Lifeboat Foundation

During deliberation, as we quietly consider our options, the neural activities representing the decision variables that reflect the goodness of each option rise in various regions of the cerebral cortex.^{1,2,3,4,5,6,7} If the options are depicted visually, we make saccades, focusing gaze on each option. Do the kinematics of these saccades reflect the state of the decision variables? To test this idea, we engaged human participants in a decision-making task in which they considered two effortful options that required walking across various distances and inclines. As they deliberated, they made saccades between the symbolic representations of their options. These deliberation period saccades had no bearing on the effort they would later expend, yet saccade velocities increased gradually and differentially: the rate of rise was faster for saccades toward the option that they later indicated as their choice. Indeed, the rate of rise encoded the difference in the subjective value of the two options. Importantly, the participants did not reveal their choice at the conclusion of deliberation, but rather waited during a delay period, and finally expressed their choice by making another saccade. Remarkably, vigor for this saccade dropped to baseline and no longer encoded subjective value. Thus, saccade vigor appeared to provide a real-time window to the otherwise hidden process of option evaluation during deliberation.

Throughout our lives, our skin goes through a lot. We get sunburns, we skin our knees, we bleed, we scar and we do it again. Our skin is our largest organ and, in many ways, serves as our protector. Beyond acting as a protective barrier between us and our environment, our skin regulates our body temperature, provides immune protection against harmful microbes and blocks out harmful sunlight in ways that benefit the whole body. And when skin is injured, blood brings healing substances to the site to promote healing as the body awaits new, replacement skin cells.

Regardless of scrapes and scratches, skin cells are constantly renewing themselves throughout our lives — a process reliant on skin stem cells. These skin stem cells turn over slowly, keeping our skin healthy and young. But as we age, these skin stem cells either numerically or functionally deplete, our skin thins and we are consequentially at higher risk for developing ulcers. The older the skin, the harder it is to heal these ulcers, meaning they can become chronic, open wounds that impact lifestyle and invite infection.

But what if we could activate a skin stem cell to be more responsive to injury? To get an 80-year-old’s skin to function like a 30-year-old’s skin? Could we reverse skin stem cell age-related deterioration and improve their turnover? What if we could do so in a way that healed wounds regeneratively, without any scarring? With these questions in mind, a collaborative team of researchers from the Mass General Brigham, Boston Children’s Hospital, and four additional Harvard institutions set off to study these powerful cells.

Partial somatic cell reprogramming has been touted as a promising rejuvenation strategy. However, its association with mechanisms of aging and longevity at the molecular level remains unclear. We identified a robust transcriptomic signature of reprogramming in mouse and human cells that revealed co-regulation of genes associated with reprogramming and response to lifespan-extending interventions, including those related to DNA repair and inflammation. We found that age-related gene expression changes were reversed during reprogramming, as confirmed by transcriptomic aging clocks. The longevity and rejuvenation effects induced by reprogramming in the transcriptome were mainly independent of pluripotency gain. Decoupling of these processes allowed predicting interventions mimicking reprogramming-induced rejuvenation (RIR) without affecting somatic cell identity, including an anti-inflammatory compound osthol, ATG5 overexpression, and C6ORF223 knockout. Overall, we revealed specific molecular mechanisms associated with RIR at the gene expression level and developed tools for discovering interventions that support the rejuvenation effect of reprogramming without posing the risk of neoplasia.

Aging is associated with the buildup of molecular damage and a gradual loss of function, culminating in chronic age-related diseases and ultimately death (1). Searching for safe and efficient interventions that can slow down or partially reverse the aging process is a major challenge in the aging field (2 – 6). In this regard, reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) has been proposed as a candidate longevity intervention due to its potential to rejuvenate cells in a targeted way (7, 8).

Pluripotency can be achieved in vitro by the ectopic expression of four transcription factors: OCT4, SOX2, KLF4, and MYC, known as OSKM or Yamanaka factors (YFs). It was demonstrated that OSKM support the generation of murine iPSCs using retroviral transduction as a delivery system and mouse embryonic fibroblasts (MEF) as the initial cell culture. Although this original experiment was inefficient in terms of the percentage of cells that terminally achieved the pluripotent state (0.1%), more advanced in vitro approaches resulted in a greatly improved efficiency, e.g. by down-regulation of methyl CpG-binding domain 3 (MBD3) levels (10). In parallel, other approaches have been developed to induce pluripotency. In particular, the expression of seven other transcription factors (7F: Jdp2-Jhdm1b-Mkk6-Glis1-Nanog-Essrb-Sall4) resulted in high efficiency of reprogramming (11).

A star orbiting a supermassive black hole at the centre of a distant galaxy was ripped apart in a tidal disruption event, the furthest ever observed.

Microsoft has disclosed details of a now-patched security flaw in Apple macOS that could be exploited by an attacker to get around security protections imposed to prevent the execution of malicious applications.

The shortcoming, dubbed Achilles (CVE-2022–42821, CVSS score: 5.5), was addressed by the iPhone maker in macOS Ventura 13, Monterey 12.6.2, and Big Sur 11.7.2, describing it as a logic issue that could be weaponized by an app to circumvent Gatekeeper checks.

“Gatekeeper bypasses such as this could be leveraged as a vector for initial access by malware and other threats and could help increase the success rate of malicious campaigns and attacks on macOS,” Jonathan Bar Or of the Microsoft 365 Defender Research Team said.

Facebook has taken steps to disrupt accounts and infrastructure operated by spyware vendors from a number of countries.

IARPA is putting together its REASON program that aims to help analysts identify crucial overlooked pieces of information while automatically generating comments to aid their intelligence reporting.

— Dr Thompson, Jun/2022, ABC.