Category Archives: medicine

Resisting silver’s microbial properties?

Yes, it is possible for bacteria to become resistant to silver nanoparticles. However, that yes comes with some qualifications according to a July 13, 2021 news item on ScienceDaily (Note: Links have been removed),

Antimicrobials are used to kill or slow the growth of bacteria, viruses and other microorganisms. They can be in the form of antibiotics, used to treat bodily infections, or as an additive or coating on commercial products used to keep germs at bay. These life-saving tools are essential to preventing and treating infections in humans, animals and plants, but they also pose a global threat to public health when microorganisms develop resistance to them, a concept known as antimicrobial resistance.

One of the main drivers of antimicrobial resistance is the misuse and overuse of antimicrobial agents, which includes silver nanoparticles, [emphases mine] an advanced material with well-documented antimicrobial properties. It is increasingly used in commercial products that boast enhanced germ-killing performance — it has been woven into textiles, coated onto toothbrushes, and even mixed into cosmetics as a preservative.

The Gilbertson Group at the University of Pittsburgh [Pennsylvania, US} Swanson School of Engineering used laboratory strains of E.coli to better understand bacterial resistance to silver nanoparticles and attempt to get ahead of the potential misuse of this material. The team recently published their results in Nature Nanotechnology.

Caption: A depiction of hyper-motile E.coli, a strain of bacteria found to resist silver nanoparticles’ antimicrobial properties after repeated exposure. Credit: Lisa Stabryla/University of Pittsburgh.

A July 13, 2021 University of Pittsburgh news release (also on EurekAlert), which originated the news item, provides more insight into the research,

“Bacterial resistance to silver nanoparticles is understudied, so our group looked at the mechanisms behind this event,” said Lisa Stabryla, lead author on the paper and a recent civil and environmental PhD graduate at Pitt. “This is a promising innovation to add to our arsenal of antimicrobials, but we need to consciously study it and perhaps regulate its use to avoid decreased efficacy like we’ve seen with some common antibiotics.”

Stabryla exposed E.coli to 20 consecutive days of silver nanoparticles and monitored bacterial growth over time. Nanoparticles are roughly 50 times smaller than a bacterium.

“In the beginning, bacteria could only survive at low concentrations of silver nanoparticles, but as the experiment continued, we found that they could survive at higher doses,” Stabryla noted. “Interestingly, we found that bacteria developed resistance to the silver nanoparticles but not their released silver ions alone.”

The group sequenced the genome of the E.coli that had been exposed to silver nanoparticles and found a mutation in a gene that corresponds to an efflux pump that pushes heavy metal ions out of the cell.

“It is possible that some form of silver is getting into the cell, and when it arrives, the cell mutates to quickly pump it out,” she added. “More work is needed to determine if researchers can perhaps overcome this mechanism of resistance through particle design.”

The group then studied two different types of E.coli: a hyper-motile strain that swims through its environment more quickly than normally motile bacteria and a non-motile strain that does not have physical means for moving around. They found that only the hyper-motile strain developed resistance.

“This finding could suggest that silver nanoparticles may be a good option to target certain types of bacteria, particularly non-motile strains,” Stabryla said.

In the end, bacteria will still find a way to evolve and evade antimicrobials. The hope is that an understanding of the mechanisms that lead to this evolution and a mindful use of new antimicrobials will lessen the impact of antimicrobial resistance.

“We are the first to look at bacterial motility effects on the ability to develop resistance to silver nanoparticles,” said Leanne Gilbertson, assistant professor of civil and environmental engineering at Pitt. “The observed difference is really interesting and merits further investigation to understand it and how to link the genetic response – the efflux pump regulation – to the bacteria’s ability to move in the system.

“The results are promising for being able to tune particle properties for a desired response, such as high efficacy while avoiding resistance.”

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

Role of bacterial motility in differential resistance mechanisms of silver nanoparticles and silver ions by Lisa M. Stabryla, Kathryn A. Johnston, Nathan A. Diemler, Vaughn S. Cooper, Jill E. Millstone, Sarah-Jane Haig & Leanne M. Gilbertson. Nature Nanotechnology (2021) DOI: https://doi.org/10.1038/s41565-021-00929-w Published: 21 June 2021

This paper appears to be open access.

“The Immune System: Our Great Protector Against Dangerous Stuff” talk at Simon Fraser University’s (SFU) Café Scientifique on Thursday January 27, 2022 from 5:00 pm – 6:30 pm PST

This is from a January 13, 2022 SFU Café Scientifique notice (received via email),

Happy New Year! We are excited to announce our next virtual SFU Café
Scientifique!

