Monthly Archives: April 2021

Cheat Sheet: What a radical GOP antitrust bill that would kill big tech acquisitions has in common with the Democrats push for reform – Digiday

Posted: April 19, 2021 at 7:17 am

Republican Sen. Josh Hawley of Missouri has put what he called woke mega-corporations on notice, particularly tech platform giants including Facebook and Google.

However, new antitrust legislation he proposed could place drastic new restrictions on all sorts of big businesses.

Despite some similarities to a recent antitrust reform bill from Sen. Amy Klobuchar of Minnesota, bipartisan momentum behind Hawleys bill is likely to be tepid at best considering his polarizing push to contest the Electoral College vote on Jan. 6 certifying Joseph Biden as president. Still, the legislation could step up congressional dialogue around updating the governments approach to defining what anti-competitive behavior looks like in a tech-ruled era.

Hawleys bill is bold and could start a more vibrant discussion around antitrust reform in the Senate, suggestedBarry Pupkin, a senior partner focused on antitrust at law firm Squire Patton Boggs.Itseems sort of, I guess, radical, he said. I think you straitjacket a lot of possibly decent transactions, Pupkin continued, adding, I think though, it starts a dialogue.

So, whats so radical about it? Heres whatHawleysTrust-Busting for the Twenty-First Century Act,introducedon April 12, proposes:

The Democratic bill

On the other side of the aisle, anantitrust reform bill introducedin February by Democratic Sen. Amy Klobuchar, gives both the FTC and the Justice Department, the federal governments other trust-busting agency,more penalty power against companies, more resources and more money for hiring additional personnel. Heres whats important:

What the bills have in common

There is a key similarity between the two bills.Notably, said Pupkin, both Klobuchars and Hawleys proposals seek to shift the burden of proof away from the federal government to the defendant. Hawleys bill requires the party making the acquisition, rather than government regulators, to establish evidence that an acquisitions pro-competitive effects outweigh any anti-competitive impact. Klobuchars bill also would require corporations making acquisitions that are extremely large or could significantly increase market concentration to prove that snapping up other companies wouldnt harm competition.

Youre changing the burden of proof, said Pupkin. Right now, he said, The government has the burden of proving illegality.

Other big tech antitrust lawsuits are underway

Efforts related to anti-competitive practices among the big digital platforms are already underway at both the FTC and the DOJ.The FTC in December launched itsinvestigation into Facebook, alleging the company has maintained its monopoly on the social media industry by acquiring emerging rival Instagram in 2012 and mobile messaging appWhatsApp in 2014.The DOJ, several states and even a publisher group have filedantitrust lawsuits against Google, arguing that aspects of its search, digital ad business and decisions about third-party cookies are anti-competitive.

Hawleys history of fighting big techWhile Hawleys bill would affect all sorts of large companies beyond the tech industry, he has taken special interest in fighting tech platforms, arguing they have too much power and make biased decisions that stifle conservative voices.

A small group of woke mega-corporations control the products Americans can buy, the information Americans can receive and the speech Americans can engage in, said Hawley in a press statement introducing his bill.

Hawley has been a vocal critic of Facebook and Twitter for their decisions to ban prominent conservatives from their platforms for posting false or misleading information. These monopoly powers control our speech, our economy, our country and their control has only grown because Washington has aided and abetted their quest for endless power, he continued in the statement.

In addition to filing antitrust suits against Google and Facebook while attorney general of Missouri, in the last Congress he introducedreforms to Section 230, which protects websites from liabilities associated with information posted by others on their sites. His proposalwould stop large tech firms from discrimination when enforcing terms of service and allow users to sue them for breaching their contractual duty of good faith. And hesent a letter last year to TwitterCEO Jack Dorsey arguing the company did not deserve immunity under the Section 230 law after Twitter labeled as incorrect or misleading former President Donald Trumps tweets making false claims about the legitimacy of President Joseph Bidens presidential win.

Hawleys bill is unlikely to garner support from the left, butSome elements of Hawleys bill that would drastically limit business growth and advantage through acquisition might appeal to Democrats or progressives, suggested Pupkin. However, considering the senators reputation as a staunch Trump backer who led the push to block acceptance of the 2020 Electoral College results, Pupkin said the political optics would likely deter any bipartisan support or even real momentum behind the legislation.

Given Hawleys history in the last three months, particularly around Jan. 6, I think hes going to have tough time getting much of anything through, said Pupkin. A lot of Democrats might be willing to go along with legislation that prevents giant companies from growing, he suggested, but they wouldnt be able to go along with Hawley.

https://digiday.com/?p=410846

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Cheat Sheet: What a radical GOP antitrust bill that would kill big tech acquisitions has in common with the Democrats push for reform - Digiday

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Clubhouse, big tech or newcomers: who’ll win the social audio race? – Sifted

Posted: at 7:17 am

A few months after its beta version went live in March last year, social audio app Clubhouse had around 1.5k users. Fast track to January this year, and it hit 2m. A month later it had reached 10m and, across the same time period, its valuation has risen from $100m to $1bn.

Clubhouse is the most famous platform, but its not the only one. Its part of a growing cohort of new social media trying to capitalise off an increasing interest in audio content.

Jeremiah Owyang, a tech analyst and investor, describes audio as the Goldilocks medium: its not as impersonal as text but also not as invasive as video something particularly important for the Zoom-fatigued user.

For Leni Andronicos, the founder of new social audio app Logcast which went live on the App Store in Sweden this week the move to audio is all about users desires for a more authentic media.

Its almost like weve done a full 360 on the media evolution, she says. I believe the reason audio has become so popular is because, ultimately, language makes us human and language is the oldest form of building community and social relationships. Its through language that we get to know each other.

But things arent all rosy in audio app land. There are reports that, after the initial flux of new joiners to Clubhouse, retention is falling and so are app downloads.

Theres also a growing number of Clubhouse sceptics, including Twitters head of product Shaan Puri who, in this thread, laid out why he thinks the app will fail.

Puri said that the app has an interesting-ness problem: apps like TikTok and YouTube have millions of pieces of content to show their users, and an algorithm to select the right stuff. Clubhouse doesnt have that, because the content shown to the user has to be live.

Users need to be shown good content within seven seconds of opening an app, Puri said, and thats hard when you only have live (and therefore less) content to choose from. There are also those who say that the app just did well initially because the world was in lockdown and people wanted someone to chat to.

So, if this new cohort of audio apps can compete with Clubhouse, can they overcome the problems levelled at it too?

Andronicos says shes grateful for what Clubhouse has done for audio content. She started building Logcast in September 2019, six months before Clubhouses team started and back then, she says, investors didnt see why they should fund social audio.

Im thankful for Clubhouse because it accelerated the social audio space by at least three to five years, and made audio one of the hottest industries for investors.

Still, she maintains, Logcast is very different from Clubhouse. The central idea is to create a more informal version of podcasting, and to make the form social.

Users record logs of up to 10 minutes and upload them onto the app. Other users can follow their favourite creators and like their content or direct message them.

In an attempt to encourage authentic content, the app doesnt allow pre-recorded uploads; instead, users have one shot at pressing the record button, recording the content and publishing.

We want Gen Z teenagers in a couple of years to say oh whats a podcast, I only log!

We see ourselves in the sweet spot between Spotify who look after full length podcasts and Clubhouse, which is about live talks and jump-ins. Logcast is in the middle, for people who dont feel comfortable recording a longform podcast, but also dont feel confident jumping into a live conversation.Logcast doesnt rely on live content so perhaps could overcome the problem that Puri suggested Clubhouse is encountering; but it would still need to curate a lot of content before it was able to offer users the same instant gratification that apps like TikTok and YouTube achieve through their algorithms.

Although Logcast is building a mobile app, the companys really building it for the Airpods generation, says Andronicos.

I really believe that the next major computing interface will be Airpods and we wont be walking around holding phones anymore, well be using Airpods to communicate, build community and share social updates, she says.

We want Gen Z teenagers in a couple of years to say oh whats a podcast, I only log!

At present, Logcasts early users include comedians, entrepreneurs, influencers, parents and wellness experts.

There are a number of other companies building social audio apps, a lot of which are based in the US.

American entrepreneur Mark Cuban is developing an app, Fireside Chat, which is described as a next-gen podcast app where users can record live conversations then record and broadcast them. The app will also have built-in analytics so creators can work out which content performs best and monetise it.

In the US, theres also Discord, which runs audio hangout rooms for groups and Chalk, which does a similar thing providing secure voice hangout rooms.

In Europe, alongside Logcast, theres Soapbox, built by a Swiss and German team.

Soapbox differs from Logcast and Clubhouse in that it wants to create serendipitous conversations between people, rather than being about semi-professionalised content creation.

Clubhouse is your conference. Soapbox is your living room, says Dean Eigenmann, the apps founder. The app places you into a conversation with strangers and provides mini games for users to play together. The next iteration of the app will match users together based on their interests.

Our mission is to provide a space for people to have naturally flowing conversations in a way that builds upon and enhances the real life experience of hanging out with friends and meeting new people, says Eigenmann.

