Category Archives: Evolution

A researcher with a personal mission to cure genetic muscle diseases has developed a more targeted and effective approach for delivering healthy copies of faulty genes into muscle cells.

As a teenager, Sharif Tabebordbar watched his father struggle with muscular dystrophy, a genetic disease that causes muscle loss over time. As his father grew weaker and eventually unable to walk on his own, Tabebordbar decided he had to do something to help.

Working in Howard Hughes Medical Institute Investigator Pardis Sabetis lab at Harvard University, Tabebordbar has developed a targeted therapy that reverses symptoms of muscular dystrophy in mice. This new method delivers gene therapy to muscle cells more precisely and efficiently than current approaches do, the team reports September 9, 2021, in the journal Cell.

This system is clearly better than what we have now, and it will be exciting to see it move into the clinic, says Jeffrey Chamberlain, a muscular dystrophy researcher at the University of Washington School of Medicine who was not involved with the work.

Muscular dystrophy is a group of diseases in which defective genes trigger the constant breakdown of muscle tissue. Nearly 20 years ago, when the teenaged Tabebordbar learned that just one gene was at the root of most genetic muscle diseases, he thought fixing it should be simple. We know what gene is defective, he says. If we can just replace that one gene, that would be it. So why is it taking so long?

Gene therapy seeks to fix genetic problems at their source. The technology was first successfully used in 1990 to treat a child with severe combined immunodeficiency (known as bubble boy disease). Today, not only can genes be replaced as in treatments now used for inherited retinal diseases but scientists are also testing CRISPR gene editing technology to repair defective genes, such as those in sickle cell disease. Gene therapy for muscular dystrophy has faced numerous obstacles, though, including how to deliver it efficiently into muscles throughout the body.

As a graduate student at Harvard, Tabebordbar developed a gene therapy in mice to repair Duchenne muscular dystrophy. During this time, he met two MIT graduate students, Eric Wang and Albert Almada, who had family members with the disease, and they decided to collaborate. After finishing his PhD, Tabebordbar joined Editas Medicine, a gene editing company based inCambridge, Massachusetts, to start moving his therapy to humans. Everything seemed to be coming together and then he hit a roadblock. Most of the delivered genes were ending up in the liver, he discovered, not in the muscles, where its needed.

Gene therapy delivers new genetic instructions to cells using harmless viruses, or pieces of viruses, which excel at entering cells. As with many gene therapies, Tabebordbar had chosen to use an adeno-associated virus, or AAV, because it enters cells without making people sick or triggering a strong immune response. But up to 90 percent of the virus infused into patients for muscular dystrophy traveled to the liver, where it can be toxic.

Tabebordbar realized that he needed a better way to target the virus to muscle. AAV is like a delivery vehicle for gene therapy, he says and it needed improved directions. He decided to take advantage of viruses natural ability to evolve. Viruses frequently evolve to target host cells more effectively. In this case, Tabebordbar wanted to create viruses that home in on muscles. Thats where Sabeti, who studies viral evolution, could help.

In Sabetis lab, Tabebordbar and colleagues found a promising family of AAVs with capsids, or protein shells, that specifically target muscle and heart cells. The team injected mice and monkeys with these viruses, and then tracked which ones best targeted muscle cells. They repeated this process to direct the evolution of the AAVuntil they had a virusthat could effectively deliver gene therapy at doses as low as a hundredth of those currently used in clinical trials.

Its pretty amazing to see how exquisitely these viruses can adapt to target a very specific cell type, Sabeti says.

The new capsids seem to have advantages that are the best of both worlds, says Chamberlain, who first reported that AAVs could be used to deliver genes to muscles throughout the body in 2004. They get into muscle better, and they show a reduced propensity to get into the liver.

He notes that gene therapy for muscular dystrophy must still overcome other challenges that have arisen in clinical trials, such as avoiding attack by antibodies and efficiently getting into muscle stem cells, which help regenerate muscle tissue. Still, he calls the improved delivery system very promising.

Tabebordbar is now working toward testing his new technologies in human trials.

Sabeti says shes proud of how a team of students and technicians in her laboratory came together around his project. I think that when people have this deep personal understanding of the importance of the work, it can move them to do pretty tremendous things, she says.

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Citation

Mohammadsharif Tabebordbar et al. Directed evolution of a family of AAV capsid variants enabling potent muscle-directed gene delivery across species. Cell. Published online September 9, 2021. doi: 10.1016/j.cell.2021.08.028

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How Virus Evolution Is Improving Gene Therapy for Muscular Dystrophy - Howard Hughes Medical Institute

Image: Bacterial flagellar motor, from Unlocking the Mystery of Life, Illustra Media.