 Thursday January 27, 2022, 5:00-6:30 pm

 Dr. Jonathan Choy, SFU Molecular Biology and Biochemistry

The Immune System: Our Great Protector Against Dangerous Stuff

Our bodies are constantly in contact with material in the environment,
such as microbes, that are harmful to our health. Despite this, most
people are healthy because the immune system patrols our bodies and
protects us from these harmful environmental components. In this Cafe
Scientifique, Dr. Jonathan Choy from the Department of Molecular Biology
and Biochemistry will discuss how the immune system does this.

Register here to receive a zoom invite:

 
https://www.eventbrite.ca/e/sfu-cafe-scientifique-january-2022-tickets-227344733217

I found Dr. Choy’s profile page on the SFU website and found this description for his research interests,

T Cell Biology 

T cells are specialized cells of the immune system that protect host organisms from infection but that also contribute to a wide array of human diseases. Research in my laboratory is focused on understanding the mechanisms by which T cells become inappropriately activated in disease settings and how they cause organ damage. We have provided particular attention to how innate immune signals, such as cytokines secreted by innate immune cells and vascular cells, control the outcome of T cell responses. Within this context, processes that inhibit the activation of T cells are also being studied in order to potentially prevent disease-causing immune responses. Our studies on this topic are applied most directly to inflammatory vascular diseases, such as transplant arteriosclerosis and giant cell arteritis.

Nitric Oxide Signaling and Production 

Nitric oxide (NO) is a bioactive gas that controls many cell biological responses. Dysregulation of its production and/or bioactivity is involved in many diseases. My laboratory is interested in understanding how NO effects cell signaling and how its production is controlled by NO synthases. We are specifically interested in how NO-mediated protein S-nitrosylation, a post-translational modification caused by NO, affects cell signaling pathways and cellular functions.

I gather from the Café Scientifique write up that Dr. Choy’s talk is intended for a more general audience as opposed to the description of his research interests which are intended for students of molecular biology and biochemistry/

For those who are unfamiliar with it, Simon Fraser University is located in the Vancouver area (Canada).

Restoring words with a neuroprosthesis

There seems to have been an update to the script for the voiceover. You’ll find it at the 1 min. 30 secs. mark ( spoken: “with up to 93% accuracy at 18 words per minute`’ vs. written “with median 74% accuracy at 15 words per minute)".

A July 14, 2021 news item on ScienceDaily announces the latest work on a a neuroprosthetic from the University of California at San Francisco (UCSF),

Researchers at UC San Francisco have successfully developed a “speech neuroprosthesis” that has enabled a man with severe paralysis to communicate in sentences, translating signals from his brain to the vocal tract directly into words that appear as text on a screen.

The achievement, which was developed in collaboration with the first participant of a clinical research trial, builds on more than a decade of effort by UCSF neurosurgeon Edward Chang, MD, to develop a technology that allows people with paralysis to communicate even if they are unable to speak on their own. The study appears July 15 [2021] in the New England Journal of Medicine.

A July 14, 2021 UCSF news release (also on EurekAlert), which originated the news item, delves further into the topic,

“To our knowledge, this is the first successful demonstration of direct decoding of full words from the brain activity of someone who is paralyzed and cannot speak,” said Chang, the Joan and Sanford Weill Chair of Neurological Surgery at UCSF, Jeanne Robertson Distinguished Professor, and senior author on the study. “It shows strong promise to restore communication by tapping into the brain’s natural speech machinery.”

Each year, thousands of people lose the ability to speak due to stroke, accident, or disease. With further development, the approach described in this study could one day enable these people to fully communicate.

Translating Brain Signals into Speech

Previously, work in the field of communication neuroprosthetics has focused on restoring communication through spelling-based approaches to type out letters one-by-one in text. Chang’s study differs from these efforts in a critical way: his team is translating signals intended to control muscles of the vocal system for speaking words, rather than signals to move the arm or hand to enable typing. Chang said this approach taps into the natural and fluid aspects of speech and promises more rapid and organic communication.

“With speech, we normally communicate information at a very high rate, up to 150 or 200 words per minute,” he said, noting that spelling-based approaches using typing, writing, and controlling a cursor are considerably slower and more laborious. “Going straight to words, as we’re doing here, has great advantages because it’s closer to how we normally speak.”

Over the past decade, Chang’s progress toward this goal was facilitated by patients at the UCSF Epilepsy Center who were undergoing neurosurgery to pinpoint the origins of their seizures using electrode arrays placed on the surface of their brains. These patients, all of whom had normal speech, volunteered to have their brain recordings analyzed for speech-related activity. Early success with these patient volunteers paved the way for the current trial in people with paralysis.

Previously, Chang and colleagues in the UCSF Weill Institute for Neurosciences mapped the cortical activity patterns associated with vocal tract movements that produce each consonant and vowel. To translate those findings into speech recognition of full words, David Moses, PhD, a postdoctoral engineer in the Chang lab and lead author of the new study, developed new methods for real-time decoding of those patterns, as well as incorporating statistical language models to improve accuracy.

