Abstract The heterogeneity in triple-negative breast cancer (TNBC) is one of the classical characteristics that contribute to its aggressiveness. The absence of oestrogen, progesterone, and low expression of HER2 receptors making chemotherapy is the only therapeutic mainstay in TNBC. Displaying high sensitivity to chemotherapy, disease recurrence is often a common event in TNBC patients too. Transforming Growth Factor β (TGFβ) is a growth factor ligand that releases cytokines highly reported in TNBC progression and response to drugs. The distinctive roles of molecular mechanisms in TNBC development between TGFβ isoforms are not fully established. Therefore, this study aimed to elucidate the cryptic intra-tumoral transcriptomic characteristics of each isoform (TGFβ1, TGFβ2, TGFβ3) from publicly available TNBC GEO datasets (GSE58812, GSE76124, GSE83937, and GSE95700). A total of 486 TNBC samples were stratified to represent TGFβ1-high versus TGFβ1-low, TGFβ2-high versus TGFβ2-low, and TGFβ3-high versus TGFβ3-low. The differential gene expression analysis showed distinct genes being expressed downstream to each isoform (TGFβ1-high–573 genes; TGFβ2-high–41 genes; TGFβ3-high–36). Interestingly, gene ontology and pathway analysis exhibited similar enrichment of the metabolic, cellular polarity, and Rap1 signalling pathways, all of which play critical roles in cancer progression through interplay crosstalk, represented in all isoforms. Some of the highlighted gene signatures were shown to possess clinical relevance in TNBC samples; each represents either protective or poorer prognostic effects, delineating potential targetable genes with diagnostic and prognostic values. This data offers a platform to explore further the roles of each isoform for better stratifying TNBC patients for treatment invention strategies.
Calum J. Pritchard, Nabeil K. G. Salama, Iain Berrill
et al.
Abstract Minimum landing sizes are a fisheries management tool conventionally used to exclude juveniles from fisheries. Harvest slot limits (HSL) are an alternative fisheries management tool used to exclude both juveniles and larger individuals from a fishery through the implementation of both minimum and maximum landing sizes. However, fishery‐dependent data from HSL‐managed fisheries are only representative of a small portion of the population. These data do not meet the requirements for conventional stock assessments nor harvest control rules, so these fisheries cannot be assessed without additional and expensive fishery‐independent data. The objective of this research was to develop a novel harvest control rule able to produce catch advice for fisheries managed by HSL using fishery‐dependent data. The SlotLim method, and corresponding R package, were developed and applied to the data‐limited Scottish live ballan wrasse Labrus bergylta fishery. Within SlotLim, the advised catch is a product of the previous catch and two multipliers: the targeted biomass adjustment (TBA) and size adherence multiplier (SAM). The TBA assesses the rate of change in an abundance or biomass index, adjusted for the proportion of the population targeted by HSL. The SAM assesses fishers' compliance with HSL. The methodology follows a simple premise: the advised catch increases with increasing abundance/biomass indices and adherence to HSL. The minimum data requirements are two consecutive years of catch, length frequency and an abundance or biomass index (all from fishery‐dependent sources), species‐specific growth rate coefficients and the natural mortality rate. The SlotLim method advised catch for a reduction in catch by 17% for the Scottish ballan wrasse fishery due to an observed reduction in abundances indices and non‐adherence to maximum landing sizes. Solution. The SlotLim method allows HSL‐managed fisheries to be assessed at limited expense, contributing to the continued sustainable use of these resources. HSL may also be considered a viable strategy for other data‐limited fisheries upon the availability of this harvest control rule.
Blood and Other Body Fluids is the first of the biological handbooks to appear under the general direction of the Committee on Biological Handbooks, Federation of American Societies for Experimental Biology. This volume, however, does not inaugurate a new series, but is in fact a continuation of the handbooks prepared under the auspices of the National Academy of Sciences—National Research Council. This handbook presents comprehensive data on blood and other body fluids specifically compiled for reference purposes. The material is conveniently organized in the form of tables, graphs, diagrams, nomograms and line charts.
