C9orf72 Expansion Disrupts ATM-mediated Chromosomal Break Repair

A hexanucleotide repeat expansion represents the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, though the mechanisms by which the expansion cause neurodegeneration are poorly understood. We report elevated levels of DNA/RNA hybrids (R-loops) and double-strand breaks (DSBs) in rodent neurons, human cells, and in C9orf72-ALS patient spinal cord tissues. Accumulation of endogenous DNA damage is concomitant with defective ATM-mediated DNA repair signalling and accumulation of protein-linked DNA breaks. We further reveal that defective ATM-mediated DNA repair is a consequence of p62 accumulation, which impairs H2A ubiquitylation and perturbs ATM signalling. Adeno-associated virus- mediated expression of C9orf72-related RNA and dipeptide repeats in the murine central nervous system causes elevated DSBs, ATM defects, and triggers neurodegeneration. These findings identify R-Loops, DSBs, and defective ATM-mediated repair as pathological consequences of C9orf72 expansions, and suggest that C9orf72-linked neurodegeneration is driven, at least in part, by genomic instability

DNA Homeostasis and Senescence: Lessons from the Naked Mole Rat

As we age, our bodies accrue damage in the form of DNA mutations. These mutations lead to the generation of sub-optimal proteins, resulting in inadequate cellular homeostasis and senescence. The build-up of senescent cells negatively affects the local cellular micro-environment and drives ageing associated disease, including neurodegeneration. Therefore, limiting the accumulation of DNA damage is essential for healthy neuronal populations. The naked mole rats (NMR) are from eastern Africa and can live for over three decades in chronically hypoxic environments. Despite their long lifespan, NMRs show little to no biological decline, neurodegeneration, or senescence. Here, we discuss molecular pathways and adaptations that NMRs employ to maintain genome integrity and combat the physiological and pathological decline in organismal function

Anchoring Fe3O4 nanoparticles in a reduced graphene oxide aerogel matrix via polydopamine coating

Reduced graphene oxide–magnetite hybrid aerogels attract great interest thanks to their potential applications, e.g., as magnetic actuators. However, the tendency of magnetite particles to migrate within the matrix and, ultimately, escape from the aerogel structure, remains a technological challenge. In this article we show that coating magnetite particles with polydopamine anchors them on graphene oxide defects, immobilizing the particles in the matrix and, at the same time, improving the aerogel structure. Polydopamine coating does not affect the magnetic properties of magnetite particles, making the fabricated materials promising for industrial applications

Resource Recovery from Synthetic Nitrified Urine in the Hydroponic Cultivation of Lettuce (Lactuca sativa Var. capitata L.)

The application of hydroponic cultivation fertilized with biologically nitrified synthetic urine can produce nitrate-rich fertilizer for lettuce (Lactuca sativa var. capitata L.). The mounting water crisis and depletion of natural resources makes nitrogen recovery from human urine a practical option. Nitrified urine can be used in indoor vertical hydroponic cultivation and is characterized by a high degree of element recovery. Because of its high ammonium content, hydrolyzed fresh urine may be toxic. A nitrification sequencing batch reactor with suspended activated sludge biomass ensured urine stabilization and biological conversion into nitrate-rich fertilizer. The diluted nitrate-rich fertilizer was then supplied for soilless cultivation. The results show that diluted nitrified urine is an excellent source of bioavailable nitrogen and phosphorus and, with proper enrichment with microelements, could replace commercial fertilizers in hydroponic systems. The yield and quality parameters of lettuce cultivated with enriched urine were comparable to those obtained with a commercial fertilizer. The mass balance calculation showed that industry-scale lettuce production can be based on urine fertilizer collected from a few hundred people for a single unit

Enhancement of Electronic and Optical Properties of ZnO/Al₂O₃ Nanolaminate Coated Electrospun Nanofibers

Nanolaminates are new class of promising nanomaterials with outstanding properties. Here we explored on the tuning of structural properties and the enhancement of electronic and optical properties of 1D PAN ZnO/Al₂O₃ nanolaminates designed by atomic layer deposition (ALD) and electrospinning. The influence of ZnO/Al₂O₃ bilayer thicknesses on the fundamental properties of 1D PAN ZnO/Al₂O₃ nanolaminates has been investigated. Due to the quantum confinement effect, the shift of XPS peaks to higher energies has been observed. Work function of Al₂O₃ was mostly independent of the bilayers number, whereas the ZnO work function decreased with an increase of the bilayer number. Photoluminescence of the 1D PAN ZnO/Al₂O₃ nanolaminates corresponded to emission bands in ZnO nanolayers. Due to quantum confinement and surface band bending, no excitonic peaks were observed. The defect emission band was affected by the band bending and defect concentration. The enhanced photoluminescence of the 1D PAN ZnO/Al₂O₃ nanolaminates allows applications in optical (bio)­sensing field