Congenital Diseases of DNA Replication: Clinical Phenotypes and Molecular Mechanisms

Deoxyribonucleic acid (DNA) replication can be divided into three major steps: initiation, elongation and termination. Each time a human cell divides, these steps must be reiteratively carried out. Disruption of DNA replication can lead to genomic instability, with the accumulation of point mutations or larger chromosomal anomalies such as rearrangements. While cancer is the most common class of disease associated with genomic instability, several congenital diseases with dysfunctional DNA replication give rise to similar DNA alterations. In this review, we discuss all congenital diseases that arise from pathogenic variants in essential replication genes across the spectrum of aberrant replisome assembly, origin activation and DNA synthesis. For each of these conditions, we describe their clinical phenotypes as well as molecular studies aimed at determining the functional mechanisms of disease, including the assessment of genomic stability. By comparing and contrasting these diseases, we hope to illuminate how the disruption of DNA replication at distinct steps affects human health in a surprisingly cell-type-specific manner.     

Effect of PAN-based and pitch-based carbon fibres on microstructure and properties of continuous Cf/ZrB2-SiC UHTCMCs

In this paper the microstructure and mechanical properties of two different C_f/ZrB₂-SiC composites reinforced with continuous PyC coated PAN-derived fibres or uncoated pitch-derived fibres were compared.Pitch-derived carbon fibres showed a lower degree of reaction with the matrix phase during sintering compared to PyC/PAN-derived fibres. The reason lies in the different microstructure of the carbon. The presence of a coating for PAN-derived fibres was found to be essential to limit the reaction at the fibre/matrix interface during SPS. However, coated bundles were more difficult to infiltrate, resulting in a less homogeneous microstructure.As far as the mechanical properties are concerned, specimens reinforced with coated PAN-derived fibres provided higher strengths and damage tolerance than uncoated pitch-derived fibres, due to the higher degree of fibre pull-out. On the other hand, the weaker fibre/matrix interface resulted in lower interlaminar shear, off-axis strength and ablation resistance.     

Toward a better understanding of multifunctional cement-based materials: The impact of graphite nanoplatelets (GNPs)

The impact of graphite nanoplatelets (GNPs) on the physical and mechanical properties of cementitious nanocomposites was investigated. A market-available premixed mortar was modified with 0.01% by weight of cement of commercial GNPs characterized by two distinctively different aspect ratios.The rheological behavior of the GNP-modified fresh admixtures was thoroughly evaluated. Hardened cementitious nanocomposites were investigated in terms of density, microstructure (Scanning Electron Microscopy, SEM and micro–Computed Tomography, μ-CT), mechanical properties (three-point bending and compression tests), and physical properties (electrochemical impedance spectroscopy, EIS and thermal conductivity measurements). At 28 days, all GNP-modified mortars showed about 12% increased density. Mortars reinforced with high aspect ratio GNPs exhibited the highest compressive and flexural strength: about 14% and 4% improvements compared to control sample, respectively. Conversely, low aspect ratio GNPs led to cementitious nanocomposites characterized by 36% decreased electrical resistivity combined with 60% increased thermal conductivity with respect to the control sample.     

Microstructural,mechanical, and thermal properties of microwave-sintered KLS-1 lunar regolith simulant

KLS-1 Lunar regolith simulant was microwave sintered to explore its potential applicability in future lunar construction. The effects of sintering temperature on linear shrinkage, density, porosity, and microstructural, mechanical, and thermal properties were investigated. As the sintering temperature increased, linear shrinkage and density increased and porosity decreased. Structural evolution in the sintered samples was characterized by scanning electron microscopy and X-ray diffraction. Unconfined compressive strength testing showed that mechanical strength increased significantly with increasing sintering temperature, with 1120 °C giving the highest strength of 37.0 ± 4.8 MPa. The sintered samples exhibited a coefficient of thermal expansion of approximately 5 × 10⁻⁶ °C⁻¹, which was well-maintained even after cyclic temperature stress between −100 and 200 °C. Therefore, this microwave processing appears promising for the fabrication of building material with sufficient mechanical strength and thermal durability for lunar construction.     