Abstract Cryogenic electron microscopy (cryoEM) has revolutionized structural biology by enabling atomic-resolution visualization of biomacromolecules. To automate atomic model building from cryoEM maps, artificial intelligence (AI) methods have emerged as powerful tools. Although high-quality, task-specific datasets play a critical role in AI-based modeling, assembling such resources often requires considerable effort and domain expertise. We present CryoDataBot, an automated pipeline that addresses this gap. It streamlines data retrieval, preprocessing, and labeling, with fine-grained quality control and flexible customization, enabling efficient generation of robust datasets. CryoDataBot’s effectiveness is demonstrated through improved training efficiency in U-Net models and rapid, effective retraining of CryoREAD, a widely used RNA modeling tool. By simplifying the workflow and offering customizable quality control, CryoDataBot enables researchers to easily tailor dataset construction to the specific objectives of their models, while ensuring high data quality and reducing manual workload. This flexibility supports a wide range of applications in AI-driven structural biology.
The free-form single-layer reticulated shell structure has the characteristics of complex shape, a high degree of static indeterminacy, and difficult node positioning in the construction process, and the nodal deviations that may occur in the construction stage have a significant impact on the reliability performance of the structure. In order to evaluate the influence of the nodal deviation on the reliability performance of the structure in the process of shape optimization, this paper takes the free-form surface of the rectangular plane as the initial structure. Shape optimization is carried out with the objective function of minimizing the strain energy under the uniform vertical load, and the influence of the nodal deviation on the reliability performance of the optimized structure is performed by analyzing changes in the structural response’s probability density function (PDF). The elastic modulus, yield strength, and nodal deviation of the material were selected as the basic random variables, and the PDF of the structural response was calculated using the probability density evolution method. In the case of considering and ignoring the nodal deviation, respectively, the PDF of the maximum displacement response of the structure under the same iteration step is calculated and compared. The results indicate that compared with the initial structure, the reliability performance of the optimized structure is significantly less sensitive to node deviations.
Reactive Black 5 (RB-5) dye is extensively used in industries such as textile, paper, and leather, raising environmental concerns due to its persistence and adverse effects. This study aimed to develop efficient and eco-friendly strategies for RB-5 dye removal from industrial wastewater. RB-5 dye-degrading bacteria, namely NAF1, NAF2, NAF3, and NAF4, were isolated from soil contaminated with textile effluents. Evaluation of their decolorization potential revealed NAF4 as the most effective, achieving a decolorization percentage of 89%, followed by NAF3 and the co-culture at 75% and 73%, respectively. NAF2 exhibited the lowest decolorization potential. The isolate NAF4 showed significant production of tyrosinase and laccase enzymes, with lower quantities of lignin peroxidase and azoreductase. Phylogenetic analysis confirmed the identities of the isolates as Bacillus, Pseudomonas, Escherichia, and Citrobacter. The decolorization potential exhibited by Bacillus wiedmannii NAF4 has instigated the investigation of its capacity to secrete degradative enzymes implicated in the breakdown of azo dyes. Substantial enzyme production was observed over a duration of 192 hours. The biodegradation potential of B. wiedmannii strain NAF4 for RB-5 dye was assessed using Surface Response Optimization (SRO) modeling. The optimized conditions for RB-5 degradation were determined to be an agitation speed of 115.777 rpm, pH of 7.449, inoculum size of 12.255, and temperature of 29.74°C. The SRO model exhibited high statistical significance with an F-value of 53.30 and low p-values (<0.0001), as well as a correlation coefficient (R2) value of 0.9813. Validation studies confirmed the adequacy and precision of the model. The maximum RB-5 degradation achieved was 90.2291%. Three-dimensional plots visually represented the validated optimum conditions of variables and responses. The successful application of Response Surface Methodology (RSM) as an optimization tool highlights its effectiveness in enhancing degradation processes. This study provides insights into the potential applicability of RSM for optimizing degradation processes in various contexts. The developed eco-friendly strategies offer promising solutions for RB-5 dye removal from industrial wastewater, mitigating its environmental impact.In conclusion, the application of Response Surface Methodology (RSM) as an optimization tool proved effective in maximizing the degradation process by optimizing the degradation parameters. The success of this approach suggests its potential applicability in other contexts to enhance degradation processes.
