Tag: Academic research

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Scramblase Dynamics Uncovered by Single-Vesicle Fluorescence Microscopy

A new single-protein analysis technique gives researchers newfound ability to study scramblases, physiologically important proteins that translocate phospholipids bidirectionally across cell membranes.  

In the study published in Nature Structural & Molecular Biology titled, “A single-vesicle fluorescence microscopy platform to quantify phospholipid scrambling,” researchers from Weill Cornell Medicine and Ruhr University Bochum have developed a fluorescence imaging-based technique to measure the activity rates of individual scramblase proteins. 

“I’m excited about this new platform as it is versatile and provides unprecedented information on exactly how fast a single scramblase works,” said Anant Menon, PhD, professor of biochemistry and biophysics at Weill Cornell Medicine and co-corresponding author of the study.

Scramblases are key drug targets with roles in the assembly of cell membranes, modification of proteins with sugars, cell survival, muscle development and molecular trafficking. Yet, strategies for understanding scramblase dynamics have been limited.

Traditionally, researchers purify scramblase proteins for further study using vesicles to record average scramblase activity. However, this bulk approach is unable to measure the transport rate of individual scramblases and capture how scramblase variability impact biological processes.

The authors used fluorescently-tagged scramblases to achieve high resolution and evaluated a scramblase protein, known as VDAC1, best known as a membrane channel protein within mitochondria. Two copies of VDAC must align to provide a pathway for lipid movement. These dimers have a wide range of scrambling rates, from fewer than 100 to more than 1,000 lipids per second.

“These findings indicate that only certain dimer conformations are capable of rapid scrambling, directly validating predictions from computer simulations,” Menon said.

The team demonstrated the versatility of their approach by applying the platform to measure lipid-scrambling by opsin, a cell-membrane receptor and scramblase that is involved in light-detection in the eye. Results showed that individual opsin proteins scramble lipids faster than VDAC dimers, achieving rates in excess of 10,000 lipids per second.

The new platform can study how drug molecules impact scramblase function. Additionally, the authors aim to combine their functional studies of scramblases with high-resolution imaging to understand how scramblase shape relates to activity rates. The team also plans to use the technique to study other lipid-moving proteins called flippases and floppases.

The post Scramblase Dynamics Uncovered by Single-Vesicle Fluorescence Microscopy appeared first on GEN – Genetic Engineering and Biotechnology News.

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Turning Rejection Into a Roadmap: Advice for the Next Generation of Mental Health Leaders

A Conversation with Tom Osborn, Founder of Africa’s Largest Mental Health Provider Shamiri Institute

Aaliyah Nadirah Madyun, program director at the Stavros Niarchos Foundation (SNF) Global Center for Child and Adolescent Mental Health at the Child Mind Institute, recently sat down with Tom Osborn, founder of the Shamiri Institute and an International Advisory Board member at the SNF Global Center. They discussed Osborn’s remarkable journey as a young entrepreneur.

At just 18, while studying at Harvard University, Osborn founded the Shamiri Institute, which has since grown into Africa’s largest youth mental health provider — now reaching over 100,000 young people annually and having trained and employed more than 3,000 providers. In this candid conversation, Osborn shares hard-won lessons on resilience, mentorship, and well-being. He offers advice to the SNF Global Center’s Youth Council members — many of whom are launching their own mental health initiatives in communities across Greece, Brazil, South Africa, and beyond.

AM: You founded Shamiri when you were just 18. Many members of our SNF Global Center Youth Councils are now launching their own mental health organizations. What advice would you give them?

TO: I think these past three to five years post-COVID have been quite good for mental health. There’s just more dialogue, more conversation. It’s maybe one of the best times to start working in mental health. There is a big space for young people to be leaders. On the other hand, it’s also very difficult.

AM: What kind of difficulties can young people expect to encounter?