Technical review: Improvement of mechanical properties and suitability towards armor applications – Alumina composites

Ceramic Matrix Composites (CMCs) have many interesting properties, mainly light weight, cost efficiency, low density, high compressive strength, high hardness and durability. Hence, they emerged as a boon to the development of personnel armors in the past. The current work aims to review various new methodologies adapted for the reinforcement of Alumina (Al₂O₃) CMCs in recent times, including some of the interesting results obtained with respect to mechanical properties, suitability of the synthesized composites for armor applications, and the upcoming reinforcement trends. Finally, studies related to reinforcement in Al₂O₃ CMCs, specifically towards armor applications have been consolidated to arrive at some of the important inferences for concluding reasonably.     

CuxNi1-xO nanostructures and their nanocomposites with reduced graphene oxide: Synthesis,characterization, and photocatalytic applications

NiO nanostructure was synthesized using a simple co-precipitation method and was embedded on reduced graphene oxide surface via ultrasonication. Structural investigations were made through X-ray diffraction (XRD) and functional groups were confirmed by Fourier transform infrared spectroscopy (FTIR). XRD analysis revealed the grain size reduction with doping. Fourier transform infrared spectroscopy confirmed the presence of metal-oxygen bond in pristine and doped NiO nanostructure as well as the presence of carbon containing groups. Scanning electron microscopy (SEM) indicated that the particle size decreased when NiO nanostructure was doped with copper. BET surface area was found to increase almost up to 43 m²/g for Cu doped NiO nanostructure/rGO composite. Current-voltage measurements were performed using two probe method. UV–Visible spectroscopic profiles showed the blue and red shift for Cu doped NiO nanostructure and Cu doped NiO Nanostructure/rGO composite respectively. Rate constant for Cu doped NiO nanostructure/rGO composite found to increase 4.4 times than pristine NiO nanostructure.     

Mitochondrial and Autophagic Regulation of Adult Neurogenesis in the Healthy and Diseased Brain

Adult neurogenesis is a highly regulated process during which new neurons are generated from neural stem cells in two discrete regions of the adult brain: the subventricular zone of the lateral ventricle and the subgranular zone of the dentate gyrus in the hippocampus. Defects of adult hippocampal neurogenesis have been linked to cognitive decline and dysfunction during natural aging and in neurodegenerative diseases, as well as psychological stress-induced mood disorders. Understanding the mechanisms and pathways that regulate adult neurogenesis is crucial to improving preventative measures and therapies for these conditions. Accumulating evidence shows that mitochondria directly regulate various steps and phases of adult neurogenesis. This review summarizes recent findings on how mitochondrial metabolism, dynamics, and reactive oxygen species control several aspects of adult neural stem cell function and their differentiation to newborn neurons. It also discusses the importance of autophagy for adult neurogenesis, and how mitochondrial and autophagic dysfunction may contribute to cognitive defects and stress-induced mood disorders by compromising adult neurogenesis. Finally, I suggest possible ways to target mitochondrial function as a strategy for stem cell-based interventions and treatments for cognitive and mood disorders.     

Tunable multicolor upconversion luminescence of Yb3+ sensitized Na3La(VO4)2 crystals

Multicolor upconversion luminescence materials show significantly applications in materials science. In this paper, the novel Yb³⁺-sensitized Na₃La(VO₄)₂ upconversion luminescence crystals are synthesized by the solid-state reaction method. Three primary colors upconversion luminescence are successfully achieved in Na₃La(VO₄)₂:Yb³⁺,Tm³⁺, Na₃La(VO₄)₂:Yb³⁺,Er³⁺, and Na₃La(VO₄)₂:Yb³⁺,Ho³⁺ crystals excited by the single 980 nm LD. Multicolor upconversion luminescence can be obtained by simply adjusting the combination ratios of these three samples. Luminescence mechanisms of the Yb³⁺-sensitized system are discussed in detail. In the Na₃La(VO₄)₂ host material, the Yb³⁺/Ho³⁺ codoped system exhibits unusual red upconversion luminescence based on the short decay time of Ho³⁺ ion ⁵I₆ level, which provides the possibility of three primary color luminescence under 980 nm excitation.