Browse Articles

The first complete mitochondrial genome of Sumatran striped rabbit Nesolagus netscheri (Schlegel, 1880), and its phylogenetic relationship with other Leporidae

Determining anatomically-safe corridors for placement of lateral mass screws in the first cervical vertebra of the Emirati population – a CT study

Machine learning analysis of cervical balance in early-onset scoliosis post-growing rod surgery: a case-control study

Will Europe ramp up defence research? War prompts major rethink

Cytotoxic mechanisms of pemetrexed and HDAC inhibition in non-small cell lung cancer cells involving ribonucleotides in DNA

Abstract The cytotoxic mechanisms of thymidylate synthase inhibitors, such as the multitarget antifolate pemetrexed, are not yet fully understood. Emerging evidence indicates that combining pemetrexed with histone deacetylase inhibitors (HDACi) may enhance therapeutic efficacy in non-small cell lung cancer (NSCLC). To explore this further, A549 NSCLC cells were treated with various combinations of pemetrexed and the HDACi MS275 (Entinostat), and subsequently assessed for cell viability, cell cycle changes, and genotoxic markers. Proteomic alterations were analyzed using label-free shotgun and targeted LC–MS/MS. MS275 enhanced the sensitivity of A549 cells to pemetrexed, but only when administered following prior treatment with pemetrexed. Both HeLa (p53 negative) and A549 (p53 positive) showed robust activation of γH2AX upon treatment with this combination. Importantly, CRISPR/Cas9 knockout of the uracil-DNA glycosylase UNG did not affect γH2AX activation or sensitivity to pemetrexed. Proteomic analysis revealed that MS275 altered the expression of known pemetrexed targets, as well as several proteins involved in pyrimidine metabolism and DNA repair, which could potentiate pemetrexed cytotoxicity. Contrary to the conventional model of antifolate toxicity, which implicates futile cycles of uracil incorporation and excision in DNA, we propose that ribonucleotide incorporation in nuclear and mitochondrial DNA significantly contributes to the cytotoxicity of antifolates like pemetrexed, and likely also of fluorinated pyrimidine analogs. HDAC inhibition apparently exacerbates cytotoxicity of these agents by inhibiting error-free repair of misincorporated ribonucleotides in DNA. The potential of HDACis to modulate pyrimidine metabolism and DNA damage responses offers novel strategies for improving NSCLC outcomes.

Analysis of DNA cox1 barcoding revealed novel haplotype in Schistosoma haematobium isolated from Western Sudan

AI-designed antivenoms could help treat lethal snakebites

Plasma levels of anti phosphocholine IgM antibodies are negatively correlated with bone mineral density in humans

Abstract Phosphatidylcholine is a ubiquitous phospholipid. It contains a phosphocholine (PC) headgroup and polyunsaturated fatty acids that, when oxidized, form reactive oxidized phospholipids (PC-OxPLs). PC-OxPLs are pathogenic in multiple diseases and neutralized by anti-PC IgM antibodies. The levels of anti-PC IgM increase as the levels of PC-OxPLs increase and, in humans, are inversely correlated with the incidence of cardiovascular diseases and steatohepatitis. PC-OxPLs also decrease bone mass in mice. Overexpression of anti-PC IgM ameliorates atherosclerosis and steatohepatitis, increases bone mass in young mice, and protects against high fat diet- and age-associated osteoporosis. We investigated the relationship between anti-PC IgM plasma levels and bone mineral density (BMD) in a cross-sectional study of 247 participants [mean age: 65.5 (± 8.6) years] without medical conditions known to influence BMD or antibody production. Anti-PC IgM levels negatively correlated with both T- and Z-scores at the lumbar spine, femur and, to a lesser extent, the forearm. These correlations were maintained after adjustment for age, race, and sex. These results raise the possibility that higher levels of anti-PC IgM in patients with lower BMD reflect exposure to higher levels of PC-OxPLs, which are known to affect bone mass, and could be a novel risk marker for osteoporosis.

The impact of a humanized bile acid composition on atherosclerosis development in hypercholesterolaemic Cyp2c70 knockout mice

Clinical validation of explainable AI for fetal growth scans through multi-level, cross-institutional prospective end-user evaluation

Astragaloside IV attenuates cadmium induced nephrotoxicity in rats by activating Nrf2

An effective feature selection approach based on hybrid Grey Wolf Optimizer and Genetic Algorithm for hyperspectral image

High genomic connectivity within Anatoma at hydrothermal vents along the Central and Southeast Indian Ridge

