A New Law of Physics Could Support the Idea We’re Living In a … – Slashdot

A physicist from the University of Portsmouth has explored whether a new law of physics could support the theory that we're living in a computer simulation. Phys.Org reports: Dr. Melvin Vopson has previously published research suggesting that information has mass and that all elementary particles -- the smallest known building blocks of the universe -- store information about themselves, similar to the way humans have DNA. In 2022, he discovered a new law of physics that could predict genetic mutations in organisms, including viruses, and help judge their potential consequences. It is based on the second law of thermodynamics, which establishes that entropy -- a measure of disorder in an isolated system -- can only increase or stay the same. Dr. Vopson had expected that the entropy in information systems would also increase over time, but on examining the evolution of these systems he realized it remains constant or decreases. That's when he established the second law of information dynamics, or infodynamics, which could significantly impact genetics research and evolution theory.

A new paper, published in AIP Advances, examines the scientific implications of the new law on a number of other physical systems and environments, including biological, atomic physics, and cosmology. Key findings include:

- Biological systems: The second law of infodynamics challenges the conventional understanding of genetic mutations, suggesting that they follow a pattern governed by information entropy. This discovery has profound implications for fields such as genetic research, evolutionary biology, genetic therapies, pharmacology, virology, and pandemic monitoring. - Atomic physics: The paper explains the behavior of electrons in multi-electron atoms, providing insights into phenomena like Hund's rule; which states that the term with maximum multiplicity lies lowest in energy. Electrons arrange themselves in a way that minimizes their information entropy, shedding light on atomic physics and stability of chemicals. - Cosmology: The second law of infodynamics is shown to be a cosmological necessity, with thermodynamic considerations applied to an adiabatically expanding universe supporting its validity. "The paper also provides an explanation for the prevalence of symmetry in the universe," added Dr. Vopson. "Symmetry principles play an important role with respect to the laws of nature, but until now there has been little explanation as to why that could be. My findings demonstrate that high symmetry corresponds to the lowest information entropy state, potentially explaining nature's inclination towards it."

"This approach, where excess information is removed, resembles the process of a computer deleting or compressing waste code to save storage space and optimize power consumption. And as a result supports the idea that we're living in a simulation."

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A New Law of Physics Could Support the Idea We're Living In a ... - Slashdot

Kelly Slater gifts incurably ill surf filmmaker Greg Browning and … – BeachGrit

The "momentum of professional surfing" looking less and less real.

It has, by any measure, been a rough year for our World Surf League. Small waves cursed the tour from the very beginning, its CEO Erik Logan got up to some monkey business in Brazil leading to his unceremonious firing and, to cap it all off, its once-proud Santa Monica headquarters placed on the market, forcing the global home of surfing to share space with injured animals.

Eight, or such, years ago there were only wide open vistas for the WSL. Future so bright. It had a billionaire funding and a bullish chief, Paul Speaker, who vowed to soon outgrown the powerful National Football League.

Alas, bummer upon bummer upon bummer until today where we have the NFLs Miami Dolphins straight robbing the WSL, officially being dubbed The Greatest Show on Surf.

There is speed for days with Tyreek Hill, DeVon Achane, Raheem Mostert being fed the skin by Hawaiis Tuanigamanuolepola Tagovailoa, and the team is pressing every advantage.

The Dolphins were honored with the tag after amassing 2568 total yards of offense in the first five games of the season, surpassing the 2000 St. Louis Rams teams 2527 yards.

Those Rams were The Greatest Show on Turf.

The Greatest Show on Surf much cooler.

But there is certainly scrambling in the new WSL headquarters today. Chief of Sport Jessi Miley-Dyer scrambling around, trying to call various newspapermen in order to share viewership numbers from the most recent Finals Day at Lower Trestles.

Smashing into veterinarians along the way.

Weeping the momentum of professional surfing is REAL!

Is it though?

More as the story develops.

