Search Results (138)

Human zinc finger Ran-binding protein 3 (ZRANB3) is crucial for DNA damage tolerance (DDT), as it prevents excessive damage, restores fork progression, and ultimately maintains genome stability. This unique and ancient architecture mainly exerts its function during replication fork reversal (RFR) and within the p53/Polι axis; thus, ZRANB3 is considered a tumour suppressor. However, possible additional roles in DNA synthesis and cell metabolism have been proposed. In tumour cells, ZRANB3 gene expression is deregulated, a condition that is frequently associated with poor survival and adverse clinical outcomes. ZRANB3 can be altered by functional mutations, gene copy number alterations, and a combination of the two. Although its mRNA levels typically correlate with p53 expression, this correlation breaks down in the context of p53 mutations and high proliferative activity. This comprehensive review integrates the currently available yet fragmented literature on ZRANB3, both at the gene and protein levels, examines its regulation in cancer development, and discusses the evidence supporting its role as a tumour suppressor and prognostic biomarker. Full article

The SNF2-related chromatin remodeler Srcap is the principal ATPase responsible for the deposition of the histone variant H2A.Z at promoters and regulatory chromatin regions. Although this activity is known to modulate transcription, its contribution to DNA replication remains unexplored. Here we show that Srcap is required for efficient replication fork progression and origin firing in mammalian cells. Using RNA interference in human PC3 cells, we found that Srcap depletion leads to a ~25% reduction in fork elongation rate, decreased replication fork density, accumulation of the replication-stress marker γH2AX, and reduced chromatin-bound H2A.Z. High-resolution expansion microscopy further revealed diminished intensity and increased spacing of replication foci, consistent with reduced origin activation. Transcriptomic analysis of published data identified broad downregulation of replication-associated genes. These data uncover a dual mechanism by which Srcap sustains replication efficiency—through both H2A.Z-dependent chromatin organization and transcriptional maintenance of the replication machinery. Our findings establish Srcap as an important coordinator of replication dynamics, with implications for genome stability. Full article

This study examines the impact of technological progress on food price dynamics and supply stability across the 27 European Union Member States during 2011–2024. Using a balanced panel dataset, the analysis explores four dependent indicators—consumer food prices, food price inflation, price volatility, and food supply variability—while controlling for trade openness, GDP per capita growth, and population. Technological progress is estimated through panel least squares regression with fixed effects. The results reveal that technological advancement significantly reduces food prices and inflation, suggesting that innovation-driven productivity and efficiency gains stabilize consumer markets. However, its influence on food price volatility and supply variability is statistically insignificant, indicating that innovation alone cannot fully mitigate systemic risks in the European food system. The results provide policy-relevant evidence supporting the integration of technological innovation into food system governance across the European Union. They underline the need for targeted investment and regulatory coordination to translate innovation gains into tangible resilience outcomes, thus offering practical guidance for policymakers and stakeholders involved in implementing the European Green Deal and the Farm to Fork Strategy. Full article

This article demonstrates that 3D-printed parts can replace metal parts in optomechanics in the correct circumstances. Three examples are shown: a clamping fork for pedestal holders where stability is important, an adjustable mirror holder where the rigidity is the main criterion, and a stray light shield where the transmissivity is critical. By combining carbon-fiber-reinforced polymers (CFRPs) with 3D printing, it is possible to produce components that fill the gap between standard 3D-printed plastics and metal parts in terms of strength and stability. These parts are designed to be lighter, more compact, and easier to modify, while keeping good mechanical properties such as resistance to vibration, shape accuracy, and controlled thermal expansion. The article focuses on the application of composite 3D printing on optomechanical components. It compares different methods of composite 3D printing, including fused filament fabrication (FFF) with either chopped fibers or with continuous fiber reinforcement. Three examples from the HiLASE Centre demonstrate how these parts are used in practice, confirming that it is indeed possible to 3D print components that are lighter and cheaper yet still highly functional compared to their off-the-shelf counterparts—for example, lightweight and stiff mounts, shielding against stray laser light, or flexible elements allowing fine mechanical adjustments. Simulations of the deformations are included to compare the printed and metal versions. The article ends with a summary of the benefits and limitations of using 3D-printed composites in optomechanics. Full article