Karosham Diren Reddy, Dikaia Xenaki, Ian M. Adcock
et al.
<b>Background:</b> Chronic obstructive pulmonary disease (COPD) is characterized by progressive and incurable airflow obstruction and chronic inflammation. Both TGF-β1 and CXCL8 have been well described as fundamental to COPD progression. DNA methylation and histone acetylation, which are well-understood epigenetic mechanisms regulating gene expression, are associated with COPD progression. However, a deeper understanding of the complex mechanisms associated with DNA methylation, histone post-translational changes and RNA methylation in the context of regulatory pathways remains to be elucidated. We here report on how DNA methylation and histone acetylation inhibition differentially affect CXCL8 signaling in primary human non-COPD and COPD airway cells. <b>Methods:</b> Airway smooth muscle (ASM) cells, a pivotal cell type in COPD, were isolated from the small airways of heavy smokers with and without COPD. Histone acetylation and DNA methylation were inhibited before the TGF-β1 stimulation of cells. Subsequently, CXCL8 production and the abundance and activation of pertinent transcription regulatory proteins (NF-κB, p38 MAPK and JNK) were analyzed. <b>Results:</b> TGF-β1-stimulated CXCL8 release from ASM cells from ‘healthy’ smoker subjects was significantly modulated by DNA methylation (56.32 pg/mL and 56.60 pg/mL) and acetylation inhibitors (27.50 pg/mL and 48.85 pg/mL) at 24 and 48 h, respectively. However, modulation via the inhibition of DNA methylation (34.06 pg/mL and 43.18 pg/mL) and acetylation (23.14 pg/mL and 27.18 pg/mL) was observed to a lesser extent in COPD ASM cells. These changes were associated with differences in the TGF-β1 activation of NF-κB and MAPK pathways at 10 and 20 min. <b>Conclusions:</b> Our findings offer insight into differential epigenetics in controlling COPD ASM cells and provide a foundation warranting future studies on epigenetic differences associated with COPD diagnosis. This would provide a scope for developing therapeutic interventions targeting signaling and epigenetic pathways to improve patient outcomes.
Samuel V. Hulse, Janis Antonovics, Michael E. Hood
et al.
Abstract Host‐shifts, where pathogens jump from an ancestral host to a novel host, can be facilitated or impeded by standing variation in disease resistance, but only if resistance provides broad‐spectrum general resistance against multiple pathogen species. Host resistance comes in many forms and includes both general resistance, as well as specific resistance, which may only be effective against a single pathogen species or even genotype. However, most evolutionary models consider only one of these forms of resistance, and we have less understanding of how these two forms of resistance evolve in tandem. Here, we develop a model that allows for the joint evolution of specific and general resistance and asks if the evolution of specific resistance drives a decrease in the evolution of general resistance. We also explore how these evolutionary outcomes affect the risk of foreign pathogen invasion and persistence. We show that in the presence of a single endemic pathogen, the two forms of resistance are strongly exclusionary. Critically, we find that specific resistance polymorphisms can prevent the evolution of general resistance, facilitating the invasion of foreign pathogens. We also show that specific resistance polymorphisms are a necessary condition for the successful establishment of foreign pathogens following invasion, as they prevent the exclusion of the foreign pathogen by the more transmissible endemic pathogen. Our results demonstrate the importance of considering the joint evolution of multiple forms of resistance when evaluating a population's susceptibility to foreign pathogens.
Marie V. Brasseur, Jonas J. Astrin, Matthias F. Geiger
et al.
