Author Archives: Maryse de la Giroday

Nanoparticle-based delivery platform for CRISPR-Cas9 (gene-editing technology)

A February 18, 2018 King Abdullah University of Science and Technology (KAUST; Saudi Arabia) news release (also on EurekAlert but published on Feb. 20, 2018) describes a new technology for delivering CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 into cells,

A new delivery system for introducing gene-editing technology into cells could help safely and efficiently correct disease-causing mutations in patients.

The system, developed by KAUST scientists, is the first to use sponge-like ensembles of metal ions and organic molecules to coat the molecular components of the precision DNA-editing technology known as CRISPR/Cas9, allowing efficient release of the genome-editing machinery inside the cell.

“This method presents an easy and economically feasible route to improve on the delivery problems that accompany RNA-based therapeutic approaches,” says Niveen Khashab, the associate professor of chemical sciences at KAUST who led the study. “This may permit such formulations to be eventually used for treating genetic diseases effectively in the future.”

CRISPR/Cas9 has a double delivery problem: For the gene-editing technology to work like a molecular Swiss Army knife, both a large protein (the Cas9 cutting enzyme) and a highly charged RNA component (the guide RNA used for DNA targeting) must each get from the outside of the cell into the cytoplasm and finally into the nucleus, all without getting trapped in the tiny intracellular bubbles that are known as endosomes.

To solve this problem, Khashab and her lab turned to a nano-sized type of porous material known as a zeolitic imidazolate framework, which forms a cage-like structure into which other molecules can be placed. The researchers encapsulated the Cas9 protein and guide RNA in this material and then introduced the resulting nanoparticles into hamster cells.

The encapsulated CRISPR-Cas9 constructs were not toxic to the cells. And because particles in the coating material become positively charged when absorbed into endosomes, they caused these membrane-bound bubbles to burst, freeing the CRISPR-Cas9 machinery to travel to the nucleus, home to the cell’s genome. There the gene-editing technology could get to work.

Using a guide RNA designed to target a gene that caused the cells to glow green under fluorescent light, Khashab and her team showed that they could reduce the expression of this gene by 37 percent over four days with their technology. “These cage-like structures are biocompatible and can be triggered on demand, making them smart options to overcome delivery problems of genetic materials and proteins,” says the study’s first author Shahad Alsaiari, a Ph.D. student in Khashab’s lab.

The researchers’ plan to test their system in human cells and in mice, and eventually, they hope, in clinical trials.

The zeolitic imidazolate framework forms a cage-like scaffold over the CRISPR/Cas9 machinery.. Reprinted (adapted) with permission from Alsaiari, S.K., Patil, S., Alyami, M., Alamoudi, K.O., Aleisa, F.A., Merzaban, J., Li M. & Khashab, N.M. Endosomal escape and delivery of CRISPR/Cas9 genome editing machinery enabled by nanoscale zeolitic imidazolate framework. Journal of the American Chemical Society 140, 143–146 (2018). © 2018 American Chemical Society; KAUST Xavier Pita and Heno Huang ][downloaded from https://discovery.kaust.edu.sa/en/article/475/a%250adelivery-platform-for-gene-editing-technology]

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

Endosomal Escape and Delivery of CRISPR/Cas9 Genome Editing Machinery Enabled by Nanoscale Zeolitic Imidazolate Framework by Shahad K. Alsaiari, Sachin Patil, Mram Alyami, Kholod O. Alamoudi, Fajr A. Aleisa, Jasmeen S. Merzaban, Mo Li, and Niveen M. Khashab. J. Am. Chem. Soc., 2018, 140 (1), pp 143–146 DOI: 10.1021/jacs.7b11754 Publication Date (Web): December 22, 2017

Copyright © 2017 American Chemical Society

This paper is behind a paywall.

Café Scientifique Vancouver (Canada) talk on May 29th, 2018: Insects in the City: Shrinking Beetles and Disappearing Bees. How Bugs Help Us Learn About the Ecological Effects of Urbanization and Climate Change

I received this Café Scientifique April 30, 2018 notice (received via email),

Our next café will happen on TUESDAY, MAY 29TH at 7:30PM in the back
room at YAGGER'S DOWNTOWN (433 W Pender). Our speaker for the
evening will be DR. MICHELLE TSENG, Assistant Professor in the Zoology
department at UBC. Her topic will be:

INSECTS IN THE CITY: SHRINKING BEETLES AND DISAPPEARING BEES. HOW BUGS
HELP US LEARN ABOUT THE ECOLOGICAL EFFECTS OF URBANIZATION AND CLIMATE
CHANGE

Living in the city, we don’t always see the good bugs amongst the
pesky ones. In this presentation, I’ll take you on a trip down insect
lane and share with you the incredible diversity of insects that have
lived in Vancouver over the last 100 years. Many of these bugs have been
collected and preserved in museums and these collections provide us with
a historical snapshot of insect communities from the past. My students
and I have made some remarkable discoveries using museum insect
collections, and these findings help us understand how these fascinating
creatures are changing in response to warming climates and increased
development.

Michelle Tseng is a professor of insect ecology at the UBC Biodiversity
Research Centre. She and her students study the impacts of habitat and
climate change on plankton and insects. Her group’s work has been
featured in national and international media, and on CBC’s Quirks and
Quarks. Michelle is also the zoologist on the award-winning CBC kids
show Scout and the Gumboot Kids.