Background/Objectives: DNA2 is a conserved nuclease–helicase that plays a crucial role in DNA replication and repair by responding to replication stress. Previous studies have established the role of DNA2 in Okazaki fragment processing, the recovery of stalled replication forks, and double-strand break repair. This study investigates the role of Drosophila melanogaster Dna2 in response to exogenous DNA damage and replication stress as well as during developmental stages involving intensive DNA replication. Methods: We used the Drosophila mutant alleles, Dna2^D1 and Dna2^D2, which differ in the presence of the helicase 1A domain, to assess sensitivity to mutagens that cause various types of replication stress and DNA damage. We examined reproductive fitness through Mendelian ratio calculations, fecundity, egg viability assays, and assessed DNA damage via immunostaining of ovarian germaria. Lifespan assays were also conducted to examine adult survival. Results: Dna2 mutants demonstrated significant sensitivity to replication stress induced by MMS, hydroxyurea, topotecan, and nitrogen mustard. Dna2^lS/S1 mutants exhibited higher survival than Dna2^lS/D2 upon exposure to topotecan and bleomycin, suggesting a possible helicase-specific role in damage response. Mutants exhibited decreased fecundity, reduced egg viability, and elevated DNA damage in mitotically active germline cells. Adult lifespan was not reduced in Dna2 mutants, implying potential compensatory stress-response mechanisms. Conclusions: Our findings support a requirement of Dna2 in managing replication stress during critical developmental phases in Drosophila. These insights clarify the nuanced contributions of the nuclease and helicase domains of DNA2, suggesting potential domain-specific functions in genomic stability and repair mechanisms. This work provides a foundation that will enable future researchers to further dissect the complex roles of DNA2 in replication and repair pathways. Full article

WRN helicases play a key role in DNA replication, repair, and other processes in a variety of tumors. It has become one of the hot targets of genotoxic drugs, but the effect and mechanism of targeting WRN against prostate cancer is still unclear. In our previous study, we found a quinazoline compound kzl052, which has a WRN-dependent inhibitory effect on prostate cancer cells, but its molecular mechanism needs to be further explored. In this study, kzl052 significantly inhibited the growth of PC3 (IC₅₀ = 0.39 ± 0.01 μM) and LNCaP (IC₅₀ = 0.11 ± 0.01 μM) cells in vitro and showed a good inhibition effect on PCa in vivo. It inhibits PC3 cell growth by binding to WRN proteins and affecting its non-enzymatic function. Then the mechanism of kzl052 against prostate cancer progression was revealed to be by regulating the stability of DNA replication forks and the RB pathway. This study will provide a theoretical basis and treatment strategy for targeting WRN helicase in the treatment of prostate cancer. Full article

Root zone restriction (RZR) technology optimizes plant growth and quality. However, the fleshy root system of Paeonia ostii exhibits sensitivity to spatial constraints, and research on the plasticity of its root architecture and adaptation mechanisms remains inadequate. This study provides a functional analysis of biomass allocation and root architectural responses to the root-zone restriction (RZR) in P. ostii, comparing three container volumes (8.5, 17, and 34 L). While the total biomass increased with root zone volume (e.g., shoot biomass rose from 9.30 g to 59.94 g), RZR induced a 44.8% increase in root-to-shoot ratio, indicating carbon reallocation to enhance belowground resource acquisition. The principal component analysis identified root biomass, volume, and surface area as key plasticity drivers. Optimal root efficiency occurred at 26.09–28.23 L, where root length and tip/fork numbers peaked. Mechanistically, RZR elevated superoxide dismutase (SOD) activity by 49.74% but reduced catalase (CAT) by 74.24%, disrupting H₂O₂ homeostasis. Concurrently, auxin transporter genes (PIN1, AUX1) were upregulated, promoting root elongation and lateral branching through auxin redistribution. We hypothesize that ROS–auxin crosstalk mediates architectural reconfiguration to mitigate spatial stress, with thickened roots enhancing structural stability in restricted environments. The study underscores the need to optimize root zone volume in woody species cultivation, providing thresholds (e.g., >28 L for mature plants) to balance biomass yield and physiological costs in horticultural management. Full article

In this paper, an all-fiber light-induced thermoelastic spectroscopy (LITES) sensor based on hollow-core anti-resonant fiber (HC-ARF) and self-designed low-frequency quartz tuning fork (QTF) is reported for the first time. By utilizing HC-ARF as both the transmission medium and gas chamber, the laser tail fiber was spatially coupled with the HC-ARF, and the end of the HC-ARF was directly guided onto the QTF surface, resulting in an all-fiber structure. This design eliminated the need for lens combinations, thereby enhancing system stability and reducing cost and size. Additionally, a self-designed rectangular-tip QTF with a low resonant frequency of 8.69 kHz was employed to improve the sensor’s detection performance. Acetylene (C₂H₂), with an absorption line at 6534.37 cm⁻¹ (1.53 μm), was chosen as the target gas. Experimental results clearly demonstrated that the detection performance of the rectangular-tip QTF system was 2.9-fold higher than that of a standard commercial QTF system. Moreover, it exhibited an outstanding linear response to varying C₂H₂ concentrations, indicating its high sensitivity and reliability in detecting C₂H₂. The Allan deviation analysis was used to assess the system’s stability, and the results indicated that the system exhibits excellent long-term stability. Full article

