bluuebunny/crossref_metadata_2025 huggingface dataset:
Galectin-3 promotes secretion of proteases that decrease epithelium integrity in human colon cancer cells
Authors: Li Shun , Pritchard David Mark , Yu Lu-Gang
Published: April 2023

Galectin-3 is a galactoside-binding protein that is commonly overexpressed in many epithelial cancers. It is increasingly recognized as a multi-functional, multi-mode promoter in cancer development, progression, and metastasis. This study reports that galectin-3 secretion by human colon cancer cells induces cancer cell secretion, in an autocrine/paracrine manner, of a number of proteases including cathepsin-B, MMP-1 and MMP-13. The secretion of these proteases causes disruption of epithelial monolayer integrity, increases its permeability and promotes tumour cell invasion. This effect of galectin-3 is shown to be mediated through induction of cellular PYK2-GSK3α/β signalling and can be prevented by the presence of galectin-3 binding inhibitors. This study thus reveals an important mechanism in galectin-3-mediated promotion of cancer progression and metastasis. It provides further evidence to the increased realization of galectin-3 as a potential therapeutic target for the treatment of cancer.
Previously uncharacterized rectangular bacterial structures in the dolphin mouth
Authors: Dudek Natasha K. , Galaz-Montoya Jesus G. , Shi Handuo , Mayer Megan , Danita Cristina , Celis Arianna I. , Viehboeck Tobias , Wu Gong-Her , Behr Barry , Bulgheresi Silvia , Huang Kerwyn Casey , Chiu Wah , Relman David A.
Published: April 2023

Much remains to be explored regarding the diversity of uncultured, host-associated microbes. Here, we describe rectangular bacterial structures (RBSs) in the mouths of bottlenose dolphins. DNA staining revealed multiple paired bands within RBSs, suggesting the presence of cells dividing along the longitudinal axis. Cryogenic transmission electron microscopy and tomography showed parallel membrane-bound segments that are likely cells, encapsulated by an S-layer-like periodic surface covering. RBSs displayed unusual pilus-like appendages with bundles of threads splayed at the tips. We present multiple lines of evidence, including genomic DNA sequencing of micromanipulated RBSs, 16S rRNA gene sequencing, and fluorescence in situ hybridization, suggesting that RBSs are bacterial and distinct from the genera Simonsiella and Conchiformibius (family Neisseriaceae), with which they share similar morphology and division patterning. Our findings highlight the diversity of novel microbial forms and lifestyles that await characterization using tools complementary to genomics such as microscopy.
Vibrio cholerae biofilms use modular adhesins with glycan-targeting and nonspecific surface binding domains for colonization
Authors: Huang Xin , Nero Thomas , Weerasekera Ranjuna , Matej Katherine H. , Hinbest Alex , Jiang Zhaowei , Lee Rebecca F. , Wu Longjun , Chak Cecilia , Nijjer Japinder , Gibaldi Isabella , Yang Hang , Gamble Nathan , Ng Wai-Leung , Malaker Stacy A. , Sumigray Kaelyn , Olson Rich , Yan Jing
Published: April 2023

Bacterial biofilms are formed on environmental surfaces and host tissues, and facilitate host colonization and antibiotic resistance by human pathogens. Bacteria often express multiple adhesive proteins (adhesins), but it is often unclear whether adhesins have specialized or redundant roles. Here, we show how the model biofilm-forming organism Vibrio cholerae uses two adhesins with overlapping but distinct functions to achieve robust adhesion to diverse surfaces. Both biofilm-specific adhesins Bap1 and RbmC function as a “double-sided tape”: they share a β-propeller domain that binds to the biofilm matrix exopolysaccharide, but have distinct environment-facing domains. Bap1 adheres to lipids and abiotic surfaces, while RbmC mainly mediates binding to host surfaces. Furthermore, both adhesins contribute to adhesion in an enteroid monolayer colonization model. We expect that similar modular domains may be utilized by other pathogens, and this line of research can potentially lead to new biofilm-removal strategies and biofilm-inspired adhesives.
Electrochemistry-assisted selective butadiene hydrogenation with water
Authors: Yan Yong-Qing , Chen Ya , Wang Zhao , Chen Li-Hua , Tang Hao-Lin , Su Bao-Lian
Published: April 2023