In July Icoveredapaperin the journalBIO-Complexitythat reviewed engineering constraints on the bacterial flagellum. I noted that the author, Waldean Schulz, an engineer with a PhD in computer science, was preparing future papers that would explore questions about flagellar evolution, such as, Would such partial systems be preserved long enough for additional cooperating components to evolve? Now Schulz has published a second peer-reviewed scientific paper inBIO-Complexity, An Engineering Perspective on the Bacterial Flagellum: Part 2 Analytic View, which begins to address that question.

His first paper took a top down approach to determining the components and design necessary to fulfill the functional constraints of the flagellum. The second paper takes a bottom up approach, and reviews the known 40+ protein components and the observed and inferred structure, control, and assembly of a typical bacterial flagellum. He provides a clear diagram of an archetypical flagellum, labeling features such as the motor stator, filament, hook, and rod:

Schulz notes that the assembly process requires a regular set of components and procedures in order to work properly on this point, he quotes Cohenet al.(2017) fromSciencewho state:

The bacterial flagellum exemplifies a system where even small deviations from the highly regulated flagellar assembly process can abolish motility and cause negative physiological outcomes. Consequently, bacteria [possess] robust regulatory mechanisms to ensure that flagellar morphogenesis follows a defined path, with each component self-assembling to predetermined dimensions.

Schulz further explains that these proteins components themselves are fine-tuned to Note that all proteins in each rotary subassembly need to (non-covalently) bind tightly to themselves and to the proteins of the adjacent subassemblies. This is noteworthy: the combinatorial configurations of the ensemble of proteins must be very specifically orchestrated.

Schulz considers not just the design and construction of the flagellum, but also the biochemical basis of chemotaxis. Its a long passage but its worth reading to appreciate the complexity, elegance, and control of the system:

While there are diverse chemotaxis systems for differing bacteria, generally the concentrations of environmental chemistry are sensed by transmembrane methyl-accepting chemotaxis proteins (MCP). In the case of our archetypical bacterium, these MCPs include Tar, Tsar, Trg, Tap (E. coli) or Tcp (Salmonella), and Aer. They have a periplasmic ligand binding region and a cytosolic signalling region. These are bound to CheA by CheW to form clusters located at one or both polar ends. CheA auto-phosphorylates according to the methylation of the MCPs. Presence of nutrients increases methylation; toxins or repellants decrease it. The methylation state implements the short-term memory of the sensor system. Rebbapragada states, Repellent binding to a chemotaxis receptor induces a conformational change in the signalling domain [of the MCP] that increases the rate of CheA autophosphorylation. The phosphoryl residue from CheA is transferred to CheY. CheY-P in its phosphorylated state, diffuses to a flagellum, and binds to the flagellar rotor. That causes the rotor to switch the direction of rotation of the filament so that the bacterium tumbles. Tumbling causes a random new direction for forward travel after CheZ dephosphorylates CheY-P. Then CheY unbinds from the switch, default (counterclockwise) rotation ensues, and forward travel resumes. This periodic tumbling occurs about every second. The upshot is a biased random climb up an attractant gradient.

Meanwhile the methyl esterase protein CheB demethylates the MCP-Che-CheW complex, eventually resetting it back to its non-signalling state. The response of CheB is slower than the transfer of phosphorylation to CheY, so CheY-P can interact with the flagellar motor rotor before CheW responds (as a kind of delayed negative feedback). In parallel, CheZ removes the phosphorylated state of CheY. So, CheB and CheZ provide adaptation (hysteresis) by a time-delayed negative feedback. If stimuli are present in abundance, the phosphorylation of CheA outdoes the negative feedback effect of CheB. If stimuli decrease, then the effect of CheB starts winning out, too few CheY proteins are phosphorylated, and the flagellum rotation reverts to its default rotation.

This control system alters the period between tumbles, with longer periods occurring in the presence of increasing attractants to prevent unneeded redirection.

Schulz also explores the mechanisms by which the flagellum generates torque to spin the filament. While this process is not fully understood, he notes that the power output of the motor is nearly 100% efficient, and proposes that it involves proteins that effectively function as gears:

MotA in effect forms a gear and always rotates in the same CW direction. During normal CCW rotation for forward motion, the C-rings FliG engages with the side of MotA that is nearer to the C-ring axis. During CW rotation for tumbling, the MotA reconfigures so the C-ring engages with the side of the MotA cog gear that is farther from the C-ring axis. If this hypothesis is correct, the protein configurations of FliG and of MotA are exquisitely matched.