Theres also Anyone, which, like Logcast, is based in Sweden (the country tends to do well on audio, following in Spotifys footsteps). Anyone allows people to schedule five minute conversations with people offering advice, from financial guidance to relationship support.

As well as new companies popping up to produce social audio apps, big tech companies like Twitter, Spotify and Facebook are also looking to capitalise off the interest in voice content.

In March, Spotify acquired Locker Room, a live audio app where, at present, users talk specifically about sports.

Spotify has said itll expand the areas Locker Room covers to include music and culture too, and use it to give professional athletes, writers, musicians, songwriters and podcasters opportunity to host real-time discussions with their fans.

The acquisition forms part of the companys future of formats of audio manifesto, set out in February this year, which highlighted the need for podcasting to move beyond being a one-way street from creators to listeners with little opportunity for feedback.

Twitter, meanwhile, has been working on Twitter Spaces, which is in test mode but is expected to be rolled out to more users very soon. The idea is that a host could start a room where followers can join and discuss a topic.

It was also reported that Twitter tried to buy Clubhouse itself, with people close to the matter saying a figure of $4bn was discussed.

Facebooks also reported to be working on a feature to rival Clubhouse. Last year, the company launched Rooms, which allows users to video call in groups, and its rumoured to be working on an audio-only equivalent.

Sameer Singh is an investor who also advises startups on network effects. He used to work at App Annie, and is interested in new forms of social media.

Getting the network right is still a challenge for social audio; its easy to create something that goes viral then falls off a cliff, Singh says. Building something that people flock to for the novelty is relatively achievable, but its a lot harder to make something with a network that sticks around.

People are more likely to tap into Spaces to see whats going on. That behaviour isnt likely on Clubhouse.

The biggest challenge with audio is that if you want to do live conversations, you need an audience who you know will be there. Thats hard if your product isnt very here and now already.

That puts Twitter in a strong position, Singh says. If it can figure out the strategy for Spaces, he says, Twitter will have a huge advantage because it already has a high level of live engagement on its news feed.

People are more likely to tap into Spaces to see whats going on. That behaviour isnt likely on Clubhouse.

This means apps like Logcast, which are focused on asynchronous content and arent trying to compete with Twitter on a live engagement front, could do well.

Theres room for Clubhouse to do well too, Singh says, if it focuses on being a scheduled destination app, something its moving increasingly towards. But if Twitter can work out a way to hack scheduled conversations as well, it could come to dominate on both fronts.

Freya Pratty is Sifteds news reporter. She tweets from @FPratty

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Digital Transformation Experts Debate Future of Banking, Big Tech & Fintech – The Financial Brand

Posted: at 7:17 am

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The outlook for the branch, the need for a much better digital onboarding experience, the future of relationships between financial institutions, fintechs and big techs are all hot topics in banking. But Jim Marous says making sure your financial institution has a future comes down to one word: Google.

Marous, Co-Publisher of The Financial Brand, CEO of the Digital Banking Report and host of the Banking Transformed Podcast, is one of the leading commentators on digital change in banking. He spent some time in banking and still remembers with pleasure the smell of fresh ink on product brochures. But thats nostalgia, he admits, and not the present, let alone the future.

The reality is that you have to realize that in the world were living in now, people start shopping for financial accounts on Google, says Marous during a debate with fellow industry analyst Ron Shevlin, Research Director at Cornerstone Advisors and author of the Forbes Fintech Snark Tank blog. If they dont find your bank or credit unions offerings through paid or organic search, they will find the likes of Chime or one of the big five banks, says Marous. And after that, any institution that offers a clunky or only partly digital onboarding experience risks losing the prospect after all.

During a pair of debates sponsored by MX Marous and Shevlin debated each other (as well as the status quo) concerning the future of banking and fintech.

For his part, Shevlin says people make too much about fintechs ability to score huge wins simply by the word of mouth of ecstatic fans.

You keep hearing how they do alternative marketing and that they dont do traditional TV or print advertising, says Shevlin. But he says the really successful fintech players spend buckets of money on marketing.

Chime spends $50, $60 million a year on TV alone, says Shevlin. This is a key part of what makes fintechs repeated funding rounds so important. Getting off the ground and staying airborne demands hunks of marketing spending.

But Marous believes that even with lots of marketing dollars or great word of mouth, the growing room for fintechs isnt as wide and as deep as some bank and credit union executives might think.

Im going to argue that its hard if youre not really something new and different, says Marous. Im not so sure there are many new and different fintechs out there. There are different flavors of the same themes.

In some ways the pairs discussion revealed that even fintechs, the wunderkinds of finance for a decade, have their own challenges, including from big techs like Google, Apple, Amazon and more.

Shevlin says that many fintechs, especially those coming from overseas, insist that what they bring to the market is a better customer experience, especially on mobile devices. However, he says he doesnt see the bank experience lacking, especially not among the largest U.S. banks.

And it is not as if every fintech or challenger bank steps up to the plate and smacks a home run. For every Chime or Dave there are others that have morphed into something else or disappeared.

I think a lot of those challengers that failed did so because they were not focused on solving the right problems, says Shevlin.

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The common wisdom is that banks sit on huge amounts of incredibly valuable data that can be turned into customer insights that will yield amazing results. The argument is that banks just dont know how to extract the value.

Shevlin offers this counterpoint: A good deal of the data isnt all that valuable in the first place. Often financial institutions completely delude themselves when they think, Oh, we have so much great data internally. They dont.

However, even what they do have could be useful. To a large extent, incumbent institutions just go to market with generic products and services and dont really bake their data into it, Shevlin points out.

Marous puts it another way: Its not that banks dont have data or dont utilize it. Theyve got to move from making great reports to making great experiences. Too often data doesnt get deployed outside of the IT department.

Data comes both from without and from within, of course. As an example of a fintech that makes great use of data, Shevlin cites Aspiration. The company offers banking services to consumers who place high value on their money supporting environmentally and socially conscious activities. Part of how it enforces that is a regimented system for scoring companies for their behavior and policies.

Separately, Shevlin says that there is a great deal of hype in the market concerning lending on the basis of alternative data. Different people define this different ways, ranging from increasingly accepted measures such as a record of making rent payments on a timely basis to more unusual methods.

Im still a little bit amazed that there are people who think they can make lending decisions based on who your social media contacts are, says Shevlin.

Drive Transformation and Maximize Customer Lifetime Value

Are financial institutions leveraging current digital customer communication trends to drive Customer Lifetime Value and fast track their digital banking transformation efforts?

Wednesday, April 28th at 2pm (ET)

The debaters looked at two masters of data analytics who have had strong interest in financial services: Amazon and Google.

Marous continues to be impressed by Amazon and its ability to pinpoint products for consumers based on data. He sees Amazons revenues as the ultimate funding vehicle for competing with banking institutions.

If Amazon put together a checking account tomorrow and offered me $250 to open one, Im there, says Marous. They could open millions of accounts.

He believes banking has found itself to be in a very narrow space, in terms of the activities it can pursue, while Amazon, true to its A to Z roots, can get into nearly anything. It has already done more than nibbling in some financial areas. In fact, he says Amazons success and size enables it to do things no banking institution could.

Case in point is product returns: To cut costs, Amazon sometimes will replace an item without asking the consumer to return it. Wrong color? Wrong size? Keep it. We got this, is Amazons attitude, he says. Theres not a financial institution out there that could say that.

Shevlin doesnt see anything like Amazon Bank happening. First, he says, the regulatory burdens of actually being a bank are unappealing. Why go there when you can partner? Amazon has done that, and Google, with its Google Plex partnerships, has as well.

Beyond this, Shevlin made a picks and shovels argument. Both Amazon and Google make huge amounts of money serving the cloud computing needs of financial institutions and can reap those profits without being regulated. So why, he asks, would they endanger that?

Fintechs have long brought unbankerly speed to the table. People have even been willing to pay much higher interest rates on small business loans, for example, in exchange for the speed that online nonbank business lenders began providing.

Shevlin and Marous were asked if speed and reliability trump security today.

Admitting to being snarky, Shevlin says they clearly do. If you have a security breach, you can always blame it on someone else, he says. More seriously, he says that consumers have grown so used to hearing about data breaches that that alone wouldnt turn them off unless the app or other service already lacked speed and reliability.

Indeed, the issue of trust in fintechs came up in this context.

Marous points out that many apps break up the monolithic banking relationship into smaller parts that do one or two things really well. More recently the movement has been for the narrower fintechs to start broadening their offerings and approaches.

If these organizations scale to different areas of banking that theyre not currently in Im going to trust them because theyve proven their worth, says Marous.

For his part, Shevlin isnt sold on trust in fintechs. They do deliver on their promises, he says, but they part ways with traditional institutions in the area of risk management.

It is built into banks culture to be risk averse, says Shevlin, but the startups in this space, especially those that go after consumers, have less of that risk aversion.

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Much of the discussion recounted above reflects very current thinking in financial services practices. The thing of it is, for every traditional institution that has been sweating to innovate, there are many more that havent done much to adapt to financial evolution.

