Browse Articles
Discover research articles across all indexed journals
The brain prioritizes the basic level of object category abstraction
Comparison of oxidative stress status in the kidney tissue of male rats treated with paraquat and nanoparaquat
Robust proteome profiling of cysteine-reactive fragments using label-free chemoproteomics
Abstract Identifying pharmacological probes for human proteins represents a key opportunity to accelerate the discovery of new therapeutics. High-content screening approaches to expand the ligandable proteome offer the potential to expedite the discovery of novel chemical probes to study protein function. Screening libraries of reactive fragments by chemoproteomics offers a compelling approach to ligand discovery, however, optimising sample throughput, proteomic depth, and data reproducibility remains a key challenge. We report a versatile, label-free quantification proteomics platform for competitive profiling of cysteine-reactive fragments against the native proteome. This high-throughput platform combines SP4 plate-based sample preparation with rapid chromatographic gradients. Data-independent acquisition performed on a Bruker timsTOF Pro 2 consistently identified ~23,000 cysteine sites per run, with a total of ~32,000 cysteine sites profiled in HEK293T and Jurkat lysate. Crucially, this depth in cysteinome coverage is met with high data completeness, enabling robust identification of liganded proteins. In this study, 80 reactive fragments were screened in two cell lines identifying >400 ligand-protein interactions. Hits were validated through concentration-response experiments and the platform was utilised for hit expansion and live cell experiments. This label-free platform represents a significant step forward in high-throughput proteomics to evaluate ligandability of cysteines across the human proteome.
Wavelength-tunable infrared metasurfaces with chiral bound states in the continuum
Prognosis of invasive encapsulated follicular variant and classical papillary thyroid carcinoma: a propensity score-matched study using the SEER database
Harnessing orbital Hall effect in spin-orbit torque MRAM
AbstractSpin-Orbit Torque (SOT) Magnetic Random-Access Memory (MRAM) devices offer improved power efficiency, nonvolatility, and performance compared to static RAM, making them ideal, for instance, for cache memory applications. Efficient magnetization switching, long data retention, and high-density integration in SOT MRAM require ferromagnets (FM) with perpendicular magnetic anisotropy (PMA) combined with large torques enhanced by Orbital Hall Effect (OHE). We have engineered a PMA [Co/Ni]3 FM on selected OHE layers (Ru, Nb, Cr) and investigated the potential of theoretically predicted larger orbital Hall conductivity (OHC) to quantify the torque and switching current in OHE/[Co/Ni]3 stacks. Our results demonstrate a ~30% enhancement in damping-like torque efficiency with a positive sign for the Ru OHE layer compared to a pure Pt layer, accompanied by a ~20% reduction in switching current for Ru compared to pure Pt across more than 250 devices, leading to more than a 60% reduction in switching power. These findings validate the application of Ru in devices relevant to industrial contexts, supporting theoretical predictions regarding its superior OHC. This investigation highlights the potential of enhanced orbital torques to improve the performance of orbital-assisted SOT-MRAM, paving the way for next-generation memory technology.