Schulz then turns to the assembly of the flagellum and notes that they have remarkably similar control across different species: All flagellar systems coordinate flagellar gene expression through a transcriptional hierarchy central to an integrated regulatory network of multiple regulatory components. These networks exhibit a number of conserved circuit architectures reflective of the strong conservation found within the structural components of the flagellum. In a series of illustrations he diagrams the flagellar assembly process through various pathways and at major stages in the production of various subcomponents. He notes that the complexity of the flagellum poses a challenge to evolutionary biologists:

The future work for an evolutionary biologist is twofold: (1) to provide a detailed explanation for how all the tightly constrained interlocking coherence described above could have evolved stepwise and naturalistically under real-world constraints; (2) to show evidence that such a scenario actually occurred in the past.

After concluding his review, Schulz expresses the view that a step-by-step evolutionary pathway is unlikely:

[T]he evolutionary biological community has yet to hypothesize a likely, detailed, step-by-step scenario to explain how the flagellum and its control system could have been blindly engineered naturalistically. Yet even that would still fall short of real evidence that such a thing actually happened, given real-world constraints. The flagellum seemingly is irreducible. How would portions of an incomplete, nascent flagellum be protected from degradation for generations while the remainder was yet to be gradually added? If some of the subassemblies discussed above could be omitted, what function would result?

Although Schulz notes that these are hard questions, he says they should not be dismissed: These are real questions, and the challenge is to answer them. In the meantime, despite our lack of total knowledge, he concludes that a design-option should remain on the table: it seems disingenuous to dismiss teleology and intelligent causation, when so much is already known about the apparently ingenious, coordinated hierarchical assembly, control, and function of the flagellum.

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Paper Details Flagellum's Function and Assembly - Discovery Institute

In the spring of 2020, the COVID-19 pandemic engulfed New York City. Hospitals began filling up with the virus that at that point no one knew how to treat successfully. And theMontefiore Moses divisionof the Montefiore Health System became one of the first designated COVID centers, and the first to achieve in-house COVID-19 testing in New York City using the polymerase chain reaction.

As with health care in general, Montefiore experienced more HAIs. In the early days of the pandemic, before the realization of treatment protocols for COVID-19, Montefiore struggled to find therapy regimens and had a lack of medical devices and equipment so these things had to be shared.

Priya Nori, MD, director, Antimicrobial Stewardship, Montefiore Health System and associate professor, Medicine & Orthopedic Surgery, Albert Einstein College of Medicine, program director of the infectious diseases fellowship program, talked about the data from studies showing increased incidence rate of HAIs. We know now that this is a pandemic surge-driven phenomenon, Nori said. And this is because healthcare workers were overwhelmed; our capacity to take care of people was overwhelmed.

In the second installment of an interview with Nori, she spoke about how COVID-19 care has changed since the beginning of the pandemic, offered some insights into the bacterial infections they saw, and how they combatted them with infection prevention measures. To see the first interview, go here.

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The Evolution of COVID-19 Care - Contagionlive.com

Damon was first urged to read Eric Jagers book The Last Duel, about a dark and dramatic episode in 14th-century France, with a mind to its movie potential, back in 2011. He demurred. Hearing that Martin Scorsese already had the rights, he felt it would be a waste of his time: I said, Well, if Marty has it, hes going to do it with Leo. Seven years later, the rights now available, Damon relented.

At first, he couldnt see it. Twenty pages in, I was just thinking, We cant do this, he says. Like, these guys are absolute savages. These guys are born in the middle of a hundred--year war, they do nothing but rape and pillage and fight for their entire lives. But then the central story gripped him: of two men, one accused of rape by the others wife, and of the woman at the center. She had, at great risk to first her reputation and then to herself, stood up and told the truth, again and again and again, says Damon. It was just pretty amazing. He sent the book to Ridley Scott, whom he had wanted to work with again since their successful collaboration on The Martian. Scott shared his enthusiasm. Now they needed a script.

One evening, Damon had dinner with Ben Affleck. Over the years, the two teenage friends have remained close, in a way thatas they separately acknowledgefar transcends the cartoon best-Hollywood-buddy way it can often be depicted.

Like, I dont want to be his friend in public, you know what I mean? Damon says. Its way too important a friendship for that, and it goes so beyond this career or anything. You know, its a significant part of my life and not for public consumption in that way.

