Search Results (59)

We aimed to explore SARS-CoV-2 evolution during in vitro neutralisation using next generation sequencing, and to determine whether sera from individuals immunised with two doses of the Pfizer-BioNTech vaccine (BNT162b2) were as effective at neutralising the variant of concern (VOC) Delta (B.1.617.2) compared to the earlier lineages Beta (B.1.351) and wild-type (A.2.2) virus. Using a live-virus SARS-CoV-2 neutralisation assay in Vero E6 cells, we determined neutralising antibody titres (nAbT) against three SARS-CoV-2 strains (wild type, Beta, and Delta) in 14 participants (vaccine-naïve (n = 2) and post-second dose of BNT162b2 vaccination (n = 12)), median age 45 years [IQR 29–65]; the median time after the second dose was 21 days [IQR 19–28]. The determination of nAbT was based on cytopathic effect (CPE) and in-house quantitative reverse transcriptase real-time quantitative polymerase chain reaction (RT-qPCR) to confirm SARS-CoV-2 replication. A total of 110 representative samples including inoculum, neutralisation breakpoints at 72 h, and negative and positive controls underwent genome sequencing. By integrating live-virus neutralisation assays with deep sequencing, we characterised both functional antibody responses and accompanying viral genetic changes. There was a reduction in nAbT observed against the Delta and Beta VOC compared with wild type, 4.4-fold (p ≤ 0.0006) and 2.3-fold (p = 0.0140), respectively. Neutralising antibodies were not detected in one vaccinated immunosuppressed participant and the vaccine-naïve participants (n = 2). The highest nAbT against the SARS-CoV-2 variants investigated was obtained from a participant who was vaccinated following SARS-CoV-2 infection 12 months prior. Limited consensus level mutations occurred in the various SARS-CoV-2 lineage genomes during in vitro neutralisation; however, consistent minority allele frequency variants (MFV) were detected in the SARS-CoV-2 polypeptide, spike (S), and membrane protein. Findings from countries with high COVID-19 incidence may not be applicable to low-incidence settings such as Australia; as seen in our cohort, nAbT may be significantly higher in vaccine recipients previously infected with SARS-CoV-2. Monitoring viral evolution is critical to evaluate the impact of novel SARS-CoV-2 variants on vaccine effectiveness, as mutational profiles in the sub-consensus genome could indicate increases in transmissibility and virulence or suggest the development of antiviral resistance. Full article

Understanding structural regime shifts in crypto asset markets is vital for early detection of systemic risk. This study applies the Generalized Sup Augmented Dickey–Fuller (GSADF) test to daily high-frequency price data of five major crypto assets—BTC, ETH, SOL, AAVE, and BCH—from 2023 to 2025. The results reveal asset-specific structural breaks: BTC and BCH aligned with macroeconomic shocks, while DeFi tokens (e.g., AAVE, SOL) exhibited fragmented, project-driven shifts. The S&P 500 index, in contrast, showed no persistent regime shifts, indicating greater structural stability. To examine inter-asset linkages, we construct co-occurrence matrices based on GSADF breakpoints. These reveal strong co-explosivity between BTC and other assets, and unexpectedly weak synchronization between ETH and AAVE, underscoring the sectoral idiosyncrasies of DeFi tokens. While the GSADF test remains central to our analysis, we also employ a Markov Switching Model (MSM) as a secondary tool to capture short-term volatility clustering. Together, these methods provide a layered view of long- and short-term market dynamics. This study highlights crypto markets’ structural heterogeneity and proposes scalable computational frameworks for real-time monitoring of explosive behavior. Full article