This study compares the performance of a quartz tuning fork (QTF) with a highly sensitive ultrasound microphone in the context of acoustic measurements, applying the substitution calibration method. QTF sensors are increasingly used for high-precision tasks due to their sensitivity and stability, while microphones are still the standard in general acoustic measurements. The aim of this study is to evaluate both technologies across several key performance metrics, including linearity of response, sensitivity, noise characteristics, and acoustic detection limit. Which sensor is better suited to which acoustic and physical condition? The results show that QTFs perform exceptionally well in applications requiring high precision, especially in high-frequency and narrow-band measurements. The signal-to-noise-ratio (SNR) of the QTF at its resonance frequency is 14 dB higher than that of the microphone, whereas the detection limit and linearity are comparable. The findings suggest that QTF sensors are particularly advantageous for specialized applications like photoacoustic spectroscopy (PAS). Full article

Background: Aging is associated with a decline in both motor and sensory functions that destabilizes posture, increasing the risk of falls. Dynamic standing balance is strongly linked to fall risk in older adults. Sensory information from the soles and trunk is essential for balance control. Few studies have demonstrated the efficacy of targeted sensory training on balance improvement. Objectives: To assess vibratory sensation function in the trunk and sole using a vibration device and evaluate the effects of trunk and sole tactile sensation training on dynamic standing balance performance in older adults. Methods: In this randomized controlled trial, eighteen older adults were randomly assigned to three groups: control (n = 8, mean age 66.6 ± 3.4), trunk training (n = 5, mean age 71.0 ± 1.9), and sole training (n = 5, mean age 66.4 ± 3.6). The training lasted for 10 weeks, utilizing vibratory stimulation at 128 Hz through tuning forks for 15 min during each session, conducted three times a week. The primary outcomes were vibratory sensitivity, assessed with a belt-fitted device on the trunk and a plate equipped with vibrators on the soles, and dynamic balance, evaluated through force plate testing that measured limits of stability (LoS) in multiple directions. Results: Correct response rates for trunk vibratory stimulation significantly improved in the trunk training group (p < 0.05). The rate of two-stimuli discrimination improved in both training groups. Significant advancements in balance metrics were observed in the trunk and sole training groups when compared to the control group, especially regarding anterior–posterior tilts (p < 0.05). A positive correlation was identified between two-point vibratory discrimination and LoS test performance. Conclusions: Sensory training of the trunk and sole enhances balance performance in older adults, suggesting potential benefits for fall prevention. Future studies should assess long-term effects and explore optimal training duration with larger sample sizes. Full article

Accurate DNA replication is essential for the maintenance of genome stability and the generation of healthy offspring. When DNA replication is challenged, signals accumulate at blocked replication forks that elicit a multifaceted cellular response, orchestrating DNA replication, DNA repair and cell cycle progression. This replication stress response promotes the recovery of DNA replication, maintaining chromosome integrity and preventing mutations. Defects in this response are linked to heightened genetic instability, which contributes to tumorigenesis and genetic disorders. Iron–sulfur (Fe-S) clusters are emerging as important cofactors in supporting the response to replication stress. These clusters are assembled and delivered to target proteins that function in the cytosol and nucleus via the conserved cytosolic Fe-S cluster assembly (CIA) machinery and the CIA targeting complex. This review summarizes recent advances in understanding the structure and function of the CIA machinery in yeast and mammals, emphasizing the critical role of Fe-S clusters in the replication stress response. Full article

The rapid development of flexible sensor technology has made flexible sensor arrays a key research area in various applications due to their exceptional flexibility, wearability, and large-area-sensing capabilities. These arrays can precisely monitor physical parameters like pressure and strain in complex environments, making them highly beneficial for sectors such as smart wearables, robotic tactile sensing, health monitoring, and flexible electronics. This paper reviews the fabrication processes, operational principles, and common materials used in flexible sensors, explores the application of different materials, and outlines two conventional preparation methods. It also presents real-world examples of large-area pressure and strain sensor arrays. Fabrication techniques include 3D printing, screen printing, laser etching, magnetron sputtering, and molding, each influencing sensor performance in different ways. Flexible sensors typically operate based on resistive and capacitive mechanisms, with their structural designs (e.g., sandwich and fork-finger) affecting integration, recovery, and processing complexity. The careful selection of materials—especially substrates, electrodes, and sensing materials—is crucial for sensor efficacy. Despite significant progress in design and application, challenges remain, particularly in mass production, wireless integration, real-time data processing, and long-term stability. To improve mass production feasibility, optimizing fabrication processes, reducing material costs, and incorporating automated production lines are essential for scalability and defect reduction. For wireless integration, enhancing energy efficiency through low-power communication protocols and addressing signal interference and stability are critical for seamless operation. Real-time data processing requires innovative solutions such as edge computing and machine learning algorithms, ensuring low-latency, high-accuracy data interpretation while preserving the flexibility of sensor arrays. Finally, ensuring long-term stability and environmental adaptability demands new materials and protective coatings to withstand harsh conditions. Ongoing research and development are crucial to overcoming these challenges, ensuring that flexible sensor arrays meet the needs of diverse applications while remaining cost-effective and reliable. Full article