We hope to see you there!

It says Dr. Tseng is in the zoology department but I also found a profile page for her in the botany department and that one had a little more information,

The Tseng lab investigates ecological and evolutionary responses of populations and communities to novel environments.  We test and refine theory related to predator-prey dynamics, body size variation, intra- and interspecific competition, and the maintenance of genetic variation, using laboratory and field experiments with freshwater plant and animal communities.  We also use museum collections to investigate long term patterns in organism phenotype.

Enjoy!

Cellulose aerogels for new wood-based composites

‘Frozen smoke’ or ‘solid smoke’ as it’s sometimes described, aerogel fascinates scientists.The latest on cellulose aerogels derived from wood is the focus for a February 14, 2018 Nanowerk Sportlight article by Michael Berger (Note: Links have been removed),

Aerogels, sometimes called frozen smoke, are nanoscale foams: solid materials whose sponge-like structure is riddled by pores as small as nanometers across. They can be made from different materials, for instance silicon.

Aerogels are among the lightest solid substances in the world yet flexible, extremely strong and water repellent, which makes them very interesting materials for engineers.

Cellulose aerogels, made from nanofibrils found in plants, have several unique features, one of which is super high oil absorption capacity that is several times higher than commercial sorbents available in the market.

“Encouraged from our previous work on transparent wood (“Transparent wood for functional and structural applications”; “Optically Transparent Wood from a Nanoporous Cellulosic Template: Combining Functional and Structural Performance”; “Nanostructured Wood Hybrids for Fire-Retardancy Prepared by Clay Impregnation into the Cell Wall”), we started to develop porous wood/epoxy biocomposite materials, which preserves the original hierarchical and porous structure of wood,” Qi Zhou, an associate professor in the Department of Chemistry at KTH Royal Institute of Technology, tells Nanowerk.

“Our strategy is different from traditional wood modification methods,” explains Zhou. “It involves two steps, a simple chemical treatment to remove the lignin (delignification) at first, then back infiltration of the wood cell wall with epoxy, leaving the lumen (a void space) open. In traditional wood polymer composites, both the cell wall and cell lumen are filled with polymer.”

The scientists don’t seem to have any particular applications in mind but they are hopeful that new materials will inspire new uses. Here’s a link to and a citation for Zhou’s latest paper,

Wood Nanotechnology for Strong, Mesoporous, and Hydrophobic Biocomposites for Selective Separation of Oil/Water Mixtures by Qiliang Fu, Farhan Ansari, Qi Zhou, and Lars A. Berglund. ACS Nano, Article ASAP DOI: 10.1021/acsnano.8b00005 Publication Date (Web): February 7, 2018

Copyright © 2018 American Chemical Society

This paper is behind a paywall.

Eye implants inspired by glasswing butterflies

Glasswinged butterfly. Greta oto. Credit: David Tiller/CC BY-SA 3.0

My jaw dropped on seeing this image and I still have trouble believing it’s real. (You can find more image of glasswinged butterflies here in an Cot. 25, 2014 posting on thearkinspace. com and there’s a video further down in the post.)

As for the research, an April 30, 2018 news item on phys.org announces work that could improve eye implants,

Inspired by tiny nanostructures on transparent butterfly wings, engineers at Caltech have developed a synthetic analogue for eye implants that makes them more effective and longer-lasting. A paper about the research was published in Nature Nanotechnology.

An April 30, 2018 California Institute of Technology (CalTech) news release (also on EurekAlert) by Robert Perkins, which originated the news item, goes into more detail,

Sections of the wings of a longtail glasswing butterfly are almost perfectly transparent. Three years ago, Caltech postdoctoral researcher Radwanul Hasan Siddique–at the time working on a dissertation involving a glasswing species at Karlsruhe Institute of Technology in Germany–discovered the reason why: the see-through sections of the wings are coated in tiny pillars, each about 100 nanometers in diameter and spaced about 150 nanometers apart. The size of these pillars–50 to 100 times smaller than the width of a human hair–gives them unusual optical properties. The pillars redirect the light that strikes the wings so that the rays pass through regardless of the original angle at which they hit the wings. As a result, there is almost no reflection of the light from the wing’s surface.

In effect, the pillars make the wings clearer than if they were made of just plain glass.

That redirection property, known as angle-independent antireflection, attracted the attention of Caltech’s Hyuck Choo. For the last few years Choo has been developing an eye implant that would improve the monitoring of intra-eye pressure in glaucoma patients. Glaucoma is the second leading cause of blindness worldwide. Though the exact mechanism by which the disease damages eyesight is still under study, the leading theory suggests that sudden spikes in the pressure inside the eye damages the optic nerve. Medication can reduce the increased eye pressure and prevent damage, but ideally it must be taken at the first signs of a spike in eye pressure.

“Right now, eye pressure is typically measured just a couple times a year in a doctor’s office. Glaucoma patients need a way to measure their eye pressure easily and regularly,” says Choo, assistant professor of electrical engineering in the Division of Engineering and Applied Science and a Heritage Medical Research Institute Investigator.

Choo has developed an eye implant shaped like a tiny drum, the width of a few strands of hair. When inserted into an eye, its surface flexes with increasing eye pressure, narrowing the depth of the cavity inside the drum. That depth can be measured by a handheld reader, giving a direct measurement of how much pressure the implant is under.