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Kelly Slater gifts incurably ill surf filmmaker Greg Browning and ... - BeachGrit

Long-Dormant Viruses Are Now Waking Up After 50,000 Years as … – Slashdot

This week Bloomberg explored so-called "zombie viruses" that is, long-dormant microbes which they call "yet another risk that climate change poses to public health" as ground that's been frozen for "milleniums" suddenly starts thawing for example, in the Arctic, which they write is warming "faster than any other area on earth." With the planet already 1.2C warmer than pre-industrial times, scientists are predicting the Arctic could be ice-free in summers by 2030s. Concerns that the hotter climate will release trapped greenhouse gases like methane into the atmosphere as the region's permafrost melts have been well-documented, but dormant pathogens are a lesser explored danger. Last year, virologist Jean-Michel Claverie's team published research showing they'd extracted multiple ancient viruses from the Siberian permafrost, all of which remained infectious...

Ways in which this could present a threat are still emerging. A heat wave in Siberia in the summer of 2016 activated anthrax spores, leading to dozens of infections, killing a child and thousands of reindeer. In July this year, a separate team of scientists published findings showing that even multicellular organisms could survive permafrost conditions in an inactive metabolic state, called cryptobiosis. They successfully reanimated a 46,000-year-old roundworm from the Siberian permafrost, just by re-hydrating it...

Claverie first showed "live" viruses could be extracted from the Siberian permafrost and successfully revived in 2014. For safety reasons his research focused only on viruses capable of infecting amoebas, which are far enough removed from the human species to avoid any risk of inadvertent contamination. But he felt the scale of the public health threat the findings indicated had been under-appreciated or mistakenly considered a rarity. So, in 2019, his team proceeded to isolate 13 new viruses, including one frozen under a lake more than 48,500 years ago, from seven different ancient Siberian permafrost samples evidence to their ubiquity. Publishing the findings in a 2022 study, he emphasized that a viral infection from an unknown, ancient pathogen in humans, animals or plants could have potentially "disastrous" effects.

"50,000 years back in time takes us to when Neanderthal disappeared from the region," he says. "If Neanderthals died of an unknown viral disease and this virus resurfaces, it could be a danger to us."

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Long-Dormant Viruses Are Now Waking Up After 50,000 Years as ... - Slashdot

World-First Trial of Gene Therapy To Cure Form of Deafness Begins – Slashdot

An anonymous reader quotes a report from the Financial Times: A world-first trial of a gene therapy to cure a form of deafness has begun, potentially heralding a revolution in the treatment of hearing loss. Up to 18 children from the UK, Spain and the US are being recruited to the study, which aims to transform treatment of auditory neuropathy, a condition caused by the disruption of nerve impulses traveling from the inner ear to the brain. Participants will be monitored for five years to gauge whether their hearing improves, with initial results expected to be published next February.

Auditory neuropathy can be due to a variation in a single gene -- known as the OTOF gene -- which produces a protein called otoferlin. This protein typically allows the inner hair cells in the ear to communicate with the hearing nerve. Mutations in the OTOF gene can be identified by genetic testing. However, [Professor Manohar Bance, an ear surgeon at Cambridge University Hospitals NHS Foundation Trust who is leading the trial in the UK] said it was a condition often missed when newborn babies were screened for potential hearing problems. "This is one of the few conditions where everything works except the transmission between the hair cells and the nerve. So everything else looks fine when you test it, but they can't hear anything. So these poor kids' [difficulties] end up being missed," Bance added.

The new gene therapy aims to deliver a working copy of the faulty OTOF gene using a modified, non-pathogenic virus. It will be delivered via an injection into the cochlea under general anaesthetic. Bance estimates that about 20,000 people across the US and five European countries -- the UK, Germany, France, Spain and Italy -- have auditory neuropathy due to OTOF mutations, underlining the potential significance of a successful treatment.[...] "If it works, it's 'one and done'" but the cost to health systems "is something that worries me," he added, noting that gene therapies could be priced in "the million dollar range" per patient. However, he hoped that "economies of scale" as the technology developed further would ultimately allow them to be provided more cheaply.

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World-First Trial of Gene Therapy To Cure Form of Deafness Begins - Slashdot

Patients accept therapy using embryonic stem cells for Parkinson’s … – BMC Medical Ethics

Discrete choice experiment

Preferences of patients with PD for potential cell-based therapies to treat PD were assessed by a Discrete Choice Experiment (DCE) in Swedish patients with PD. The DCE is a cross-sectional survey method to investigate individuals preferences and can be used to determine the relative importance of different characteristics of an intervention and predict uptake of different interventions [15]. Respondents of a DCE are faced with a set of hypothetical choice questions with two or more alternatives, characterized by different characteristics (i.e., attributes) with varying levels. The DCE method also allows for the calculation of attribute trade-offs [16].