Flooding frequency in the lower Yellow River (YR) exhibited an abrupt increase post-934 CE, causing catastrophic societal disruptions. However, the quantitative relationship between this abrupt increase and the intensification of human activity in the midstream Loess Plateau (LP)’s Primary Sediment Source Area (PSSA) remains uncertain. This study systematically evaluates the threshold effects of human activities on YR flooding through multi-proxy historical records, GIS-based spatial analysis, and nonparametric statistical tests. The results show that from 934 to 1102 CE, the population density in the PSSA surged from 1.3 to 19.8 persons/km² (a 14.2-fold increase, p = 0.005). A 2400-year-scale comparison using 934 CE as the breakpoint revealed that the mean population density in this region increased from 5.2 to 51 persons/km² (a 9.8-fold increase). This dramatic population surge drove a 1.4-fold increase in the cultivation rate (from 8.6% to 20.5%), leading to a 5.4-fold rise in sediment yield (1.6 × 10⁸ → 1.02 × 10⁹ t/yr, p = 0.035), a 10-fold acceleration in downstream sedimentation rate (0.3 → 3.3 cm/yr, p = 0.001), and ultimately a 5.5-fold escalation in flooding frequency (from 1.6 to 10.4 events per 20 years, p < 0.0001). The study identifies 19.8 persons/km² as the ecological pressure threshold. It proposes converting population density to ecological pressure equivalents adjusted for soil–water conservation coverage (e.g., terracing/afforestation). When the equivalent ecological pressure exceeds 19.8 persons/km², pre-defined sediment control measures (e.g., tillage restrictions/afforestation mandates) should be enforced in the PSSA. Full article

Background/Objectives: Antimicrobial resistance of the E. coli O25 ST131 clonal lineage poses a significant therapeutic challenge worldwide, often involving resistance to fluoroquinolones and extended-spectrum beta-lactamase (ESBL) production. This retrospective study compared the dissemination of multidrug-resistant E. coli O25 ST131 isolated from the urine of outpatients at the largest Croatian clinical microbiology department across six years over two study periods. Methods: The E. coli O25 ST131 clonal lineage was detected via a rapid PCR method using pabB and trpA primers after positive agglutination with E. coli serogroup O25 antisera. ESBL phenotypes and antibiotic susceptibility were investigated according to EUCAST guidelines and breakpoint tables. Results: In the first period, there were a total of 45 isolates of E. coli O25 ST131, among which 30 were isolates with proven ESBL production. In the second period, a total of 114 isolates of E. coli O25 ST131 were detected, among which 75 (65.8%) were ESBL-positive (p > 0.05). In ESBL-negative strains, the multidrug-resistant (MDR) phenotype was characterized by simultaneous resistance to ampicillin, co-trimoxazole, and fluoroquinolones (with an equal proportion of 3/15 isolates in the first period and 7/39 isolates in the second period, p > 0.05). There was no statistically significant difference in the frequency of MDR detection across the two study periods (36/45 and 98/114, p > 0.05). This is the first detection of E. coli O25 ST131 in the outpatient population in Zagreb. Conclusions: There was no statistically significant difference in the frequency of detecting the E. coli O25 ST 131 clone across the two study periods. The high frequency of MDR phenotype among ESBL-negative isolates of E. coli O25 ST131 and an equally high proportion of MDR strains among ESBL producers in this clonal lineage, with the total detection of MDR isolates ≥ 80% in both study periods, are the reasons why this bacterial clone poses a public health threat and why further investigation into its metabolic and virulence characteristics is needed in order to estimate its spreading potential among the outpatient population in Zagreb. Full article