A highly sensitive light-induced thermoelastic spectroscopy (LITES) sensor employing a charge amplifier (CA) is reported for the first time in this invited paper. CA has the merits of high input impedance and strong anti-interference ability. The usually used transimpedance amplifier (TA) and voltage amplifier (VA) were also studied under the same conditions for comparison. A standard commercial quartz tuning fork (QTF) with a resonant frequency of approximately 32.76 kHz was used as the photothermal signal transducer. Methane (CH₄) was used as the target gas in these sensors for performance verification. Compared to the TA-LITES sensor and VA-LITES sensor, the reported CA-LITES sensor shows improvements of 1.83 times and 5.28 times in the minimum detection limit (MDL), respectively. When compared to the LITES sensor without an amplifier (WA-LITES), the MDL has a 19.96-fold improvement. After further optimizing the gain of the CA, the MDL of the CA-LITES sensor was calculated as 2.42 ppm, which further improved the performance of the MDL by 30.3 times compared to the WA-LITES. Additionally, long-term stability is analyzed using Allan deviation analysis. When the average time of the sensor system is increased to 50 s, the MDL of the CA-LITES sensor system can be improved to 0.58 ppm. Full article

RAD18 is a conserved eukaryotic E3 ubiquitin ligase that promotes genome stability through multiple pathways. One of these is gap-filling DNA synthesis at active replication forks and in post-replicative DNA. RAD18 also regulates homologous recombination (HR) repair of DNA breaks; however, the current literature describing the contribution of RAD18 to HR in mammalian systems has not reached a consensus. To investigate this, we examined three independent RAD18-null human cell lines. Our analyses found that loss of RAD18 in HCT116, but neither hTERT RPE-1 nor DLD1 cell lines, resulted in elevated sister chromatid exchange, gene conversion, and gene targeting, i.e., HCT116 mutants were hyper-recombinogenic (hyper-rec). Interestingly, these phenotypes were linked to RAD18’s role in PCNA K164 ubiquitination, as HCT116 PCNA^K164R/+ mutants were also hyper-rec, consistent with previous studies in rad18^−/− and pcna^K164R avian DT40 cells. Importantly, the knockdown of UBC9 to prevent PCNA K164 SUMOylation did not affect hyper-recombination, strengthening the link between increased recombination and RAD18-catalyzed PCNA K164 ubiquitination, but not K164 SUMOylation. We propose that the hierarchy of post-replicative repair and HR, intrinsic to each cell type, dictates whether RAD18 is required for suppression of hyper-recombination and that this function is linked to PCNA K164 ubiquitination. Full article

Open source software (OSS) projects rely on voluntary contributions, but their long-term survivability depends on sustained community engagement and effective problem-solving. Survivability, critical for maintaining project quality and trustworthiness, is closely linked to issue activity, as unresolved issues reflect a decline in maintenance capacity and problem-solving ability. Thus, analyzing issue retention rates provides valuable insights into a project’s health. This study evaluates OSS survivability by identifying the features that influence issue activity and analyzing their relationships with survivability. Kaplan–Meier survival analysis is employed to quantify issue activity and visualize trends in unresolved issue rates, providing a measure of project maintenance dynamics. A random forest model is used to examine the relationships between project features—such as popularity metrics, community engagement, code complexity, and project age—and issue retention rates. The results show that stars significantly reduce issue retention rates, with rates dropping from 0.62 to 0.52 as stars increase to 4000, while larger codebases, higher cyclomatic complexity, and older project age are associated with unresolved issue rates, rising by up to 15%. Forks also have a nonlinear impact, initially stabilizing retention rates but increasing unresolved issues as contributions became unmanageable. By identifying these critical factors and quantifying their impacts, this research offers actionable insights for OSS project managers to enhance project survivability and address key maintenance challenges, ensuring sustainable long-term success. Full article