But their success in decoding speech in participants who were able to speak didn’t guarantee that the technology would work in a person whose vocal tract is paralyzed. “Our models needed to learn the mapping between complex brain activity patterns and intended speech,” said Moses. “That poses a major challenge when the participant can’t speak.”

In addition, the team didn’t know whether brain signals controlling the vocal tract would still be intact for people who haven’t been able to move their vocal muscles for many years. “The best way to find out whether this could work was to try it,” said Moses.

The First 50 Words

To investigate the potential of this technology in patients with paralysis, Chang partnered with colleague Karunesh Ganguly, MD, PhD, an associate professor of neurology, to launch a study known as “BRAVO” (Brain-Computer Interface Restoration of Arm and Voice). The first participant in the trial is a man in his late 30s who suffered a devastating brainstem stroke more than 15 years ago that severely damaged the connection between his brain and his vocal tract and limbs. Since his injury, he has had extremely limited head, neck, and limb movements, and communicates by using a pointer attached to a baseball cap to poke letters on a screen.

The participant, who asked to be referred to as BRAVO1, worked with the researchers to create a 50-word vocabulary that Chang’s team could recognize from brain activity using advanced computer algorithms. The vocabulary – which includes words such as “water,” “family,” and “good” – was sufficient to create hundreds of sentences expressing concepts applicable to BRAVO1’s daily life.

For the study, Chang surgically implanted a high-density electrode array over BRAVO1’s speech motor cortex. After the participant’s full recovery, his team recorded 22 hours of neural activity in this brain region over 48 sessions and several months. In each session, BRAVO1 attempted to say each of the 50 vocabulary words many times while the electrodes recorded brain signals from his speech cortex.

Translating Attempted Speech into Text

To translate the patterns of recorded neural activity into specific intended words, Moses’s two co-lead authors, Sean Metzger and Jessie Liu, both bioengineering graduate students in the Chang Lab, used custom neural network models, which are forms of artificial intelligence. When the participant attempted to speak, these networks distinguished subtle patterns in brain activity to detect speech attempts and identify which words he was trying to say.

To test their approach, the team first presented BRAVO1 with short sentences constructed from the 50 vocabulary words and asked him to try saying them several times. As he made his attempts, the words were decoded from his brain activity, one by one, on a screen.

Then the team switched to prompting him with questions such as “How are you today?” and “Would you like some water?” As before, BRAVO1’s attempted speech appeared on the screen. “I am very good,” and “No, I am not thirsty.”

Chang and Moses found that the system was able to decode words from brain activity at rate of up to 18 words per minute with up to 93 percent accuracy (75 percent median). Contributing to the success was a language model Moses applied that implemented an “auto-correct” function, similar to what is used by consumer texting and speech recognition software.

Moses characterized the early trial results as a proof of principle. “We were thrilled to see the accurate decoding of a variety of meaningful sentences,” he said. “We’ve shown that it is actually possible to facilitate communication in this way and that it has potential for use in conversational settings.”

Looking forward, Chang and Moses said they will expand the trial to include more participants affected by severe paralysis and communication deficits. The team is currently working to increase the number of words in the available vocabulary, as well as improve the rate of speech.

Both said that while the study focused on a single participant and a limited vocabulary, those limitations don’t diminish the accomplishment. “This is an important technological milestone for a person who cannot communicate naturally,” said Moses, “and it demonstrates the potential for this approach to give a voice to people with severe paralysis and speech loss.”

… all of UCSF. Funding sources [emphasis mine] included National Institutes of Health (U01 NS098971-01), philanthropy, and a sponsored research agreement with Facebook Reality Labs (FRL), [emphasis mine] which completed in early 2021.

UCSF researchers conducted all clinical trial design, execution, data analysis and reporting. Research participant data were collected solely by UCSF, are held confidentially, and are not shared with third parties. FRL provided high-level feedback and machine learning advice.

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

Neuroprosthesis for Decoding Speech in a Paralyzed Person with Anarthria by David A. Moses, Ph.D., Sean L. Metzger, M.S., Jessie R. Liu, B.S., Gopala K. Anumanchipalli, Ph.D., Joseph G. Makin, Ph.D., Pengfei F. Sun, Ph.D., Josh Chartier, Ph.D., Maximilian E. Dougherty, B.A., Patricia M. Liu, M.A., Gary M. Abrams, M.D., Adelyn Tu-Chan, D.O., Karunesh Ganguly, M.D., Ph.D., and Edward F. Chang, M.D. N Engl J Med 2021; 385:217-227 DOI: 10.1056/NEJMoa2027540 Published July 15, 2021

This paper is mostly behind a paywall but you do have this option: “Create your account to get 2 free subscriber-only articles each month.”

Skin healing with nanoscale borate bioactive glass?