We performed a scoping literature review to identify attributes of treatments for PD that potentially were of importance for patients with PD when choosing treatment. Qualitative and quantitative papers investigating preferences of patients with PD related to treatment for PD were included. All literature searches were performed in PubMed and the keywords used were Parkinson disease, patient preferences, preferences, treatment, medication, and attributes. We identified 193 papers, including 29 papers that were relevant for this project, of which 20 papers remained after excluding duplicates. After reading the full text papers, 209 potential attributes were identified. Out of the 209 attributes identified in the scoping literature review, 115 attributes were unique. These attributes were condensed down to 45 by merging similar concepts. The identified attributes were discussed in a group consisting of a representative patient of a Parkinson patient organization, neurologists, a research coordinator, a nurse working with patients with PD, and researchers knowledgeable in DCE methodology. Based on the discussions in this group, 11 attributes remained. We let 17 patients with PD rank the 11 attributes from most to least important, for their decision about PD treatment. Based on the mean ranks of the attributes and discussions with clinicians, eight attributes remained. These were re-categorized into the five attributes that were assigned relevant levels to be assessed by the DCE: (i) type of treatment, (ii) aim of treatment, (iii) available knowledge of the different types of treatments, (iv) effect on symptoms, and (v) risk for severe side effects (Table1).

We followed methodological guidelines to estimate the sample size needed to identify preferences of patients with PD and differences within those preferences [17]. We considered the number of attributes in the DCE (Table1) and the number of choice questions for each respondent (n=9). Based on the sample size requirements for a DCE and accounting for subgroup analysis, we aimed for a sample size of 500 respondents.

Patients with PD were recruited from neurology clinics at two university hospitals in Sweden. This study was approved by the Swedish Ethical Review Authority (Dnr 201906539). Information about the study was sent out by mail to all potential respondents fulfilling the inclusion criteria: patients diagnosed with PD, 18 years or older, able to read and understand Swedish. Patients with a known dementia diagnosis were excluded. Information about the study was sent out to 1266 patients. Patients who had not responded within two weeks were sent a reminder by mail. All respondents provided their informed consent before entering the survey. Two patients formally declined participation, and five patients were unable to participate due to technical or health-related restrictions. In total, 498 patients participated in the study (i.e., 39% response rate).

This survey was administered as a web-based survey that included three parts: (i) information about the attributes and levels, (ii) the DCE with hypothetical choice scenarios, and (iii) demographic and attitude questions (see supplementary file for survey). The survey was created for this study and administered using Sawtooth Software (Sawtooth Software Inc.). Each respondent was faced with nine hypothetical choice scenarios that each included three alternatives. The respondents were asked to select the alternative that they most preferred out of the three presented to them. The first two alternatives were experimentally designed to assess preferences for potential treatment alternatives for PD and the third was a fixed profile (i.e., nonexperimental) to represented standard care (drugs) for patients with PD (Fig.1). We used a Bayesian D-efficient design to construct the choice scenarios for the DCE using the NGene program (version1.2.1; ChoiceMetrics 2012). Prior information on the attribute importance was gathered from a pilot test (n=142) in patients with PD. The design used 500 Halton draws and 1000 repetitions. Using the pilot data, a multinomial logit (MNL) model was fitted, and the beta estimates was used as priors for the final experimental DCE design.

Some conditions were posted on the design: if the aim of treatment was to repair damage caused by disease, the treatment could not consist of electric stimulation or drug. If the aim of the treatment was to slow down disease progression, the treatment could not consist of electric stimulation. The final discrete choice survey consisted of 36 unique choice scenarios divided into four blocks; each respondent was randomized into one block and answered nine choice scenarios. The choice questions also included a hover function with further explanations of the attributes and the levels (see Table1 for full description of the attribute levels).

Example of a choice scenario

The demographical and attitude questions included background questions (e.g., age, gender, and education) and disease-related questions (e.g., disease duration, treatment, and side effects). Moreover, the respondents attitudes were gauged with a ranking exercise with eight statements that they were asked to place in the order they found most important. The attitude questions asked respondents about their moral stands on the status of an embryo, and a ranking exercise to prioritize eight statements.