Alkene feedstocks are used to produce polymers with a market expected to reach 128.4 million metric tons by 2027. Butadiene is one of the impurities poisoning alkene polymerization catalysts and is usually removed by thermocatalytic selective hydrogenation. Excessive use of H2, poor alkene selectivity and high operating temperature (e.g. up to 350 °C) remain the most significant drawbacks of the thermocatalytic process, calling for innovative alternatives. Here we report a room-temperature (25~30 °C) electrochemistry-assisted selective hydrogenation process in a gas-fed fixed bed reactor, using water as the hydrogen source. Using a palladium membrane as the catalyst, this process offers a robust catalytic performance for selective butadiene hydrogenation, with alkene selectivity staying around 92% at a butadiene conversion above 97% for over 360 h of time on stream. The overall energy consumption of this process is 0.003 Wh/mLbutadiene, which is thousands of times lower than that of the thermocatalytic route. This study proposes an alternative electrochemical technology for industrial hydrogenation without the need for elevated temperature and hydrogen gas.
Non-solvent post-modifications with volatile reagents for remarkably porous ketone functionalized polymers of intrinsic microporosity
Authors: Wongwilawan Sirinapa , Nguyen Thien S. , Nguyen Thi Phuong Nga , Alhaji Abdulhadi , Lim Wonki , Hong Yeongran , Park Jin Su , Atilhan Mert , Kim Bumjoon J. , Eddaoudi Mohamed , Yavuz Cafer T.
Published: April 2023

Chemical modifications of porous materials almost always result in loss of structural integrity, porosity, solubility, or stability. Previous attempts, so far, have not allowed any promising trend to unravel, perhaps because of the complexity of porous network frameworks. But the soluble porous polymers, the polymers of intrinsic microporosity, provide an excellent platform to develop a universal strategy for effective modification of functional groups for current demands in advanced applications. Here, we report complete transformation of PIM-1 nitriles into four previously inaccessible functional groups – ketones, alcohols, imines, and hydrazones – in a single step using volatile reagents and through a counter-intuitive non-solvent approach that enables surface area preservation. The modifications are simple, scalable, reproducible, and give record surface areas for modified PIM-1s despite at times having to pass up to two consecutive post-synthetic transformations. This unconventional dual-mode strategy offers valuable directions for chemical modification of porous materials.
Non-functional ubiquitin C-terminal hydrolase L1 drives podocyte injury through impairing proteasomes in autoimmune glomerulonephritis
Authors: Reichelt Julia , Sachs Wiebke , Frömbling Sarah , Fehlert Julia , Studencka-Turski Maja , Betz Anna , Loreth Desiree , Blume Lukas , Witt Susanne , Pohl Sandra , Brand Johannes , Czesla Maire , Knop Jan , Florea Bogdan I. , Zielinski Stephanie , Sachs Marlies , Hoxha Elion , Hermans-Borgmeyer Irm , Zahner Gunther , Wiech Thorsten , Krüger Elke , Meyer-Schwesinger Catherine
Published: April 2023

Little is known about the mechanistic significance of the ubiquitin proteasome system (UPS) in a kidney autoimmune environment. In membranous nephropathy (MN), autoantibodies target podocytes of the glomerular filter resulting in proteinuria. Converging biochemical, structural, mouse pathomechanistic, and clinical information we report that the deubiquitinase Ubiquitin C-terminal hydrolase L1 (UCH-L1) is induced by oxidative stress in podocytes and is directly involved in proteasome substrate accumulation. Mechanistically, this toxic gain-of-function is mediated by non-functional UCH-L1, which interacts with and thereby impairs proteasomes. In experimental MN, UCH-L1 becomes non-functional and MN patients with poor outcome exhibit autoantibodies with preferential reactivity to non-functional UCH-L1. Podocyte-specific deletion of UCH-L1 protects from experimental MN, whereas overexpression of non-functional UCH-L1 impairs podocyte proteostasis and drives injury in mice. In conclusion, the UPS is pathomechanistically linked to podocyte disease by aberrant proteasomal interactions of non-functional UCH-L1.
Nucleocytoplasmic transport of active HER2 causes fractional escape from the DCIS-like state
Authors: Wang Lixin , Paudel B. Bishal , McKnight R. Anthony , Janes Kevin A.
Published: April 2023