I’d hadn’t heard about skin healing with glass (of any kind) before this July 6, 2021 news item on phys.org,

Recently, with the help of a steady-state strong magnetic field experimental device, scientists constructed nano-scale borate bioactive glass (Nano-HCA@BG), which can effectively reduce the biological toxicity of borate bioglass, improve the biocompatibility of the glass, and promote the effect of borate bioglass on skin repair.

Prof. Wang Junfeng from the Hefei Institutes of Physical Science (HFIPS) of the Chinese Academy of Sciences (CAS), collaborating with Prof. Zhang Teng from Fuzhou University in this study, said, “it is expected to become the next generation of skin wound repair dressings.” Related research was published in Chemical Engineering Journal.

A July 5, 2021 Hefei Institutes of Physical Science, Chinese Academy of Sciences press release (two apparently identical [to each other and to the July 5 version] copies July 6, 2021 and July 13, 2021 also appear on EurekAlert), which originated the news item, explains the advantages of using borate bioglass for skin repair,

Borate bioglass is a glass with boron element (B) as the glass network matrix. With good dopability and degradability, it has great potential in the field of skin tissue repair. However, It releases a large amount of alkaline ions, and the explosive release of these ions will change the acid-base environment of the tissue around the glass material, thereby inhibiting cell proliferation.

In addition, the effective surface area of micron-sized borate bioglass in contact with tissues at the wound is small, and the ions on the glass surface are not conducive to the deposition of collagen, so scars are easily formed at the wound after healing. Therefore, preparing a nano-scale borate bioglass with no biological toxicity and excellent biological performance is an urgent problem to be solved.

In this study, the researchers used a special mobile phase, for the first time, to pre-treat micron-sized borate bioglass by melting method in vitro. They obtained Nano-scale (~50nm) borate bioglass (Nano-HCA@BG), which was covered with an amorphous hydroxyapatite (HCA) layer.

During the processing, the ions (PO43- and CO32-) in the mobile phase were deposited on the surface of the glass to form the HCA layer, which effectively inhibited the rapid release of boron and calcium in the remaining glass and thereby reduced the biological toxicity of the glass itself to cells.

In addition, HCA, as an important inorganic component in bones, has good biocompatibility, and can accelerate the induction of collagen synthesis in tissues.

The results of in vitro degradation experiments, cell experiments, and animal experiments showed that compared with the existing commercialized bioactive glass, HCA and micron-sized borate bioglass, nano-HCA@BG slow-released boron calcium, and other elements can effectively accelerate wound cells migration and further up-regulation of the expression of vascular-related growth factors in the wound.

Besides, the amorphous HCA layer on the surface of the glass not only reduces the rapid release of the glass, but also promotes the deposition of collagen in the wound, which in turn promotes the healing of the wound more quickly.

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

Nanosized HCA-coated borate bioactive glass with improved wound healing effects on rodent model by Ruiguo Chen, Qian Li, Qi zhang, Shuai Xu, Jian Han, Peiyan Huang, Zhiwu Yu, Daping Jia, Juanjuan Liu, Huiling Jia, Ming Shen, Bingwen Hu, Howard Wang, Hongbing Zhan, Teng Zhang, Kun Ma, and Junfeng Wang. Chemical Engineering Journal Volume 426, 15 December 2021, 130299 DOI: https://doi.org/10.1016/j.cej.2021.130299 Available online 12 May 2021

This paper is behind a paywall.

‘Playing telephone’ with multivalent gold nanoparticles

A July 7, 2021 news item on phys.org describes what ‘playing telephone’ has to do with gold nanoparticles,

Cells play a precise game of telephone, sending messages to each other that trigger actions further on. With clear signaling, the cells achieve their goals. In disease, however, the signals break up and result in confused messaging and unintended consequences. To help parse out these signals and how they function in health—and go awry in disease—scientists tag proteins with labels they can follow as the proteins interact with the molecular world around them.

The challenge is figuring out which proteins to label in the first place. Now, a team led by researchers from Tokyo University of Agriculture and Technology (TUAT) has developed a new approach to identifying and tagging the specific proteins. They published their results on June 1 [2021] in Angewandte Chemie.

A July 8, 2021 TUAT press release on EurekAlert, which originated the news item, delves further into the research (I appreciate how clearly the work is explained),

“We are interested in exploring protein receptors of certain carbohydrate molecules that are involved in mediating cell signaling, particularly in cancer cells,” said paper author Kaori Sakurai, associate professor in the Department of Biotechnology and Life Science at TUAT.

The carbohydrate molecules, called ligands, are typically expressed on the surface of cells and are known to dynamically form complexes with protein receptors to coordinate complicated cellular functions. However, Sakurai said, the proteins responsible for binding the carbohydrates have been difficult to identify because they bond so weakly with the molecules.

The researchers designed a new type of carbohydrate probe that would not only link to the molecules, but tightly bind to them.