The respondents were asked about their views on how to regard the products left over after IVF procedures, which may be used for hESC isolation, that is, the blastocyst. Whether this material was regarded as a lump of cells or something more was used to dichotomize the answers. Questions to assess respondents health literacy [18] and health numeracy [19] were also included to define the sample.

The statistical analyses, in particular the estimation of the latent class model were performed using R 4.0.2 (R Core Team, 2018), the mlogit (version 1.1-1; Yves Croissant, 2009) and the gmnl (version 1.13.3; Mauricio Sarrias, 2017) [20].

Demographics describing the populations age, gender, country of birth, occupational situation, education, health numeracy, health literacy, drug frequency, disease duration, number of experienced side effects, and experience of advanced treatment were presented in mean, median, and percentages. The overall level of health literacy and numeracy was calculated for each respondent. Individuals who responded strongly disagree or disagree to one of the items were categorized as having low health literacy. Individuals who responded with neither agree nor disagree with one of the items were categorized as having medium health literacy. Individuals responding agree or strongly agree to all the items were categorized as having high health literacy, and likewise for numeracy.

Respondents attitude toward the moral status of a couple of days old human embryo was assessed using this question: The human is perceived to have a special moral position, in the sense of having rights just by being human. What moral position does a human embryo that is only a few days old have? The respondents had four statements from which to select: (1) The embryo is just a lump of cells; it is meaningless to discuss its moral status, (2) The embryo has a moral status that is in between being just a lump of cells and being a human being, (3) The embryo in its moral status is closer to being a human than just a lump of cells, and (4) The embryo has the same moral status as a human being. The variable was dichotomized based on the frequency of the data. Respondents answering The embryo is just a lump of cells; it is meaningless to discuss its moral status formed one group, and the rest another group. One-way analysis of variance and nonparametric measures were used to test the differences between the personal characteristics and the different perceptions of whether an embryo is more than a lump or cells or not.

The most important attitudinal statement was given a 1, the second most important the number 2 and so forth. The ranking exercise was illustrated with a boxplot by the median value of each statement, stratified on the different perceptions of whether an embryo is more than a lump of cells.

The latent class analysis was based on the a priori hypothesis that the authors thought would be associated with the willingness to accept a new treatment. Five variables were tested for class membership: (1) a summary of experience of different treatment, (2) experience of the summary of different side effects, (3) the perception of the moral status of the embryo, (4) experience of advanced treatment, and (5) the importance of religion. A sum of how many treatments each respondent had was calculated, and also how many side effects they had experienced. Advanced treatment was based on treatment experience with one or more of apomorphine subcutaneous injection, apomorphine subcutaneous infusion, deep brain stimulation, levodopa-carbidopa intestinal infusion, and levodopa-entacapone-carbidopa intestinal infusion. The variable the perception of the moral status of the embryo did not influence class membership and was therefore not included in the final class assignment model.

The statistical analyses of the preference data were based on a latent class model. A preference weight (i.e., coefficient) and a corresponding SE were estimated for all but one level of each attribute (i.e., reference attribute level) [21]. Dummy coding of the variables was selected for this analysis (i.e., corresponding to zero as the reference value). Each p-value is a measure of the statistical significance of the difference between the estimated preference weights for each level of the attribute compared to the reference attribute level. All results were considered statistically significant at p<0.05. Confidence intervals (95%) were also provided for each preference weight. The Akaike information criterion (AIC) and the log-likelihood values were considered when selecting the appropriate model.

The latent class model was used to identify hidden (latent) classes of respondents preferences [22]. In latent class analysis, unobserved preference heterogeneity among respondents preferences is modeled as classes with similar preference patterns but with different variances across classes. Once preference patterns have been stratified into classes, the model determines the extent to which demographic characteristics impact the likelihood of belonging to a certain class. The systematic utility component (V) describes the latent construct that participant r belonging to class c reported for alternative A, B or C in choice task t. The final utility functions were as follows:

Vr,t,A&B|c=1 * consist_hESCr,t,A&B|c+2 * consist_iPSr,t,A&B|c+3 * consist_electricr,t,A&B|c+4 * aim_slowr,t,A&B|c+5 * aim_repairer,t,A&B|c+6 * know_500r,t,A&B|c+7 * know_5000r,t,A&B|c+8 * effect_50r,t,A&B|c+9 * effect_80r,t,A&B|c+10 * sideeffects_0.001r,t,A&B|c+11 * sideeffects_0.01r,t,A&B|c+.