I cant speak for Matt, Affleck offers, but my own kind of sanity and mental health really benefited from having someone who I grew up with and knew as a child who was also going through something similarthis 20-year-plus journey of being in the public eyewho I could reflect on it with honestly, talk things over with, be myself with, who I knew why we were friends, why he was interested and loved me, why I loved him. I often think of people who just become successful and then get thrust into this, and I think, How do they do it without having somebody that they can talk to? Who they can trust? Who knew them before? Its just been such an asset to meand, I think, I hope, to Mattthis relationship that weve had.

The two of them have remained periodic work colleaguesthey share a production companybut after winning their Good Will Hunting Oscar, they had never even attempted to collaborate on another script. To a large extent this was a reflection of just how successful their initial strategy has beenkick-started by that movies success, both had long been busy with the kind of opportunities they could once have only dreamed of. But it was also that what they had done back then seemed too cumbersome to ever repeat.

The process of writing was so time consuming when we did it, when we were 22 and 20, says Damon.

We didnt have jobs, we didnt have anything else to do, echoes Affleck. We had two years to sort of muddle our way through a draft, and then another draftto spend time sitting around and drinking beer and talking about the themes and playing video games and bullshitting.

We really understood the characters, and so we would take them and we would put them in these different scenarios, Damon explains, and then at the end, we kind of mashed these disjointed parts together into what could cohere as some kind of narrative. And thats a really inefficient way to write. And I think both of us just intuitively felt like: Well, were never going to have enough time to do that again.

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The Evolution of Matt Damon - GQ Magazine

Okay, so the E161 is in the state of kind of completion. It's been a battle to get it here, hasn't it?

So what did you change from the first version?

You've gone from 29 to mullet. Was that just a feel thing whilst you've been riding it?

Have you have made a bike that feels the same as your 161 enduro bike but with a motor in it?

We have mentioned him a lot already, how important was Matt Stuttard to developing this bike?

[PCOLUMNS

So, much more of the same from Privateer, build-kit wise, still at a good price point?

The big thing with Privateer is that it's about durability and that when the bike takes a pounding, it keeps coming back for more. Is it more of the same here?

What about motor wise - what motor and battery are you using?

I know it's hard to say with all the supply chain issues, but when do you think it will be launched?

So how are you coping with supply chain issues? Obviously, you're not a massive company, you're not one of the big brands, is that causing you issues?

Okay, so that the Fox X2 sat in the heart of the suspension, that's custom-tuned for you?

What's next for the bike?

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Interview: The Evolution of the Privateer E161 eMTB - Pinkbike.com

September 8, 2021

For every generation, there is at least one collective, momentous occasion that leaves an indelible mark on the timeline of their lives. For boomers, Gen Xers and a good number of millennials, the moment the first plane crashed into the north tower of the World Trade Center on Sept. 11, 2001, is unquestionably one of those occasions.

Twenty years on, what does 9/11 an event that radically altered the arc of global history mean to Generation Z, many of whom werent even alive at the time? And what might it mean to the generations that follow?

Since I was 2 when it happened, I wasn't old enough to understand it in the moment and have that impact me going forward. So I was kind of removed from it. I dont think it affected me as much personally as it would have if I was older, said ASU psychology senior Lillian Lynch, 22.

But I would definitely be open to hearing about the experiences of people who remember it well, because it was just such an impactful part of our history," she continued. "I think its important to know more about it, and they could probably teach me more than just a chapter in a history book.

As program manager for the Osher Lifelong Learning Institute at Arizona State University for going on seven years, Abby Baker has facilitated myriad intergenerational conversations and engagement activities. She said that opportunity to learn from one another is whats at the heart of meaningful intergenerational connections.

To me, intergenerational relations are all about education, Baker said. We each have something unique to learn from each other among, between and across generations.

And, she continued, that sentiment becomes especially salient when it pertains to traumatic events whose consequences ripple throughout time.

Each generation has its traumatic historical events the events that happen in their youth which, in part, shape their worldview and, in turn, shape the ways they make decisions about money, careers, family and so much more, Baker said. I think it is important to, once again, make connections across generations so it doesn't matter if a person has lived through the traumatic event in question we've all lived through a traumatic event, and there is universality in that.

Getting to that point of mutual understanding can be somewhat tricky, though, as former ASU Professor of English and bestselling novelist Jewell Parker Rhodes noted in an April 2021 interview with Publishers Weekly about writing Towers Falling, a childrens book that aims to teach them about 9/11 from the safe distance of fictional characters.

When I presented my book in the school, the kids were so curious but lots of teachers were crying; they said they still didnt want to teach it, Parker Rhodes said in the interview. What I discovered was that was very typical of parents, teachers, librarians whod lived through it. They did not want to talk about it. The trauma was still so present. It was that sense that history is not so far past.