Shevlin is pretty blunt about this: I dont think theres a single bank or credit union CEO out there who thinks that he or she and the rest of their management team has a legacy mindset. Even when they hear the word, legacy, they will tend to think of legacy computer processing.

Replacing old core systems is important, but what concerns Shevlin more is legacy thinking about financial services. Case in point: Having seen the dramatic shift to digital channels during the pandemic, many financial institutions are talking today about getting branches open again as if the last year hadnt happened.

People have to start thinking more about how technology can enable those person-to-person interactions that traditionally happened in branches, not necessarily to replace them, but to augment them, says Shevlin.

Marous says institutions have to hold onto legacy leaders experience while introducing new thinking. With their experience, the leaders have to pull the trigger to make change happen, he says.

The two experts differ markedly in their thinking of how to make change happen.

Marous portrays the typical employee base as full of scared people worried about becoming unemployed because of change. Banks and credit unions must train them for changing conditions and methods and for new roles. They still have a role, he says, because consumers want a humanized version of digital.

Such measures, and involving lower-level employees in transformation efforts, will help smooth the shifts. So will partnering up with providers who can help the institution and its people make the transition.

Shevlin believes that in recent years financial institution strategic planning has deteriorated into a budgeting exercise, with no real planning. Based on what he has seen so far, instead of taking a more serious look at all aspects of the future, post-Covid institutions seem to be focused on budgeting again.

So directors and managers need to focus harder on transformation. Shevlin says employees have a stake and ought to be involved in these discussions in some way, too, but that wont happen until leadership does its job.

Marous says the employee support will be critical once management and directors decide to get moving. A big catch-up challenge looms and he says institutions must get used to having five, six or even seven major transformation projects in motion at once.

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Blood Clots, Birth Control, and the Johnson & Johnson Vaccine: What We Mean by Medical Risk – The New Republic

Posted: at 7:16 am

The greatest risk inequitably enforced in this country is the most essential: general well-being. It is allowable, under our present systems, for trans people, for women, for Black women in particular, for poor people, for fat people, for the mentally ill, for the chronically ill and disabled, all to have worse health outcomesthese things are accepted and narrated to us by powerful institutions as an unfortunate but inescapable fact of medicine. And in doing so, they reiterate that these people are of lesser value, and are in fact inconvenient. These people are a burden, and so they should be grateful for what they get.

There was a hope among some at the very early start of the pandemic that, as horrific as it was going to be, it might force people with privilege to see how inextricably all of our lives are intertwined, how the health of one person isnt just their health but yours, too. We had to learn to wear masks not to protect ourselves but to protect others. Those with money suffered inconvenience at the very least from the fact that the people who serve and enable their lifestyles had no access to health care, to childcare, to workplace protections, to a real, functioning social safety netto any of the things that would allow them to stay home when sick, instead of risking a widespread infection to pack boxes for Amazon.

It would be impossible, as well as wholly undesirable, to avoid risk entirely in medical enterprise. Medicine is science, and science is experimentation, and experimentation can only happen if we take risks. And theres just no such thing as a risk-free existence. Aversion to risk in some contexts contributed to the inequities were dealing with today: In the 1970s, the FDA decided women of childbearing age shouldnt participate in clinical trials, out of concern not for the participants themselves but for possible future fetuses. As a result, it became the norm for new medicine to be developed exclusively on men; eight of the 10 prescription drugs withdrawn from the market between 1997 and 2000 posed greater health risks for women than for men.

The problem arises when a constitutionally unequal system assumes that the calculus by which we accept risk is neutral, rather than critically analyzing not just how research and regulatory decisions are made but how services are both distributed and received. A medical establishment predicated on the acceptance of profit-driven health care will inevitably favor the wealthy and the powerful, at the expense of everyone else.

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[Full text] Binding of the SARS-CoV-2 Spike Protein | HMER – Dove Medical Press

Posted: at 7:16 am

Introduction

SARS-CoV-2 is the virus responsible for the COVID-19 pandemic and its damaging effects on both health and economics worldwide. Transmission and pathology of the virus appears to be mediated through the respiratory system via interaction of the viral spike protein with the ACE-2 receptor13 differentially presented on various cells within the respiratory system.4,5 Expression of ACE-2 has been reported on lung alveolar epithelial cells, enterocytes of the small intestine, circulatory endothelial cells, arterial smooth muscle cells,6 adipose tissue, bone marrow, duodenum, endometrium, heart, kidney, testis, and thyroid7 suggesting a potential direct effect of COVID-19 on those tissues. Additionally, infection with COVID-19 has been associated with significant liver injuries and altered liver function tests.8

Alterations in liver function have been attributed to secondary effects of cytokine cascade, hypoxia, underlying liver disease,911 or infection of ACE-2 positive cholangiocytes.12 There have also been reports of coronavirus particles in hepatocytes without a defined mechanism for infection.13

In a recent report studying the receptome of spike binding, ACE-2 was confirmed as the primary receptor for the spike protein via the binding domain (RBD) on the spike 1 portion of the molecule and the N-terminal-domain as the sites critical for virushost interaction.14 Additionally, the report described binding of the spike protein with ectopically expressed ASGR1 and KREMEN1 in transfected non-liver cells. The results strongly suggested the existence of additional entry points into cells for the SARS-CoV-2 virus via the spike protein. Differences in primary infection sites and clinical manifestations of SARS-CoV and SARS-CoV-2, both utilizing ACE-2 as the primary site of cellular infection, suggested that other cellular receptors may be involved in SARS-CoV-2 host interactions.14

E12 TERT-immortalized multi-lineage progenitor cells (MLPC) derived from human umbilical cord blood have been differentiated into immortalized AT2-like cells (AT2) (manuscript submitted) and fused directly with primary human hepatocytes to create immortalized hepatocyte-like cells (HLC).15 The resultant E12 AT2-like cells expressed the characteristics of small airway epithelial cells associated with alveolar type 2 cells and not alveolar type 1 cells. The E12/PHH fusion cells (HLC) expressed the characteristics of fully mature and highly differentiated hepatocytes.15

This report studied the interactions of the SARS-CoV-2 spike protein with potential receptors on human cord blood-derived MLPC differentiated AT2, HLC and primary human hepatocytes (PHH) by confocal analysis. The characteristics of spike protein binding were examined using biotinylated spike proteins and blockade of binding by un-labeled spike proteins, spike protein-directed neutralizing antibodies and an antibody directed against the hepatocyte surface membrane asialoglycoprotein receptor 1 (ASGr1). The results suggested that binding and inhibition analyses can be used to assess the potential mechanisms of viral host cell interactions with a myriad of different target cells in the body, but also to assess therapeutics designed to inhibit that binding.

Immortalized AT2 and HLC could provide accurate and reproducible tools to study the differential virushost interactions between these targets of COVID-19 infection and aid in the development of therapeutics designed to inhibit binding and infection by the SARS-CoV-2 virus. In addition, the potential binding of spike protein to the ASGr1 on hepatocytes suggested a mechanism of viral entry via the clathrin-coated pit receptor-mediated pathway and direct injury to the liver.16,17

MLPC are multi-potent non-hematopoietic stem cells isolated from human umbilical cord blood.15 Umbilical cord blood was collected as part of an FDA submission to market PrepaCyte-CB, a product to de-bulk cord blood for cryo-banking and transplantation. IRB approval of the studies was conducted by the University of Minnesota, the Saint Louis Cord Blood Bank and by Quorum Review Protocol #800, March 3, 2005. The cord blood samples were collected by the American Red Cross Cord Blood Program (Saint Paul, Minnesota) and Ridgeview Medical Center (Waconia, MN). Donations were collected with donor consent for research use only.

Briefly, isolated leukocytes were incubated overnight in MSCGM (PT-4105, Lonza, Walkerville, MD) after which non-adherent cells were removed. Cells were cultured in MSCGM until 8090% of cells had a fibroblastic morphology. These cells were transfected with the gene for TERT, as previously described15 and were cloned by limited dilution. The E12 clone was selected for both immortality and differentiating potential. The E12 MLPC, expanded and cryopreserved for over 14 years, were used as undifferentiated control cells and as the source of cells for the development of the AT2-like cells and the fusion partner in the development of MLPC/hepatocyte hybrid cells.15 For confocal analysis, E12 cells (106/mL in MSCGM, 200 L per well) were plated in non-coated 16 well chamber slides (Nalge, Nunc International, Rochester, NY) and allowed to attach overnight before use in the analysis.

AT2-like cells were developed from the differentiation of E12 MLPC. Briefly, E12 cells (3 x 105 cells/mL) in MSCGM were added to non-coated tissue culture vessels and allowed to attach overnight. Medium was then exchanged with SAGM (SAGM, Lonza, Walkerville, MD, cat # 3118) and allowed to culture for 814 days with 3 medium changes per week. Upon achieving 70% confluence, cells were harvested by treatment with Tryp-LE (12605028, Life Technologies, Grand Island, NY) allowed to dissociate from the culture vessel and used for confocal analysis, as a positive control for binding spike proteins and ACE-2 expression. Cells (106/mL in SAGM, 200 L per well) were plated in non-coated 16 well chamber slides and allowed to adhere overnight prior to confocal analysis.