Abstract Mitochondrial DNA (mtDNA) sequences are often found as byproducts in next‐generation sequencing (NGS) datasets that were originally created to capture genomic or transcriptomic information of an organism. These mtDNA sequences are often discarded, wasting this valuable sequencing information. We developed MitoGeneExtractor, an innovative tool which allows to extract mitochondrial protein coding genes (PCGs) of interest from NGS libraries through multiple sequence alignments of sequencing reads to amino acid references. General references, for example on order level are sufficient for mining mitochondrial PCGs. In a case study, we applied MitoGeneExtractor to recently published genomic datasets of 1993 birds and were able to extract complete or nearly complete sequences for all 13 mitochondrial PCGs for a large proportion of libraries. Compared to an existing assembly guided sequence reconstruction algorithm, MitoGeneExtractor was faster and substantially more sensitive. We compared COI sequences mined with MitoGeneExtractor to COI databases. Mined sequences show a high sequence similarity and correct taxonomic assignment between the recovered sequence and the assigned morphospecies in most samples. In some cases of incongruent taxonomic assignments, we found evidence for contamination in NGS libraries. MitoGeneExtractor allows a fast extraction of mitochondrial PCGs from a wide range of NGS datasets. We recommend to routinely harvest and curate mitochondrial sequence information from genomic resources. MitoGeneExtractor output can be used to identify contaminated NGS libraries and to validate the species identity of the sequenced animal based on the extracted COI sequences.
Petros Petrounias, Panagiota P. Giannakopoulou, Aikaterini Rogkala
et al.
This study was based on the reduction of the extraction of natural resources and, at the same time, was focused on the use of by-products and various wastes in construction applications by following the principles of circular economy. Sterile natural rocks (limestones, basalts), industrial by-products (slags), hotel construction wastes (bathroom wastes) and electronic wastes (e-wastes) were tested for pervious concrete aggregates. For this reason, ten concrete specimens were prepared and tested petrographically, structurally, and physically. The physical properties of the tested raw materials directly depended on their petrographic characteristics and played crucial role for the permeability of the produced concrete specimens, for their mechanical behavior, and for the freeze–thaw test results. Generally, from this study, strong encouraging results were achieved as concrete made by variable wastes and by-products can be compatible for concrete production as they show similar performance both in the mechanical strength test and in the freeze–thaw test with those made by natural aggregates. Another goal of this study was to recommend to other researchers the extended use of by-products, construction wastes, and e-wastes as concrete aggregates for producing eco-friendly constructions.
Cancer stem cells play crucial roles in colorectal cancer (CRC) tumorigenesis and treatment response. This study aimed to determine the value of the mRNA stemness index (mRNAsi) in CRC and introduce a stemness-related classification to predict the outcome of patients. mRNAsi scores and RNA sequence data of CRC patients were analyzed. We found that high mRNAsi scores were related to early-stage CRC and a better patient prognosis. Two stemness-based subtypes (subtype I and II) were identified. Patients in subtype I presented a significantly better prognosis than those in subtype II. Patients in these two subtype groups presented significantly different tumor immunity scores and immune cell infiltration patterns. Genomic variations revealed that patients in subtype I had a lower tumor mutation burden than those in subtype II. A three-gene stemness subtype predictor was established, showing good diagnostic value in discriminating patients in different subtypes. A prognostic signature based on five stemness-related genes was established and validated in two independent cohorts and clinical samples, showing a better predictive performance than other clinical parameters. We concluded that mRNAsi scores were associated with the clinical outcome in CRC patients. The stemness-related classification was a promising prognostic predictor for CRC patients.
Tomoaki Mori, Kosuke Takenaka, Fumiya Domoto
et al.