The interconnectedness of past and present, and how it influences the identities of the books main characters the daughter of a man who has trouble maintaining a job because of illnesses that resulted from the attack; a boy whose father is an Iraq War veteran; and a Muslim girl is ultimately realized by them when they visit the Sept. 11 memorial and witness the firsthand accounts retold there.

Mark Tebeau, an associate professor of public history at ASUs School of Historical, Philosophical and Religious Studies, has directed more than two dozen digital humanities, oral history and public history projects. We document history for several reasons, he said.

One is to mark that I was here; to say we existed, Tebeau said. But its also about enlightenment. Documenting the human experience provides a way of making sense of the world and defining our identities at any given moment. And that is learned and passed down through generations.

Just as important as the fact that humans document history at all is how we document it. For example, Tebeau said, archives of World War I are more likely to have been created by members of the elite and to contain more documents from formal sources, such as newspaper clippings and professionally filmed battle footage, rather than informal sources like letters and personal photos, simply because the average person didnt always have the means to create such records. Whereas nowadays, in the age of ubiquitous smartphone use, an archive might contain far more informal, personal documents supplied by a broader swath of society.

That makes (history) more personal, for sure. It also makes it more accessible to younger generations, Tebeau said.

By 2001, the proliferation of the personal computer and the increasing accessibility of the internet were giving rise to a democratization of historical documentation. One result was the September 11 Digital Archive, one of the first crowdsourced digital archives. Just a few years later, Hurricane Katrina spawned the Hurricane Digital Memory Bank. Both archives employed the same open-source web-publishing platform (Omeka) that Tebeau would later use to create A Journal of the Plague Year: An Archive of COVID-19 in 2020.

With the computer age, what happens is we start to see a more broadly sourced record of a moment in time, Tebeau said. But more doesnt always mean better. So that might mean its more relatable, but the sheer volume of stuff can actually make it incomprehensible.

There is also the concern that, compounded by a lack of context, the ease with which traumatic historical events can be accessed and the tangibility afforded by modern technology have the potential to do more harm than good, something else Parker Rhodes noted in her Publishers Weekly interview.

Due to technology, we can see the towers being attacked over and over and over again. We cant see the Civil War repeating, she said. We have another kind of trauma: We risk having our children misinformed because they only see the physical impact upon our nation.

Though a reasonable argument, some posit that perhaps precisely because younger generations have grown up in a world of overstimulation, they are actually better at coping with the side effects.

Younger generations openness to discussing their traumas and prioritizing their mental health has been both derided and celebrated in recent years.

Niki Gueci, executive director of ASUs Center for Mindfulness, Compassion and Resilience, is among those celebrating, noting that research findings have proven, time and again, that prioritizing our well-being can lead to enhanced professional and academic outcomes, less burnout and more life satisfaction.

Were seeing that living in a no-sleep, constantly busy, hustle culture is not sustainable, Guecisaid. Celebrities and others in high profile positions experienced public consequences after bouts of physical and mental exhaustion, citing stress and the feeling of being overwhelmed.

And although she stresses that the desire to live a more mindful life in the name of overall health is not a new trend, she has noticed more amenability to the idea among younger populations.

Younger generations are fully embracing whole-person well-being and implementing strategies that work for them in their lives, on their terms, Gueci said. What I see now within our own ASU community is there is more awareness, more acceptance and more credence given to building resilience into individual lives and social structures.

No matter how one engages with the memory of 9/11, it will always be an opportunity to reflect, to commiserate and to learn. Which lessons we choose to pass on to subsequent generations remains to be seen.

Top illustration by Alex Davis/ASU

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School of Human Evolution and Social Change welcomes 5 new faculty - ASU News Now

Sept. 7, 2021 3:03 pm ET

H.G. Wellss fictional vision of human evolution in The Time Machine (1895) is a bifurcation of our species 800,000 years in the future. Wells was much more accurate about the direction of our evolution than about the timeline. In Imagine a Future Without Sex (op-ed, Sept. 1), James Lee explains how current reproductive technology can be used to screen embryos for higher intelligence prior to in-vitro fertilization.

Human life becomes more and more a commodity. The possibilities are humbling: screen embryos for low intelligence to provide docile labor, screen for aggression to supply soldiers, screen for universal organ donors. Mr. Lees theme can be extended: Why not produce perfect surrogate mothers? Product lines of specialty humans could then be produced in factories full of such surrogate mothers. No need to bother with sex, pregnancy and childbirth; order your child from a catalog. There is a point here: As we start to design humans, we have almost no idea of the consequences. The potential for tragedy by far outweighs that of anything else we have done, including making nuclear weapons.