Hepatocyte-like fusion cells were created by the fusion of E12 MLPC with primary human hepatocytes, as previously described.15 Equal numbers of E12 MLPC and primary hepatocytes were fused using 50% polyethylene glycol in RMPI + 0.01% EDTA. Resultant cells were plated into collagen-coated 75 cm2 tissue culture flasks and were cultured for 7 days in RPMI + 20% FBS. After 7 days, non-fused PHH were no longer viable and did not contribute to the HLC cell lines. HLC were examined for hepatocyte-specific markers including albumin and urea production. HLC were demonstrated to express markers and production consistent with fully mature and well-differentiated hepatocytes. HLC (106/mL in hepatocyte expansion medium, 200 L per well) were plated in collagen-coated 16 well chamber slides and were allowed to adhere overnight prior to confocal analysis. Hepatocyte expansion medium consisted of Williams Medium E supplemented with 2% fatty acid-free BSA (Sigma, A7030), 1% ITS solution (Lonza, 17838Z), 5mM hydrocortisone 21-hemisuccinate (Sigma, H2270) and glutamax (35050, Gibco) supplemented with FGF basic (20 ng/mL) (233-FB), FGF-4 (20 ng/mL) (7460-F4), HFG (40 ng/mL) (294-HG), SCF (40 ng/mL) (255-SC), Oncostatin M (20 ng/mL) (295-OM), BMP-4 (20 ng/mL) (314-BP), EGF (40 ng/mL) (236-EG) and IL-1 (20 ng/mL)(201-LB) all from R&D Systems (Minneapolis, MN).

Cryo-preserved primary human hepatocytes and media were obtained from Zenotech (Kansas City, KS). Cells were thawed with OptiThaw medium and enumerated with OptiCount medium in a standard hemacytometer. Hepatocytes were diluted to a final concentration of 106 cells/mL of OptiPlate medium and were plated in collagen-coated 16 well chamber slides at 200 L per well. After 4 hours of plating, the medium was changed to OptiCulture medium to allow overnight attachment and spread of cells prior to confocal analysis.

Cells were prepared for staining with antibodies and binding of spike proteins by fixing the cells in 1% formaldehyde for 1 hour. Cells were then washed x 2 with PermaCyte permeabilization medium (WBP-1000, CMDG, St. Paul, MN). All staining took place in the presence of PermaCyte. Cells were incubated with an unlabeled primary antibody (100 ng) for 30 minutes at room temperature. ACE-2 (labeled with alexa 594, FAB9332T), albumin (MAB1456) and asialoglycoprotein receptor 1 (MAB4394) antibodies were obtained from R&D Systems (Minneapolis, MN). Unbound antibody was removed by washing with PermaCyte and the cells were counterstained with a secondary antibody specific for mouse (A-11005) antibody labelled with Alexa 594 dye (Life Technologies, (Eugene, OR)). Marker expression was confirmed by positive staining when compared to cells stained with antibody isotype controls (QTC1000, CMDG, St. Paul, MN). The nuclei of the cells were visualized by staining with DAPI.

The binding of SARS-CoV-2 spike and spike 1 proteins was analyzed by confocal microscopy using biotinylated spike proteins. Cells were prepared as described above. Cells were labelled with 250 ng of either biotinylated spike (RBD) (SPD-C8E9, ACROBiosystems, Newark, DE) or biotinylated spike 1 protein (SIN-C82E8, ACROBiosystems) for 30 minutes. Unbound spike proteins were removed by washing cells twice with PermaCyte medium. Bound spike proteins were visualized by secondary staining with streptavidin-alexa 594 (S11227 Life Technologies). Cells were counterstained with DAPI to visualize the nuclei.

Specificity of biotinylated spike proteins binding to the cells was confirmed by blockade of binding by a 5 molar excess of unlabeled spike protein. Cells were prepared as per the confocal analysis of antibody binding. Cells were incubated with 1.25 g of unlabeled spike protein (ACROBiosystems, SPD-S52H6) or spike 1 protein (ACROBiosystems, S1N-C52H3) for 1 hour. Without washing the unbound unlabeled spike protein, biotinylated spike and spike 1 proteins were added to the cells and incubated for 30 minutes. Cells were washed twice with PermaCyte medium to remove any unbound proteins. Bound biotinylated spike proteins were observed by secondary labeling with streptavidin-alexa 594. Cells were counterstained with DAPI to visualize the nucleus.

The effects of antibodies on the binding of the spike proteins to the cells were examined using two commercially available neutralizing antibodies obtained from ACROBiosystems (SAD-S35) and Novatein Biosystems (PR-nCOV-mABS1, Boston, MA) and the ASGr1-specific antibody (R&D Systems). One g of either neutralizing antibody was preincubated with the spike protein for one hour prior to the addition of the mixture to the cells prepared as described for binding of the spike proteins. The ASGr1 antibody (300 ng) was preincubated with cells prior to the addition of the spike protein. Visualization of the binding of biotinylated spike protein was accomplished by secondary staining with streptavidin-alexa 594. The nuclei of the cells were visualized with DAPI.

Cells were analyzed on the Olympus Fluoview 1000 confocal microscope. The confocal images in Figures 14 are representative of at least 3 studies done on different days.

Figure 1 Biotinylated spike and spike 1 protein binding to E12 differentiated AT2-like cells and inhibition by unlabeled spike protein and neutralizing antibodies. Bound biotinylated spike proteins were visualized by sequential labeling with streptavidin-alexa 594. Cells positive for binding are shown by red fluorescence. Blue nuclei were visualized by counterstaining with DAPI. (A) Binding of biotinylated spike protein (containing RBD). (B) Inhibition of biotinylated spike protein binding by co-incubation with a 5 molar excess of unlabeled spike protein (RBD). (C) Binding of spike 1 protein. (D) Inhibition of biotinylated spike protein binding by preincubation with a neutralizing antibody from ACROBiosystems. (E) Lack of binding inhibition by neutralizing antibody from Novatein Bio. (F) Inhibition of biotinylated spike 1 binding by unlabeled spike (RBD) protein.

Abbreviation: RBD, receptor-binding domain.

Figure 2 Expression of ACE-2, ASGr1 and serum albumin. Undifferentiated E12 MLPC data are shown in (AD). E12 HLC fusion cell results are presented in (EH). Primary human hepatocytes (PHH) are shown in (IL). Cells were incubated with unlabeled primary antibody and sequentially stained with secondary antibody labeled with alexa-594. Positive binding is shown by red fluorescence. Blue nuclei were visualized by DAPI counterstaining. Figures (A, E and I) were stained with isotype control antibodies. Figures (B, F and J) were stained with antibody specific for ACE-2. Figures (C, G and K) were stained with antibody specific for the asialoglycoprotein receptor 1 (ASGr1). Figures (D, H and L) were stained with antibody specific for serum albumin.

Figure 3 Undifferentiated E12 MLPC confocal microscopy is shown in (AD). E12 HLC fusion cell data are presented in (E-H). Primary human hepatocytes (PHH) are shown in (IL). Positive binding is indicated by red fluorescence. Blue nuclei were visualized with DAPI counterstaining. Figures (A, E and I) were labeled with Sav-594. Figures (B, F and J) were labeled with biotinylated spike protein followed by sequential staining with streptavidin-alexa 594. Figures (C, G and K) were labeled with biotinylated spike 1 protein followed by sequential staining with streptavidin-alexa 594. Figures (D, H and L) biotinylated spike protein binding was blocked by a 5 molar excess of unlabeled spike protein (RBD) followed by sequential staining with streptavidin-alexa 594.

Figure 4 Inhibition of biotinylated spike binding by neutralizing antibodies to spike 1, spike and ASGr1. E12 HLC fusion cell data are shown in (AD). Primary human hepatocytes (PHH) are shown in (EH). Positive binding of biotinylated spike proteins is shown by red fluorescence. Blue nuclei are visualized by counterstaining with DAPI. Figures (A and E) confocals show the inability of a 5 molar excess of unlabeled spike 1 protein to block the binding of biotinylated spike protein. Figures (B and F) show inhibition of binding of biotinylated spike protein by neutralizing antibody from ACROBiosystems. Figures (C and G) show binding inhibition of biotinylated spike protein by neutralizing antibody from Novatein Bio. Figures (D and H) demonstrate inhibition of any detectable binding of biotinylated spike protein by antibody specific for the hepatocyte membrane ASGr1.

In a parallel study that surveyed the differentiation of E12 MLPC to AT2-like cells, it was demonstrated that AT2-like cells were positive for markers associated with AT2 cells (surfactant protein C, ACE2, TM4SF1, HT2-280), negative for markers associated with AT1 cells (AGER, caveolin 1 and aquaporin) and positive for markers not unique to AT2 cells but known to be expressed on AT2 cells (CK19, CD26 and EpCAM). These results were identical to primary small airway epithelial cells. Both cell types were also shown to bind spike and spike 1 proteins. Biotinylated spike proteins could be blocked by unlabeled spike protein (RBD). Pre-incubation with neutralizing antibodies prevented the binding of biotinylated spike protein by the ACROBiosystems neutralizing antibody, but not the Novatein antibody. Expressions of ACE-2, spike protein binding and inhibition were repeated for this study to confirm the involvement of the ACE-2 receptor (Figure 1).