Activation of HER2/ErbB2 coincides with escape from ductal carcinoma in situ (DCIS) premalignancy and disrupts 3D organization of cultured breast-epithelial spheroids. The 3D phenotype is infrequent, however, and mechanisms for its incomplete penetrance have been elusive. Using inducible HER2/ErbB2–EGFR/ErbB1 heterodimers, we match phenotype penetrance to the frequency of co-occurring transcriptomic changes and uncover a reconfiguration in the karyopherin network regulating ErbB nucleocytoplasmic transport. Induction of the exportin CSE1L inhibits nuclear accumulation of ErbBs, whereas nuclear ErbBs silence the importin KPNA1 by inducing miR-205. When these negative feedbacks are incorporated into a validated systems model of nucleocytoplasmic transport, steady-state localization of ErbB cargo becomes ultrasensitive to initial CSE1L abundance. Erbb2-driven carcinomas with Cse1l deficiency outgrow less irregularly from mammary ducts, and NLS-attenuating mutants or variants of HER2 favor escape in 3D culture. We conclude here that adaptive nucleocytoplasmic relocalization of HER2 creates a systems-level molecular switch at the premalignant-to-malignant transition.
Dandelion uses the single-cell adaptive immune receptor repertoire to explore lymphocyte developmental origins
Authors: Suo Chenqu , Polanski Krzysztof , Dann Emma , Lindeboom Rik G. H. , Vilarrasa-Blasi Roser , Vento-Tormo Roser , Haniffa Muzlifah , Meyer Kerstin B. , Dratva Lisa M. , Tuong Zewen Kelvin , Clatworthy Menna R. , Teichmann Sarah A.
Published: April 2023

Assessment of single-cell gene expression (single-cell RNA sequencing) and adaptive immune receptor (AIR) sequencing (scVDJ-seq) has been invaluable in studying lymphocyte biology. Here we introduce Dandelion, a computational pipeline for scVDJ-seq analysis. It enables the application of standard V(D)J analysis workflows to single-cell datasets, delivering improved V(D)J contig annotation and the identification of nonproductive and partially spliced contigs. We devised a strategy to create an AIR feature space that can be used for both differential V(D)J usage analysis and pseudotime trajectory inference. The application of Dandelion improved the alignment of human thymic development trajectories of double-positive T cells to mature single-positive CD4/CD8 T cells, generating predictions of factors regulating lineage commitment. Dandelion analysis of other cell compartments provided insights into the origins of human B1 cells and ILC/NK cell development, illustrating the power of our approach. Dandelion is available athttps://www.github.com/zktuong/dandelion.
Pan-cancer analysis reveals IGFL2 as a potential target for cancer prognosis and immunotherapy
Authors: Wang Yuqi , Yuan Hongwei , Yue Genquan , Zhao Lingyan , Xia Yuan , Zhang Nan , Li Hailing , Liu Dongyang , Su Yubo , Wang Haisheng , Gao Yumin
Published: April 2023

Insulin-like growth factor like family member 2 (IGFL2) is a gene in the IGFL family, located on chromosome 19, whose role in cancer is unclear, and the aim of this study was to investigate the relevance of IGFL2 expression, prognosis, immunity, and mutation in pan-cancer. Obtaining information from The Cancer Genome Atlas and The Genotype-Tissue Expression Project (GTEx) databases for expression analysis and combining with The Gene Expression Profile Interaction Analysis database for prognostic aspects. Analysis of immune cell infiltration by TIMER and CIBERSORT algorithms. Calculation of correlation of immune-related genes with IGFL2 expression and tumor mutational burden and microsatellite instability. Mutations and DNA methylation were analyzed using the cBioPortal database and the UALCAN database, and functional enrichment was performed using Gene set enrichment analysis (GSEA). IGFL2 expression is significantly elevated in tumor tissue and high expression has a worse prognosis in most cancers. In immune correlation analysis, it was associated with most immune cells and immune-related genes. In most cancers, IGFL2 methylation is lower and the group with mutations in IGFL2 has a worse prognosis than the normal group. The GSEA analysis showed that IGFL2 was significantly enriched in signaling and metabolism. IGFL2 may be involved in the development of many types of cancer, influencing the course of cancer with different biological functions. It may also be a biomarker for tumor immunotherapy.
EU climate action through an energy poverty lens
Authors: Vandyck Toon , Della Valle Nives , Temursho Umed , Weitzel Matthias
Published: April 2023