One weakness of the implant, however, has been that in order to get an accurate measurement, the optical reader has to be held almost perfectly perpendicular–at an angle of 90 degrees (plus or minus 5 degrees)–with respect to the surface of the implant. At other angles, the reader gives an incorrect measurement.

And that’s where glasswing butterflies come into the picture. Choo reasoned that the angle-independent optical property of the butterflies’ nanopillars could be used to ensure that light would always pass perpendicularly through the implant, making the implant angle-insensitive and providing an accurate reading regardless of how the reader is held.

He enlisted Siddique to work in his lab, and the two, working along with Caltech graduate student Vinayak Narasimhan, figured out a way to stud the eye implant with pillars approximately the same size and shape of those on the butterfly’s wings but made from silicon nitride, an inert compound often used in medical implants. Experimenting with various configurations of the size and placement of the pillars, the researchers were ultimately able to reduce the error in the eye implants’ readings threefold.

“The nanostructures unlock the potential of this implant, making it practical for glaucoma patients to test their own eye pressure every day,” Choo says.

The new surface also lends the implants a long-lasting, nontoxic anti-biofouling property.

In the body, cells tend to latch on to the surface of medical implants and, over time, gum them up. One way to avoid this phenomenon, called biofouling, is to coat medical implants with a chemical that discourages the cells from attaching. The problem is that such coatings eventually wear off.

The nanopillars created by Choo’s team, however, work in a different way. Unlike the butterfly’s nanopillars, the lab-made nanopillars are extremely hydrophilic, meaning that they attract water. Because of this, the implant, once in the eye, is soon encased in a coating of water. Cells slide off instead of gaining a foothold.

“Cells attach to an implant by binding with proteins that are adhered to the implant’s surface. The water, however, prevents those proteins from establishing a strong connection on this surface,” says Narasimhan. Early testing suggests that the nanopillar-equipped implant reduces biofouling tenfold compared to previous designs, thanks to this anti-biofouling property.

Being able to avoid biofouling is useful for any implant regardless of its location in the body. The team plans to explore what other medical implants could benefit from their new nanostructures, which can be inexpensively mass produced.

As if the still image wasn’t enough,

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

Multifunctional biophotonic nanostructures inspired by the longtail glasswing butterfly for medical devices by Vinayak Narasimhan, Radwanul Hasan Siddique, Jeong Oen Lee, Shailabh Kumar, Blaise Ndjamen, Juan Du, Natalie Hong, David Sretavan, & Hyuck Choo. Nature Nanotechnology (2018) doi:10.1038/s41565-018-0111-5 Published: 30 April 2018

This paper is behind a paywall.

ETA May 25, 2018:  I’m obsessed. Here’s one more glasswing image,

Caption: The clear wings make this South-American butterfly hard to see in flight, a succesfull defense mechanism. Credit: Eddy Van 3000 from in Flanders fields – Belgiquistan – United Tribes ov Europe Date: 7 October 2007, 14:35 his file is licensed under the Creative Commons Attribution-Share Alike 2.0 Generic license. [downloaded from https://commons.wikimedia.org/wiki/File:E3000_-_the_wings-become-windows_butterfly._(by-sa).jpg]

Getting chipped

A January 23, 2018 article by John Converse Townsend for Fast Company highlights the author’s experience of ‘getting chipped’ in Wisconsin (US),

I have an RFID, or radio frequency ID, microchip implanted in my hand. Now with a wave, I can unlock doors, fire off texts, login to my computer, and even make credit card payments.

There are others like me: The majority of employees at the Wisconsin tech company Three Square Market (or 32M) have RFID implants, too. Last summer, with the help of Andy “Gonzo” Whitehead, a local body piercer with 17 years of experience, the company hosted a “chipping party” for employees who’d volunteered to test the technology in the workplace.

“We first presented the concept of being chipped to the employees, thinking we might get a few people interested,” CEO [Chief Executive Officer] Todd Westby, who has implants in both hands, told me. “Literally out of the box, we had 40 people out of close to 90 that were here that said, within 10 minutes, ‘I would like to be chipped.’”

Westby’s left hand can get him into the office, make phone calls, and stores his living will and drivers license information, while the chip in his right hand is using for testing new applications. (The CEO’s entire family is chipped, too.) Other employees said they have bitcoin wallets and photos stored on their devices.

The legendary Gonzo Whitehead was waiting for me when I arrived at Three Square Market HQ, located in quiet River Falls, 40 minutes east of Minneapolis. The minutes leading up to the big moment were a bit nervy, after seeing the size of the needle (it’s huge), but the experience was easier than I could have imagined. The RFID chip is the size of a grain of basmati rice, but the pain wasn’t so bad–comparable to a bee sting, and maybe less so. I experienced a bit of bruising afterward (no bleeding), and today the last remaining mark of trauma is a tiny, fading scar between my thumb and index finger. Unless you were looking for it, the chip resting under my skin is invisible.