TO: It’s very difficult for a few reasons. We normally start this work because we have a lot of passion, enthusiasm, and commitment to the cause. But that is not the day-to-day of being a social entrepreneur. It’s convincing people to partner with you, to fund you, etc., which is a completely different skill set to learn. And the second part is getting a level of comfort with failure. Because the reality is, on average, nine out of ten doors that you try to open will not open; especially when you are starting. For example, if you’re in Brazil and there are 100 other young people trying to start something, there is a finite pool of opportunities and resources. So, when you are starting, part of the initial process requires you to develop resilience and a growth mindset.

AM: Could you speak about the role mentorship has played in your journey, and how young entrepreneurs can leverage mentorship to navigate the challenges of building something from the ground up?

TO: Mentorship is really crucial. Finding folks — researchers, practitioners, or just folks in the community — who can help provide guidance as you build the skills you need to be an effective entrepreneur.

AM: How would you recommend young people go about finding a mentor? It seems like that ability, identifying and cultivating a mentoring relationship, might be a skill set in itself.

TO: In my experience, there are three pathways. In many countries we have what we call accelerators, which look for young people who literally have an idea and enthusiasm, and then take them through 10–16 weeks of bootcamp where they can learn the skills to develop their idea. So, that’s one pathway. The second pathway, which really worked for me but may sound intimidating, is direct outreach to folks who have done something similar. So, you can do some research. It doesn’t have to even be related to mental health. It can be education or some broader thing. But find someone who has built something that you admire. You will be surprised how many people are willing to support and pay it forward, because we all have benefited from the help of someone else. I created an Excel spreadsheet with a list of people who I looked up to, and I reached out to them on LinkedIn. Sometimes you can even find their email. Some people said “no”, but if you reach out to 10 or 20 people, some people will talk to you. And the third pathway is . . . increasingly we have a lot of resources like the SNF Global Center Youth Councils and international organizations that deal with mental health. You can join these organizations to expand your network.

AM: Could you share your story with us and tell us how you got started?

TO: I started when I was in University as part of a research project I was doing when I was studying psychology. I needed to do something for my thesis and in the process of doing that I applied to an accelerator. I also went to my professor and asked him, ‘Do you know anyone who could connect me with?’ In fact, he helped me write my first grant and gave me the opportunity to learn those entrepreneurial skills.

AM: Starting at such a young age, one can imagine that you must have encountered many challenges and setbacks. What were the key lessons you took away from that growth period?

TO: The reality of this work, and not to discourage people but to give a factual picture, is that there are more setbacks than there are wins. Part of the process is that you learn from the setbacks. I can give you an example of some of my own setbacks. In my first year of doing this, we tried to raise money. We applied for grants, sent out proposals, etc.; but we couldn’t raise any money. So, what I did after getting the rejection is I would email and ask, “Do you have any feedback for us about why we didn’t get the funding?” or “Can we jump on a call so you can explain what we can do better?” What I learned from that was the way I was communicating what we were doing made sense in my mind, but I wasn’t putting myself in the shoes of the person who was reviewing the proposal. I only have five to ten minutes of someone’s time. So, how can I really simplify my message? For example, my first proposal was, “Shamiri does task-shifting mental health interventions for adolescent depression, anxiety, etc.” If you are in the field, you maybe get it. But if you are somebody who is just reading grants on mental health education, you don’t really get it. Now we say, “Shamiri means thrive and we enable young people to thrive.” So that invites people to ask how we’re helping people to thrive.

AM: What is another setback that surprised you?

A second example of a failure is getting buy-in from the beneficiaries that we were trying to work with. I thought, “We have this great idea, we’ve done this research, and it works. We’re going to go to schools and they’re going to be like, ‘This is great! Come work with us.’ Teachers are going to want to work with us.” But actually, in our first three years we were trying to work with 25,000 students and we ended up working with only 1,000 students. We really struggled with getting people to sign up. The lesson from that was we were thinking more from the idea this was our product, rather than thinking, “What is the problem that I am trying to solve for this person?” To give a concrete example, there are three people we need to get buy-in from: young people in schools, teachers, and parents. Just having a great product does not mean that people are going to use it. You need to figure out what the problem is. How can I solve it? How do I communicate this to users?