Vr,t,C|c=1 * consist_drugr,t,C|c+2 ** aim_reliefr,t,C|c+3 * know_5000r,t,C|c+4 * effect_50r,t,C|c+5 * sideeffects_0.01r,t,C|c+.

A class assignment model was fitted after the specified utility function. The variables: experience in treatment, side effects, advanced treatment therapy and religious beliefs were tested for their potential impact on class membership in the model. The final class assignment function was:

Vn|c=0+1* treatment_sum|c+2 * experience_sideeffects|c+3 * advanced_treatment|c+4 * Religion_dum|c+.

The relative importance of the attributes included in the DCE was calculated by estimating the difference in preference weights of the latent class model between the most preferred level of an attribute and the least preferred level of the same attribute [21]. The highest difference value was normalized to 1, which represents the most important value. The difference values were divided by the highest value to reveal the relative distance between all other attributes.

We calculated the predicted acceptance uptake for a potential treatment scenario using hESCs to treat patients with PD. Predicted acceptability can be understood as the probability that a participant will accept a described scenario. The scenario represents a hypothetical treatment scenario of treatments with hESCs based on the attributes assessment in the DCE. Attribute estimates assessed by the latent class model were used to calculate the predicted acceptability of attribute levels (treatment with hESCs, risk of severe side effects is 1 out of 1000 and 50 patients received treatment) in relevant future scenarios; (A) effect on symptoms is 2 out of 10, (B) effect on symptoms is 5 out of 10, and (C) effect on symptoms is 8 out of 10.

The predicted acceptability is presented as the percentage of 100 who would accept the presented scenario. The utility for the specific scenario was calculated by using the following equation:

VScenario 1=A+B+C.

The predicted acceptability, the probability of accepting a specific scenario, was then calculated by using the following equation:

Predicted acceptance uptake=1/(1+expVScenario 1).

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Patients accept therapy using embryonic stem cells for Parkinson's ... - BMC Medical Ethics

Automation is the key to future advances, says the Head of the … – National Health Executive

Below, Lee highlights how his passion for stem cell research brought him to the UKSCB, its role in the development of advanced therapeutics and discusses how automation and machine learning in the manufacturing process could mean faster patient access to stem cell therapies in the future.

My career has been hugely varied, taking me around the world across the public, private and academic sectors, but one thing has remained constant: my fascination with cell and gene therapies, and through research, bringing these closer to patients.

Ive been lucky enough to study cell and gene therapies in many different ways over the last twenty years, from the potential of stem cells as a therapy for Type I Diabetes and the role of genes in the cancer cell cycle, to perfecting techniques that differentiate stem cells into precursors for adult blood cells for transfusion therapies. But theres always more to discover.

One application that excites me the most is the use of stem cells for immuno-oncology, where immune cells are used to treat cancer. Were now able to take immune cells from donors and use gene modification so they can fight cancer in patients where they would normally be rejected.

These stem cells can provide an unlimited supply of cancer-fighting T cells, available off-the-shelf to treat anyone quickly when referred to a clinic. This living drug has the potential to constantly adapt to cancer, combating resistance, and existing within patients to continue fighting the disease indefinitely.

In fact, this simplest form of cell can become almost any cell type for many applications in cell therapies, and the UKs national repository for all human embryonic stem cell lines derived within the UK, is here, at the MHRAs UK Stem Cell Bank.

Established 20 years ago to curate all human embryonic stem cells created in the UK and to regulate their use and provision for research and in the clinic, the UKSCB at the MHRAs South Mimms Laboratories is now recognised globally as a leading repository with over 180 different human embryonic stem cell lines.

During this time, weve received support from the Medical Research Council (MRC) and National Institute for Health Research (NIHR) to deliver our banking activities and, together with the lines available for research, weve banked over 30 lines now available for clinical application, making the UKSCB the largest source of clinical grade human embryonic stem cells in the world.

As part of the MHRA, the UKSCB plays an important role in providing regulatory guidance and workshops to the stem cell health sector across the UK, and weve established links with Harvard University to support international training programmes.

The UKSCB is a unique asset within the MHRA, sitting at the forefront of the advanced therapies landscape in the UK, and Im eager to build on its great history and legacy at a time where were only just starting to realise the full potential and application of advanced cell therapies.

