cannot feel it to know it’s there. As high glucose levels also thicken capillary walls, blood circulation slows, making it more difficult for these wounds to heal. It’s a perfect storm for a small nick to become a limb-threatening — or life-threatening — wound.

The secret behind Ameer’s regenerative bandage is laminin, a protein found in most of the body’s tissues including the skin. Laminin sends signals to cells, encouraging them to differentiate, migrate and adhere to one another. Ameer’s team identified a segment of laminin — 12 amino acids in length — called A5G81 that is critical for the wound-healing process.

“This particular sequence caught our eye because it activates cellular receptors to get cells to adhere, migrate and proliferate,” Ameer said. “Then we cut up the sequence to find the minimum size that we needed for it to work.”

By using such a small fragment of laminin rather than the entire protein, it can be easily synthesized in the laboratory — making it more reproducible while keeping manufacturing costs low. Ameer’s team incorporated A5G81 into an antioxidant hydrogel bandage that it previously developed in the laboratory.

The bandage’s antioxidant nature counters inflammation. And the hydrogel is thermally responsive: It is a liquid when applied to the wound bed, then rapidly solidifies into a gel when exposed to body temperature. This phase change allows it to conform to the exact shape of the wound — a property that helped it out-perform other bandages on the market.

“Wounds have irregular shapes and depths. Our liquid can fill any shape and then stay in place,” Ameer said. “Other bandages are mostly based on collagen films or sponges that can move around and shift away from the wound site.”

Patients also must change bandages often, which can rip off the healing tissue and re-injure the site. Ameer’s bandage, however, can be rinsed off with cool saline, so the regenerating tissue remains undisturbed.

Not only will the lack of drugs or biologics make the bandage move to market faster, it also increases the bandage’s safety. So far, Ameer’s team has not noticed any adverse side effects in animal models. This is a stark difference from another product on the market, which contains a growth factor linked to cancer.

“It is not acceptable for patients who are trying to heal an open sore to have to deal with an increased risk of cancer,” Ameer said.

Next, Ameer’s team will continue to investigate the bandage in a larger pre-clinical model.

Here’s a link to and a citation for the paper,

Potent laminin-inspired antioxidant regenerative dressing accelerates wound healing in diabetes by Yunxiao Zhu, Zdravka Cankova, Marta Iwanaszko, Sheridan Lichtor, Milan Mrksich, and Guillermo A. Ameer. PNAS [Proceedings of the National Academy of Science] June 11, 2018. 201804262; published ahead of print June 11, 2018. https://doi.org/10.1073/pnas.1804262115

This paper is behind a paywall.

Therapeutic nanoparticles for agricultural crops

Nanoscale drug delivery systems developed by the biomedical community may prove useful to farmers. The Canadian Broadcasting Corporation (CBC) featured the story in a May 26, 2018 online news item (with audio file; Note: A link has been removed),

Thanks to a fortuitous conversation between an Israeli chemical engineer who works on medical nanotechnology and his farmer friend, there’s a new way to deliver nourishment to nutrient-starved crops.

Avi Schroeder, the chemical engineer and cancer researcher from Technion — Israel Institute of Technology asked his friend what are the major problems facing agriculture today. “He said, ‘You know Avi, one of the major issues we’re facing is that in some of the crops we try to grow, we actually have a lack of nutrients. And then we end up not growing those crops even though they’re very valuable or very important crops.'”

This problem is only going to become more acute in many regions of the world as global population approaches eight billion people.

“Feeding them with healthy food and nutritious food is becoming a major limiting factor. And … the land we can actually grow crops on are also becoming smaller and smaller in every country because people need to build houses too. So what we want is to get actually more crops per hectare.”

The way farmers currently deliver nutrients to malnourished agricultural crops is very inefficient. Much of what is added to the leaves of the plant is wasted. Most of it washes away or isn’t taken up by the plants.

If plants don’t get the nutrients they need, their leaves start to yellow, their growth becomes stunted and they don’t produce as much food as nutrient-rich crops.

“We work primarily in the field of medicine,” says Schroeder. “What we do many times is we’ll load minuscule doses of medicine into nanoparticles — we’ll inject them into the patient. And those nanoparticles will actually be able to detect the disease site inside the body. That sounded very, very similar to the problem the farmers were actually facing — how do you get a medicine into a crop or a nutrient into a crop and get it to the right region within the crop where it’s actually necessary.”

The nanoparticles Schroeder developed are tiny packages that can deliver nutrients — any nutrients — that are placed inside.

A June 6, 2018 news item on Nanowerk offers a few more details,

An innovative technology developed at the Technion [Israel Institute of Technology] could lead to significant increases in agricultural yields. Using a nanometric transport platform on plants that was previously utilized for targeted drug delivery, researchers increased the penetration rate of nutrients into the plants, from 1% to approximately 33%.

A May 27,2018 Technion press release, which originated the news item, fleshes out the details,

The technology exploits nanoscale delivery platforms which until now were used to transport drugs to specific targets in the patient’s body. The work was published in Scientific Reports and will be presented in Nature Press.

The use of the nanotechnology for targeted drug delivery has been the focus of research activity conducted at the Laboratory for Targeted Drug Delivery and Personalized Medicine Technologies at the Wolfson Faculty of Chemical Engineering. The present research repurposes this technology for agricultural use; and is being pursued by laboratory director Prof. Avi Schroeder and graduate student Avishai Karny.

“The constant growth in the world population demands more efficient agricultural technologies, which will produce greater supplies of healthier foods and reduce environmental damage,” said Prof. Schroeder. “The present work provides a new means of delivering essential nutrients without harming the environment.”

The researchers loaded the nutrients into liposomes which are small spheres generated in the laboratory, comprised of a fatty outer layer enveloping the required nutrients. The particles are stable in the plant’s aqueous environment and can penetrate the cells. In addition, the Technion researchers can ‘program’ them to disintegrate and release the load at precisely the location and time of interest, namely, in the roots and leaves. Disintegration occurs in acidic environments or in response to an external signal, such as light waves or heat. The molecules comprising the particles are derived from soy plants and are therefore approved and safe for consumption by both humans and animals.

In the present experiment, the researchers used 100-nanometer liposomes to deliver the nutrients iron and magnesium into both young and adult tomato crops. They demonstrated that the liposomes, which were sprayed in the form of a solution onto the leaves, penetrated the leaves and reached other leaves and roots. Only when reaching the root cells did they disintegrate and release the nutrients. As said, the technology greatly increased the nutrient penetration rate.

In addition to demonstrating the effectivity of this approach as compared to the standard spray method, the researchers also assessed the regulatory limitations associated with the spread of volatile particles.

”Our engineered liposomes are only stable within a short spraying range of up to 2 meters,” explained Prof. Schroeder. “If they travel in the air beyond that distance, they break down into safe materials (phospholipids). We hope that the success of this study will expand the research and development of similar agricultural products, to increase the yield and quality of food crops.”

This is an illustration of the work,

Each liposome (light blue bubble) was loaded with iron and magnesium particles. The liposomes sprayed on the leaves, penetrated and then spread throughout the various parts of the plant and released their load within the cells. Courtesy: Technion

Here’s a link to and a citation for the paper,

Therapeutic nanoparticles penetrate leaves and deliver nutrients to agricultural crops by Avishai Karny, Assaf Zinger, Ashima Kajal, Janna Shainsky-Roitman, & Avi Schroeder. Scientific Reportsvolume 8, Article number: 7589 (2018) DOI: https://doi.org/10.1038/s41598-018-25197-y Published 17 May 2018

This paper is open access.