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The Murky Next Stage in Human Evolution - The Wall Street Journal

COVID-19 still has major impacts on our daily lives and will continue to affect us in the years to come. But I believe without a doubt that a new era will begin that will be covered in history textbooks. I predict this era will be known as an era of rebuilding in regards to both the individual and society. On both a micro and macro level, we have had to re-establish a new normal.

With this in mind, I urge you to practice the art of forgiveness.

Forgiveness is not just a practice regarding other people. In practice, forgiveness is leading with a gentle and compassionate outlook. It is also applicable to the big and the small experiences that may negatively impact your life. This can be anything from spilling coffee on your favorite shirt to being rejected from your top school.

The shirt is replaceable and the school failed to see what you have to offer, so instead of fixating on what you lost, think about what you can gain from these experiences. Some people fail to realize that this applies to your relationship with yourself as well.

For instance, both examples above are self-inflicted occurrences. It is not one elses fault that you spilled coffee or got rejected from an Ivy League Institution, no matter how graceful or academic you may be. However, it is important to remain confident in yourself. Your failures do not define who you are. They only make you human.

Like everyone else, I had ample time to do some self-reflection during the past year and a half. To pass what seemed like excruciatingly slow days, I threw myself into new activities. From hopping on the baked oat fad to downloading Sam Harris miraculous meditation app Waking Up I developed new facets of interest.

The commonality between these new activities boils down to the practice of mindfulness. According to The Greater Good Science Center at the University of California, Berkeley, mindfulness describes the habit of being aware of our current experiences, thoughts and emotions. It encourages us to live in the present moment and accept our current situation without judging ourselves based on our emotional responses.

To simplify even further, it boils down to the practice of self-love and acceptance.

Mindfulness in practice looks different for everyone. This makes sense because everyone has complex needs and emotions rooted in their own situation. However, I would like to think that inner peace and happiness are universal human emotions, or at least can be with the correct mindset.

Along with mindfulness, forgiveness is key. When thinking about the new era approaching post-covid, forgiveness is something at the forefront of my mind. When you forgive and let go, it is solely a positive experience. This is because anger and resentment manifest internally: No matter how wronged you feel, you are the only one hung up on these negative emotions. Do not give the power of a mind at ease away to anyone. You need to understand just how in control you are.

So, why wouldnt everyone forgive if it makes you feel better? There is a certain threshold of maturity required to truly forgive yourself and others. It means silencing your ego and letting yourself process your pain in order to discard it forever, and some people are simply not there yet.

I recently came across the psychology term radical acceptance. This was huge.

Radical acceptance is a practice used to stop painful feelings from becoming suffering. It is as simple as accepting your reality for what it is. This idea ties into forgiveness because it reinforces the belief that fixating on past emotional trauma does no good in the present.

I would argue that this change in how I viewed my emotions was more impactful and meaningful to me than the change of uprooting my life from California to Boston. In some ways, the pandemic sparked growth that I do not know would have been possible without it.

The time I spent alone was time that I dedicated to mindfulness, and through that, I landed on the power of forgiveness. Of course, I am 19 years old and have my days. After all, my college years are being spent in a pandemic-induced purgatory.

But when you forgive yourself and others, this translates to living a life of gratitude. This is because when you are not fixating on the wrongs, you will find yourself fixating on all that is right.

Youve most likely heard or used phrases like let go of the past or it is what it is. These popularly coined phrases facilitate the same idea as radical acceptance. Next time you hear one of these phrases, I encourage you to refrain from rolling your eyes and open your mind instead.

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Intentional Evolution: Forgive to forget The Daily Free Press - Daily Free Press

New Nollywood saw films particularly distinguished by their enhanced narrative complexity, aesthetic value, and overall production quality compared to the films made during the video boom. While some films in this wave are still released directly on DVD, most are released theatrically to teeming fans via cinemas or streaming platforms.

What happened before New Nollywood?Long before the Ini Dima-Okojies and Timini Egbusons of today, cinema for most people was in the form of playing companies and travelling troupes. They performed in various cities and attracted a huge crowd of faithful looking to unwind and have a good time. These plays, either funded by the court, church or audiences, were promoted via advertisements and posters disseminating information to potential audiences.