Truth is, the applications for RFID implants are pretty cool. But right now, they’re also limited. Without a near-field communication (NFC) writer/reader, which powers on a “passive” RFID chip to write and read information to the device’s memory, an implant isn’t of much use. But that’s mostly a hardware issue. As NFC technology becomes available, which is increasingly everywhere thanks to Samsung Pay and Apple Pay and new contactless “tap-and-go” credit cards, the possibilities become limitless. [emphasis mine]

Health and privacy?

Townsend does cover a few possible downsides to the ‘limitless possibilities’ offered by RFID’s combined with NFC technology,

From a health perspective, the RFID implants are biologically safe–not so different from birth control implants [emphasis mine]. [US Food and Drug Administration] FDA-sanctioned for use in humans since 2004, the chips neither trigger metal detectors nor disrupt [magnetic resonance imaging] MRIs, and their glass casings hold up to pressure testing, whether that’s being dropped from a rooftop or being run over by a pickup truck.

The privacy side of things is a bit more complicated, but the undeniable reality is that privacy isn’t as prized as we’d like to think [emphasis mine]. It’s already a regular concession to convenience.

“Your information’s for sale every day,” McMullen [Patrick McMullen, president, Three Square Market] says. “Thirty-four billion avenues exist for your information to travel down every single day, whether you’re checking Facebook, checking out at the supermarket, driving your car . . . your information’s everywhere.

Townsend may not be fully up-to-date on the subject of birth control implants. I think ‘safeish’ might be a better description in light of this news of almost two years ago (from a March 1, 2016 news item on CBS [Columbia Broadcasting Service] News [online]), Note: Links have been removed,

[US] Federal health regulators plan to warn consumers more strongly about Essure, a contraceptive implant that has drawn thousands of complaints from women reporting chronic pain, bleeding and other health problems.

The Food and Drug Administration announced Monday it would add a boxed warning — its most serious type — to alert doctors and patients to problems reported with the nickel-titanium implant.

But the FDA stopped short of removing the device from the market, a step favored by many women who have petitioned the agency in the last year. Instead, the agency is requiring manufacturer Bayer to conduct studies of the device to further assess its risks in different groups of women.

The FDA is requiring Bayer to conduct a study of 2,000 patients comparing problems like unplanned pregnancy and pelvic pain between patients getting Essure and those receiving traditional “tube tying” surgery. Agency officials said they have reviewed more than 600 reports of women becoming pregnant after receiving Essure. Women are supposed to get a test after three months to make sure Essure is working appropriately, but the agency noted some women do not follow-up for the test.

FDA officials acknowledged the proposed study would take years to complete, but said Bayer would be expected to submit interim results by mid-2017.

According to a Sept. 25, 2017 article by Kerri O’Brien for WRIC.com, Bayer had suspended sales of their device in all countries except the US,

Bayer, the manufacturer of Essure, has announced it’s halting sales of Essure in all countries outside of the U.S. In a statement, Bayer told 8News it’s due to a lack of interest in the product outside of the U.S.

“Bayer made a commercial decision this Spring to discontinue the distribution of Essure® outside of the U.S. where there is not as much patient interest in permanent birth control,” the statement read.

The move also comes after the European Union suspended sales of the device. The suspension was prompted by the National Standards Authority of Ireland declining to renew Essure’s CE marketing. “CE,” according to the European Commission website signifies products sold in the EEA that has been assessed to meet “high safety, health, and environmental protection requirements.”

These excerpts are about the Essure birth control implant. Perhaps others are safer? That noted, it does seem that Townsend was a bit dismissive of safety concerns.

As for privacy, he does investigate further to discover this,

As technology evolves and becomes more sophisticated, the methods to break it also evolve and get more sophisticated, says D.C.-based privacy expert Michelle De Mooy. Even so, McMullen believes that our personal information is safer in our hand than in our wallets. He  says the smartphone you touch 2,500 times a day does 100 times more reporting of data than does an RFID implant, plus the chip can save you from pickpockets and avoid credit card skimmers altogether.

Well, the first sentence suggests some caution. As for De Mooy, there’s this from her profile page on the Center for Democracy and Technology website (Note: A link has been removed),

Michelle De Mooy is Director of the Privacy & Data Project at the Center for Democracy & Technology. She advocates for data privacy rights and protections in legislation and regulation, works closely with industry and other stakeholders to investigate good data practices and controls, as well as identifying and researching emerging technology that impacts personal privacy. She leads CDT’s health privacy work, chairing the Health Privacy Working Group and focusing on the intersection between individual privacy, health information and technology. Michelle’s current research is focused on ethical and privacy-aware internal research and development in wearables, the application of data analytics to health information found on non-traditional platforms, like social media, and the growing market for genetic data. She has testified before Congress on health policy, spoken about native advertising at the Federal Trade Commission, and written about employee wellness programs for US News & World Report’s “Policy Dose” blog. Michelle is a frequent media contributor, appearing in the New York Times, the Guardian, the Wall Street Journal, Vice, and the Los Angeles Times, as well as on The Today Show, Voice of America, and Government Matters TV programs.

Ethics anyone?

Townsend does raise some ethical issues (Note: A link has been removed),

… Word from CEO Todd Westby is that parents in Wisconsin have been asking whether (and when) they can have their children implanted with GPS-enabled devices (which, incidentally, is the subject of the “Arkangel” episode in the new season of Black Mirror [US television programme]). But that, of course, raises ethical questions: What if a kid refused to be chipped? What if they never knew?