Effect of cobalt ions doping on morphology and electrochemical properties of hydroxyapatite coatings for biomedical applications
Explainable quality assessment of effective aligned skeletal representations for martial arts movements by multi-machine learning decisions
Anti-dendrite separator interlayer enabling staged zinc deposition for enhanced cycling stability of aqueous zinc batteries
Structural dimensions of physical function and their associations with working memory in adults aged 60–74 years
Response of carbon storage to land use change and multi-scenario predictions in Zunyi, China
Antiferromagnetic semimetal terahertz photodetectors enhanced through weak localization
Optimizing concrete crack detection an echo state network approach with improved fish migration optimization
Impaired cardiac pumping function and increased afterload as determinants of early hemodynamic alterations in Cushing disease
PhpCNF-Y transcription factor infiltrates heterochromatin to generate cryptic intron-containing transcripts crucial for small RNA production
AbstractThe assembly of repressive heterochromatin in eukaryotic genomes is crucial for silencing lineage-inappropriate genes and repetitive DNA elements. Paradoxically, transcription of repetitive elements within constitutive heterochromatin domains is required for RNA-based mechanisms, such as the RNAi pathway, to target heterochromatin assembly proteins. However, the mechanism by which heterochromatic repeats are transcribed has been unclear. Using fission yeast, we show that the conserved trimeric transcription factor (TF) PhpCNF-Y complex can infiltrate constitutive heterochromatin via its histone-fold domains to transcribe repeat elements. PhpCNF-Y collaborates with a Zn-finger containing TF to bind repeat promoter regions with CCAAT boxes. Mutating either the TFs or the CCAAT binding site disrupts the transcription of heterochromatic repeats. Although repeat elements are transcribed from both strands, PhpCNF-Y-dependent transcripts originate from only one strand. These TF-driven transcripts contain multiple cryptic introns which are required for the generation of small interfering RNAs (siRNAs) via a mechanism involving the spliceosome and RNAi machinery. Our analyses show that siRNA production by this TF-mediated transcription pathway is critical for heterochromatin nucleation at target repeat loci. This study reveals a mechanism by which heterochromatic repeats are transcribed, initiating their own silencing by triggering a primary cascade that produces siRNAs necessary for heterochromatin nucleation.
Unveiling chemical industry secrets: Insights gleaned from scientific literatures that examine internal chemical corporate documents—A scoping review
Objective Examine peer-reviewed scientific articles that used internal industry documents in the chemical sector to reveal corporate influence. Summarize sources of internal documents used in prior scientific papers to identify ongoing corporate strategies within the chemical field. Compare the corporate strategies identified in the chemical sector with the ones identified already identified in the pharmaceutical sector. Propose a theoretical framework for categorizing and examining the different form of corporate capture at play. Design Performed a scoping review to pinpoint scientific papers employing internal industry/corporate documents within the chemical sector. Methods We conducted a systematic search using broad and case study-derived keywords, detailed in the S1 Appendix. This resulted in 351 sources from 28 databases, encompassing peer-reviewed articles analyzing internal documents of chemical corporations. We complemented our efforts with a snowball sampling method to uncover additional case studies and journal articles not initially captured by our search. Results were categorized and analyzed using Marc-Andre Gagnon and Sergio Sismondo’s ghost management framework. Results The final results included and analyzed 18 scientific papers. Legal proceedings served as the primary source of internal document data for all examined articles. We uncovered and categorized dynamic strategies employed by chemical corporations to protect and advance their interests, including scientific capture (n = 16), regulatory capture (n = 15), professional capture (n = 7), civil society capture (n = 6), media capture (n = 4), legal capture (n = 4), technological capture (n = 3), and market capture (n = 2). Comparative analysis The limited scientific literature meeting our criteria confirms early findings by Wieland et al, highlighting a research gap in the chemical industry. Our analysis, building on the ghost-management framework, shows a different emphasis in the way internal documents were used in scientific literature to understand corporate strategies at play in the chemical sector as compared to the pharmaceutical sector. In contrast to Gagnon and Dong’s pharmaceutical corporate capture review, which identified 37 papers before 2022, our chemical industry findings reveal a lower count, with only 18 papers identified. Notably, the vast majority of the papers in both sectors shows an emphasis on analyzing strategies used for scientific capture. However, the area of regulatory capture reveals a significant distinction: only 6 of the 37 articles related to