The introduction of technology made it possible for these plays to be recorded and screened in tiny picture houses across cinemas in the industry. As a result, the local content, especially productions from Western Nigeria, owing to former theatre practitioners such as Hubert Ogunde and Moses Olaiya, were on the big screen. This way, they reached a larger audience, and this saw a significant increase in the 70s.

By the 80s, the purchasing power of most Nigerians had increased (all thanks to the oil boom of the late 70s). This single action saw an increase in cinema visits as more people could spend more going to the cinemas. It also saw home television sets become a staple in Nigerian homes. The latter would then birth family television shows, and sitcoms created for families and revolved around the quintessential Nigerian home. These shows like New Masquerade, Basi & Company, to mention but a few, were riveting and aired at times when every family member was home from the daily hustle and bustle.

These television productions were later released on video, leading to the development of a small scale informal video trade, and subsequently the much talked about video boom of the 1990s. Despite all the success, this era of Nollywood was not easy as it was plagued with multiple errors. Like the oil boom was integral to purchasing power, its crash affected the industry as well. There were also issues revolving around lack of finance and marketing support, lack of standard film studios and production equipment and, very importantly, a lack of experience on the part of practitioners.

Also, owning television sets at home came with its problem more and more households rejected the idea of visiting cinemas. It also didnt help that the films produced during this era were screened over a single weekend, making them available on video immediately. Eventually, more families consumed films together as it had become inbuilt behaviour. These films were educational and taught the difference between good and evil, and already there was a culture of communal watching which made it all the better.

By the 90s, most cinema houses had collapsed due to a lack of activity. Churches acquired others that had not collapsed. As expected, video on demand was the thing, and films like Kenneth Nnabues Living in Bondage had paved the way for this. Video rental clubs thrived for families, and the allure was paying as little as N100 for a limited amount to a film.

Resting on the Shoulders of New NollywoodNew Nollywood may not have kicked in until recently, but its groundwork has been a long time in the works. Few years into the 2000s, there was a vibrant rebirth of cinemas designed for societys middle and upper echelon. By this time, televisions were still trendy, and films went from VHS (Video Home System) to VCD (video compact discs). Nonetheless, more people craved some form of social interaction. The cinemas afforded them some level of social activity and a modified sort of entertainment beyond film watching, seeing as they were located in prominent and busy malls. The Silverbird Group was one of the first significant players here, opening up a high scale mall in Victoria Island, which had a cinema and other entertainment attractions. Upon Silverbirds success, more and more cinemas erupted and spread into the less affluent neighbourhoods in the society.

Also, during this period, grants were provided by the government and various institutions to filmmakers to produce high-quality titles and aid proper distribution as piracy was eating deeply into the industry at that point. Some of these grants allowed filmmakers to take film courses and learn at prestigious schools. Other filmmakers tried to make breakaway films, which were quite different from the norm. These include Tunde Kelanis Thunderbolt, Tade Ogidans Dangerous Twins and Mildred Okwos 30 Days.

By the end of 2013, the film industry reportedly hit a record-breaking revenue of 1.72 trillion. One year later, the industry was worth 853.9 billion, making it the third most valuable film industry in the world, behind the United States and India.

With New Nollywood, Nigerian films have been elevated from what they used to be in the video boom area. They have considerably bigger budgets, extended film production periods and are better equipped to take the storytelling up a notch. Also, a little freedom with the range of stories to tell was introduced. One could argue that New Nollywood may not have gotten storytelling better than its predecessors, but there seems to be time to correct that mistake if the industry seems willing to.

Another exciting thing that came with New Nollywood was video-on-demand platforms and pay-TV networks, another interesting way technology has helped the industry. Although cinemas are great for social activity, theres an audience that either misses out on films due to their short stay in cinemas or just plain unwillingness to watch them. In 2020, Netflix launched locally in Nigeria and South Africa to prioritise content made by Africans. Since then, its commissioned a few original TV shows and films, most recently Kemi Adetibas seven-part series King of Boys: The Return of the King. Before its launch, the streaming giant had also been paying for content by Africans for streaming on its platform.

Before then, French television company Canal+ acquired the ROK film studio from VOD company IROKOtv for an undisclosed amount. According to a public statement released, ROK was expected to produce thousands of hours of Nollywood content to deliver films and original TV series for Canal+ Groups audiences. These are just some of the many platforms accessible for film in Nigeria.

On Creating For New AudiencesWhile looking at New Nollywood and Old Nollywood, one thing sticks out evolution. A lot of things have changed and created room for more. First was an evolution in cinema culture, then an evolution in technology which made and will keep making things better for filmmakers. As globalisation continues to affect everything, Nigerian cinema will not be left out.