Final comments on implanted RFID chips and bodyhacking

It doesn’t seem that implantable chips have changed much since I first wrote about them in a May 27, 2010 posting titled: Researcher infects self with virus.  In that instance, Dr Mark Gasson, a researcher at the University of Reading. introduced a virus into a computer chip implanted in his body.

Of course since 2010, there are additional implantable items such as computer chips and more making their way into our bodies and it doesn’t seem to be much public discussion (other than in popular culture) about the implications.

Presumably, there are policy makers tracking these developments. I have to wonder if the technology gurus will continue to tout these technologies as already here or having made such inroads that we (the public) are presented with a fait accompli with the policy makers following behind.

Hedy Lamarr documentary

It was the tech community which brought Hedy Lamarr’s scientific and technical accomplishments to light in the 1990s. The movie actress was better known for other aspects of her work and life.

She was the first actress to portray an orgasm on screen, the movie was Ecstasy (in English), the year was 1933; and, Hedy Lamarr was 18 years-old. Shortly after the film was released, Lamarr, of Jewish descent, married Friedrich Mandl, a wealthy Austrian with ties to fascist regimes led by Adolph Hitler and Benito Mussolini. A controlling and jealous man, she eventually escaped Mandl in the middle of the night with all the jewels she could pack on her person.

That’s just the prelude for a documentary celebrating the extraordinary Lamarr. ‘Bombshell: The Hedy Lamarr Story’ (directed and written by Alexandra Dean) has been making its way around the festival circuit for the last several months. I saw it at the Vancouver International Film Festival (VIFF) in October 2017 and the house was packed.

(If you missed it on the festival circuit, don’t worry. It’s being broadcast by most, if not all PBS stations, on May 18, 2018 as part of the American Masters series.)

*ETA video clips May 18, 2018 at 0945 hours PDT*

Over the last few decades there’s been a major reevaluation of Lamarr’s place in history. She was dangerous not just for her beauty (bombshell) but also in the way that people who aren’t easily categorized are always dangerous.

Before she did her ground-breaking work as an inventor and after her dramatic middle-of-the-night escape, Lamarr made her way to London* where she sought out Louis B. Mayer in 1937 and turned down his offer of a contract at MGM. Not enough money. Instead, she booked passage n a ship bound for New York City which was also carrying Louis B. Mayer and his wife. By the time they landed, Lamarr had gotten a contract that she was happy with and a brand-new name. Hedwig Eva Maria Kiesler effectively became Hedy Lamarr for the rest of her life.

Lamarr’s famous quote: “Any girl can be glamorous. All you have to do is stand still and look stupid,” provides an interesting juxtaposition with her role (along with avant-garde musician and composer George Antheil) in developing a technology that laid the basis for secure Wi-Fi, GPS (global positioning system), and Bluetooth. Or as some of us think of it, life in the 21st century.

She claimed to have advised Howard Hughes on the design for the of his airplanes; she was inspired by the wings on birds and fins on fish. She created a tablet that when reconstituted with water became a carbonated drink (according to Lamarr, it was not very tasty). There was also her influence in the field of plastic surgery. Those incisions that are in hard-to-see places? That was at Hedy Lamarr’s suggestion.

Her inventions spanned electrical engineering (telecommunications), bio-inspired engineering and physics (airplane wings), chemistry (the drink tablets), and plastic surgery. That’s an extraordinary range and there’s more. She created her own movie production company in 1945/46* (it was a failure) and was instrumental in designing a resort (she was never fairly recompensed for that).

She suffered throughout her life in various ways.The US government shafted her and George Antheil by politely refusing their invention in 1942. To be fair, it would have been difficult to use with the technology available at the time but somebody must have recognized its potential. At some point in the 1950s the US Navy developed the technology (without informing either inventor or compensating them as had been their deal).

There was more, her achievements were ignored or, worse, attributed to anyone except her the better part of her life; the Hollywood factory is not kind to older actresses, especially those of Lamarr’s generation; and she made serious mistakes.

Ironically, one of those mistakes involved plastic surgery. It’s hard to know what the effect will be on television but in the movie house, there was a big gasp when some footage from her last years was shown. She’s not monstrous but after an hour or more of footage from her ‘glamorous’ years, it’s a bit of a shock. If you can see past the effects of some ‘bad’ plastic surgery, you’ll find a woman who despite everything kept on. She never gave up and there’s a kind of beauty in that act which is indelible in a way that her physical beauty could never hope to be.

The documentary is fascinating not only for what it includes but for what it doesn’t. You’d think she’d never had a woman friend in her life but according to J. E. Smyth’s 2018 book ‘Nobody’s Girl Friday; The Women Who Ran Hollywood’, she and Bette Davis were good friends. There’s also mention of her poverty but none of her late life litigiousness and the $3M estate she left when she died in 2000.*** At a guess, having learned from the debacle with the US Navy (she could have sued but didn’t realize she had the right), she litigated her way into some financial health. As for the ‘Time’s Up’ and ‘Me Too’ movements which have formed since the Hollywood sex scandals of 2017 – ????, one can only imagine what Lamarr’s stories might have been.

If you have the time, see the documentary. Lamarr was a helluva dame.

*’Paris’ corrected to ‘London’ and ‘1945’ changed to 1945/46′ on on May 21, 2018 after watching the PBS broadcast of the documentary on May 18, 2018.