Carbon pricing can steer energy choices towards low-carbon fuels and foster energy conservation efforts. Simultaneously, higher fossil fuel prices may exacerbate energy poverty. A just portfolio of climate policies therefore requires a balanced instrument mix to jointly combat climate change and energy poverty. We review recent policy developments in the EU aimed at addressing energy poverty and the social implications of the climate neutrality transition. We then operationalise an affordability-based definition of energy poverty and numerically illustrate that recent EU climate policy proposals risk raising the number of energy poor when not accompanied with complementary measures, while alternative climate policy designs could lift more than 1 million households out of energy poverty through income-targeted revenue recycling schemes. While these schemes have low informational requirements and appear sufficient to avoid exacerbating energy poverty, the findings suggest that more tailored interventions are needed. Finally, we discuss how insights from behavioural economics and energy justice can help shape optimal policy packages and processes.
A longitudinal experiment demonstrates that honey bee colonies managed organically are as healthy and productive as those managed conventionally
Authors: Underwood Robyn M. , Lawrence Brooke L. , Turley Nash E. , Cambron-Kopco Lizzette D. , Kietzman Parry M. , Traver Brenna E. , López-Uribe Margarita M.
Published: April 2023

Honey bee colony management is critical to mitigating the negative effects of biotic and abiotic stressors. However, there is significant variation in the practices implemented by beekeepers, which results in varying management systems. This longitudinal study incorporated a systems approach to experimentally test the role of three representative beekeeping management systems (conventional, organic, and chemical-free) on the health and productivity of stationary honey-producing colonies over 3 years. We found that the survival rates for colonies in the conventional and organic management systems were equivalent, but around 2.8 times greater than the survival under chemical-free management. Honey production was also similar, with 102% and 119% more honey produced in conventional and organic management systems, respectively, than in the chemical-free management system. We also report significant differences in biomarkers of health including pathogen levels (DWV, IAPV,Vairimorpha apis,Vairimorpha ceranae) and gene expression (def-1,hym,nkd,vg). Our results experimentally demonstrate that beekeeping management practices are key drivers of survival and productivity of managed honey bee colonies. More importantly, we found that the organic management system—which uses organic-approved chemicals for mite control—supports healthy and productive colonies, and can be incorporated as a sustainable approach for stationary honey-producing beekeeping operations.
Data integration reveals dynamic and systematic patterns of breeding habitat use by a threatened shorebird
Authors: Ellis Kristen S. , Anteau Michael J. , MacDonald Garrett J. , Swift Rose J. , Ring Megan M. , Toy Dustin L. , Sherfy Mark H. , Post van der Burg Max
Published: April 2023

Incorporating species distributions into conservation planning has traditionally involved long-term representations of habitat use where temporal variation is averaged to reveal habitats that are most suitable across time. Advances in remote sensing and analytical tools have allowed for the integration of dynamic processes into species distribution modeling. Our objective was to develop a spatiotemporal model of breeding habitat use for a federally threatened shorebird (piping plover,Charadrius melodus). Piping plovers are an ideal candidate species for dynamic habitat models because they depend on habitat created and maintained by variable hydrological processes and disturbance. We integrated a 20-year (2000–2019) nesting dataset with volunteer-collected sightings (eBird) using point process modeling. Our analysis incorporated spatiotemporal autocorrelation, differential observation processes within data streams, and dynamic environmental covariates. We evaluated the transferability of this model in space and time and the contribution of the eBird dataset. eBird data provided more complete spatial coverage in our study system than nest monitoring data. Patterns of observed breeding density depended on both dynamic (e.g., surface water levels) and long-term (e.g., proximity to permanent wetland basins) environmental processes. Our study provides a framework for quantifying dynamic spatiotemporal patterns of breeding density. This assessment can be iteratively updated with additional data to improve conservation and management efforts, because reducing temporal variability to average patterns of use may cause a loss in precision for such actions.
Optimization of synergic antibacterial activity of Punica granatum L. and Areca nut (P.G.L.A.N) extracts through response surface methodology
Authors: Gharbani Parvin , Jam Neda , Doshmanfekan Hossein , Mehrizad Ali
Published: April 2023