Abstract Hydrothermal vents are ecosystems inhabited by a highly specialized fauna. To date, more than 30 gastropod species have been recorded from vent fields along the Central and Southeast Indian Ridge and all of them are assumed to be vent-endemic. During the INDEX project, 701 representatives of the genus Anatoma (Mollusca: Vetigastropoda) were sampled from six abyssal hydrothermal vent fields. Traditional morphology and COI barcoding of Hoffman et al. (Eur J Taxon 826:135–162, 2022) were combined with 2b-RAD sequencing to investigate the anatomid community structure and connectivity between the different vent fields. Consequently, 2b-RAD sequencing supported the primary species hypothesis (based on morphology) for 125 individuals of the recently described taxa A. discapex, A. declivis, A. laevapex and A. paucisculpta. We assigned 22 additional specimens to species with 2b-RAD sequencing and updated the community analyses that confirmed the pattern of expanding populations. Population structure and FST values indicated high connectivity along the six sampled vent fields for the three most abundant species. High levels of gene flow are suggested, pointing to high dispersal potential of the target species along the study area. However, low levels of heterozygosity revealed a small gene pool and therefore an increased vulnerability towards environmental change. Our results demonstrate that 2b-RAD sequencing, in combination with other molecular methods, can accurately characterise macrobenthic mollusc communities. Sequencing technology is an essential tool for ongoing monitoring. Furthermore, we highlight that the inferred molecular and ecological patterns provide valuable insights into hydrothermal vent ecosystems, which are crucial for the successful conservation of these ecosystems.

Road trip

Two-photon NAD(P)H-FLIM reveals unperturbed energy metabolism of Ascaris suum larvae, in contrast to host macrophages upon artemisinin derivatives exposure

Abstract Soil-transmitted helminths (STH) are widespread, with Ascaris lumbricoides infecting millions globally. Malaria and STH co-infections are common in co-endemic regions. Artemisinin derivatives (ARTs)—artesunate, artemether, and dihydroartemisinin—are standard malaria treatments and are also known to influence the energy metabolism of parasites, tumors, and immune cells. Herein, we explore the potential of ARTs to influence ascariasis either by directly targeting larvae or indirectly by modifying macrophage responses. Ascaris suum third-stage larvae and porcine IL-4 polarized (M2-like) macrophages were exposed to ARTs in vitro, and their metabolism was evaluated using two-photon NAD(P)H-FLIM. Both larvae and M2-like macrophages exhibited a steady-state bioenergetic profile of high oxidative phosphorylation and low anaerobic glycolysis. In A. suum larvae, two metabolically distinct regions were identified, with particularly high DUOX activity in the pharynx compared to the midgut; however, ARTs did not alter these profiles. In contrast, exposure of M2-like macrophages to ARTs induced a metabolic shift towards high anaerobic glycolysis and reduced metabolic activity, suggesting a possible indirect effect of ARTs on the helminth infection. Overall, two-photon NAD(P)H-FLIM proved to be a powerful tool for studying specific metabolic pathways in Ascaris larvae and host macrophages, offering valuable insights into the metabolic mechanisms of drug action on both parasite and host.

Delayed onset of ocean acidification in the Gulf of Maine

Abstract The Gulf of Maine holds significant ecological and economic value for fisheries and communities in north-eastern North America. However, there is apprehension regarding its vulnerability to the effects of increasing atmospheric CO2. Substantial recent warming and the inflow of low alkalinity waters into the Gulf of Maine have raised concerns about the impact of ocean acidification on resident marine calcifiers (e.g. oysters, clams, mussels). With limited seawater pH records, the natural variability and drivers of pH in this region remain unclear. To address this, we present coastal water pH proxy records using boron isotope (δ11B) measurements in long-lived, annually banded, crustose coralline algae (1920–2018 CE). These records indicate seawater pH was low (~ 7.9) for much of the last century. Contrary to expectation, we also find that pH has increased (+ 0.2 pH units) over the past 40 years, despite concurrent rising atmospheric CO2. This increase is attributed to an increased input of high alkalinity waters derived from the Gulf Stream. This delayed onset of ocean acidification is cause for concern. Once ocean circulation-driven buffering effects reach their limit, seawater pH decline may occur swiftly. This would profoundly harm shellfisheries and the broader Gulf of Maine ecosystem.

Gene drives development of brain’s emotional centre and its connections

Age-period-cohort analysis of self-harm incidence rates by gender in Iran among individuals aged 10–39 years, 1990–2019

A mutation makes plant roots more welcoming to beneficial microbes

Microstructure and magnetism of austenitic steels in relation to chemical composition, severe plastic deformation, and solution annealing

Abstract Three types of commercial austenitic stainless steels, 1.4307 (AISI 304 L), 1.4404 (AISI 316 L) 1.4845 (AISI 310 S) with different chemical compositions, are subjected to severe plastic deformation at room temperature by a unique Dual Rolling Equal Channel Extrusion (DRECE) method. Its impact is evaluated from the viewpoint of microstructure analyses, X-ray diffraction, and macroscopic magnetic properties completed by microscopic Mössbauer characteristics. The study also includes the solution annealing at 950 °C for 0.5 h to follow the recovering austenitic structure and paramagnetic state of steels with the aim to offer more information with respect to new technical applications. The results show the importance of the steel’s chemical composition and microstructure, mainly grain size, on the stability of the austenitic structure closely associated with the paramagnetic behaviour.