This video is the 1st of a series of “What is Aging” webinars that aims to unravel what aging is, how we age, why we age, and how to reverse it.
We welcome Jason C. Mercurio, MFE, Dr. Jose Cordeiro, and Dr. Ian Hale to discuss the topic.
Stanford University researchers have discovered a rapid and sustainable way to synthetically produce a promising cancer-fighting compound right in the lab. The compound’s availability has been limited because its only currently known natural source is a single plant species that grows solely in a small rainforest region of Northeastern Australia.
The compound, designated EBC-46 and technically called tigilanol tiglate, works by promoting a localized immune response against tumors. The response breaks apart the tumor’s blood vessels and ultimately kills its cancerous cells. EBC-46 recently entered into human clinical trials following its extremely high success rate in treating a kind of cancer in dogs.
Given its complex structure, however, EBC-46 had appeared synthetically inaccessible, meaning no plausible path seemed to exist for producing it practically in a laboratory. However, thanks to a clever process, the Stanford researchers demonstrated for the first time how to chemically transform an abundant, plant-based starting material into EBC-46.
Companies creating lab-grown steak, chicken, and fish see a recent White House announcement as a signal that meat grown without animal slaughter is on the cusp of being legally sold and eaten in the US.
“We are laser focused on commercial-scale production, and for us, that means moving into competing with conventional meat products in scale,” said Eric Schulze, vice president of product and regulation at Upside Foods, a cultivated meat company, as the industry calls itself. The goal is to be selling its meat on the US market within the year.
The traditional meat and poultry industry reacted strongly to President Joe Biden’s executive order last month on biotechnology and biomanufacturing, which observers say could push federal agencies to allow commercial sales of meat grown from an animal’s cells.
Accurate detection and manipulation of endogenous proteins is essential to understand cell biological processes, which motivated laboratories across cell biology to develop highly efficient CRISPR genome editing methods for endogenous epitope tagging (Auer et al., 2014; Nakade et al., 2014; Lackner et al., 2015; Schmid-Burgk et al., 2016; Suzuki et al., 2016; Nishiyama et al., 2017; Artegiani et al., 2020; Danner et al., 2021). Multiplex editing using NHEJ-based CRISPR/Cas9 methods remains limited because of the high degree of cross talk that occurs between two knock-in loci (Gao et al., 2019; Willems et al., 2020). In the current study we present CAKE, a mechanism to diminish cross talk between NHEJ-based CRISPR/Cas9 knock-ins using sequential activation of gRNA expression. We demonstrate that this mechanism strongly reduces cross talk between knock-in loci, and results in dual knock-ins for a wide variety of genes. Finally, we showed that CAKE can be directly applied to reveal new biological insights. CAKE allowed us to perform two-color super-resolution microscopy and acute manipulation of the dynamics of endogenous proteins in neurons, together revealing new insights in the nanoscale organization of synaptic proteins.
The CAKE mechanism presented here creates a mosaic of CreON and CreOFF knock-ins, and the number of double knock-in cells depends on the efficacy of each knock-in vector. Therefore, to obtain a high number of double knock-in cells, the efficacy of both the CreON and CreOFF knock-in vector must be optimized. We identified three parameters that regulate the efficacy for single and double knock-ins in neurons. First, the efficacy of gRNAs varies widely, and even gRNAs that target sequences a few base pairs apart in the same locus can have dramatically different knock-in rates (Willems et al., 2020; Danner et al., 2021; Fang et al., 2021; Zhong et al., 2021). Thus, the efficacy of each individual gRNA must be optimized to increase the chance of successful multiplex labeling in neurons. gRNA performance is dependent on many factors, including the rate of DNA cleavage and repair (Rose et al., 2017; Liu et al., 2020; Park et al.
Thanks to new RNA vaccines, we humans have been able to protect ourselves incredibly quickly from new viruses like SARS-CoV-2, the virus that causes COVID-19. These vaccines insert a piece of ephemeral genetic material into the body’s cells, which then read its code and churn out a specific protein—in this case, telltale “spikes” that stud the outside of the coronavirus—priming the immune system to fight future invaders.
The technique is effective, and has promise for all sorts of therapies, says Eerik Kaseniit, Ph.D. student in bioengineering at Stanford. At the moment, though, these sorts of RNA therapies can’t focus on specific cells. Once injected into the body, they indiscriminately make the encoded protein in every cell they enter. If you want to use them to treat only one kind of cell—like those inside a cancerous tumor—you’ll need something more precise.
Kaseniit and his advisor, assistant professor of chemical engineering Xiaojing Gao, may have found a way to make this possible. They’ve created a new tool called an RNA “sensor”—a strand of lab-made RNA that reveals its contents only when it enters particular tissues within the body. The method is so exact that it can home in on both cell types and cell states, activating only when its target cell is creating a certain RNA, says Gao. The pair published their findings Oct. 5 in the journal Nature Biotechnology.
Carnegie Mellon University researchers have pioneered the CMU Array—a new type of microelectrode array for brain computer interface platforms. It holds the potential to transform how doctors are able to treat neurological disorders.