.***ETA May 21, 2018: See the Hedy Lamarr Wikipedia entry for more about her estate and other details of her life.***

CRISPR-Cas12a as a new diagnostic tool

Similar to Cas9, Cas12a is has an added feature as noted in this February 15, 2018 news item on ScienceDaily,

Utilizing an unsuspected activity of the CRISPR-Cas12a protein, researchers created a simple diagnostic system called DETECTR to analyze cells, blood, saliva, urine and stool to detect genetic mutations, cancer and antibiotic resistance and also diagnose bacterial and viral infections. The scientists discovered that when Cas12a binds its double-stranded DNA target, it indiscriminately chews up all single-stranded DNA. They then created reporter molecules attached to single-stranded DNA to signal when Cas12a finds its target.

A February 15, 2018 University of California at Berkeley (UC Berkeley) news release by Robert Sanders and which originated the news item, provides more detail and history,

CRISPR-Cas12a, one of the DNA-cutting proteins revolutionizing biology today, has an unexpected side effect that makes it an ideal enzyme for simple, rapid and accurate disease diagnostics.

blood in test tube

(iStock)

Cas12a, discovered in 2015 and originally called Cpf1, is like the well-known Cas9 protein that UC Berkeley’s Jennifer Doudna and colleague Emmanuelle Charpentier turned into a powerful gene-editing tool in 2012.

CRISPR-Cas9 has supercharged biological research in a mere six years, speeding up exploration of the causes of disease and sparking many potential new therapies. Cas12a was a major addition to the gene-cutting toolbox, able to cut double-stranded DNA at places that Cas9 can’t, and, because it leaves ragged edges, perhaps easier to use when inserting a new gene at the DNA cut.

But co-first authors Janice Chen, Enbo Ma and Lucas Harrington in Doudna’s lab discovered that when Cas12a binds and cuts a targeted double-stranded DNA sequence, it unexpectedly unleashes indiscriminate cutting of all single-stranded DNA in a test tube.

Most of the DNA in a cell is in the form of a double-stranded helix, so this is not necessarily a problem for gene-editing applications. But it does allow researchers to use a single-stranded “reporter” molecule with the CRISPR-Cas12a protein, which produces an unambiguous fluorescent signal when Cas12a has found its target.

“We continue to be fascinated by the functions of bacterial CRISPR systems and how mechanistic understanding leads to opportunities for new technologies,” said Doudna, a professor of molecular and cell biology and of chemistry and a Howard Hughes Medical Institute investigator.

DETECTR diagnostics

The new DETECTR system based on CRISPR-Cas12a can analyze cells, blood, saliva, urine and stool to detect genetic mutations, cancer and antibiotic resistance as well as diagnose bacterial and viral infections. Target DNA is amplified by RPA to make it easier for Cas12a to find it and bind, unleashing indiscriminate cutting of single-stranded DNA, including DNA attached to a fluorescent marker (gold star) that tells researchers that Cas12a has found its target.

The UC Berkeley researchers, along with their colleagues at UC San Francisco, will publish their findings Feb. 15 [2018] via the journal Science’s fast-track service, First Release.

The researchers developed a diagnostic system they dubbed the DNA Endonuclease Targeted CRISPR Trans Reporter, or DETECTR, for quick and easy point-of-care detection of even small amounts of DNA in clinical samples. It involves adding all reagents in a single reaction: CRISPR-Cas12a and its RNA targeting sequence (guide RNA), fluorescent reporter molecule and an isothermal amplification system called recombinase polymerase amplification (RPA), which is similar to polymerase chain reaction (PCR). When warmed to body temperature, RPA rapidly multiplies the number of copies of the target DNA, boosting the chances Cas12a will find one of them, bind and unleash single-strand DNA cutting, resulting in a fluorescent readout.

The UC Berkeley researchers tested this strategy using patient samples containing human papilloma virus (HPV), in collaboration with Joel Palefsky’s lab at UC San Francisco. Using DETECTR, they were able to demonstrate accurate detection of the “high-risk” HPV types 16 and 18 in samples infected with many different HPV types.

“This protein works as a robust tool to detect DNA from a variety of sources,” Chen said. “We want to push the limits of the technology, which is potentially applicable in any point-of-care diagnostic situation where there is a DNA component, including cancer and infectious disease.”

The indiscriminate cutting of all single-stranded DNA, which the researchers discovered holds true for all related Cas12 molecules, but not Cas9, may have unwanted effects in genome editing applications, but more research is needed on this topic, Chen said. During the transcription of genes, for example, the cell briefly creates single strands of DNA that could accidentally be cut by Cas12a.

The activity of the Cas12 proteins is similar to that of another family of CRISPR enzymes, Cas13a, which chew up RNA after binding to a target RNA sequence. Various teams, including Doudna’s, are developing diagnostic tests using Cas13a that could, for example, detect the RNA genome of HIV.

infographic about DETECTR system

(Infographic by the Howard Hughes Medical Institute)

These new tools have been repurposed from their original role in microbes where they serve as adaptive immune systems to fend off viral infections. In these bacteria, Cas proteins store records of past infections and use these “memories” to identify harmful DNA during infections. Cas12a, the protein used in this study, then cuts the invading DNA, saving the bacteria from being taken over by the virus.