The growth of Nollywood has created a demand for local Nigerian productions all over the world. With more and more streaming platforms archiving some classics, theres constantly a demand for more Nollywood productions. This demand has seen big players step into the market in Nollywoods attempts to make things accessible for audiences far and wide. And thanks to the internet and social media, memes from old classics like Tchidi Chikeres 2014 comedy, Pretty Liars, have made their way to our pop culture today. Thats not forgetting the millions of videos and pictures from evergreen film characters Aki (Chinedu Ikezie) and Pawpaw (Osita Iheme) that have achieved global fame and sparked curious interest from foreigners.

Likewise, theres a Y2K trend on Tiktok from the 2006 Girls Cot that is reminiscent of the Plastics from Mean Girls, and there are even themed parties from this era everywhere on social media. Things like this have created an interest amongst younger people to watch Nollywood, if not for anything, for context on the popular memes and gifs they use.

Also, one of the ways that Nollywood has also tapped into the power of globalisation is by featuring foreign cast members in their productions. In most cases, the goal for this is to corner a different, more diverse demographic. A good example is Biyi Bandeles Half of a Yellow Sun which cast Thandie Newton, Anika Noni Rose, and Chiwetel Ejiofor in lead roles. While this strategy hasnt entirely been successful, films like Namaste Wahala with Ini Dima Okojie and Ruslaan Mumtaz have benefitted from this.

Film festivals have also played a crucial role in discovering new audiences for Nollywood. In previous times, multiple films have screened at various festivals worldwide, with a slew of awards to validate the filmmakers efforts. In September 2019, Joel Kachi Bensons Daughters of Chibok won the Best Virtual Reality Story at the prestigious Venice International Film Festival. Likewise, Juju Stories by the Surreal16 Collective recently won the Boccalino dOro Award for Best Film at Locarno Film Festival. Eyimofe, a Guardian Digital Studios (GDN) production, has since clinched awards including the Achille Valdata Award at the 2020 Torino International Film Festival. There are showcases reserved for Nigerian cinema for some film festivals to show off the structures, material, and people behind the relevant films from the country.

The Nigerian audience has been particularly receptive to the films in both eras. After all, film is but an essential part of our culture. Marketing efforts are geared towards getting them into the cinemas seeing as its pivotal to profits for filmmakers and box office, which is also vital in determining the films journey and whether it ends up on specific streaming platforms. In December 2018, the Cinema Exhibitors Association of Nigeria (CEAN) revealed that Nigerians spent N680 million watching films at cinemas between the 14th and the 31st of the month. While this data covers both Nollywood and Hollywood films and may not be an appropriate visualisation of the costs in Nollywood, it shows the opportunities that can happen when films become much better than they are today.

With all the growth that Nollywood has seen, it is easy to think that the industry is at its highest potential it isnt. Access to funds for filmmakers remains one of the biggest problems that the industry faces, with a lack of talents and story development coming behind. New Nollywood may have the better everything, but the golden era still had better stories. Nonetheless, the industry is growing massively, and there is room for further development.

In 2019, Genevieve Nnajis directorial debut, Lionheart, was submitted as Nigerias first-ever submission to the Best International Feature Film at the Oscars. Since then, Desmond Ovbiageles The Milkmaid has also gotten as far as being the countrys submission but not making the shortlist. However, because of these opportunities, more filmmakers can dream of winning that category one day, and these are just some of the future aspirations for the industry.

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The Evolution Of The Nigerian Film Industry Guardian Life - Guardian Nigeria

Evolving Pokmon in Pokmon GO is typically a pretty straightforward affair: stock up on some delicious candy and feed it to your respective mon to evolve. However, some Pokmon have required a bit more TLC before they morph into their other forms. Sometimes you need to walk a specific distance, while others are require a specific time of day or the happiness of the Pokmon to evolve. But with todays introduction of Inkay, things take a turn (literally).

In order to evolve Inkay in Pokmon GO, youll need to first stock up on 50 Inkay Candy. Once you have enough, head on over to the Inkay status menu, and flip your phone upside down. If placed down correctly, the EVOLVE icon will flip as well and will allow you to press it.

Easy enough? Sure is! As always, were loving the unique ways Niantic finds to personalize Pokmon evolutions in GO.

Nintendo super fan since birth, Jason is the creator of Amiibo News and editor-in-chief at Nintendo Wire. One of his life goals is to provide the latest Nintendo news to fellow gamers with his natural know-how.

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How to Evolve Inkay in Pokmon GO | New Evolution Mechanic! - Nintendo Wire