the pharmaceutical industry analyzed this dimension, as compared to 15 of the 18 articles related to the chemical industry. This body of work suggests that existing research on the chemical industry is particularly concerned with analyzing how the sector navigates and circumvents regulatory oversight. Both industries employ strategies involving conflicts of interest and the legitimization of their actions to shield themselves from public policy scrutiny and protect their interests. However, their goals seem to be significantly different. The scientific literature analyzing the pharmaceutical industry’s internal document tends to identify strategies maximizing profits through the biased promotion of health products, whereas the scientific literature analyzing the chemical industry’s internal documents is more inclined in identifying strategies institutionalizing ignorance about existing risks, evading accountability, and preventing regulatory actions. Strengths Our scoping review shows how internal documents can reveal how the chemical industry strategically institutionalizes ignorance to manage business risks. It exposes intentional efforts by chemical corporations to promote ignorance and foster conflicts of interest, thereby legitimizing their business models and safeguarding corporate interests. We shared our research findings on the Dataverse/ Borealis platform (https://doi.org/10.5683/SP3/EOIOAU), making them accessible for future studies to apply the same analytical framework seamlessly. Limitations We excluded papers that did not meet our research criteria, prioritizing those that analyzed internal corporate documents for uncovering covert ghost management captures. Beyond scientific literature, various grey literature sources have conducted quality investigations on ghost management strategies in the chemical industry, and many leaked internal documents in the chemical industry, often available through toxicdocs.org, were not analyzed in the scientific literature. Also, market concentration and other corporate captures can be investigated using publicly available resources. Despite searching scientific papers in various languages, no relevant publications were found outside of English. This presents an opportunity for future research to conduct a separate scoping review.
MANF overexpression ameliorates oxidative stress-induced apoptosis of human nucleus pulposus cells by facilitating mitophagy through promoting MFN2 expression
Effectiveness of tacrolimus therapy in refractory ulcerative colitis compared to infliximab with propensity score matching
AbstractThere is insufficient evidence comparing the outcomes of tacrolimus-based remission induction therapy with infliximab in refractory ulcerative colitis (UC) and evidence regarding optimal strategies after tacrolimus-based remission induction therapy. We conducted a multi-institutional retrospective study of patients with UC treated with tacrolimus or infliximab between January 2010 and March 2019. The proportion of clinical remission at week 8 and cumulative colectomy-free rate were examined using propensity score matching analysis. The predictors for colectomy after tacrolimus induction were also investigated. Ninety patients in the tacrolimus group and 151 in the infliximab group were enrolled. The proportion of patients in clinical remission at week 8 was 65.2% in the matched tacrolimus group and 37.3% in the matched infliximab group (P = 0.0016), and the long-term colectomy-free rate was lower in the matched tacrolimus group than in the matched infliximab group (P = 0.0003). After clinical remission with tacrolimus, a serum albumin level of ≤ 3.5 g/dL at week 8 was extracted as a factor predicting colectomy (area under the curve: 0.94). Tacrolimus showed a higher remission induction effect for UC compared to infliximab. However, a high rate of colectomy after transition to maintenance treatment was found to be a concern for tacrolimus therapy.
Molecular insights into a distinct class of terpenoid cyclases
Patterns and predictors of mortality in the first 24 hours of admission among children aged 1–59 months admitted at a Regional Referral Hospital in South Western Uganda
Most deaths among children under 5 years occur within the first 24 hours of hospital admission from preventable causes such as diarrhea, pneumonia, malaria, and HIV/AIDS. The predictors of these deaths are not yet well documented in our setting. This study aimed to describe the patterns and predictors of these mortalities among children aged 1–59 months at a regional hospital in South Western Uganda. We conducted a prospective cohort study among 208 children aged 1–59 months admitted to Mbarara Regional Referral Hospital. The mortality rate within the first 24 hours was 7.7% (95% CI 4–12) and the median time to death was 7.3(2.62–8.75) hours. Most deaths occurred in infants, with severe pneumonia, severe acute malnutrition, and malaria as leading causes. Factors predicting mortality included admission during the night (AHR: 3.7, 95% CI 1.02–13.53, p-value 0.047) and abnormal neutrophil count(AHR: 3.5, 95% CI 1.10–11.31, p-value 0.034). The study highlights the importance of timely interventions, particularly for infants, and suggests extra monitoring for those admitted at night or with abnormal neutrophil counts.