Abstract Objective Tomato yellow leaf curl virus (TYLCV) is one of the pathogens severely damaging tomato crops. Therefore, methods to treat or prevent TYLCV infection need to be developed. For this purpose, a method to conveniently and quickly assess infection of tomatoes by TYLCV is desired. In the present study, we established a quick method to evaluate TYLCV infection using cotyledons of Micro-Tom, a miniature tomato cultivar. Results First, we constructed a binary plasmid harboring 1.5 copies of the TYLCV genome and transformed Agrobacterium with the plasmid. By injecting agroinoculum from the resulting transformant into the branches of Micro-Tom, we confirmed the susceptibility of Micro-Tom to TYLCV. To shorten the evaluation process of TYLCV infection further, we agroinoculated cotyledons of Micro-Tom 10 days after sowing seeds. We consistently observed typical symptoms of TYLCV infection on true leaves 10 days after agroinoculation. Molecular analysis detected TYLCV progeny DNA in all leaves demonstrating symptoms 6 days after agroinoculation. Therefore, our new protocol enabled assessment of TYLCV infection within 20 days after sowing seeds. Thus, agroinoculation of Micro-Tom cotyledons will accelerate the process of screening TYLCV-resistant Micro-Toms and enable screening of larger numbers of plants more quickly, contributing to the development of TYLCV-resistant tomatoes.
Mrinmay Kumar Mallik, Kusum Kapila, Asit Kumar Mohanty
et al.
Background: Early detection of pancreatic adenocarcinomas is essential for improving survival. In this regard, endoscopic ultrasound-guided fine-needle aspiration cytology (EUS-FNAC) has established itself as the method of choice for its ability to target lesions smaller than those which could be targeted by the traditional imaging methods like transabdominal ultrasound. Identifying these tumors correctly on FNA may be challenging because pancreatic adenocarcinomas may show a wide range of morphological features and the presence of contaminants from the gastrointestinal tract may show up as potential pitfalls. This study presents detailed cytomorphological analyses of 59 cases reported as pancreatic adenocarcinomas on smears and cell blocks. The clinical and histopathology follow-up data wherever available have also been presented. Materials and Methods: EUS-FNAC smears and cell blocks from cases reported as pancreatic adenocarcinomas were retrospectively evaluated with individual assessments of a range of features related to cellularity, cellular arrangement, cytoplasmic qualities, and nuclear features. Aspirates from peripancreatic lymph nodes, histopathology sections, and clinical records were reviewed wherever available. Results: Nonneoplastic cells like pancreatic ductal cells and acinar cells, duodenal, and gastric epithelia were detected along with neoplastic cells showing a wide range of variations in different cytomorphological characters. Often, a mixture of features was noted in the same case. Cell block preparations served as useful adjuncts since they made it possible to render unequivocal diagnoses of malignancies in cases where smears were hypocellular. Conclusion: The study creates a useful knowledge base of cytomorphological features of pancreatic adenocarcinomas.
Florian Weinberger, Swantje Sundt, Nadja Staerck
et al.
Beach visitors rate beach quality in large part by its appearance. Removal of natural beach litter (called beach wrack) has, therefore, high priority for beach managers in coastal areas dependent on revenues from tourism. Focusing on the German Baltic Sea coast, the amount of beach wrack has increased by a factor of approximately 3.4 between 1977 and 2012/2013. At the same time, the composition of macrophyte communities underwent a severe change from late successional stages (eelgrass and bladder wrack) toward more ephemeral communities. Correspondingly, the contribution of bladder wrack to seaweed litter alone dropped from 75% in 1977 to 18.1% today, while the contribution of ephemeral and nutrient-opportunistic seaweeds increased by a factor larger than 6.2 to approximately 44%. Such seaweed opportunists could have a higher potential for olfactorial nuisance than late successional macrophytes. To test this hypothesis, odors extracted from equal amounts of nutrient-opportunistic and non-opportunistic species that had been partially degraded under equal conditions were compared in a public survey. Participants graded the smell of opportunistic species, in particular Ceramium tenuicorne, consistently as more intense and less pleasant than the odor of non-opportunistic species. The particularly high potential of Ceramium litter and the relatively lower potential of eelgrass litter for deterrence were confirmed in field experiments. We conclude that the documented compositional shift in macrophyte communities at German Baltic Sea coasts since the onset of eutrophication has caused a shift of beach wrack composition toward species with a higher potential for olfactorial deterrence, which could explain recent concerns of beach managers about beach wrack despite the limited increase of biomass in the study area.