Background: It is widely accepted that the 3D chromatin organization in human cell nuclei is not random and recent investigations point towards an interactive relation of epigenetic functioning and chromatin (re-)organization. Although chromatin organization seems to be the result of self-organization of the entirety of all molecules available in the cell nucleus, a general question remains open as to what extent chromatin organization might additionally be predetermined by the DNA sequence and, if so, if there are characteristic differences that distinguish typical regions involved in dysfunction-related aberrations from normal ones, since typical DNA breakpoint regions involved in disease-related chromosome aberrations are not randomly distributed along the DNA sequence. Methods: Highly conserved k-mer patterns in intronic and intergenic regions have been reported in eukaryotic genomes. In this article, we search and analyze regions deviating from average spectra (ReDFAS) of k-mer word frequencies in the human genome. This includes all assembled regions, e.g., telomeric, centromeric, genic as well as intergenic regions. Results: A positive correlation between k-mer spectra and 3D contact frequencies, obtained exemplarily from given Hi-C datasets, has been found indicating a relation of ReDFAS to chromatin organization and interactions. We also searched and found correlations of known functional annotations, e.g., genes correlating with ReDFAS. Selected regions known to contain typical breakpoints on chromosomes 9 and 5 that are involved in cancer-related chromosomal aberrations appear to be enriched in ReDFAS. Since transposable elements like ALUs are often assigned as major players in 3D genome organization, we also studied their impact on our examples but could not find a correlation between ALU regions and breakpoints comparable to ReDFAS. Conclusions: Our findings might show that ReDFAS are associated with instable regions of the genome and regions with many chromatin contacts which is in line with current research indicating that chromatin loop anchor points lead to genomic instability. Full article

Flashiness refers to the rapidity and frequency of fluctuations in river flow. It can provide insights into flooding, by capturing dramatic increases in river flow, as well as contaminant transport, relating to concentrations of diffuse pollution. Despite a very well gauged river system, there is limited research in Great Britain targeting this component of river flow. This study addresses that gap in knowledge, with a detailed spatio-temporal analysis of river flashiness in Great Britain. Using 513 gauging stations, with historical records of at least 30 years, the average Richards–Baker flashiness index ($\overline{RBI}$) was calculated for 1990–2020, showing an overall west- (0.6–0.8) to east-coast (0.1–0.2) gradient, being higher in the west (with the exception of some gauges in the south-east). Employing random forest models, the main predictor for flashiness was found to be soil composition, with some additional region-specific predictors. These include flood attenuation by reservoirs and catchment areas, affecting flashiness in the north and west of Great Britain. Additionally, using a subset of 208 gauging stations with data recorded from 1970 to 2020, a temporal analysis examined significant breakpoints and/or trends in yearly flashiness, using the Pettitt test and Mann–Kendall trend test, respectively. Increases in flashiness were found mainly in the north-east and south-west of Great Britain, with implications in flooding and river health. On a seasonal scale, and using a monthly $\overline{RBI}$, the timing of flashy events was found to oscillate between autumn and spring over the 50 years, gravitating around winter. Full article

CDKL5 deficiency disorder (CDD) is an X-linked dominant epileptic encephalopathy, characterized by early-onset and drug-resistant seizures, psychomotor delay, and slight facial features. Genomic variants inactivating CDKL5 or impairing its protein product kinase activity have been reported, making next-generation sequencing (NGS) and chromosomal microarray analysis (CMA) the standard diagnostic tests. We report a suspicious case of CDD in a female child who tested negative upon NGS and CMA and harbored an X chromosome de novo pericentric inversion. The use of recently developed genomic techniques (optical genome mapping and whole-genome sequencing) allowed us to finely characterize the breakpoints, with one of them interrupting CDKL5 at intron 1. This is the fifth case of CDD reported in the scientific literature harboring a structural rearrangement on the X chromosome, providing evidence for the hypothesis that this type of anomaly can represent a recurrent pathogenic mechanism, whose frequency is likely underestimated, with it being overlooked by standard techniques. The identification of the molecular etiology of the disorder is extremely important in evaluating the pathological outcome and to better investigate the mechanisms associated with drug resistance, paving the way for the development of specific therapies. Karyotype and genomic techniques should be considered in all cases presenting with CDD without molecular confirmation. Full article

