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Recently recycled synaptic vesicles use multi-cytoskeletal transport and differential presynaptic capture probability to establish a retrograde net flux during ISVE in central neurons

Presynapses locally recycle synaptic vesicles to efficiently communicate information. During use and recycling, proteins on the surface of synaptic vesicles break down and become less efficient. In order to maintain efficient presynaptic function and accommodate protein breakdown, new proteins are regularly produced in the soma and trafficked to presynaptic locations where they replace older protein-carrying vesicles. Maintaining a balance of new proteins and older proteins is thus essential for presynaptic maintenance and plasticity. While protein production and turnover have been extensively studied, it is still unclear how older synaptic vesicles are trafficked back to the soma for recycling in order to maintain balance. In the present study, we use a combination of fluorescence microscopy, hippocampal cell cultures, and computational analyses to determine the mechanisms that mediate older synaptic vesicle trafficking back to the soma. We show that synaptic vesicles, which have recently undergone exocytosis, can differentially utilize either the microtubule or the actin cytoskeleton networks. We show that axonally trafficked vesicles traveling with higher speeds utilize the microtubule network and are less likely to be captured by presynapses, while slower vesicles utilize the actin network and are more likely to be captured by presynapses. We also show that retrograde-driven vesicles are less likely to be captured by a neighboring presynapse than anterograde-driven vesicles. We show that the loss of synaptic vesicle with bound molecular motor myosin V is the mechanism that differentiates whether vesicles will utilize the microtubule or actin networks. Finally, we present a theoretical framework of how our experimentally observed retrograde vesicle trafficking bias maintains the balance with previously observed rates of new vesicle trafficking from the soma.

Cytoskeleton-based trafficking mechanics have long been explored because of their essential role in neuronal function and maintenance (Westrum et al., 1983; Okada et al., 1995; Sorra et al., 2006; Perlson and Holzbaur, 2007; Tao-Cheng, 2007; Hirokawa et al., 2009; Staras and Branco, 2010; Tang et al., 2013; Wu et al., 2013; Maeder et al., 2014; Guedes-Dias et al., 2019; Gramlich et al., 2021; Watson et al., 2023). Protein trafficking via cytoskeleton transport is essential for synaptogenesis (Perlson and Holzbaur, 2007; Santos et al., 2009; Klassen et al., 2010; Wu et al., 2013; Guedes-Dias et al., 2019; Guedes-Dias and Holzbaur, 2019; Kurshan and Shen, 2019; Watson et al., 2023) and to replace older proteins with newer proteins for efficient function (Cohen et al., 2013; Dörrbaum et al., 2018, 2020; Heo et al., 2018; Truckenbrodt et al., 2018; Jähne et al., 2021; Watson et al., 2023).

Remarks by Dr. Liz Sherwood-Randall Assistant to the President for Homeland Security on Countering Bioterrorism in an Era of Technology Convergence

Ash carter exchange remarks as prepared.

I’m grateful to be here today with a group of kindred spirits focused on tackling some of the hardest problems we face at the intersection of technology and national security.

Ash Carter devoted his life to working in this arena, and many of you are here because of the impact he had on you and your careers.

Study: Women Can Boost Longevity With Half as Much Exercise as Men

A new study has unveiled a surprising revelation: Women may need only half the amount of exercise as men to achieve similar benefits in terms of longevity. This groundbreaking research challenges conventional wisdom and underscores the importance of personalized approaches to physical fitness based on gender differences.

As the world grapples with rising concerns over sedentary lifestyles and their impact on health outcomes, these findings offer invaluable insights into optimizing exercise regimens for women.

The study also revealed that women who engage in regular physical activity may significantly extend their life spans. The findings, published in the Journal of the American College of Cardiology, shed light on the vital role of exercise in promoting longevity among women.

OTPS seeks input from the lunar community to inform a framework for further work on non-interference of lunar activities

NASA’s Office of Technology, Policy, and Strategy (OTPS) is asking members of the lunar community to respond to a new Lunar Non-Interference Questionnaire that will inform the development of a framework for further work on non-interference of lunar activities. There is no funding or solicitation expected to follow.

OTPS was created in November 2021 within the Office of the NASA Administrator to work transparently in collaboration across NASA and with the broader space community to provide NASA leadership with a trade space of data-and evidence-driven options to develop and shape NASA policy, strategy, and technology.

As dozens of countries and private sector companies have expressed interest in establishing lunar operations by the end of the decade, including many in the South Pole region, it will be critical to determine how to minimize interference and contamination in lunar activities. Deconfliction has been identified as an area of further work in Section 11 of the Artemis Accords and will be an area of increasing importance as the number of commercial and international actors operating on the lunar surface grows.