The expressions of ACE-2, ASGr1 and albumin in control E12 MLPC, HLC and PHH were studied by antibody staining. E12 MLPC were shown to be negative for ACE-2, ASGr1 and albumin expression. In contrast, ASGr1 and albumin were shown to be strongly expressed by both HLC and PHH. ACE-2 was not detectible in either cell type (Figure 2).

The ability of E12 MLPC, HLC and PHH to bind spike and spike 1 proteins was studied using biotinylated spike proteins. E12 MLPC were unable to bind either spike or spike 1 proteins. HLC and PHH were able to bind spike protein but not spike 1 protein. The binding of biotinylated spike protein could be blocked by pre-incubation with unlabeled spike protein (Figure 3). The binding of biotinylated spike protein could not be blocked by spike 1, but could be blocked by ACROBiosystems and Novatein neutralizing antibodies and also an antibody directed against the ASGr1 (Figure 4).

It is critical to elucidate the mechanisms of virus/host interactions of the SARS-CoV-2 for the development of therapeutics designed to inhibit the binding and internalization of the virus to a myriad of cell types. The overarching strategy for the development of vaccines or therapeutics has involved the interaction between the S1 portion of the viral spike protein and the ACE-2 cellular receptor found in the respiratory tract and in various other tissues.47 Differences in transmission, pathology and organ involvement between SARS-CoV and SARS-CoV-2 (both dependent upon ACE-2 binding) suggested that additional receptors may contribute to the attachment and internalization of the SARS-CoV-2 virus14 in both the respiratory lungs and other organ systems.

The potential infection of tissues that are ACE-2 negative has spurred the search for additional receptor interactions of the spike protein. Some of these potential spike protein receptor targets include neuropilin-1,18 ASGR1 and KREMEN1.14 The observation of SARS-CoV-2 particles in hepatocytes8 and the robust expression of ASGr1 receptors and neuropilin-1 on hepatocytes suggested that altered liver function associated with COVID-19 infection may be directly caused by infection with the virus and mediated by binding to one or both receptors.

We investigated the potential virus: receptor interactions via the spike protein using fluorescent confocal microscopy and biotinylated spike (RBD) and spike 1 proteins. In a parallel study, E12 MLPC were differentiated to AT2-like cells (manuscript submitted). These cells expressed markers associated with AT2 cells (surfactant protein C, ACE2, TM4SF1, HT2-280), negative for markers associated with AT1 cells (AGER, caveolin 1 and aquaporin) and positive for markers not unique to AT2 cells but known to be expressed on AT2 cells (CK19, CD26 and EpCAM). These results were identical to primary small airway epithelial cells. The binding of biotinylated spike proteins and specific blocking by unlabeled protein and neutralizing antibodies confirmed that the primary interaction of spike protein with AT2-like cells and primary small airway epithelial cells was via the S1 portion of the protein with the ACE-2 receptor. We repeated those studies in support of our findings with the HLC and PHH. The differential inhibition of spike protein binding with two different antibodies suggested that viral neutralization could result from mechanisms other than direct inhibition of S1 (RBD) binding to ACE-2.

The characteristics of SARS-CoV-2 interactions with hepatocytes were studied by observing the binding of biotinylated spike (RBD) and spike 1 proteins to HLC and PHH using the undifferentiated E12 as a known negative control. It was observed that HLC and PHH were both negative for ACE-2, precluding that as a potential site of viral binding. This was confirmed by the inability of the cells to bind S1 protein. The binding of biotinylated spike protein and blockade by unlabeled spike protein on HLC and PHH suggested that the binding was specific, and via a mechanism distinct from ACE-2. The complete inhibition of spike binding by an antibody directed against the ASGr1 is strongly suggestive that ASGr1 is a binding site for the spike protein on hepatocytes. Interestingly, blockade of spike binding by both neutralizing antibodies on HLC and PHH was distinct from AT2 cells where inhibition occurred solely with the antibody that was directed against the RBD. This is suggestive of neutralizing activity that can occur outside the RBD.

Utilization of multiple cell types to study the interactions of spike protein binding will help identify additional receptor pathways for infection with COVID-19. They could also provide a powerful tool to aid in the development of therapeutics against multiple sites on the spike protein or receptors of the host cells. With the existent emergence of new variants and mutations of the SARS-CoV-2 exhibiting enhanced transmissibility, it is especially important to expand our repertoire of cellular models to investigate the effects of the mutations on the binding characteristics of the virus to host cells. The availability of immortalized cells with the stable characteristics of human alveolar type 2 cells and mature well-differentiated hepatocytes could provide an accurate and reproducible tool to effectively study the various virushost interactions via spike proteins by providing potential viral receptors that are segregated according to cell type. We believe that AT2 and HLC provide such a tool.

Dr Daniel P Collins reports personal fees from BioE, LLC, during the conduct of the study. In addition, Dr Daniel P Collins has a patent Composition for an in vitro culture medium to maintain and expand stem cell-derived hepatocyte-like cells pending, as well as,a patent Methods to develop immortalized hybrid hepatocyte-like cells, also pending. The authors report no other conflicts of interest in this work.

1. Shang J, Wan Y, Luo C, et al. Cell entry mechanisms of SARS-CoV-2. Proc Natl Acad Sci USA. 2020;117(21):1172711734. doi:10.1073/pnas.2003138117

2. Lan J, Ge J, Yu J, et al. Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature. 2020;581(7807):215220. doi:10.1038/s41586-020-2180-5

3. Premkumar L, Segovia-Chumbez B, Jadi R, et al. The receptor-binding domain of the viral spike protein is an immunodominant and highly specific target of antibodies in SARS-CoV-2 patients. Sci Immunol. 2020;5(48):eabc8413. doi:10.1126/sciimmunol.abc8413

4. Hikmet F, Mar L, Edvinsson , et al. The protein expression profile of ACE2 in human tissues. Mol Sys Biol. 2020;16(7):e9610. doi:10.15252/msb.20209610

5. Sungnak W, Huang N, Bcavin C, et al. SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nat Med. 2020;26(5):681687. doi:10.1038/s41591-020-0868-6

6. Hamming I, Timens W, Bulthuis MLC, Lely AT, Navis GJ, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS corona virus. A first step in understanding SARS pathogenesis. J Pathol. 2004;203(2):631637. doi:10.1002/path.1570

7. Wang D, Eraslan B, Weiland T, et al. A deep proteome and transcriptome abundance atlas of 29 healthy human tissues. Mol Syst Biol. 2019;15(2):e8503. doi:10.15252/msb.20188503

8. Wang Y, Liu S, Liu H, et al. SARS-CoV-2 infection of the liver directly contributes to hepatic impairment in patients with COVID-19. J Hepatol. 2020;73(4):807816. doi:10.1016/jhep.2020.05.002

9. Desai N, Neyaz A, Szabolcs A, et al. Temporal and spatial heterogeneity of host response to SARS-CoV pulmonary infection. Nat Comm. 2020;11(1):6319. doi:10.1038/s41467-020-20139-7

10. Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):10331034. doi:10.1016/S0140-6736(20)30628-0

11. Chu H, Chan JF, Wang Y, et al. Comparative replication and immune activation profiles of SARS-CoV-2 and SARS-CoV in human lungs: an ex vivo study with implications for the pathogenesis of COVID-19. Clin Infect Dis. 2020;71(6):14001409. doi:10.1093/cid/ciaa410

12. Chai X, Hu L, Zhang Y, et al. Specific ACE2 expression in cholangiocytes may cause liver damage after 2019-nCoV infection. bioRxiv. 2020. doi:10.1107/2020.02.03.931/766

13. Lozano-Sepulveda SA, Galan-Huerta K, Martnez-Acua N, Arellanos-Soto D, Rivas-Estilla AM. SARS-CoV-2 another kind of liver aggressor, how does it do that? Ann Hepatol. 2020;19(6):592596. doi:10.1016/j.aohep.2020.08.062

14. Gu Y, Cao J, Zhang X, et al. Interaction network of SARS-CoV-2 with host receptome through spike protein. bioRxiv. 2020. doi:10.1101/2020.09.09.28/508

15. Collins DP, Hapke JH, Aravalli RN, Steer CJ. Development of immortalized human hepatocyte-like hybrid cells by fusion of multi-lineage progenitor cells with primary hepatocytes. PLoS One. 2020;15(6):e234002. doi:10.1371/journal.pone.0234002

16. DSouza AA, Devarajan PV. Asialoglycoprotein receptor mediated hepatocyte targeting strategies and applications. J Control Release. 2015;203:126139. doi:10.1016/j.jconrel.2015.02.022

17. Huang X, Leroux JC, Castagner B. Well-defined multivalent ligands for hepatocytes targeting via asialoglycoprotein receptor. Bioconjug Chem. 2017;28(2):283295. doi:10.1021/acs.bioconjchem.6b00651

18. Daly JL, Simonetti B, Klein K, et al. Neuropilin-1 is a host factor for SARS-CoV-2 infection. Science. 2020;370:861865. doi:10.1126/science.abd3072

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[Full text] Binding of the SARS-CoV-2 Spike Protein | HMER - Dove Medical Press

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In Canada, psychedelics re-emerge in treatment of depression – The Japan Times

Posted: at 7:15 am

Toronto To manage her stress and fears, Andrea Bird who is suffering from terminal cancer uses psychedelics, which are seeing a sudden re-emergence in Canada as a possible treatment for mental health conditions such as anxiety and depression.