AM: I can imagine that dealing with failures and setbacks is extremely hard, especially for a young person. What would you say to a young person who is currently experiencing this?

TO: Finding ways to stay grounded and healthy from a well-being perspective is really crucial. Identify what matters to you and connect with those things. And ideally if you can find a way to build a routine around that, it could help. Doing this work takes a big toll. If you don’t find ways to ground yourself and get the energy to continue with this, you may burn out.

AM: Do you have some final words for our Youth Council members and other young people reading this?

TO: Those closest to the problem are those closest to the solution. I am from Kenya, which is a really young country. The median age is 19 and 70 percent of the population is under 30. If we are to solve some of these pressing problems, including mental health, those solutions are going to have to come from young people.

The post Turning Rejection Into a Roadmap: Advice for the Next Generation of Mental Health Leaders appeared first on Child Mind Institute.

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The Download: the first brain implant power user and South Korea’s AI obsession

This is today’s edition of The Download, our weekday newsletter that provides a daily dose of what’s going on in the world of technology.

This man with ALS is the first “power user” of a brain implant that lets him speak

Casey Harrell has had a set of electrodes embedded in his brain for almost three years. Harrell, who has ALS and is paralyzed, first used his brain-computer interface (BCI) to “speak” in 2023. Since then, he’s clocked thousands of hours of use. 

Harrell can now use the device largely independently. His team has added new features to it, and he also uses it to surf the web and perform his job. “Living with a disease like ALS, you are supposed to have diminished dreams. I do not,” Harrell told MIT Technology Review. 

The team behind the device call Harrell “the first power user of a speech BCI.” They now plan to add further enhancements to the device.

Dive into the groundbreaking impact of Casey Harrell’s BCI.

—Jessica Hamzelou

Why do South Koreans love AI so much?

While a public backlash against AI brews across the US, South Koreans are optimistic. Only 16% say they are more concerned than excited about AI—the lowest of the 25 countries surveyed by the Pew Research Center—while 50% of Americans were more worried than excited. 

South Koreans share a deep conviction that embracing technology is integral to modernizing the country and cementing its place in the global order. Their fascination with AI is just the latest incarnation of that ethos—and it’s making them anxious to stay ahead.

Read the full story on South Korea’s AI fervour.

—Michelle Kim

This story is from The Algorithm, our weekly newsletter giving you the inside track on all things AI. Sign up to receive it in your inbox every Monday.

The must-reads

I’ve combed the internet to find you today’s most fun/important/scary/fascinating stories about technology.

1 The US says it restricted Anthropic AI over foreign intelligence risks
Commerce chief Lutnick said he acted over national security fears. (Reuters $)
+ Following the ban, Anthropic disabled access to its new models. (BBC)
+ Both sides are increasingly desperate for a resolution. (WSJ $)

2 DeepSeek just became China’s most valuable startup
It raised $7 billion, the largest-ever first-round funding for an AI startup. (The Information $)
+ The deal values DeepSeek at over $50 billion. (WSJ $)
+ Its unusual structure preserves founder control. (Reuters $)
+ DeepSeek’s new flagship model has caused a stir. (MIT Technology Review)
 
3 Alibaba has unveiled AI models for robots amid a shift from chatbots
It’s joined a global race to move AI into the physical world. (SCMP)
+ AI is learning to understand its surroundings. (MIT Technology Review)
 
4 Fox is buying streaming giant Roku for $22 billion
The deal creates the third-largest player in US TV by viewing share. (BBC)
+ Fox is making a big bet on free streaming. (Washington Post $)

5 EA has launched a new way to advertise “directly into gameplay”
EA Advertising allows brands to become part of the game itself. (CNBC)
+ Xbox’s new chief strategy officer is also eyeing in-game ads. (PC Gamer)
+ GenAI could reinvent what it means to play. (MIT Technology Review)

6 It’s trivially easy to use Reddit to manipulate AI search
A tiny snippet of text can trick ChatGPT and Google’s AI search. (404 Media)
+ AI search is being manipulated to generate dangerous biases. (BBC)
 