“We used gold nanoparticles as a scaffold to attach both carbohydrate ligands and electrophiles — a chemical that loves to react with other molecules — in a multivalent fashion,” Sakurai said. “This way, we were able to greatly increase binding affinity and reaction efficiency toward carbohydrate-binding proteins.”

The researchers applied the designed probes to cell lysate, a fluid containing the innards of broken-apart cells.

“The probes quickly found the target carbohydrate-binding proteins, triggering the electrophilic groups to react with electron-donating amino acid residues on nearby proteins,” Sakurai said. “This resulted in proteins firmly cross-linked to the gold nanoparticles’ surface, making it easy to subsequently analyze their identities.”

The team evaluated several electrophilic groups to identify the most efficient type for labeling their target proteins.

“We found that a particular electrophilic group called aryl sulfonyl fluoride is best suited for affinity labeling of carbohydrate-binding proteins,” said co-author Nanako Suto, a graduate student in the Department of Biotechnology and Life Science of TUAT. “However, they have rarely been used to identify target proteins, presumably because they would non-selectively react with various other, undesired proteins.”

However, the scale of aryl sulfonyl fluoride use appears to mitigate the issue.

“The non-selectivity isn’t a problem if aryl sulfonyl fluoride is used at very low concentrations, at the range of the nanoscale,” said co-author Shione Kamoshita, also a graduate student in the Department of Biotechnology and Life Science, TUAT.

The gold nanoparticle scaffolding displays many copies of the electrophilic group, which keeps aryl sulfonyl fluoride’s local concentration high on the nanoparticle surface but restrains them from the general cell system and reacting to undesired proteins. With the high concentration at the nano-level, some copies of electrophilic groups can efficiently react with target proteins.

“Through this process, we were able to achieve highly efficient and selective affinity labeling of carbohydrate-binding proteins in cell lysate,” Sakurai said. “We will apply the new method in target identification of several cancer-related carbohydrate ligands and investigate their function in cancer development. In parallel, we aim to explore the general utility of this new probe design for various other bioactive small molecules, so that we can accelerate the elucidation of their mechanisms.”

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

Exploration of the Reactivity of Multivalent Electrophiles for Affinity Labeling: Sulfonyl Fluoride as a Highly Efficient and Selective Label by Nanako Suto, Shione Kamoshita, Dr. Shoichi Hosoya, Prof. Kaori Sakurai. Angewandte Chemie Volume 60, Issue 31 July 26, 2021 Pages 17080-17087 DOI: https://doi.org/10.1002/anie.202104347 First published: 01 June 2021

This paper is behind a paywall.

INTER/her, a talk with Camille Baker about an immersive journey inside the female body on Friday, December 3, 2021

Before getting to the announcement, this talk and Q&A (question and answer) session is being co-hosted by ArtSci Salon at the Fields Institute for Research in Mathematical Sciences and the OCAD University/DMG Bodies in Play (BiP) initiative.

For anyone curious about OCAD, it was the Ontario College of Art and Design and then in a very odd government/marketing (?) move, they added the word university. As for DMG, in their own words and from their About page, “DMG is a not-for-profit videogame arts organization that creates space for marginalized creators to make, play and critique videogames within a cultural context.” They are located in Toronto, Ontario. Finally, the Art/Sci Salon and the Fields Institute are located at the University of Toronto.

As for the talk, here’s more from the November 28, 2021 Art/Sci Salon announcement (received via email),

Inspired by her own experience with the health care system to treat a
post-reproductive disease, interdisciplinary artist [Camille] Baker created the
project INTER/her, an immersive installation and VR [virtual reality] experience exploring
the inner world of women’s bodies and the reproductive diseases they
suffer. The project was created to open up the conversation about
phenomena experienced by women in their late 30’s (sometimes earlier)
their 40’s, and sometimes after menopause. Working in consultation
with a gynecologist, the project features interviews with several women
telling their stories. The themes in the work include issues of female
identity, sexuality, body image, loss of body parts, pain, disease, and
cancer. INTER/her has a focus on female reproductive diseases explored
through a feminist lens; as personal exploration, as a conversation
starter, to raise greater public awareness and encourage community
building. The work also represents the lived experience of women’s
pain and anger, conflicting thoughts through self-care and the growth of
disease. Feelings of mortality are explored through a medical process in
male-dominated medical institutions and a dearth of reliable
information. https://inter-her.art/ [1]

In 2021, the installation was shortlisted for the Lumen Prize.

 Join us for a talk and Q&A with the artist to discuss her work and its
future development.

 Friday, December 3,

6:00 pm EST

 Register in advance for this meeting:

https://utoronto.zoom.us/meeting/register/tZ0rcO6rpzsvGd057GQmTyAERmRRLI2MQ4L1

After registering, you will receive a confirmation email containing
information about joining the meeting.

