Lifeboat Foundation: Safeguarding Humanity
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Category: biotech/medical – Page 1,867

Reprogramming of differentiated cells into induced pluripotent stem cells has been recently achieved in vivo in mice. Telomeres are essential for chromosomal stability and determine organismal life span as well as cancer growth. Here, we study whether tissue dedifferentiation induced by in vivo reprogramming involves changes at telomeres. We find telomerase-dependent telomere elongation in the reprogrammed areas. Notably, we found highly upregulated expression of the TRF1 telomere protein in the reprogrammed areas, which was independent of telomere length. Moreover, TRF1 inhibition reduced in vivo reprogramming efficiency. Importantly, we extend the finding of TRF1 upregulation to pathological tissue dedifferentiation associated with neoplasias, in particular during pancreatic acinar-to-ductal metaplasia, a process that involves transdifferentiation of adult acinar cells into ductal-like cells due to K–Ras oncogene expression. These findings place telomeres as important players in cellular plasticity both during in vivo reprogramming and in pathological conditions associated with increased plasticity, such as cancer.

Keywords: in vivo reprogramming, telomeres, stem cells, TRF1, tumorigenesis, cellular plasticity, cancer, transdifferentiation, ADM, regeneration.

Reprogramming into full pluripotency has been achieved in vivo in the context of mouse tissues (Abad et al., 2013). Thus, induction of the reprogramming factors in transgenic mice (so-called reprogrammable mice) results in reprogramming events marked by the expression of the pluripotency factor NANOG in multiple organs, tissue dedifferentiation, and teratoma formation. Therefore, these mice could be useful for a deeper understanding of the molecular mechanisms that govern tissue dedifferentiation in vivo. Interestingly, mammalian cell reprogramming can also occur spontaneously during regeneration after injury or damage conditions (Yanger et al., 2013). Differentiated cells can be converted in vivo into another cell type and also into functional multipotent stem-like cells (Tata et al., 2013). This capacity of somatic cells to dedifferentiate into stem-like cells in vivo may have a pivotal role in physiological tissue regeneration or during tumorigenesis.

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A little-studied liver protein may be responsible for the well-known benefits of exercise on the aging brain, according to a new study in mice by scientists in the UC San Francisco Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research. The findings could lead to new therapies to confer the neuroprotective effects of physical activity on people who are unable to exercise due to physical limitations.

Exercise is one of the best-studied and most powerful ways of protecting the from and has been shown to improve cognition in individuals at risk of neurodegenerative disease such as Alzheimer’s disease and frontotemporal dementia —even those with rare gene variants that inevitably lead to dementia.

But many are not able to exercise regularly due to or disabilities, and researchers have long searched for therapies that could confer some of the same neurological benefits in people with low physical activity levels.

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Say something Eric Klien.

Given the increasing proliferation of AI, I recently carried out a systematic review of AI-driven regulatory gaps. My review sampled the academic literature on AI in the hard and social sciences and found fifty existing or future regulatory gaps caused by this technology’s applications and methods in the United States. Drawing on an adapted version of Lyria Bennett-Moses’s framework, I then characterized each regulatory gap according to one of four categories: novelty, obsolescence, targeting, and uncertainty.

Significantly, of the regulatory gaps identified, only 12 percent represent novel challenges that compel government action through the creation or adaptation of regulation. By contrast, another 20 percent of the gaps are cases in which AI has made or will make regulations obsolete. A quarter of the gaps are problems of targeting, in which regulations are either inappropriately applied to AI or miss cases in which they should be applied. The largest group of regulatory gaps are ones of uncertainty in which a new technology is difficult to classify, causing a lack of clarity about the application of existing regulations.

Novelty. In cases of novel regulatory gaps, a technology creates behavior that requires bespoke government action. Of the identified cases, 12 percent are novel. This includes, for example, the Food and Drug Administration’s (FDA) standard for certifying the safety of high-risk medical devices which is applicable to healthcare algorithms, also called black-box medicine.

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Balloon shaping isn’t just for kids anymore. A team of researchers from the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) has designed materials that can control and mold a balloon into pre-programmed shapes. The system uses kirigami sheets—thin sheets of material with periodic cuts—embedded into an inflatable device. As the balloon expands, the cuts in the kirigami sheet guide the growth, permitting expansion in some places and constricting it in others. The researchers were able to control the expansion not only globally to make large-scale shapes, but locally to generate small features.

The team also developed an inverse design strategy, an algorithm that finds the optimum design for the kirigami inflatable device that will mimic a target shape upon inflation.

“This work provides a new platform for shape-morphing devices that could support the design of innovative medical tools, actuators and reconfigurable structures,” said Katia Bertoldi, the William and Ami Kuan Danoff Professor of Applied Mechanics at SEAS and senior author of the study.

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Rigid electromagnetic actuators have a variety of applications, but their bulky nature limits human-actuator integration or machine-human collaborations. In a new report on Science Advances, Guoyong Mao and a team of scientists in soft matter physics and soft materials at the Johannes Kepler University Linz, Austria, introduced soft electromagnetic actuators (SEMAs) to replace solid metal coils with liquid-metal channels embedded in elastomeric shells. The scientists demonstrated the user-friendly, simple and stretchable construct with fast and durable programmability.

They engineered a SEMA based soft miniature shark and a multi-coil flower with individually controlled petals, as well as a cubic SEMA to perform arbitrary motion sequences. The team adapted a to support device miniaturization and reduce with increased mechanical efficiency. The SEMAs are electrically controlled shape-memory systems with applications to empower soft grippers for minimally invasive medical applications. The scientists highlighted the practicality of small size and multi-coil SEMAs for promising applications in medicine, much like in the classic sci-fi movie “Fantastic Voyage,” in which a miniature submarine destroyed a blood clot to save a patient’s life. In reality, Mao et al. aim to develop and deploy SEMA-based advanced microrobots for such futuristic medical applications, including drug delivery and tissue diagnostics with nano-precision.

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Antibiotic resistance is on the rise and is recognized by both the CDC1 and the U.S. Military2 as a current – and formidable – global health threat. The U.S Department of Defense (DoD) has long documented the warfighter’s outsized risk of exposure to infectious disease, including the increasing number of multi-drug resistant (MDR) organisms that have challenged military wound care in Iraq and Afghanistan3. Despite this looming crisis, there has been a notable exodus of pharmaceutical companies from the antibiotic space, as well as several high-profile failures of biotechnology companies focused on antibiotic development4. Current therapeutics to combat microbial infections, including MDR microbes and bacterial biothreats, are insufficient to meet the growing need, and existing methods to develop new treatments are too slow and/or costly to combat emerging drug resistance in pathogenic microorganisms.

DARPA’s Harnessing Enzymatic Activity for Lifesaving Remedies (HEALR) program aims to utilize a new therapeutic design toolkit and novel strategies/modalities to effectively treat microbial infections. Specifically, HEALR seeks to develop new medical countermeasures (MCMs) by recruiting native cellular machinery to recognize and clear disease-related targets for treating these infections. These advances could result in host-driven degradation or deactivation of pathogen targets, which may not only inhibit but could stop the pathogen in its tracks.

“HEALR presents the opportunity to identify drugs that are safer, more effective, and better address drug resistance and bacterial infections than existing therapeutic modalities,” noted Seth M. Cohen, Ph.D., program manager for the DARPA HEALR program. “By harnessing innate cellular processes, such as those exploited by proteolysis targeting chimeras (PROTACs) and similar approaches, HEALR intends to achieve superior outcomes over existing therapies.”

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