The 60-year-old Canadian was diagnosed with breast cancer in 2012. Despite aggressive treatment, the disease returned five years later, spreading to her lungs, bones and brain.

As she tries to cope with her incurable ailment, Bird uses psilocybin, the psychoactive substance of hallucinogenic mushrooms that was banned in the 1970s.

I found it to be the most helpful thing that I did in coming to terms with the fact that my life is ending much sooner than I thought it would, Bird said.

Im still dying, she said matter-of-factly, but added that psilocybin makes me feel like I can stand up.

I really love my life, and I really dont want to die, but I have to find a way to surrender to what is actually happening.

Bird, who lives in Ontario, is among about 30 Canadians, most of them struggling to face the end of their lives, who have received federal dispensation since August 2020 to use psilocybin for therapeutic purposes.

TheraPsil, a nonprofit organization based in British Columbia, has helped most of them get exemptions to Canadas controlled substances and drug act for compassionate treatment.

The group also has connected patients to doctors and therapists who oversee their use of the drug.

These trial cases come amid mounting interest from researchers and investors, as well as a public push to reconsider bans on psilocybin, LSD, DMT, mescaline and other mind-altering substances such as MDMA, commonly known as ecstasy.

In the U.S., Oregon legalized psilocybin for therapeutic use last November.

Psychedelics have been used by indigenous peoples for millennia, but Western researchers only started delving into their properties and potential uses in earnest in the middle of last century.

But that work came grinding to a halt when the substances quickly became symbols of the anti-establishment counter-culture movement of the 1960s and were banned.

Over the past 20 years, however, the persistence of some researchers, a mental health crisis and a shift in public opinion toward greater tolerance of drugs such as cannabis which Canada legalized for recreational use in 2018 paved the way for a psychedelics renaissance.

Now there are more people who are willing to just look at the facts rather than the political weight they may carry, explains Rotem Petranker, associate director of the University of Torontos Psychedelic Studies Research Program, which looks at the effects of micro-dosing on mood and creativity.

Researchers are studying the potential benefits of these substances for treating depression, anxiety, post-traumatic stress disorder (PTSD), substance addictions and anorexia.

The most advanced clinical trials are focused on using psilocybin for severe or treatment-resistant depression and MDMA for PTSD.

Ecstasy powder after a seizure of drugs in Nice, France. | AFP-JIJI

Some of the studies have yielded promising results.

A recent clinical trial from Marylands Johns Hopkins University which has just opened a research center dedicated to psychedelics showed that two doses of psilocybin, accompanied by psychotherapy, produced large, rapid and sustained effects in patients suffering from serious depression.

Of the 24 participants, 71% showed a reduction of more than 50% of their symptoms after four weeks and half went into remission, the study revealed.

Another small-scale study involving 59 participants, conducted by Imperial College Londons Center for Psychedelic Research, showed psilocybin was at least as effective as conventional antidepressants, the research team said this week, though adding that larger trials were needed.

Were experiencing a revolution in psychiatry, said Alexandre Lehmann, a cognitive neuroscientist who teaches at McGill University in Montreal.

There are new approaches to alleviating and curing serious and disabling mental health problems, which affect a large number of people, and for which there are currently no good solutions.

Since their discovery in the 1950s, drug treatments for depression have hardly changed at all.

Conventional antidepressants which notably target serotonin, a key hormone that regulates mood have been criticized for being slow to act and for their side effects, including dulling emotions and reducing creativity.

They also dont always work, explains Nisha Ravindran, psychiatrist and professor at the University of Toronto.

We know that standard antidepressants dont help a significant proportion of the population. In fact, more than 30 to 40% simply dont respond and require alternatives, he said.

For some patients, psychedelics could come to the rescue through a new model of therapy involving a limited number of doses providing a transformative experience that might address their core issues.

Psychedelics can cause a profound alteration of perceptions and consciousness. The experience is unpredictable. For some, it can seem otherworldly.

Although much is still not known about how the drugs work, researchers believe they act on the brains default mode network, associated with introspective thoughts and ruminations, by temporarily lulling the ego, explains Lehmann.

Animal studies suggest they enhance brain plasticity, helping to re-organize neural connections, he says.

Psychedelics have low toxicity and are generally not addictive, but they can cause paranoia and anxiety attacks, especially in high doses. Researchers are still unsure about the addictive nature of MDMA, a derivative of amphetamines.

For therapy uses, doses are prepared in labs and the experience is supervised, so the risks are limited, Lehmann says.

The substances make patients more sensitive to their emotions and allow them to examine their thoughts from a new perspective.

Psychedelics are catalysts for psychotherapy, Lehmann says.

Before receiving government dispensation to use the drugs, Bird had twice tried psychedelics on her own, ingesting them at her home in the company of a guide.

She brewed and drank a hallucinogenic mushroom tea that led to several hours of vivid waking dreams. It took months of analysis to make sense of them, she says.

Death showed up a couple of times but it was not at all scary it was just waiting for me, she said of her first experience in late 2018.

It was the idea that this happens to everyone, that life is a gift that we get to have for a little while and then we have to give it back. And that became very clear to me.

Since the cancer spread to her brain, Bird has on the advice of her doctors reduced her intake of the drug and now takes micro-doses.

Hallucinogenic mushrooms for sale at a shop in Amsterdam. | AFP-JIJI

The potential medical benefits of psychedelics have piqued the interest of a growing number of investors in recent years.

Some startups are developing treatments based on these substances, while others are opening psychedelic therapy clinics.

Several are listed on stock exchanges, notably in Toronto and New York, which already trade shares in numerous cannabis companies.

The British firm Compass Pathways, one of the heavyweights in the sector, is currently valued at more than $1.4 billion on the Nasdaq.

Field Trip Health is one of those companies betting on psychedelics.

Founded in Toronto in 2019, it has already opened five clinics in Canada and the United States and plans to build a network of 75 clinics in North America by 2024.

Psychedelics are happening, says Ronan Levy, one of the founders.

The company offers psychotherapy enhanced by low doses of ketamine, a dissociative anesthetic that is legal for medical use, which can induce a trance-like state or a sense of disconnect between body and mind.

Ketamine has been used in surgeries since the 1960s and also became a fixture on the club scene. Some studies have suggested it may allow rapid relief of depressive symptoms for people with treatment-resistant depression.

With moss-covered walls, essential oil diffusers and comfy armchairs, the Field Trip Health clinic in Toronto located in a trendy neighborhood, in a loft with exposed pipes and with a view of the iconic CN Tower has the feel of a spa.

The clinic is accessible to those whose depression or other mental disorder is clinically resistant to treatment, meaning patients must have already tried at least two types of conventional treatments.

A typical course of treatment costing 4,700 Canadian dollars (about 409,000) includes six doses of ketamine and about ten sessions of psychotherapy.

Lying on a zero gravity chair with a mask over their eyes and music in their ears, patients let a ketamine lozenge melt under their tongues and are transported on a trip of about an hour.

A therapist stays in the room throughout the treatment, and then talks to the patients.

Mathieu, a 35-year-old who underwent treatment in June 2020 and asked only to be identified by his first name, called the experience really powerful.

I had the impression of breaking into a thousand pieces and being everywhere at the same time, he said.

When I was going back down, there was an hour window where my emotions felt pure what I had in mind came out without worry, I had no more filters.

Putting aside the hype and promising early results, the use of ketamine in mental health care is not universally backed.

The length of its effects appear to be limited, and critics point to risks of dependence and other possible complications. There is also no consensus on the value of combining its use with psychotherapy.

In the United States, many are worried about the boom in private clinics offering intravenous ketamine, without systematic psychiatric follow-up.

For Jeffrey Lieberman, chief psychiatrist at Columbia University Medical Center, it is a worrying sign that the practice has leapt ahead of the research.

More generally, others note that there is still a lack of solid evidence on the benefits of psychedelics. They say more and larger clinical trials are needed.

LSD blotter tabs on top of a U.S. coin. | AFP-JIJI

Some researchers are also concerned that the current commercial craze and enthusiasm among top proponents are giving rise to a sense that psychedelics are a miracle pill, leading some to try it alone or with low-quality substances.

In Canada, reports have surfaced of people turning to unlicensed therapists and bootleg psychedelics for personal growth or to ease pandemic fatigue, leading to a blossoming black market.

Proponents of ketamine therapy say it helps lay the groundwork for the future use of classic psychedelics such as psilocybin, with the most enthusiastic projections suggesting the first new treatments will be approved in the coming years.