7 Sperm have been made magnetic to allow IVF inside the body
The technique enables remote guidance towards an egg. (New Scientist $)
+ Automation and AI are transforming IVF. (MIT Technology Review)
 
8 The world’s leading deepfake expert no longer trusts his own eyes
He’s struggling to prove what’s real before the internet decides. (NYT $)
 
9 Meta’s CTO admits its AI reorganisation was “atrocious”
He’s promised staff better communication—and snacks. (Wired $)
 
10 Silicon Valley billionaires are pretending to kill each other for fun
In a new game show from Peter Thiel’s Founders Fund. (WSJ $)

Quote of the day

“There was a speeding ticket, and they gave Fable the death penalty.” 

—Alex Stamos, the former chief security officer of Facebook, tells the Washington Post that banning foreign access to Anthropic’s leading model is a disproportionate punishment.

One More Thing

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VICTOR KERLOW


Inside effective altruism, where the far future counts a lot more than the present

Since its birth in the late 2000s, effective altruism has aimed to answer a deceptively simple question: “How can those with means have the greatest impact?”

Directing money to evidence-based approaches is EA’s best-known technique. But as it’s expanded from an academic philosophy into a community and a movement, its ideas of the “best” way to change the world have evolved as well. 

Find out how effective altruism became one of the most influential—and contested—forces in philanthropy.

—Rebecca Ackermann

We can still have nice things

A place for comfort, fun, and distraction to brighten up your day. (Got any ideas? Drop me a line.)

+ The humble table has been reimagined as an unconventional public artifact.
+ Take a visual tour of the weird, centuries-old history of architecture’s most gruesome gargoyles.
+ A colorful parakeet unseen for an entire century was triumphantly rediscovered in an unexplored Indonesian forest.
+ This shimmering Southern Lights timelapse filmed by an astronaut on the SpaceX Dragon is stunning.

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Assessment of tenecteplase target-associated pathogenic mechanisms underlying depression in acute ischemic stroke patients: insights from artificial intelligence-driven multi-omics analysis and in vitro validation

BackgroundAs a first-line treatment for acute ischemic stroke (AIS), tenecteplase (TNK) can cause adverse effects, such as depression, in AIS patients.ObjectiveThis study aims to elucidate the TNK target-related pathogenic mechanisms underlying major depressive disorder (MDD) in AIS patients.MethodsBy analyzing six public peripheral blood bulk datasets from AIS and MDD patients using integrative bioinformatics methods (limma, non-negative matrix factorization (NMF), and machine learning), we identified TNK target-associated molecular subgroups and diagnostic models for MDD and AIS patients, respectively. Next, a hub gene involved in the pathogenesis of both MDD and AIS was identified, and its corresponding molecular characteristics were analyzed in the peripheral blood bulk profiles of MDD and AIS patients. In addition, to gain a deeper understanding of the molecular implications of the hub gene involved in the pathogenesis of MDD in AIS, we performed disease ontology (DO) analysis and virtual cell knockout (KO) of the hub gene using public AIS mouse brain single-cell datasets. Furthermore, a deep learning pipeline (DrugReflector) model and molecular docking were used to identify MDD-preventive therapeutic agents for AIS patients based on MDD and AIS public blood bulk data. Finally, the expression pattern of the hub gene was also evaluated in MDD and AIS cell models.ResultsMyeloperoxidase (MPO) can be considered an upregulated TNK target-associated gene involved in the pathogenesis of MDD in AIS patients, and BRD-K11973162 can be considered an MDD-preventive therapeutic candidate for AIS patients after TNK treatment.ConclusionOur study is the first to identify MDD-associated diagnostic and therapeutic candidates for AIS patients after TNK treatment, providing a novel strategy for their clinical management.
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Screening the optimal rTSMS frequency to orchestrate immune-fibrotic remodeling for adult spinal cord repair