This talk is  Co-Hosted by the ArtSci Salon at the Fields Institute for
Research in Mathematical Sciences and the OCAD University/DMG Bodies in
Play (BiP) initiative.

This event will be recorded and archived on the ArtSci Salon Youtube
channel

Bio

Camille Baker is a Professor in Interactive and Immersive Arts,
University for the Creative Arts [UCA], Farnham Surrey (UK). She is an
artist-performer/researcher/curator within various art forms: immersive
experiences, participatory performance and interactive art, mobile media
art, tech fashion/soft circuits/DIY electronics, responsive interfaces
and environments, and emerging media curating. Maker of participatory
performance and immersive artwork, Baker develops methods to explore
expressive non-verbal modes of communication, extended embodiment and
presence in real and mixed reality and interactive art contexts, using
XR, haptics/ e-textiles, wearable devices and mobile media. She has an
ongoing fascination with all things emotional, embodied, felt, sensed,
the visceral, physical, and relational.

Her 2018 book _New Directions in Mobile Media and Performance_ showcases
exciting approaches and artists in this space, as well as her own work.
She has been running a regular meetup group with smart/e-textile artists
and designers since 2014, called e-stitches, where participants share
their practice and facilitate workshops of new techniques and
innovations. Baker  also has been Principal Investigator for UCA for the
EU funded STARTS Ecosystem (starts.eu [2]) Apr 2019-Nov 2021 and founder
initiator for the EU WEAR Sustain project Jan 2017-April 2019
(wearsustain.eu [3]).

The EU or European Union is the agency that provided funding for S+T+Arts (Science, Technology & the Arts), which is an initiative of the European Commission’s. I gather that Baker was involved in two STARTS projects, one called the WEAR Sustain project and the other called, the STARTS Ecosystem.

Nanomaterial shapes and forms affect passage through blood brain barrier (BBB)

I meant to get this published a lot sooner.

There seems to be a lot of excitement about this research. I got an embargoed press release further in advance than usual and now the embargo is lifted, it’s everywhere except, at the time of this writing (0920 PDT July 6, 2021), on the publisher’s (Proceedings of the National Academy of Sciences [PNAS]) website.

A July 5, 2021 news item on Medical Express announces the news,

Nanomaterials found in consumer and health-care products can pass from the bloodstream to the brain side of a blood-brain barrier model with varying ease depending on their shape—creating potential neurological impacts that could be both positive and negative, a new study reveals.

A July 5, 2021 University of Birmingham press release (also on EurekAlert), which originated the news item, delves into the details,

Scientists found that metal-based nanomaterials such as silver and zinc oxide can cross an in vitro model of the ‘blood brain barrier’ (BBB) as both particles and dissolved ions – adversely affecting the health of astrocyte cells, which control neurological responses.

But the researchers also believe that their discovery will help to design safer nanomaterials and could open up new ways of targeting hard-to-reach locations when treating brain disease.

Publishing its findings today in PNAS, an international team of researchers discovered that the physiochemical properties of metallic nanomaterials influence how effective they are at penetrating the in vitro model of the blood brain barrier and their potential levels of toxicity in the brain.

Higher concentration of certain shapes of silver nanomaterials and zinc oxide may impair cell growth and cause increased permeability of the BBB, which can lead to the BBB allowing easier brain access to these compounds.

The BBB plays a vital role in brain health by restricting the passage of various chemical substances and foreign molecules into the brain from surrounding blood vessels.

Impaired BBB integrity compromises the health of the central nervous system and increased permeability to foreign substances may eventually cause damage to the brain (neurotoxicity).

Study co-author Iseult Lynch, Professor of Environmental Nanosciences at the University of Birmingham, commented: “We found that silver and zinc oxide nanomaterials, which are widely used in various daily consumer and health-care products, passed through our in vitro BBB model, in the form of both particles and dissolved ions.

“Variation in shape, size and chemical composition can dramatically influence nanomaterials penetration through the (in vitro) blood brain barrier. This is of paramount importance for tailored medical application of nanomaterials – for example targeted delivery systems, bioimaging and assessing possible risks associated with each type of metallic nanomaterial.”

The BBB is a physical barrier composed of a tightly packed layer of endothelial cells surrounding the brain which separates the blood from the cerebrospinal fluid allowing the transfer of oxygen and essential nutrients but preventing the access of most molecules.

Recent studies found nanomaterials such as zinc oxide can accumulate on the brain side of the in vitro BBB in altered states which can affect neurological activity and brain health. Inhaled, ingested, and dermally-applied nanomaterials can reach the blood stream and a small fraction of these may cross the BBB – impacting on the central nervous system.

The researchers synthesised a library of metallic nanomaterials with different particle compositions, sizes, and shapes – evaluating their ability to penetrate the BBB using an in vitro BBB model, followed by assessment of their behaviour and fate in and beyond the model BBB.