As an aging population, we can expect to receive novel treatments for disease in the form of small molecules and prescription drugs but often these only serve to manage symptoms or limit disease progression. Using stem cells, we can now develop replacement joints, neurons for improved brain function and even entire hearts can be made in the lab without the need for human donors.

But what can we do to keep up with demand and ensure quality? The UKSCB has contributed to over 100 publications in international peer reviewed journals, establishing strong links with the World Health Organisation and international partners to improve standards and controls. Weve recently completed a successful international collaboration with Japanese partners, Sinfonia, to trial their automated cell processing robot and we aim to continue with these efforts towards the cost-effective scaling up of our manufacturing.

I believe that future improvements in customer service lies in automation. Reliance on scientists for the manufacture of stem cells is labour intensive, expensive and introduces human error. Automation will alleviate a lot of the manual aspects of cell culture, allowing us to scale-up manufacturing, drive down costs and ensure the highest quality and consistency, allowing stem cell-derived advanced therapies to be more accessible to patients and affordable for healthcare systems. By introducing automation into this process, we can free-up capacity for our leading experts to move away from labour-intensive manufacturing and instead work on improving and adapting novel advanced therapies.

When I look at my role as the third custodian of the UKSCB I hope to build on the significant past achievements of Glyn Stacey and Elsa Abranches that have established us as the leading stem cell institution in the UK today. I hope to move us forward with a sustainable business model that secures the long-term viability of the UKSCB. This means expanding our operations across various cell therapy platforms, supporting the development of specific cell types for use in human cell therapies, and developing new standards, enabling regulatory approval and eventual uptake by healthcare organisations.

I also want the UKSCB to continue making an impact around the world, supporting the development of stem cell therapies and reference materials for advanced therapies with the World Health Organisation. Over the last twenty years, weve delivered more than 370 cell line vials to 25 different countries for research, and in 2022, 54% of the stem cell lines requested have been of clinical grade, rising year on year. I want to see this trend continue as demand for these lines as starting materials for cell therapies grows further.

The future of the MHRAs UKSCB is diverse and exciting and, much like the cells we curate, there are endless possibilities for us to support research and clinical advances in the UK and around the world. I cannot wait to see where the next 20 years will take us.

Image credit: iStock

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Automation is the key to future advances, says the Head of the ... - National Health Executive

DNA aptamer finds novel application in regulating cell differentiation – Science Daily

Generating specific cell lineages from induced pluripotent stem cells and embryonic stem cells is the holy grail of regenerative medicine. Guiding iPSCs toward a target cell line has garnered much attention, but the process remains challenging. Now, researchers from Japan have discovered that an anti-nucleolin DNA aptamer, iSN04, can determine a cell's lineage during differentiation. By demonstrating the generation of cardiomyocytes from murine pluripotent stem cells, their concept shows promise as a regenerative therapy.

Self-renewal and pluripotency-the capacity to form any cell lineage-are inherent characteristics of induced pluripotent stem cells (iPSCs). Furthermore, they are highly prized in regenerative therapies targeting cardiovascular, neurological, and metabolic diseases as they are immunologically suitable for transplantation back into a donor. Unfortunately, regenerative medicine is not yet feasible outside a laboratory setting as available protocols to generate target cells are complicated and expensive. This raises a pertinent question: Can regulating the fate of stem cells in clinical settings and at scale be made more economical?

A team of researchers from Shinshu University, the National Institute of Advanced Industrial Science and Technology, and the University of Shizuoka in Japan set out to address this question by leveraging nucleic acid aptamers. Aptamers are single-stranded pieces of DNA that bind to target proteins and are able to modulate signaling cascades during cell differentiation when a stem cell commits to a specific functional role or phenotype. They hold promise in regenerative medicine as they are easily modified, can be synthesized economically, and are suitable for long-term storage.

The team, led by Associate Professor Tomohide Takaya from the Department of Agricultural and Life Sciences at Shinshu University, recently discovered that an anti-nucleolin aptamer, myogenetic oligodeoxynucleotide iSN04, induced myocardial differentiation in embryonic stem cells (ESCs). The study was led by Mina Ishioka, a graduate student in Dr. Takaya's laboratory, and published in The International Journal of Molecular Sciences on 21 September 2023.