The primary objective of this study was to evaluate the use of natural compounds as opposed to chemical preservatives. This study employed response methodology to evaluate the synergistic antibacterial effect of Areca nut and Punica granatum L. extract. Independent variables included extract type (Punica granatum L., Areca nut, and their mixture), solvent (water, ethanol, methanol), bacterial type (S. aureus, Salmonella, E. coli), and extract concentration (1, 10, 100 mg/L). The sensitivity was determined using the disk diffusion method, and the diameter of the inhibitory zone was measured. On the specified bacteria, the MIC (minimum inhibitory concentration) and MBC (minimum bactericidal concentration) of each extract were ascertained using the serial dilution method. This study revealed the existence of beneficial synergistic effects between the two extracts. Results indicated that the ethanolic extracts of Punica granatum L. and Areca nut had a synergistic effect on E. coli.
A thermodynamic study on relationship between gas separation properties and microstructure of polyurethane membranes
Authors: Sepehri Sadeghian Mohammad Sajad , Raisi Ahmadreza
Published: April 2023

The lattice fluid (LF) thermodynamic model and extended Vrentas’ free-volume (E-VSD) theory were coupled to study the gas separation properties of the linear thermoplastic polyurethane (TPU) membranes with different chemical structures by analyzing their microstructures. A set of characteristic parameters were extracted using the repeating unit of the TPU samples and led to prediction of reliable polymer densities (AARD < 6%) and gas solubilities. The viscoelastic parameters, which were obtained from the DMTA analysis, were also estimated the gas diffusion vs. temperature, precisely. The degree of microphase mixing based on the DSC analysis was in order: TPU-1 (4.84 wt%) < TPU-2 (14.16 wt%) < TPU-3 (19.92 wt%). It was found that the TPU-1 membrane had the highest degree of crystallinity, but showed higher gas solubilities and permeabilities because this membrane has the least degree of microphase mixing. These values, in combination with the gas permeation results, showed that the content of the hard segment along with the degree of microphase mixing and other microstructural parameters like crystallinity were the determinative parameters.
A Multiple change-point detection framework on linguistic characteristics of real versus fake news articles
Authors: Petrou Nikolas , Christodoulou Chrysovalantis , Anastasiou Andreas , Pallis George , Dikaiakos Marios D.
Published: April 2023

Extracting information from textual data of news articles has been proven to be significant in developing efficient fake news detection systems. Pointedly, to fight disinformation, researchers concentrated on extracting information which focuses on exploiting linguistic characteristics that are common in fake news and can aid in detecting false content automatically. Even though these approaches were proven to have high performance, the research community proved that both the language as well as the word use in literature are evolving. Therefore, the objective of this paper is to explore the linguistic characteristics of fake news and real ones over time. To achieve this, we establish a large dataset containing linguistic characteristics of various articles over the years. In addition, we introduce a novel framework where the articles are classified in specified topics based on their content and the most informative linguistic features are extracted using dimensionality reduction methods. Eventually, the framework detects the changes of the extracted linguistic features on real and fake news articles over the time incorporating a novel change-point detection method. By employing our framework for the established dataset, we noticed that the linguistic characteristics which concern the article’s title seem to be significantly important in capturing important movements in the similarity level of “Fake” and “Real” articles.
Constellation of the endophytic mycobiome in spring and winter wheat cultivars grown under various conditions
Authors: Salamon Sylwia , Mikołajczak Katarzyna , Błaszczyk Lidia
Published: April 2023

The mycobiome is an integral component of every living organism. Among other fungi associated with plants, endophytes are an interesting and favorable group of microorganisms, but information regarding them is still largely unknown. Wheat is the most economically significant and essential crop for global food security, which is exposed to a range of abiotic and biotic stresses. Profiling plants’ mycobiomes can help in sustainable, chemical-reducing wheat production. The main objective of this work is to understand the structure of endogenous fungal communities in winter and spring wheat cultivars growing under different growth conditions. Further, the study attempted to investigate the effect of host genotype, host organs and plant growth conditions on the composition and distribution of fungi in wheat plant tissues. Comprehensive, high throughput analyzes of the diversity and community structure of the wheat mycobiome were performed, complemented by the simultaneous isolation of endophytic fungi, resulting in candidate strains for future research. The findings of the study revealed that the type of plant organs and growth conditions influence the wheat mycobiome. It was also assessed that fungi representing the genera Cladosporium, Penicillium, and Sarocladium form the core mycobiome of Polish spring and winter wheat cultivars. The coexistence of both symbiotic and pathogenic species in the internal tissues of wheat was also observed. Those commonly considered beneficial for plants can be used in further research as a valuable source of potential biological control factors and/or biostimulators of wheat plant growth.
Outcomes of singleton preterm very low birth weight infants born to mothers with pregnancy-induced hypertension
Authors: Kim Hye-Rim , Lee Byoung Kook
Published: April 2023