Co-author Zhiling Guo, a Research Fellow at the University of Birmingham, commented: “”Understanding these materials’ behaviour once past the blood brain barrier is vital for evaluating the neurological effects arising from their unintentional entry into the brain. Neurotoxicity potential is greater in some materials than others, due to the different ways their shapes allow them to move and be transported.”

The research team tested varied sizes of cerium oxide and iron oxide, along with zinc oxide and four different shapes of silver – spherical (Ag NS), disc-like (Ag ND), rod-shaped (Ag NR) and nanowires (Ag NW).

Zinc oxide slipped through the in vitro BBB with the greatest ease. The researchers found spherical and disc-like silver nanomaterials underwent different dissolution regimes – gradually transforming to silver-sulfur compounds within the BBB, creating ‘easier’ entry pathways.

Zinc oxide is used as a bulking agent and a colorant. In over-the-counter drug products, it is used as a skin protectant and a sunscreen – reflecting and scattering UV radiation to help reduce or prevent sunburn and premature aging of the skin. Silver is used in cosmetic and skincare products such as anti-aging creams.

There’s still a long way to go with this research. For anyone who’s unfamiliar with the term ‘in vitro’, the rough translation is ‘in glass’ meaning test tubes, petri dishes, etc. are used. Even though the research paper has been peer-reviewed (not a perfect process), once it becomes available there will be added scrutiny from scientists with regard to how the research was conducted and whether or not the conclusions drawn are reasonable. One more question should also be asked, are the results reproducible by other scientists?

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

Biotransformation modulates the penetration of metallic nanomaterials across an artificial blood–brain barrier model by Zhiling Guo, Peng Zhang, Swaroop Chakraborty, Andrew J Chetwynd, Fazel Abdolahpur Monikh, Christopher Stark, Hanene Ali-Boucetta, Sandra Wilson, Iseult Lynch, and Eugenia Valsami-Jones. PNAS 118 (28) e2105245118 DOI: https://doi.org/10.1073/pnas.2105245118 Published: July 13, 2021

This paper appears to be open access.

Clean up soil and water or deliver drugs with nanobots

Nanobots/nanorobots/nanoswimmers or whatever they’re called, could prove to be quite useful for environmental remediation efforts or medical delivery systems according to a June 29, 2021 news item on Nanowerk (Note: One link has been removed),

CU Boulder [University of Colorado at Boulder] researchers have discovered that minuscule, self-propelled particles called “nanoswimmers” can escape from mazes as much as 20 times faster than other, passive particles, paving the way for their use in everything from industrial clean-ups to medication delivery.

The findings, published in the Proceedings of the National Academy of Sciences (“Mechanisms of transport enhancement for self-propelled nanoswimmers in a porous matrix”), describe how these tiny synthetic nanorobots are incredibly effective at escaping cavities within maze-like environments. These nanoswimmers could one day be used to remediate contaminated soil, improve water filtration or even deliver drugs to targeted areas of the body, like within dense tissues.

A June 29, 2021 University of Colorado at Boulder news release (also on EurekAlert) by Kelsey Simpkins, which originated the news item, explains what makes these nanobots different,

“This is the discovery of an entirely new phenomenon that points to a broad potential range of applications,” said Daniel Schwartz, senior author of the paper and Glenn L. Murphy Endowed Professor of chemical and biological engineering.

These nanoswimmers came to the attention of the theoretical physics community about 20 years ago, and people imagined a wealth of real-world applications, according to Schwartz. But unfortunately these tangible applications have not yet been realized, in part because it’s been quite difficult to observe and model their movement in relevant environments–until now.

These nanoswimmers, also called Janus particles (named after a Roman two-headed god), are tiny spherical particles composed of polymer or silica, engineered with different chemical properties on each side of the sphere. One hemisphere promotes chemical reactions to occur, but not the other. This creates a chemical field which allows the particle to take energy from the environment and convert it into directional motion–also known as self-propulsion.

“In biology and living organisms, cell propulsion is the dominant mechanism that causes motion to occur, and yet, in engineered applications, it’s rarely used. Our work suggests that there is a lot we can do with self-propulsion,” said Schwartz.

In contrast, passive particles which move about randomly (a kind of motion known as Brownian motion) are known as Brownian particles. They’re named after 19th century scientist Robert Brown, who studied such things as the random motion of pollen grains suspended in water.

The researchers converted these passive Brownian particles into Janus particles (nanoswimmers) for this research. Then they made these self-propelled nanoswimmers try to move through a maze, made of a porous medium, and compared how efficiently and effectively they found escape routes compared to the passive, Brownian particles.

The results were shocking, even to the researchers.