"We had previously found that iSN04 promoted myogenic precursor cells (myoblasts) to differentiate into skeletal muscle cells and had hypothesized that the aptamer also enhanced differentiation of pluripotent stem cells. We were intrigued by the prospect of using iSN04 to promote iPSC differentiation into cardiomyocytes as this could lead to regenerating heart tissue," says Dr. Takaya, elaborating on the team's motivation to pursue the research.

Using various assays like RNA sequencing, cell staining and imaging, and molecular interaction and pathway analysis, the researchers investigated iSN04's effect on murine ESCs and iPSCs. iSN04 treatment under differentiating conditions inhibited stem cell commitment to the cardiac lineage. However, when these pluripotent stem cells were treated after experiencing differentiating conditions for five days, specific marker genes were upregulated, and the cells committed to forming beating cardiomyocytes.

"Ours is the first report to confirm a DNA aptamer that allows cardiomyocytes to develop from iPSCs," explains Dr. Takaya when asked about the significance of the work. "We uncovered two mechanisms of nucleolin interference with iSN04 at play whereby early treatment inhibits cardiomyogenesis, while treatment at a later stage enhances the generation of cardiac progenitors. First, iSN04 governs the translocation of nucleolin protein between the cytoplasm, plasma membrane, and nucleus. Second, it results in the modulation of the Wnt signaling pathway that governs cell differentiation."

The immunostaining experiments revealed that nucleolin was retained in the nucleoli following iSN04 treatment. Nucleolar nucleolin has a role in chromatin remodeling and gene transcription, and interestingly enough, Wnt pathway genes were differentially expressed in the RNA-seq data following iSN04 suppression. The team postulates that the iSN04-anchored nucleolin alters gene expression and Wnt signaling. Ultimately, terminal cell differentiation commits to the cardiomyocyte lineage.

And how could these findings impact regenerative medicine and patients' lives in the long term? Dr. Takaya provides insights into the broader implications of their work. "We believe there is a strong case to be made for further studies evaluating DNA aptamers in regenerative medicine. Aptamers are cost-effective and open up the possibility of producing specific cells from the patient's stem cells. But it doesn't end there! Since the aptamers can regulate stem cell fate, they can serve as therapeutic agents for many conditions linked to stem cell dysfunction," he concludes.

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DNA aptamer finds novel application in regulating cell differentiation - Science Daily

A comprehensive review of human trophoblast fusion models: recent … – Nature.com

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Cell atlases of the human brain – Science Daily

In two parallel projects, researchers at Karolinska Institutet have been involved in creating the most comprehensive atlases of human brain cells to date. The two studies, which are published in Science, provide clues on different brain diseases and give hope for medical advancements in the future, such as new cancer drugs.

Knowing what cells constitute the healthy brain, where different cell types are located and how the brain develops from the embryo stage is fundamental to the ability to compare and better understand how diseases arise. There are at present advanced atlases of the mouse brain, but not for the human brain. Until now.

A brain-cell census

"We've created the most detailed cell atlases of the adult human brain and of brain development during the first months of pregnancy," says Sten Linnarsson, professor of molecular system biology at the Department of Medical Biochemistry and Biophysics at Karolinska Institutet in Sweden. "You could say that we've taken a kind of brain-cell census."

The first project was led by Kimberly Siletti from Linnarsson's group. It was conducted in close collaboration with Ed Lein at the Allen Institute for Brain Science in Seattle, USA, as part of the international Human Cell Atlas initiative, and based on three donated human brains from adults. The researchers analysed more than three million individual cell nuclei using the technique of RNA sequencing, which reveals each cell's genetic identity. All in all, the researchers studied cells from just over a hundred brain regions and found over 3,000 cell types, some 80 per cent of which were neurons, the remainder being different kinds of glial cells.

"A lot of research has focused on the cerebral cortex, but the greatest diversity of neurons we found in the brainstem," says Professor Linnarsson. "We think that some of these cells control innate behaviours, such as pain reflexes, fear, aggression and sexuality."

Groundwork for medical advances

The researchers could also see that the cells' identity reflects the place in the brain where they first developed in the fetus, which links to the second project. Here, Emelie Braun and Miri Danan-Gotthold from Sten Linnarsson's group collaborated with the Swedish consortium for the Human Developmental Cell Atlas to analyse over a million individual cell nuclei from 27 embryos at different stages of development (between 5 and 14 weeks of fertilisation). The study enabled the researchers to show how the entire brain develops and is organised over time.