The U.S. Food and Drug Administration has already indicated that it is receptive to the idea: Since 2017, it has granted a breakthrough therapy designation for trials on psilocybin and MDMA.

In Canada, a pioneer of the cannabis industry, legalization of psychedelics is not yet on the table, but Health Minister Patty Hajdu has said she is open to supporting research, saying it would help move forward this conversation.

In addition to exemptions for patients, the government has just authorized 19 health professionals to test psilocybin themselves in an effort to understand its effects and train themselves on how to use it in a therapeutic context.

The country has also announced its intention to restore access to restricted drugs including psychedelics through its Special Access Program, which allows doctors to request the use of substances not yet approved for clinical use in dire situations. A public consultation ended in mid-February.

If the proposal is approved, requests will be handled on a case-by-case basis, meaning access to these therapies for certain patients could be facilitated.

Bird says she hesitated before speaking publicly about her use of psychedelics, but she says she felt it was important to do so to help remove the stigma and try to illuminate this option for other people.

Im not that adventurous, drug-wise, she said. But it has been really helpful to me So, why hide that?

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In Canada, psychedelics re-emerge in treatment of depression - The Japan Times

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Psychedelics re-emerge in treatment of depression in Canada – Deccan Herald

Posted: at 7:15 am

To manage her stress and fears, Andrea Bird who is suffering from terminal cancer uses psychedelics, which are seeing a sudden re-emergence in Canada as a possible treatment for mental health conditions such as anxiety and depression.

The 60-year-old Canadian was diagnosed with breast cancer in 2012. Despite aggressive treatment, the disease returned five years later, spreading to her lungs, bones and brain.

As she tries to cope with her incurable ailment, Bird uses psilocybin, the psychoactive substance of hallucinogenic mushrooms that was banned in the 1970s.

"I found it to be the most helpful thing that I did in coming to terms with the fact that my life is ending much sooner than I thought it would," Bird told AFP.

"I'm still dying," she said matter-of-factly, but added that psilocybin "makes me feel like I can stand up."

"I really love my life, and I really don't want to die, but I have to find a way to surrender to what is actually happening."

Bird, who lives in Ontario province, is among about 30 Canadians, most of them struggling to face the end of their lives, who have received federal dispensation since August 2020 to use psilocybin for therapeutic purposes.

Read |Canada Post's psychedelic trucks bring cheer amid pandemic gloom

TheraPsil, a non-profit organization based in British Columbia, has helped most of them get exemptions to Canada's controlled substances and drug act for "compassionate treatment."

The group also has connected patients to doctors and therapists who oversee their use of the drug.

The US state of Oregon legalized psilocybin for therapeutic use last November.

Psychedelics have been used by indigenous peoples for millennia, but Western researchers only started delving into their properties and potential uses in earnest in the middle of last century.

But that work came grinding to a halt when the substances quickly became symbols of the anti-establishment counter-culture movement of the 1960s and were banned.

Over the past 20 years, however, the persistence of some researchers, a mental health crisis and a shift in public opinion towards greater tolerance of drugs such as cannabis -- which Canada legalized for recreational use in 2018 paved the way for a psychedelics renaissance.

"Now there are more people who are willing to just look at the facts rather than the political weight they may carry," explains Rotem Petranker, associate director of the University of Toronto's Psychedelic Studies Research Program, which looks at the effects of micro-dosing on mood and creativity.

Researchers are studying the potential benefits of these substances for treating depression, anxiety, post-traumatic stress disorder (PTSD), substance addictions and anorexia.

The most advanced clinical trials are focused on using psilocybin for severe or treatment-resistant depression, and MDMA for PTSD.

Some of the studies have yielded promising results.

A recent clinical trial from Baltimore's Johns Hopkins University which has just opened a research centre dedicated to psychedelics -- showed that two doses of psilocybin, accompanied by psychotherapy, produced "large, rapid and sustained" effects in patients suffering from serious depression.

Of the 24 participants, 71 per cent showed a reduction of more than 50 per cent of their symptoms after four weeks and half went into remission, the study revealed.

Another small-scale study involving 59 participants, conducted by Imperial College London's Centre for Psychedelic Research, showed psilocybin was "at least as effective" as conventional antidepressants, the research team said this week, though adding that larger trials were needed.

"We're experiencing a revolution in psychiatry," Alexandre Lehmann, a cognitive neuroscientist who teaches at McGill University in Montreal, told AFP.

"There are new approaches to alleviating and curing serious and disabling mental health problems, which affect a large number of people, and for which there are currently no good solutions."

Since their discovery in the 1950s, drug treatments for depression have hardly changed at all.

Conventional antidepressants -- which notably target serotonin, a key hormone that regulates mood -- have been criticized for being slow to act and for their side effects, including dulling emotions and reducing creativity.

They also don't always work, explains Nisha Ravindran, psychiatrist and professor at the University of Toronto.

"We know that standard antidepressants don't help a significant proportion of the population. In fact, more than 30 to 40 per cent simply don't respond and require alternatives," he said.

For some patients, psychedelics could come to the rescue through a new model of therapy involving a limited number of doses providing a "transformative experience" that might address their core issues.

Psychedelics can cause a profound alteration of perceptions and consciousness. The experience is unpredictable. For some, it can seem otherworldly.

Although much is still not known about how the drugs work, researchers believe they act on the brain's default mode network, associated with introspective thoughts and ruminations, by "temporarily lulling the ego," explains Lehmann.

Animal studies suggest they enhance brain plasticity, helping to re-organize neural connections, he says.

For therapy uses, doses are prepared in labs and the experience is supervised, so the "risks are limited," says Lehmann.

The substances make patients more sensitive to their emotions and allow them to examine their thoughts from a new perspective.

"Psychedelics are catalysts for psychotherapy," says Lehmann.

Before receiving government dispensation to use the drugs, Bird had twice tried psychedelics on the sly, ingesting them at her home in the company of a "guide."

She brewed and drank a hallucinogenic mushroom tea that led to several hours of "vivid" waking dreams. It took months of analysis to make sense of them, she says.

"Death showed up a couple of times but it was not at all scary... it was just waiting for me," she said of her first experience in late 2018.

"It was the idea that this happens to everyone, that life is a gift that we get to have for a little while and then we have to give it back. And that became very clear to me."

Since the cancer spread to her brain, Bird has -- on the advice of her doctors -- reduced her intake of the drug and now takes micro-doses.

The potential medical benefits of psychedelics have piqued the interest of a growing number of investors in recent years.

Some startups are developing treatments based on these substances, while others are opening psychedelic therapy clinics.

Several are listed on stock exchanges, notably in Toronto and New York, which already trade shares in numerous cannabis companies.

The British firm Compass Pathways, one of the heavyweights in the sector, is currently valued at more than Can$1.8 billion (US$1.4 billion) on the Nasdaq.

Field Trip Health is one of those companies betting on psychedelics.

Founded in Toronto in 2019, it has already opened five clinics in Canada and the United States and plans to build a network of 75 clinics in North America by 2024.

"Psychedelics are happening," Ronan Levy, one of the founders, told AFP.

The company offers psychotherapy enhanced by low doses of ketamine, a dissociative anaesthetic that is legal for medical use, which can induce a trance-like state or a sense of disconnect between body and mind.

Ketamine has been used in surgeries since the 1960s, and also became a fixture on the club scene. Some studies have suggested it may allow rapid relief of depressive symptoms for people with treatment-resistant depression.

With moss-covered walls, essential oil diffusers and comfy armchairs, the Field Trip Health clinic in Toronto located in a trendy neighbourhood, in a loft with exposed pipes and with a view of the iconic CN Tower has the feel of a spa.

A typical course of treatment costing Can$4,700 (US$3,700) includes six doses of ketamine and about ten sessions of psychotherapy.

Lying on a zero gravity chair with a mask over their eyes and music in their ears, patients let a ketamine lozenge melt under their tongues and are transported on a "trip" of about an hour.

A therapist stays in the room throughout the treatment, and then talks to the patients.

Mathieu, a 35-year-old Canadian who underwent treatment in June 2020 and asked only to be identified by his first name, called the experience "really powerful."

"I had the impression of breaking into a thousand pieces and being everywhere at the same time," he told AFP.

"When I was going back down, there was an hour window where my emotions felt pure -- what I had in mind came out without worry, I had no more filters."

Putting aside the hype and promising early results, the use of ketamine in mental health care is not universally backed.

In the United States, many are worried about the boom in private clinics offering intravenous ketamine, without systematic psychiatric follow-up.

For Jeffrey Lieberman, chief psychiatrist at Columbia University Medical Center, it is a worrying sign that "the practice has leapt ahead of the research."

More generally, others note that there is still a lack of solid evidence on the benefits of psychedelics. They say more and larger clinical trials are needed.

Some researchers are also concerned that the current commercial craze and enthusiasm among top proponents are giving rise to a sense that psychedelics are a "miracle pill," leading some to try it alone or with low-quality substances.

In Canada, reports have surfaced of people turning to unlicensed therapists and bootleg psychedelics for personal growth or to ease pandemic fatigue, leading to a blossoming black market.