The Janus particles were incredibly effective at escaping cavities within the maze–as much as 20 times faster than the Brownian particles–because they moved strategically along the cavity walls searching for holes, which allowed them to find the exits very quickly. Their self-propulsion also appeared to give them a boost of energy needed to pass through the exit holes within the maze.

“We know we have a lot of applications for nanorobots, especially in very confined environments, but we didn’t really know how they move and what the advantages are compared to traditional Brownian particles. That’s why we started a comparison between these two,” said Haichao Wu, lead author of the paper and graduate student in chemical and biological engineering. “And we found that nanoswimmers are able to use a totally different way to search around these maze environments.”

While these particles are incredibly small, around 250 nanometers–just wider than a human hair (160 nanometers) but still much, much smaller than the head of a pin (1-2 millimeters)–the work is scalable. This means that these particles could navigate and permeate spaces as microscopic as human tissue to carry cargo and deliver drugs, as well as through soil underground or beaches of sand to remove unwanted pollutants.

Swarming nanoswimmers 

The next step in this line of research is to understand how nanoswimmers behave in groups within confined environments, or in combination with passive particles.

“In open environments, nanoswimmers are known to display emergent behavior–behavior that is more than the sum of its parts–that mimics the swarming motion of flocks of birds or schools of fish. That’s been a lot of the impetus for studying them,” said Schwartz.

One of the main obstacles to reaching this goal is the difficulty involved in being able to observe and understand the 3D movement of these tiny particles deep within a material comprising complex interconnected spaces.

Wu overcame this hurdle by using refractive index liquid in the porous medium, which is liquid that affects how fast light travels through a material. This made the maze essentially invisible, while allowing the observation of 3D particle motion using a technique known as double-helix point spread function microscopy.

This enabled Wu to track three-dimensional trajectories of the particles and create visual representations, a major advancement from typical 2D modeling of nanoparticles. Without this advancement, it would not be possible to better understand the movement and behavior of either individuals or groups of nanoswimmers.

“This paper is the first step: It provides a model system and the imaging platform that enables us to answer these questions,” said Wu. “The next step is to use this model with a larger population of nanoswimmers, to study how they are able to interact with each other in a confined environment.”

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

Mechanisms of transport enhancement for self-propelled nanoswimmers in a porous matrix by Haichao Wu, Benjamin Greydanus, and Daniel K. Schwartz. PNAS July 6, 2021 118 (27) e2101807118; DOI: https://doi.org/10.1073/pnas.2101807118

This paper is behind a paywall.

“How genome research is influencing our understanding of B-cell lymphomas” at Simon Fraser University (SFU) Café Scientifique on November 25, 2021 from 5:00 pm – 6:30 pm PST

This is from a November 8, 2021 SFU Café Scientifique notice (received via email),

We are excited to announce our next virtual SFU Café Scientifique!

NOW OPEN FOR REGISTRATION

Thursday November 25, 2021  5:00-6:30pm

Dr. Ryan Morin, SFU Department of Molecular Biology and Biochemistry

“How genome research is influencing our understanding of B-cell lymphomas”

Zoom invites will be sent to those registered, closer to the date.

Register here:

https://www.eventbrite.ca/e/how-genome-research-is-influencing-our-understanding-of-b-cell-lymphomas-tickets-203977471107

We hope to see you then!

There’s a little more of a topic description on the event registration webpage,

Every cancer arises following the accumulation of genetic changes known as mutations. Dr. Ryan Morin will discuss how genomics can allow us to understand how specific mutations influence the onset of lymphoma (and other common cancers) and can lead to new and more effective therapies.

There’s a little more detail about Morin’s work on his profile page on the BC Cancer Research Institute website,

Dr. Ryan Morin has been studying the genetic nature of lymphoid cancers using genomic methods for more than a decade. During his doctoral training at the University of British Columbia and BC Cancer, he pioneered the use of transcriptome and whole genome sequencing to identify driver mutations in non-Hodgkin lymphomas. Over the course of his training, he published a series of papers describing some of the most common genetic features of diffuse large B-cell (DLBCL) and follicular lymphomas including EZH2, KMT2D, CREBBP and MEF2B. Following his transition to an independent position at SFU, Dr. Morin has continued to identify genetic features of these and other aggressive lymphomas including non-coding (silent) regulatory drivers of cancer. His laboratory has implemented novel assays for the sensitive detection and genetic characterization of circulating tumour DNA (ctDNA). These “liquid biopsy” approaches continue to be developed as non-invasive methods for monitoring treatment response and resistance. Using these and other modern genomics tools and bioinformatics techniques, his team continues to explore the genetics of relapsed and refractory DLBCL with an ultimate goal of identifying novel biomarkers that predict treatment failure on specific therapies. This work has helped refine our understanding of genetic and gene expression differences that predict poor outcome in DLBCL.

Hopefully, Morin will be talking about the liquid biopsies and other non-invasive methods he and his team use in their work.