Even though the results are examples of molecular biological basic research, the new knowledge generated can also lay the groundwork for medical advances. Professor Linnarsson's research group has used similar methods to examine different kinds of brain tumours, one of which was a glioblastoma -- a cancer with a poor prognosis.

"The tumour cells resemble immature stem cells and it looks like they're trying to form a brain, but in a totally disorganised way," he explains. "What we observed was that these cancer cells activated hundreds of genes that are specific to them, and it might be interesting to dig into whether there is any potential for finding new therapeutic targets."

Freely available brain atlases

The brain atlases will be freely available to researchers around the world so that they can compare the brain diseases they are researching with what a normally developed brain looks like.

The studies are part of a larger package of articles published simultaneously in the scientific journal Science. The study on the adult brain was supported by a grant from the National Institutes of Health, while the embryo study was financed by the Knut and Alice Wallenberg and Erling-Persson foundations.

Sten Linnarsson is a scientific advisor at Moleculent, Combigene and Oslo University Center of Excellence in Immunotherapy. He and co-authors Alejandro Mossi Albiach and Lars E. Borm also hold shares in EEL Transcriptomics AB, which owns the intellectual property rights to the EEL method ("Spatial RNA localization"). Co-authors aneta Andrusivov and Joakim Lundeberg are scientific consultants for 10x Genomics, which holds the intellectual property rights to the Spatial Transcriptomics (Visium) technique.

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Cell atlases of the human brain - Science Daily

World Arthritis Day sheds light on innovative treatments – Omnia Health Insights

In the UAE, arthritis affects one in five people and is the top cause of disability globally. Arthritis includes over 100 autoimmune and rheumatic musculoskeletal conditions, and while it is commonly associated with ageing, younger patients are also affected.

World Arthritis Day, held on October 12 annually, emphasises the importance of recognising the symptoms of this painful disease, which can help lead to early intervention. Renowned organisations such as the Middle East Arthritis Foundation (MEAF) host focused events to further raise awareness and assist those who suffer from this debilitating disease.

While traditional treatments such as medications, physiotherapy, and surgery can alleviate symptoms, as World Arthritis Day is observed, we examine some alternatives and advancements that may offer hope for an enhanced quality of life.

Related:Understanding Systemic Juvenile Idiopathic Arthritis and gut health

The use of remote monitoring offers a promising way to decrease hospital visits for arthritic patients through a combination of self-management and telemedicine. With the potential to replace labour-intensive outpatient clinic visits, this could positively impact healthcare utilisation while keeping disease activity low.

Regenerative medicine in arthritis could utilise cell therapy, bioengineering and gene therapy to stimulate the body's natural healing response. A key development is Platelet-Rich Plasma (PRP), derived from a patient's blood, PRP can be used to treat pain, damaged tendons, hair loss and ageing skin. While it can relieve symptoms and boost healing, its effectiveness may vary based on preparation methods and patient factors.

Similar to fat-based PRP, Autologous Micro-fragmented Adipose Tissue (AMAT) involves liposuction to extract fat, which is then injected into areas needing treatment. Studies show improvements in osteoarthritis pain and function, but consistency in AMAT quality remains a challenge.

Stem cell therapy holds great potential for tissue repair and regeneration. The various stem cell types include: embryonic, adult, induced pluripotent, and very small embryonic-like stem cells. Clinical trials are ongoing and the FDA cautions against unproven therapies from for-profit clinics. It emphasises the need for standardised guidelines and further research to discover the full potential of stem cells in arthritis care.

Related:Gen AI may power the next generation of immunotherapies

Surgical options such as Osteochondral Autograft Transplantation Surgery (OATS) and Matrix-Induced Autologous Chondrocyte Implantation (MACI) use a patient's own or donor tissue to repair localised cartilage damage, preventing arthritis progression. Researchers are exploring gene editing tools like CRISPR-Cas9 to create custom-designed cells and gene therapies that target inflammatory proteins in osteoarthritis.

While these treatments in regenerative medicine demonstrate substantial potential, continuous research, protocol refinement, and establishing standardised methodologies are imperative to fully discover their benefits in the field of arthritis care.

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World Arthritis Day sheds light on innovative treatments - Omnia Health Insights