The Moirai, meaning "allotted portion" or "share", separated each sister into a different role in order to handle the fates of humans. The Fates were expected to appear within three days of a mortal's birth.[3] Clotho was the first of the three, known as "the spinner", due to the fact that she would weave the threads of human life while in the womb.[4] This act is used to represent her divine duty, also incorporating pregnancies or birth when referring to her. The second Fate, Lachesis, is known as "the Allotter," given the fact that her responsibility includes determining how much mortal life is assigned to the souls of each individual.[5] This, in turn, determines the number of tribulations that individual is predestined to face. The final Fate, Atropos, is known as the most stubborn sister of the three, coined the nickname "the un-turnable".[6] Completing the cycle, Atropos is expected to cut off the thread of life, determining when a human will die. She is typically seen hand in hand with death and the Underworld. Once Atropos cuts the thread, each soul is sent to the Underworld where they receive judgement and are sent to one of three options: Elysium, the Fields of Punishment, or the Fields of Asphodel.[7]
Chimeric antigen receptors (CARs) are synthetic receptors that target and reprogram T cells to acquire augmented antitumor properties1. CD19-specific CARs that comprise CD28 and CD3ζ signaling motifs2 have induced remarkable responses in patients with refractory leukemia3,4,5 and lymphoma6 and were recently approved by the US Food and Drug Administration7. These CARs program highly performing effector functions that mediate potent tumor elimination4,8 despite the limited persistence they confer on T cells3,4,5,6,8. Extending their functional persistence without compromising their potency should improve current CAR therapies. Strong T cell activation drives exhaustion9,10, which may be accentuated by the redundancy of CD28 and CD3ζ signaling11,12 as well as the spatiotemporal constraints imparted by the structure of second-generation CARs2. Thus, we hypothesized that calibrating the activation potential of CD28-based CARs would differentially reprogram T cell function and differentiation. Here, we show that CARs encoding a single immunoreceptor tyrosine-based activation motif direct T cells to different fates by balancing effector and memory programs, thereby yielding CAR designs with enhanced therapeutic profiles.
fates
Abstract:The serious global microplastic pollution has attracted public concern in recent years. Microplastics are widely distributed in various environments and their pollution is already ubiquitous in the ocean system, which contributes to exponential concern in the past decade and different research areas. Due to their tiny size coupled with the various microbial communities in aquatic habitats capable of accumulating organic pollutants, abundant literature is available for assessing the negative impact of MPs on the physiology of marine organisms and eventually on the human health. This study summarizes the current literature on MPs in the marine environment to obtain a better knowledge about MP contamination. This review contains three sections: (1) sources and fates of MPs in the marine environment, (2) impacts of MPs on marine organisms, and (3) bacteria for the degradation of marine MPs. Some measures and efforts must be taken to solve the environmental problems caused by microplastics. The knowledge in this review will provide background information for marine microplastics studies and management strategies in future.Keywords: source; fate; bacterial degradation; marine environment; microplastics 2ff7e9595c
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