IntroductionThe clinical translation of magnetic stimulation for central nervous system trauma is severely hindered by “parameter ambiguity”—the lack of evidence-based screen of stimulation protocol. Repetitive trans-spinal magnetic stimulation (rTSMS) holds therapeutic promise, yet its frequency-dependent effects on the complex spinal microenvironment remain poorly understood. To address this gap, this study aimed to decode the frequency-response relationship of rTSMS and establish an optimal, evidence-based frequency standard to orchestrate immune-fibrotic remodeling and promote functional recovery following spinal cord injury (SCI).MethodsUtilizing novel in vivo label-free second-harmonic generation (SHG) imaging to visualize the real-time microglia activation, we performed a high-fidelity close-loop screen of various rTSMS frequencies (10 Hz, 40 Hz, and 80 Hz). In an adult mice SCI model, we integrated transcriptomic profiling, morphological analysis, electrophysiological recordings, and behavioral assessments to comprehensively evaluate the neuroregenerative potential.ResultsWe identified 40 Hz as a privileged therapeutic frequency that specifically modulates microglia and the extracellular matrix. Unlike 10 Hz or 80 Hz regimens, 40 Hz rTSMS uniquely reprogrammed the transcriptomic landscape, driving microglia toward a restorative M2 phenotype, and most importantly, suppressing collagen fibrillogenesis. This targeted modulation effectively attenuated fibrotic scarring and preserved mitochondrial dynamics and axonal integrity. Consequently, the 40 Hz protocol significantly enhanced corticospinal tract conduction and drove robust, long term sensorimotor recovery.ConclusionOur findings define 40 Hz as the critical therapeutic standard for coupling immune modulation with fibrotic remodeling in SCI. By overcoming the barrier of inconsistent parameters, this study provides a precise, clinically translatable framework for the application of rTSMS in neurorestorative medicine.
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Brain protein burden is related to intravoxel incoherent motion: PET-MR imaging study

IntroductionDysfunction in brain protein clearance mechanisms is thought to contribute to many neurodegenerative diseases, yet non-invasive assessment of these mechanisms in humans remains challenging. This study is the first to examine whether intravoxel incoherent motion (IVIM) diffusion MRI metrics, measures of water diffusion and fluid dynamics, are associated with pathological protein accumulation and cognition in aging individuals, and hence whether they serve as a proxy for brain waste clearance function.MethodsWe analyzed data from 94 participants (n = 45 β-amyloid positive) who underwent simultaneous PET/MRI scans to calculate three key IVIM metrics: D (true diffusion coefficient), D* (pseudo-diffusion coefficient reflecting perfusion), and f (perfusion fraction) within 98 regions of interest. A machine learning model was trained to identify the most informative IVIM features for predicting β-amyloid (Aβ) status. Selected features were then evaluated for correlations with protein burden (Aβ and tau) and cognitive performance.ResultsThe model identified a subset of 25 key features that effectively predicted Aβ status, achieving a predictive accuracy of 80.0% on unseen data. Regions with important IVIM features aligned with previously identified Aβ-affected regions and showed significant correlations with Aβ burden (r = 0.53, p < 0.0001) and tau burden (r = 0.61, p < 0.0001). A significant negative correlation was observed between IVIM features and cognitive decline (r = −0.60, p < 0.0001). When stratified by Aβ status, this correlation remained significant only in the Aβ-positive group (r = −0.61, p < 0.0001), but not in the Aβ-negative group.ConclusionIVIM-derived metrics (D, D*, and f), which measure water diffusion and perfusion dynamics in the brain, may be valuable non-invasive biomarkers of protein accumulation and associated cognitive decline in the aging human brain.
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Generative AI as interactional infrastructure for meaning-centered care in later life