The association between maternal pregnancy-induced hypertension (PIH) and neonatal mortality and morbidities in preterm infants has not been consistent. This study aimed to evaluate the influence of maternal PIH on mortality and morbidities in singleton infants with very low birth weight born before 30 weeks of gestational age using the Korean Neonatal Network (KNN) database. A total of 5340 singleton infants with very low birth weight were registered in the KNN registry, who were born at 23+0 to 29+6 weeks of gestational age between January 2015 and December 2020. Baseline characteristics and neonatal mortality and morbidities were compared between infants with PIH and non-PIH mothers. After adjustment for potential confounders, infants with PIH mothers had significantly higher odds of respiratory distress syndrome (OR 1.983; 95% CI 1.285–3.061, p = 0.002) and bronchopulmonary dysplasia (OR 1.458; 95% CI 1.190–1.785, p < 0.001), and severe bronchopulmonary dysplasia (OR 1.411; 95% CI 1.163–1.713, p < 0.001) than infants with non-PIH mothers, while there were no significant differences in severe intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity, or death during neonatal intensive care unit admission between infants with PIH and non-PIH mothers. This study showed that preterm infants with PIH mothers had an increased risk of neonatal respiratory morbidities, including respiratory distress syndrome and bronchopulmonary dysplasia.
Predictive value of urinary cell cycle arrest biomarkers for all cause-acute kidney injury: a meta-analysis
Authors: Huang Feng , Zeng Yan , Lv Linghai , Chen Yaoyao , Yan Yan , Luo Laimin , Pan Rong , Jiang Jiaming , Wei Xin
Published: April 2023

The cell cycle arrest markers tissue inhibitor metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) have been identified as potential biomarkers of acute kidney injury (AKI) in critically ill adults in intensive care units and cardiac surgery-associated AKI (CSA-AKI). However, the clinical impact on all-cause AKI remains unclear. Here, we report a meta-analysis performed to evaluate the predictive value of this biomarker for all-cause AKI. The PubMed, Cochrane, and EMBASE databases were systematically searched up to April 1, 2022. We used the Quality Assessment Tool for Diagnosis Accuracy Studies (QUADAS-2) to assess the quality. We extracted useful information from these studies and calculated the sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC). Twenty studies with 3625 patients were included in the meta-analysis. The estimated sensitivity of urinary [TIMP-2] × [IGFBP7] in the diagnosis of all-cause AKI was 0.79 (95% CI 0.72, 0.84), and the specificity was 0.70 (95% CI 0.62, 0.76). The value of urine [TIMP-2] × [IGFBP7] in the early diagnosis of AKI was assessed using a random effects model. The pooled positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were 2.6 (95% CI 2.1, 3.3), 0.31 (95% CI 0.23, 0.40), and 8 (95% CI 6, 13), respectively. The AUROC was 0.81 (95% CI 0.78–0.84). No significant publication bias was observed in eligible studies. Subgroup analysis indicated that the diagnostic value was related to the severity of AKI, time measurement, and clinical setting. This study shows that urinary [TIMP-2] × [IGFBP7] is a reliable effective predictive test for all cause-AKI. However, whether and how urinary [TIMP-2] × [IGFBP7] can be used in clinical diagnosis still requires further research and clinical trials.
Helquat dyes targeting G-quadruplexes as a new class of anti-HIV-1 inhibitors
Authors: Pávová Marcela , Reyes-Gutiérrez Paul Eduardo , Kozák Jaroslav , Dobiaš Juraj , Yurenko Yevgen , Lepšík Martin , Teplý Filip , Weber Jan
Published: April 2023

The secondary structure of nucleic acids containing quartets of guanines, termed G-quadruplexes, is known to regulate the transcription of many genes. Several G-quadruplexes can be formed in the HIV-1 long terminal repeat promoter region and their stabilization results in the inhibition of HIV-1 replication. Here, we identified helquat-based compounds as a new class of anti-HIV-1 inhibitors that inhibit HIV-1 replication at the stage of reverse transcription and provirus expression. Using Taq polymerase stop and FRET melting assays, we have demonstrated their ability to stabilize G-quadruplexes in the HIV-1 long-terminal repeat sequence. Moreover, these compounds were not binding to the general G-rich region, but rather to G-quadruplex-forming regions. Finally, docking and molecular dynamics calculations indicate that the structure of the helquat core greatly affects the binding mode to the individual G-quadruplexes. Our findings can provide useful information for the further rational design of inhibitors targeting G-quadruplexes in HIV-1.
Retention of visuo-proprioceptive recalibration in estimating hand position
Authors: Wali Manasi , Lee-Miller Trevor , Babu Reshma , Block Hannah J.
Published: April 2023