The ultra-high-density microelectrode array (MEA), which is 3D-printed at the nanoscale, is fully customizable. This means that one day, patients suffering from epilepsy or limb function loss due to stroke could have personalized medical treatment optimized for their individual needs.
Increased inter-brain synchrony has been linked with social closeness (Kinreich et al., 2017), rapport (Nozawa et al., 2019), agreement (Richard et al., 2021), sense of joint agency (Shiraishi and Shimada, 2021), prosociality (Hu et al., 2017), similarity of flow states (Nozawa et al., 2021), shared meaning-making (Stolk et al., 2014), and cooperation (Cui et al., 2012; Toppi et al., 2016; Szymanski et al., 2017; Cheng et al., 2019). Phase-coupled brain stimulation has led to increased interpersonal synchrony (Novembre et al., 2017), as well as improved interpersonal learning (Pan et al., 2020b). Furthermore, preceding a learning task with synchronized physical activity led to both better rapport and increased inter-brain synchrony, although task performance was unaffected (Nozawa et al., 2019). Nonetheless, learning outcomes (Pan et al., 2020a) and team performance in a variety of tasks (Szymanski et al., 2017; Reinero et al., 2020) can be predicted with the amount of inter-brain synchrony occurring between interacting individuals. Even though collaboration is a dynamic phenomenon, previous studies reporting connections between positive social outcomes and inter-brain synchronization have not explored the temporal aspects of this phenomenon, as recently pointed out by Li et al. (2021). Their fNIRS study revealed differences in the time courses of inter-brain synchronization during two different cooperative tasks. The connection between temporal changes in inter-brain synchronization and the success of collaboration is, however, still not clear.
EEG and fNIRS allow freer movement and more natural interaction compared to magnetic imaging such as fMRI and MEG, arguably lending themselves most easily to actual interactive situations. However, interpersonal synchronization and mirroring between people engaged in social interaction involve quite fast timing precision. For example, participants’ movements were synchronized to less than 40 ms in the mirror game, in which participants improvise motion together (Noy et al., 2011). As EEG measures the electrical activity of the brain, it represents a faster changing signal than hemodynamic measurement, i.e. measures of blood flow, such as fNIRS. This makes EEG a suitable method for investigating fast changes in phase synchronization of oscillatory activity during dynamic social interaction, when taking into account the limitations of the method in regards to signal-to-noise ratio.
In this study, we wanted to investigate whether cooperative action of physically isolated participants would lead to inter-brain phase synchronization. We were especially interested in the temporal dynamics of inter-brain synchrony and its connection to performance in a collaborative task. We attempted to create an experimental setup which would facilitate the occurrence of inter-brain synchrony, while removing any bodily cues and controlling, as much as possible, for spurious synchronization. We also wanted to create a granular performance measure that could be calculated for any segment of the data, to make it possible to investigate dynamic changes in synchrony during the measurement and their connection to dynamic changes in collaborative success during the task.
“The idea was to build a society like we have for all the other disciplines in medicine,” says Evelyne Bischof, a professor of medicine at Shanghai University of Medicine and Health Sciences and the inaugural vice president of the society. She has previously spearheaded educational efforts with Zhavoronkov and others, co-developing a formal course on longevity medicine for doctors. At the ARDD meeting, Bischof announced their course had just received continuing medical education (CME) accreditation from the American Medical Association.
“Longevity medicine is crystallizing as a discipline,” says Andrea Maier, an internal medicine specialist and geriatrician at National University of Singapore who is serving as the society’s inaugural president. One thing that’s not yet clear, several experts told me, is whether longevity will come to be established as a sub-discipline of geriatrics or internal medicine or whether it will become a separate medical specialty unto itself.
“Whichever way it goes,” Maier says, “it’s happening.”
A world-first study led by Monash University engineers has demonstrated how cutting-edge 3D-printing techniques can be used to produce an ultra strong commercial titanium alloy—a significant leap forward for the aerospace, space, defense, energy and biomedical industries.
Australian researchers, led by Professor Aijun Huang and Dr. Yuman Zhu from Monash University, used a 3D-printing method to manipulate a novel microstructure. In doing so, they achieved unprecedented mechanical performance.
This research, published in Nature Materials, was undertaken on commercially available alloys and can be applied immediately.
Laser powder bed fusion, a 3D-printing technique, offers potential in the manufacturing industry, particularly when fabricating nickel-titanium shape memory alloys with complex geometries. Although this manufacturing technique is attractive for applications in the biomedical and aerospace fields, it has rarely showcased the superelasticity required for specific applications using nickel-titanium shape memory alloys. Defects generated and changes imposed onto the material during the 3D-printing process prevented the superelasticity from appearing in 3D-printed nickel-titanium.
Researchers from Texas A&M University recently showcased superior tensile superelasticity by fabricating a shape memory alloy through laser powder bed fusion, nearly doubling the maximum superelasticity reported in literature for 3D printing.
This study was recently published in vol. 229 of the Acta Materialia journal.