The chance discovery of Cas12a’s unusual behavior highlights the importance of basic research, Chen said, since it came from a basic curiosity about the mechanism Cas12a uses to cleave double-stranded DNA.

“It’s cool that, by going after the question of the cleavage mechanism of this protein, we uncovered what we think is a very powerful technology useful in an array of applications,” Chen said.

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

CRISPR-Cas12a target binding unleashes indiscriminate single-stranded DNase activity by Janice S. Chen, Enbo Ma, Lucas B. Harrington, Maria Da Costa, Xinran Tian, Joel M. Palefsky, Jennifer A. Doudna. Science 15 Feb 2018: eaar6245 DOI: 10.1126/science.aar6245

This paper is behind a paywall.

May 16, 2018: UNESCO’s (United Nations Educational, Scientific and Cultural Organization) First International Day of Light

Courtesy: UNESCO

From a May 11, 2018 United Nations Educational, Scientific and Cultural Organization (UNESCO) press release (received via email),

UNESCO will welcome leading scientists on 16 May 2018 for the 1st edition of the International Day of Light (02:30-08:00 pm) to celebrate the role light plays in our daily lives. Researchers and intellectuals will examine how light-based technologies can contribute to meet pressing challenges in diverse areas, such as medicine, education, agriculture and energy.

            UNESCO Director-General Audrey Azoulay will open this event, which will count with the participation of renowned scientists, including:

  • Kip Thorne, 2017 Nobel Prize in Physics, California Institute of Technology (United States of America).
  • Claude Cohen-Tannoudji, 1997 Nobel Prize in Physics, Collège de France.
  • Khaled Toukan, Director of the Synchrotron-light for Experimental Science and Applications in the Middle East (SESAME) based in Allan, Jordan.

The programme of keynotes and roundtables will address many key issues including science policy, our perception of the universe, and international cooperation, through contributions from experts and scientists from around the world.

The programme also includes cultural events, an illumination of UNESCO Headquarters, a photonics science show and an exhibit on the advances of light-based technologies and art.

            The debates that flourished in 2015, in the framework of the International Year of Light, highlighted the importance of light sciences and light-based technologies in achieving the United Nations Sustainable Development Goals. Several thousand events were held in 147 countries during the Year placed under the auspices of UNESCO.  

The proclamation of 16 May as the International Day of Light was supported by UNESCO’s Executive Board following a proposal by Ghana, Mexico, New Zealand and the Russian Federation, and approved by the UNESCO General Conference in November 2017.

More information:

I have taken a look at the programme which is pretty interesting. Unfortunately, I can’t excerpt parts of it for inclusion here as very odd things happen when I attempt to ‘copy and paste’. On the plus side. there’s a bit more information about this ‘new day’ on its event page,

Light plays a central role in our lives. On the most fundamental level, through photosynthesis, light is at the origin of life itself. The study of light has led to promising alternative energy sources, lifesaving medical advances in diagnostics technology and treatments, light-speed internet and many other discoveries that have revolutionized society and shaped our understanding of the universe. These technologies were developed through centuries of fundamental research on the properties of light – starting with Ibn Al-Haytham’s seminal work, Kitab al-Manazir (Book of Optics), published in 1015 and including Einstein’s work at the beginning of the 20th century, which changed the way we think about time and light.

The International Day of Light celebrates the role light plays in science, culture and art, education, and sustainable development, and in fields as diverse as medicine, communications, and energy. The will allow many different sectors of society worldwide to participate in activities that demonstrates how science, technology, art and culture can help achieve the goals of UNESCO – building the foundation for peaceful societies.

The International Day of Light is celebrated on 16 May each year, the anniversary of the first successful operation of the laser in 1960 by physicist and engineer, Theodore Maiman. This day is a call to strengthen scientific cooperation and harness its potential to foster peace and sustainable development.

Happy International Day of Light on Wednesday, May 16, 2018!

“Living” bandages made from biocompatible anti-burn nanofibers

A February 16, 2018 news item on Nanowerk announces research from a Russian team about their work on “living” bandages,

In regenerative medicine, and particularly in burn therapy, the effective regeneration of damaged skin tissue and the prevention of scarring are usually the main goals. Scars form when skin is badly damaged, whether through a cut, burn, or a skin problem such as acne or fungal infection.

Scar tissue mainly consists of irreversible collagen and significantly differs from the tissue it replaces, having reduced functional properties. For example, scars on skin are more sensitive to ultraviolet radiation, are not elastic, and the sweat glands and hair follicles are not restored in the area.

The solution of this medical problem was proposed by the researchers from the NUST MISIS [National University of Science and Technology {formerly Moscow Institute of Steel and Alloys State Technological University})] Inorganic Nanomaterials Laboratory, led by PhD Anton Manakhov, a senior researcher. The team of nanotechnology scientists has managed to create multi-layer ‘bandages’ made of biodegradable fibers and multifunctional bioactive nanofilms, which [the bandages] prevent scarring and accelerate tissue regeneration.

A February 14, 2018 NUST MISIS press release, which originated the news item, provides more detail,

The addition of the antibacterial effect by the introduction of silver nanoparticles or joining antibiotics, as well as the increase of biological activity to the surface of hydrophilic groups (-COOH) and the blood plasma proteins have provided unique healing properties to the material.