A ~3-kb deletion-type DNA copy number variation (CNV, esv3587290) located at intron 7 of the VANGL1 gene (1p13.1, MIM*610132) has been proposed as a genetic factor in lupus nephritis (LN) development in adult systemic lupus erythematosus (SLE) patients across European-descent populations, but its replication in other ethnicities has been inconsistent and its association with LN in childhood-onset SLE (cSLE) remains unknown. Here, we performed an exploratory association study in a sample of 66 unrelated cSLE Mexican patients (11 males, 55 females; ages 7.8 to 18.6 years). Two stratified groups were compared: cSLE patients with (N = 39) or without (N = 27) LN, as diagnosed by renal biopsy (N = 17), proteinuria (N = 33), urinary protein–creatinine ratio > 0.2 (N = 34), and erythrocyturia and/or granular casts in urinary sediment (N = 16). For esv3587290 CNV genotyping, we performed an end-point PCR assay with breakpoint confirmation using Sanger sequencing. We also determined the allelic frequencies of the esv3587290 CNV in 181 deidentified ethnically matched individuals (reference group). The obtained genotypes were tested for Hardy–Weinberg equilibrium using the χ² test. Associations between LN and esv3587290 CNV were tested by calculating the odds ratio (OR) and using Pearson’s χ² tests, with a 95% confidence interval and p ≤ 0.05. The esv3587290 CNV allele (OR 0.108, 95% CI 0.034–0.33, p = 0.0003) and the heterozygous genotype (OR 0.04, 95% CI 0.119–0.9811, p = 0.002) showed a significant protective effect against LN development. Finally, we characterized the precise breakpoint of the esv3587290 CNV to be NG_016548.1(NM_138959.3):c.1314+1339_1315-897del in our population. This report supports the notion that a broad genetic heterogeneity underlies the susceptibility for developing LN. Full article

Chromosomal translocations can result in phenotypic effects of varying severity, depending on the position of the breakpoints and the rearrangement of genes within the interphase nucleus of the translocated chromosome regions. Balanced translocations are often asymptomatic phenotypically and are typically detected due to a decrease in fertility resulting from issues during meiosis. Robertsonian translocations are among the most common chromosomal abnormalities, often asymptomatic, and can persist in the population as a normal polymorphism. We serendipitously discovered a Robertsonian translocation between chromosome 21 and chromosome 22, which is inherited across three generations without any phenotypic effect, notably only in females. In situ hybridization with alpha-satellite DNAs revealed the presence of both centromeric sequences in the translocated chromosome. The reciprocal translocation resulted in a partial deletion of the short arm of both chromosomes 21, and 22, with the ribosomal RNA genes remaining present in the middle part of the new metacentric chromosome. The rearrangement did not cause alterations to the long arm. The spread of an asymptomatic heterozygous chromosomal polymorphism in a population can lead to mating between heterozygous individuals, potentially resulting in offspring with a homozygous chromosomal configuration for the anomaly they carry. This new karyotype may not produce phenotypic effects in the individual who presents it. The frequency of karyotypes with chromosomal rearrangements in asymptomatic heterozygous form in human populations is likely underestimated, and molecular karyotype by array Comparative Genomic Hybridization (array-CGH) analysis does not allow for the identification of this type of chromosomal anomaly, making classical cytogenetic analysis the preferred method for obtaining clear results on a karyotype carrying a balanced rearrangement. Full article

The most common form of hereditary spastic paraplegia (HSP), SPG4 is caused by single nucleotide variants and microrearrangements in the SPAST gene. The high percentage of multi-exonic deletions or duplications observed in SPG4 patients is predisposed by the presence of a high frequency of Alu sequences in the gene sequence. In the present study, we analyzed DNA and RNA samples collected from patients with different microrearrangements in SPAST to map gene breakpoints and evaluate the mutation mechanism. The study group consisted of 69 individuals, including 50 SPG4 patients and 19 healthy relatives from 18 families. Affected family members from 17 families carried varying ranges of microrearrangements in the SPAST gene, while one individual had a single nucleotide variant in the 5′UTR of SPAST. To detect the breakpoints of the SPAST gene, long-range PCR followed by sequencing was performed. The breakpoint sequence was detected for five different intragenic SPAST deletions and one duplication, revealing Alu-mediated microhomology at breakpoint junctions resulting from non-allelic homologous recombination in these patients. Furthermore, SPAST gene expression analysis was performed using patient RNA samples extracted from whole blood. Quantitative real-time PCR tests performed in 14 patients suggest no expression of transcripts with microrearrangements in 5 of them. The obtained data indicate that nonsense-mediated decay degradation is not the only mechanism of hereditary spastic paraplegia in patients with SPAST microrearrangements. Full article

