Understanding how space travel affects the female reproductive system to the Moon and beyond

As the space industry grows exponentially and aspirations for space travel expand, we are entering a new era where we will very likely become an interplanetary species. Although reproduction is an essential human function and necessary for species survival, we have remarkably little knowledge regarding the impact of space travel on the female reproductive system. The effects of spaceflight on human reproductive potential, fertility, implantation and subsequent pregnancy resulting in a healthy live birth must be considered before planning prolonged spaceflight missions and the colonization of planets. In this review, we explore what is known and what remains to be learned about the effects of space travel on female reproductive endocrinology. We also delve deeper into reproductive endocrinology and discuss normal physiologic mechanisms at the molecular level to have a better understanding of how it may change during spaceflight. The rigors of spaceflight including radiation, gravitational stressors, and circadian rhythm changes could potentially affect ovulation, fertilization, endometrial receptivity, preimplantation embryo development, embryo implantation, placentation, and pregnancy. Thus, we will examine what is known about spaceflight effects on the hypothalamic–pituitary–gonadal (HPG) axis, ovarian folliculogenesis and steroidogenesis, early embryogenesis, endometrial receptivity, and pregnancy. We further discuss the recent advances in reproductive endocrinology and future research platforms. Establishing a better understanding of the effect of space travel on female reproductive health, as well as developing countermeasures to mitigate adverse effects, are decisive components of our species’ successful transition to an interplanetary one

Role of miR-2392 in driving SARS-CoV-2 infection

MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene regulation that have a major impact on many diseases and provide an exciting avenue toward antiviral therapeutics. From patient transcriptomic data, we determined that a circulating miRNA, miR-2392, is directly involved with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) machinery during host infection. Specifically, we show that miR-2392 is key in driving downstream suppression of mitochondrial gene expression, increasing inflammation, glycolysis, and hypoxia, as well as promoting many symptoms associated with coronavirus disease 2019 (COVID-19) infection. We demonstrate that miR-2392 is present in the blood and urine of patients positive for COVID-19 but is not present in patients negative for COVID-19. These findings indicate the potential for developing a minimally invasive COVID-19 detection method. Lastly, using in vitro human and in vivo hamster models, we design a miRNA-based antiviral therapeutic that targets miR-2392, significantly reduces SARS-CoV-2 viability in hamsters, and may potentially inhibit a COVID-19 disease state in humans

Neutronics analysis of three beam-filter assemblies for an accelerator-based BNCT facility

Three moderator materials, AlF{sub 3}/Al, D{sub 2}O and LiF, have been analyzed for clinical usefulness using the reaction {sup 7}Li(p,n) as an accelerator driven neutron source. Proton energies between 2.1 MeV and 2.6 MeV have been investigated. Radiation transport in the reflector/moderator assembly is simulated using the MCNP program. Depth-dose distributions in a head phanton are calculated with the BNCT-RTPE patient treatment planning program from INEEL using the MCNP generated neutron and photon spectra as the subsequent source. Clinical efficacy is compared using the current BMRR protocol for all designs. Depth-dose distributions are compared for a fixed normal tissue tolerance dose of 12.5 Gy-Eq. Radiation analyses also include a complete anthropomorphic phantom. Results of organ and whole body dose components are presented for several designs. Results indicate that high quality accelerator beams may produce clinically favorable treatments to deep-seated tumors when compared to the BMRR beam. Also discussed are problems identified in comparing accelerator and reactor based designs using in-air figures of merit as well as some results of spectrum-averaged RBE`s

Spatiotemporal characterization of ionizing radiation induced DNA damage foci and their relation to chromatin organization

DNA damage sensing proteins have been shown to localize to the sites of DNA double strand breaks (DSB) within seconds to minutes following ionizing radiation (IR) exposure, resulting in the formation of microscopically visible nuclear domains referred to as radiation-induced foci (RIF). This review characterizes the spatiotemporal properties of RIF at physiological doses, minutes to hours following exposure to ionizing radiation, and it proposes a model describing RIF formation and resolution as a function of radiation quality and chromatin territories. Discussion is limited to RIF formed by three interrelated proteins ATM (Ataxia telangiectasia mutated), 53BP1 (p53 binding protein 1) and γH2AX (phosphorylated variant histone H2AX), with an emphasis on the later. This review discusses the importance of not equating RIF with DSB in all situations and shows how dose and time dependence of RIF frequency is inconsistent with a one to one equivalence. Instead, we propose that RIF mark regions of the chromatin that would serve as scaffolds rigid enough to keep broken DNA from diffusing away, but open enough to allow the repair machinery to access the damage site. We review data indicating clear kinetic and physical differences between RIF emerging from dense and uncondensed regions of the nucleus. We suggest that persistent RIF observed days following exposure to ionizing radiation are nuclear marks of permanent rearrangement of the chromatin architecture. Such chromatin alterations may not always lead to growth arrest as cells have been shown to replicate these in progeny. Thus, heritable persistent RIF spanning over tens of Mbp may reflect persistent changes in the transcriptome of a large progeny of cells. Such model opens the door to a “non-DNA-centric view” of radiation-induced phenotypes

Mechanistic study of thermal behaviour and combustion performance of epoxy resins. II: TGDDM/DDS system

The kinetics of curing of tetraglycidyl 4,4′-diaminodiphenylmethane (TGDDM) with 50% or 85% of stoichiometric 4,4′-diaminodiphenylsulfone (DDS) was studied by differential scanning calorimetry. It was found that the activation energy of the process increases with advancement of curing, which is caused by concomitant homopolymerisation of TGDDM accompanied by cyclisation. The structure of the cured formulations was characterised by infrared and 13C NMR spectroscopy. The mechanistic study of thermal decomposition of TGDDM/DDS systems was carried out by thermogravimetry and differential scanning calorimetry in inert atmosphere and by thermal volatilisation analysis in vacuo. It was found that above 200 °C elimination of water from secondary alcohol groups takes place with formation of aliphatic unsaturation. Breaking of the resulting weakened allylic CN bonds leads to chain scission with formation of primary amine and quinolin-type chain ends. Scission of non-allylic CN bonds followed by evolution of acetone was observed at about 300 °C. The volatilisation of sulfur-containing species and formation of a thermostable char occurred on further heating to 400 °

Mechanistic study of thermal behaviour and combustion performance of epoxy resins. I: Homopolymerized TGDDM

Tetraglycidyl 4,4′-diaminodiphenylmethane (TGDDM) undergoes homopolymerization on heating. Intramolecular reactions which compete with crosslinking favor the formation of cyclic structures with increasing thermal and fire resistance of the resin, whereas physical mechanical properties tend to decrease. The mechanism of thermal decomposition of TGDDM is studied by thermogravimetry, differential scanning calorimetry and thermal volatilization analysis with characterization of volatiles evolved and residue left. Thermal degradation of poly-(TGDDM) starts at 260°C with elimination of water from secondary alcoholic groups which is a typical pathway for epoxy resin degradation. Resulting unsaturations weaken bonds in the β-position and provoke the first chain breaking at allyl-amine and allyl-either bonds. With increasing temperature, saturated alkyl-ether bonds and alkyl carbon-carbon bonds are broken first, followed by the most stable alkyl-aryl bonds at T>365°C. The combustion performance of TGDDM is discussed on the basis of the thermal degradation behavio

Laser evaporation as a source of small free-radicals

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