The US Food and Drug Administration (FDA) has already indicated that it is receptive to the idea: since 2017, it has granted a "breakthrough therapy" designation for trials on psilocybin and MDMA.

If the proposal is approved, requests will be handled on a case-by-case basis, meaning access to these therapies for certain patients could be facilitated.

Bird says she hesitated before speaking publicly about her use of psychedelics, but she says she felt it was important to do so to help "remove the stigma" and "try to illuminate this option for other people."

"I'm not that adventurous, drug-wise," she said. "But it has been really helpful to me... So, why hide that?"

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Psychedelics re-emerge in treatment of depression in Canada - Deccan Herald

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Psilocybins complicated relationship with creativity revealed in new placebo-controlled neuroimaging study – PsyPost

Posted: at 7:15 am

People under the influence of psilocybin the active component of magic mushrooms report having more profound and original thoughts, but tend to score lower on cognitive tests of creative ability, according to new research published in Translational Psychiatry. But the findings indicate that the psychedelic substance can still boost creative ability in the long-term.

The study also collected functional magnetic resonance imaging and proton magnetic resonance spectroscopy data, providing some new insights into the underlying neurobiological mechanisms associated with creative ability.

Creativity is an essential cognitive ability linked to all areas of our everyday life, allowing us to adapt to an ever-changing environment and come up with ways to solve problems, said lead researcher Natasha Mason (@NL_Mason), a PhD candidate at Maastricht University.

Importantly, as well as being an essential process for everyday functioning, the (in)ability to think outside of the box has also been associated with psychological disorders, such as depression and anxiety. These individuals can get stuck in maladaptive thought patterns, which can facilitate habitual (negative) behaviors. Thus, finding a way to enhance creativity is of broad interest.

Scientists had found some preliminary evidence in the 1960s that the psychedelic drug LSD could enhance creative problem-solving. There was also some evidence that the psychedelic state induced by LSD could harm creative ability. But the issue has received little scientific attention since then.

Over the years, a number of anecdotal reports have accumulated suggesting that the consumption of psychedelic drugs, like LSD and psilocybin, can enhance creativity, Mason said. Famous examples of psychedelic-affiliated creative breakthroughs include Kary Mullis discovery of the polymerase chain reaction, the 1960s California-based computer industry, and the literary works of authors, such as Aldous Huxley and Ken Kesey. That said, although there are a large number of claims that psychedelics do this, no one has investigated this in a placebo-controlled experimental trial.

In their study, the researchers examined two types of deliberate creativity convergent thinking and divergent thinking. The former represents the ability to generate a single optimal solution to a problem, while the latter represents the ability to generate many solutions to a problem with several possible answers.

The study included 60 healthy participants, who had previous experience with a psychedelic drug but not within the past 3 months.

Mason and her colleagues found that both types of creativity appeared to be impaired during the psychedelic state. But psilocybin appeared to produce lasting improvements in divergent thinking, when not under the influence of the substance. A week after receiving psilocybin, participants tended to generate more novel ideas for uses of everyday objects compared to those who received placebo.

We found that when under the influence, psychedelics do not enhance creativity per se. Instead, it seems a bit more complicated, Mason told PsyPost. We used classic measures of creativity, for example the alternate uses test, in which people have to come up with as many uses as possible for a brick. Here, we found that under the influence of a psychedelic, individuals performed worse than placebo (they came up with fewer uses for a brick, and the uses they did come up with were not any more original than during placebo).

However, individuals reported that they felt more creative throughout the day, in that they said they had more experiences of insight and were able to figure out solutions to their own, personal problems, Mason explained. This could mean one of two things either under the influence of psychedelics, peoples idea generation and evaluation (creativity) is impaired, but their feelings of the quality of ideas is enhanced. Or we are seeing a difference in types of creativity maybe psychedelics reduce individuals deliberate creativity (taskbased, with an end goal), but increases spontaneous creativity (insight).

We also asked participants to come back 7 days later and repeat the tasks, Mason said. Here we see that after psilocybin, individuals performed better on one part of the task. Namely, they were able to come up with more novel responses. Thus we see that maybe psychedelics do increase aspects of deliberate creativity in the long-term.

The researchers also found that psilocybin-induced changes in creativity were associated with connectivity patterns within the default mode network, a large-scale brain network involved with daydreaming, imagination, and spontaneous thinking, among other things. We found changes in the brain that predicted both the acute and long-term changes in creative performance after psilocybin, so we can start to get an idea of how these drugs are working to enhance or impair creative thinking, Mason said.

In particular, decreased integrity of the default mode network was associated with greater subjective feelings of insightfulness, as well as long-term increases in divergent thinking.

The findings are in line with previous research conducted by Mason and her colleagues, which took place at a psychedelic retreat. Unlike the current study, however, the past research was limited by its lack of a placebo condition.

But, despite the improved methodology, there is still a need for additional research. We dont know if under the influence of psychedelics, individuals just feel more creative or if these drugs are actually increasing the spontaneous side of creativity, so this needs to be further tested, Mason explained.

These distinctions are of particular importance, as psychedelics are currently being investigated to treat a number of mental health disorders, characterized by rigid, inflexible thought patterns (like anxiety and depression). Thus, it could be suggested that the ability of psilocybin to acutely alter different aspects of creative thinking could aid in the therapeutic process by opening up a window of opportunity where therapeutic interventions could prove more effective.

Namely, while under the influence of a psychedelic, rigid thought content could be decreased, while unguided, spontaneous thoughts may give rise to new insights and perspectives of previous events and current problems, Mason added. Subacutely, patients may then be able to integrate these insights with a therapist, and come up with new, more effective strategies that facilitate adaptive interpretation and coping abilities. Thus, future studies should be employed in clinical populations in order to assess this proposal, as well as the underlying neurobiological mechanisms.

The study, Spontaneous and deliberate creative cognition during and after psilocybin exposure, was published April 8, 2021.

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Psilocybins complicated relationship with creativity revealed in new placebo-controlled neuroimaging study - PsyPost

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Psyched Wellness: Partly psychedelics and partly consumer wellness – Proactive Investors USA & Canada

Posted: at 7:15 am

Proactive Research analyst Ed Stacey takes a closer look atLtd (CSE: PSYC) (OTCQB: PSYCF), a health supplements company developing a unique range of products which harness the properties of a specific type of mushroom.

The functional mushrooms market is a large and growing segment in consumer health, currently running at around US$30bn per year globally.

Within the sector, many companies are looking at ways to work with psychedelic mushrooms, which are believed to offer physical and mental health benefits when consumed at low doses.

Click here to read Proactive analyst Ed Stacey's initiation report on 'Psyched Wellness - The drink of the gods'

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Psyched Wellness: Partly psychedelics and partly consumer wellness - Proactive Investors USA & Canada

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J. Prince Appears to Have Bought His Own Private Island: ‘They Said It Couldn’t Be Done’ – Complex

Posted: at 7:14 am

Welcome to Prince Island No. 1.

J. Princetook to Instagram to show off what appears to be his own private island. They said itcouldnt be done,he can be overheard saying as he seems to be riding a jet ski in avideo he posted to Instagram. They told me I was dreaming too big. They told me I was crazy. They said it was impossible. I done made the impossible possible. Prince Island No. 1.Loyalty for life.

Prince doesnt give away much about the island regarding the location, how much it cost,or even how it looks up close, but we can gather from name itself is that he seems to have his sights set on getting more private islands in the future.

The Rap-A-Lot Records founderjoins a handful of celebrities who have reportedly bought an island. The Sun reports JAY-Z spent nearly $4 million in 2016 on an island in the Bahamas so that he andBeyonc can do the little things, like go to the beach with Blue Ivy. Back in 2009, Tyler Perry bought an island for his 40thbirthday. Im a loner by nature, so when Im out there on these islands, I just feel like the only person in the world, Perry explained.

Check out J. Princes video up top.

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J. Prince Appears to Have Bought His Own Private Island: 'They Said It Couldn't Be Done' - Complex

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Monthly Archives: April 2021

Cheat Sheet: What a radical GOP antitrust bill that would kill big tech acquisitions has in common with the Democrats push for reform – Digiday

Clubhouse, big tech or newcomers: who’ll win the social audio race? – Sifted

Digital Transformation Experts Debate Future of Banking, Big Tech & Fintech – The Financial Brand

Blood Clots, Birth Control, and the Johnson & Johnson Vaccine: What We Mean by Medical Risk – The New Republic

[Full text] Binding of the SARS-CoV-2 Spike Protein | HMER – Dove Medical Press

In Canada, psychedelics re-emerge in treatment of depression – The Japan Times

Psychedelics re-emerge in treatment of depression in Canada – Deccan Herald

Psilocybins complicated relationship with creativity revealed in new placebo-controlled neuroimaging study – PsyPost

Psyched Wellness: Partly psychedelics and partly consumer wellness – Proactive Investors USA & Canada

J. Prince Appears to Have Bought His Own Private Island: ‘They Said It Couldn’t Be Done’ – Complex

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