A significant acceleration of the healing process, the successful regeneration of normal skin covering tissue, and the prevention of scarring on the site of burnt or damaged skin have been observed when applying these bandages made of the developed material to an injured area. The antibacterial components of multifunctional nanofibers decrease inflammation, and the blood plasma with an increased platelet level — vital and multi-purposed for every element in the healing process — stimulates the regeneration of tissues. The bandages should not be removed or changed during treatment as it may cause additional pain to the patient. After a certain period of time, the biodegradable fiber simply “dissolves” without any side effects.

“With the help of chemical bonds, we were able to create a stable layer containing blood plasma components (growth factors, fibrinogens, and other important proteins that promote cell growth) on a polycaprolactone base. The base fibers were synthesized by electroforming. Then, with the help of plasma treatment, to increase the material`s hydrophilic properties, a polymer layer containing carboxyl groups was applied to the surface. The resulting layer was enriched with antibacterial and protein components”, noted Elizabeth Permyakova, one of the project members and laboratory scientists.

The researchers have made images of their work available including this one,

Courtesy NUST MISS [downloaded from http://en.misis.ru/university/news/science/2018-02/5219/]

There is doesn’t appear to be an accompanying published paper.

Tractor beams for artificial cells

This particular piece has videos of cells moving around. I won’t be including all of them but they are weirdly fascinating. First, a May 14, 2018 news item on Nanowerk announces the latest in tractor beam news from the Imperial College London (ICL; UK),

Researchers have used lasers to connect, arrange and merge artificial cells, paving the way for networks of artificial cells that act like tissues.

The team say that by altering artificial cell membranes they can now get the cells to stick together like ‘stickle bricks’ – allowing them to be arranged into whole new structures.

Biological cells can perform complex functions, but are difficult to controllably engineer.

Artificial cells, however, can in principle be made to order. Now, researchers from Imperial College London and Loughborough University have demonstrated a new level of complexity with artificial cells by arranging them into basic tissue structures with different types of connectivity.

These structures could be used to perform functions like initiating chemical reactions or moving chemicals around networks of artificial and biological cells. This could be useful in carrying out chemical reactions in ultra-small volumes, in studying the mechanisms through which cells communicate with one another, and in the development of a new generation of smart biomaterials.

A May 14, 2018 ICL press release by Hayley Dunning , which originated the news item, provides more detail,

Cells are the basic units of biology, which are capable of working together as a collective when arranged into tissues. In order to do this, cells must be connected and be capable of exchanging materials with one another.

The team were able to link up artificial cells into a range of new architectures, the results of which are published today in Nature Communications.

The artificial cells have a membrane-like layer as their shell, which the researchers engineered to ‘stick’ to each other. In order to get the cells to come close enough, the team first had to manipulate the cells with ‘optical tweezers’ that act like mini ‘tractor beams’ dragging and dropping cells into any position. Once connected in this way the cells can be moved as one unit.

Lead researcher Dr Yuval Elani, an EPSRC Research Fellow from the Department of Chemistry at Imperial, said: “Artificial cell membranes usually bounce off each other like rubber balls. By altering the biophysics of the membranes in our cells, we got them instead to stick to each other like stickle bricks.

“With this, we were able to form networks of cells connected by ‘biojunctions’. By reinserting biological components such as proteins in the membrane, we could get the cells to communicate and exchange material with one another. This mimics what is seen in nature, so it’s a great step forward in creating biological-like artificial cell tissues.”

Building up complexity

The team were also able to engineer a ‘tether’ between two cells. Here the membranes are not stuck together, but a tendril of membrane material links them so that they can be moved together.

Once they had perfected the cell-sticking process, the team were able to build up more complex arrangements. These include lines of cells, 2D shapes like squares, and 3D shapes like pyramids. Once the cells are stuck together, they can be rearranged, and also pulled by the laser beam as an ensemble

Finally, the team were also able to connect two cells, and then make them merge into one larger cell. This was achieved by coating the membranes with gold nanoparticles.

When the laser beam at the heart of the ‘optical tweezer’ technology was concentrated at the junction between the two cells, the nanoparticles resonated, breaking the membranes at that point. The membrane then reforms as a whole.

Merging cells in this way allowed whatever chemicals they were carrying to mix within the new, larger cell, kicking off chemical reactions. This could be useful, for example, for delivering materials such as drugs into cells, and in changing the composition of cells in real time, getting them to adopt new functions.

Professor Oscar Ces, also from the Department of Chemistry at Imperial, said: “Connecting artificial cells together is a valuable technology in the wider toolkit we are assembling for creating these biological systems using bottom-up approaches.

“We can now start to scale up basic cell technologies into larger tissue-scale networks, with precise control over the kind of architecture we create.”

Here’s one of the videos that has been embedded with ICL press release,

You can see the whole series if you go to the May 14, 2018 ICL press release.

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

Sculpting and fusing biomimetic vesicle networks using optical tweezers by Guido Bolognesi, Mark S. Friddin, Ali Salehi-Reyhani, Nathan E. Barlow, Nicholas J. Brooks, Oscar Ces, & Yuval Elani. Nature Communicationsvolume 9, Article number: 1882 (2018) doi:10.1038/s41467-018-04282-w Published: 14 May 2018

This paper is open access.