Generative artificial intelligence (GenAI) and large language models are rapidly entering mental health research and service delivery, yet their dominant use remains symptom-centric, emphasizing screening, classification, triage, and risk detection. For older adults, mental health is often inseparable from existential concerns: loss of social role, disrupted continuity of self, loneliness, diminished dignity, and questions of legacy. This perspective argues that GenAI should not be conceptualized as an autonomous substitute for clinicians, nurses, social workers, or family caregivers. Instead, it may be better understood as an interactional infrastructure for meaning-centered care in later life. Drawing on meaning-centered psychotherapy, dignity therapy, life review, gerotranscendence theory, care ethics, and implementation science, we propose a Sensing-Narrating-Connecting-Governing framework. In this model, multimodal AI systems help detect existential and relational cues, support life-review conversations, co-construct dignity-preserving narratives, connect older adults with human care networks, and operate under explicit safeguards for privacy, hallucination, dependency, crisis escalation, and cultural adaptation. The proposed framework shifts evaluation from model performance alone toward existential well-being, dignity, continuity of self, therapeutic alliance, equity, and workflow integration. We conclude that GenAI may contribute to public mental health only when deployed as a bounded, human-supervised, culturally responsive layer of relational augmentation rather than as a replacement for human presence.
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From digital access to social connectedness: the digital divide, bonding social capital, and depressive symptoms among older adults in China

IntroductionAs population aging and digital transformation continue simultaneously in China, the digital divide among older adults has become an increasingly important social issue. This study examines the associations between multiple dimensions of the digital divide and depressive symptoms among older adults, as well as the potential role of bonding social capital.MethodsDrawing on three waves of data from the China Family Panel Studies (CFPS, 2018–2022), this study employs two-way fixed effects models and mediation analyses to examine the relationships between digital access, digital usage, digital outcomes, and depressive symptoms among older adults. Robustness checks were further conducted using propensity score matching (PSM), sample restriction adjustments, and replacement of the dependent variable.ResultsInternet access was significantly associated with lower levels of depressive symptoms among older adults (p < 0.05). Compared with non-Internet users, entertainment-oriented, instrument-oriented, and mixed Internet use were all significantly associated with lower depressive symptoms (all p < 0.05). Digital outcomes were also negatively associated with depressive symptoms (p < 0.01). Bonding social capital showed significant indirect pathways linking all dimensions of the digital divide and depressive symptoms, with mediating proportions ranging from 5.95% to 26.67%. Period heterogeneity analyses further indicated that the associations remained generally stable before and during the COVID-19 period, although mixed Internet use exhibited a significant structural difference across periods (p = 0.036).DiscussionThe findings suggest that the digital divide is closely associated with the mental well-being of older adults, while bonding social capital constitutes an important social pathway linking digital engagement and psychological health. Policy efforts should move beyond technological access toward broader digital empowerment and the construction of a more inclusive digital society for aging populations.
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Experiences and wellbeing of family members and carers, regarding PARCS across Victoria

IntroductionWhen consumers experience mental health crises, carers are often key supporters and are also impacted significantly themselves. The Prevention and Recovery Care (PARC) model offers a community-based residential program for consumers, in times of mental health crisis. The potential of PARC services to engage carers is under-examined. This study addresses two questions: How do carers experience the PARC service; and what are carers’ experiences of their own wellbeing, during and after engagement with PARC?MethodsThis is a mixed-methods convergent study of carer experience, whereby quantitative survey data and qualitative survey and interview data were gathered, analysed concurrently, and integrated to report carers perspectives of PARC services. Carers reported their wellbeing across 4 timepoints (n = 71) and also their experience of PARC services in a Carer Exit Survey (n = 50). An independent sample of six family members, each from a different PARC service, engaged in semi-structured telephone interviews.ResultsFor service experience, carers rated the PARC service as highly satisfactory. Interviewees reported a sense of relief, gratitude, and period of regrouping, while valuing the PARC service and feeling positive about accessing PARC services in the future. Positive experience was defined in contrast with distressing experiences of acute wards; concerns were expressed about limits to timely access of PARC services in future if needed. Regarding carer wellbeing, time 1 levels varied across participants, and all measures showed improvement for carers over time. They reported experience of respite, with confidence to entrust their family member to the team, and learning from PARC service staff ways to cope and interact with their family member.DiscussionCarers considered the PARC service a positive environment for the person to receive treatment and support and also experienced PARC services as supporting their own quality of life and wellbeing. This study contributes evidence about how highly valued these recovery oriented sub acute residential services are for carer service users; however, there is potential to further enhance the engagement of carers in PARC service delivery, including through inclusion of carers in co-design.