Confronting the challenge of biofilm resistance and widespread antimicrobial resistance (AMR), this study emphasizes the need for innovative monitoring methods and explores the potential of bacteriophages against bacterial biofilms. Traditional methods, like optical density (OD) measurements and confocal microscopy, crucial in studying biofilm–virus interactions, often lack real-time monitoring and early detection capabilities, especially for biofilm formation and low bacterial concentrations. Addressing these gaps, we developed a new real-time, label-free radiofrequency sensor for monitoring bacteria and biofilm growth. The sensor, an open-ended coaxial probe, offers enhanced monitoring of bacterial development stages. Tested on a biological model of bacteria and bacteriophages, our results indicate the limitations of traditional OD measurements, influenced by factors like sedimented cell fragments and biofilm formation on well walls. While confocal microscopy provides detailed 3D biofilm architecture, its real-time monitoring application is limited. Our novel approach using radio frequency measurements (300 MHz) overcomes these shortcomings. It facilitates a finer analysis of the dynamic interaction between bacterial populations and phages, detecting real-time subtle changes. This method reveals distinct phases and breakpoints in biofilm formation and virion interaction not captured by conventional techniques. This study underscores the sensor’s potential in detecting irregular viral activity and assessing the efficacy of anti-biofilm treatments, contributing significantly to the understanding of biofilm dynamics. This research is vital in developing effective monitoring tools, guiding therapeutic strategies, and combating AMR. Full article

Neuroblastoma (NB) is the most frequent extracranial solid childhood tumor. Despite advances in the understanding and treatment of this disease, the prognosis in cases of high-risk NB is still poor. 17q gain has been shown to be the most frequent genomic alteration in NB. However, the significance of this remains unclear because of its high frequency and association with other genetic modifications, particularly segmental chromosomal aberrations, 1p and 11q deletions, and MYCN amplification, all of which are also associated with a poor clinical prognosis. This work reviewed the evidence on the clinical and biological significance of 17q gain. It strongly supports the significance of 17q gain in the development of NB and its importance as a clinically relevant marker. However, it is crucial to distinguish between whole and partial chromosome 17q gains. The most important breakpoints appear to be at 17q12 and 17q21. The former distinguishes between whole and partial chromosome 17q gain; the latter is a site of IGF2BP1 and NME1 genes that appear to be the main oncogenes responsible for the functional effects of 17q gain. Full article

Ozone plays an important role in the Earth’s atmosphere. It is mainly formed in the tropical stratosphere and is transported by the Brewer–Dobson Circulation to higher latitudes. In the stratosphere, ozone can filter the incoming solar ultraviolet radiation, thus protecting life at the surface. Although tropospheric ozone accounts for only ~10%, it is a powerful GHG and pollutant, harmful to the health of the environment and living beings. Several studies have highlighted biomass burning as a major contributor to the tropospheric ozone budget. Our study focuses on the Natal site (5.40°S, 35.40°W, Brazil), one of the oldest ozone-observing stations in Brazil, which is expected to be influenced by fire plumes in Africa and Brazil. Many studies that examined ozone trends used the total atmospheric columns of ozone, but it is important to assess ozone separately in the troposphere and the stratosphere. In this study, we have used radiosonde ozone profiles and daily TCO measurements to evaluate the variability and changes of both tropospheric and stratospheric ozone separately. The dataset in this study comprises daily total columns of colocalized ozone and weekly ozone profiles collected between 1998 and 2019. The tropospheric columns were estimated by integrating ozone profiles measured by ozone sondes up to the tropopause height. The amount of ozone in the stratosphere was then deduced by subtracting the tropospheric ozone amount from the total amount of ozone measured by the Dobson spectrometer. It was assumed that the amount of ozone in the mesosphere is negligible. This produced three distinct time series of ozone: tropospheric and stratospheric columns as well as total columns. The present study aims to apply a new decomposition method named Empirical Adaptive Wavelet Decomposition (EAWD) that is used to identify the different modes of variability present in the analyzed signal. This is achieved by summing up the most significant Intrinsic Mode Functions (IMF). The Fourier spectrum of the original signal is broken down into spectral bands that frame each IMF obtained by the Empirical Modal Decomposition (EMD). Then, the Empirical Wavelet Transform (EWT) is applied to each interval. Unlike other methods like EMD and multi-linear regression (MLR), the EAWD technique has an advantage in providing better frequency resolution and thus overcoming the phenomenon of mode-mixing, as well as detecting possible breakpoints in the trend mode. The obtained ozone datasets were analyzed using three methods: MLR, EMD, and EAWD. The EAWD algorithm exhibited the advantage of retrieving ~90% to 95% of ozone variability and detecting possible breakpoints in its trend component. Overall, the MRL and EAWD methods showed almost similar trends, a decrease in the stratosphere ozone (−1.3 ± 0.8%) and an increase in the tropospheric ozone (+4.9 ± 1.3%). This study shows the relevance of combining data to separately analyze tropospheric and stratospheric ozone variability and trends. It highlights the advantage of the EAWD algorithm in detecting modes of variability in a geophysical signal without prior knowledge of the underlying forcings. Full article

Tugai wetlands, including the forests of Populus euphratica Oliv. and P. pruinosa Schrenk, are major biodiversity hotspots within semi-arid and arid ecozones. However, for over a century, Central Asian river systems have been severely affected by dam regulation, water withdrawals for large-scale irrigated agriculture, and deforestation. To support sustainable use and protection of this threatened forest type, we provide information on the distribution and degradation status of Tugai wetlands in the Syr Darya floodplain using Normalized Difference Vegetation Index (NDVI) time series from Landsat 7 and Moderate Resolution Imaging Spectroradiometer (MODIS). An accuracy assessment confirmed the validity of the MODIS-based wetland map, with an overall accuracy of 78.6%. This was considerably better than the Landsat product, mainly due to the greater temporal frequency of the MODIS time series. We further calculated trends and breakpoints between 2001 and 2016 using the BFAST algorithm. We found negative trends for nearly a third of the wetlands. Breakpoint detection showed major stress events in the years 2001, 2009, and 2016. Our study revealed the temporal and spatial distribution and vitality of an endangered forest ecosystem that has rarely been studied thus far. Climate change may accelerate the destabilization of the Tugai forests at the Syr Darya floodplain. Full article

In this study, the aging process of a surface-functional titanium dioxide nanosheet (f-TNS) composited room-temperature-vulcanized silicone rubber (RTV) composite coating was simulated in a NO₂ generation device, and then the electrochemical impedance spectroscopy (EIS) of the aged composite coating was tested in a 3.5% NaCl solution. The water permeation process was analyzed by the changes in the impedance modulus, porosity, and breakpoint frequency of the composite coating. The experimental results show that the water permeability of aged RTV decreases first and then increases with the increase in the composite proportion of f-TNS. When the composite proportion of TNS was 0.3 wt.%, the composite sample had the minimum water permeability and the best resistance to NO₂ corrosion. The effect of TNS on the NO₂ aging resistance of RTV composites and its mechanism were studied by SEM, FT-IR, and XPS. The impedance modulus and porosity of the aged 0.3% f-TNS/RTV, respectively, were 1.82 × 10⁷ Ω cm² and 0.91 × 10⁻⁴%, which increased by 2.23 times and decreased by 0.37 times, respectively, compared with the values of aged pure RTV sample. In addition, the breakpoint frequency of the aged 0.3% f-TNS/RTV also significantly reduced to 11.3 Hz, whereas it was 35 Hz in aged pure RTV. Full article