The brain estimates hand position using visual and proprioceptive cues, which are combined to give an integrated multisensory estimate. Spatial mismatches between cues elicit recalibration, a compensatory process where each unimodal estimate is shifted closer to the other. It is unclear how well visuo-proprioceptive recalibration is retained after mismatch exposure. Here we asked whether direct vision and/or active movement of the hand can undo visuo-proprioceptive recalibration, and whether recalibration is still evident 24 h later. 75 participants performed two blocks of visual, proprioceptive, and combination trials, with no feedback or direct vision of the hand. In Block 1, a 70 mm visuo-proprioceptive mismatch was gradually imposed, and recalibration assessed. Block 2 tested retention. Between blocks, Groups 1–4 rested or made active movements with their directly visible or unseen hand for several minutes. Group 5 had a 24-h gap between blocks. All five groups recalibrated both vision and proprioception in Block 1, and Groups 1–4 retained most of this recalibration in Block 2. Interestingly, Group 5 showed an offline increase in proprioceptive recalibration, but retained little visual recalibration. Our results suggested that visuo-proprioceptive recalibration is robustly retained in the short-term. In the longer term, contextual factors may affect retention.
Characteristics of flight delays during solar flares
Authors: Xu X. H. , Wang Y. , Wei F. S. , Feng X. S. , Bo M. H. , Tang H. W. , Wang D. S. , Bian L. , Wang B. Y. , Zhang W. Y. , Huang Y. S. , Li Z. , Guo J. P. , Zuo P. B. , Jiang C. W. , Xu X. J. , Zhou Z. L. , Zou P.
Published: April 2023

Solar flares are one of the severest solar activities that have important effects on near-Earth space. Previous studies have shown that flight arrival delays increase as a result of solar flares, but the intrinsic mechanism behind this relationship is still unknown. In this study, we conducted a comprehensive analysis of flight departure delays during 57 solar X-ray events by using a huge amount of flight data (~ 5 × 106 records) gathered over a 5-year period. It is found that the average flight departure delay time during solar X-ray events increased by 20.68% (7.67 min) compared to quiet periods. Our analysis also revealed apparent time and latitude dependencies, with flight delays being more serious on the dayside than on the nightside and longer (shorter) delays tending to occur in lower (higher) latitude airports during solar X-ray events. Furthermore, our results suggest that the intensity of solar flares (soft X-ray flux) and the Solar Zenith Angle directly modulate flight departure delay time and delay rate. These results indicate that communication interferences caused by solar flares directly affect flight departure delays. This work expands our conventional understanding of the impacts of solar flares on human society and provides new insights for preventing or coping with flight delays.
Effects of extended mixing processes on fresh, hardened and durable properties of cement systems incorporating fly ash
Authors: Sereewatthanawut Issara , Panwisawas Chinnapat , Ngamkhanong Chayut , Prasittisopin Lapyote
Published: April 2023

Specifications that correspond with system performance may guarantee the addition of value. Most specifications for ready-mixed concrete address limits on discharge time and truck-drum revolution counts. These limits have been developed for conventional concrete. As the uses of supplementary cementing materials (SCMs) become ubiquitous, it is important to determine whether these specifications are applicable to SCMs, that is, systems containing fly ash. This paper presents results of the effects of mixing time and mixer revolution counts on characteristics of lab-made pastes and mortars containing 20% and 50% fly ash. Their characteristics assessed include time-variant ion concentrations, setting time, flow, compressive strength, porosity, and apparent chloride diffusivity coefficient. Results indicate that with increasing mixing time and mixer revolution counts, mixtures with a replacement of fly ash exhibit improved both fresh and hardened characteristics. When mixed for 60 min or 25,505 revolution count, the 28-day compressive strengths of mixtures containing 20% and 50% fly ash are 50% to 100% higher than the neat cement. Fly ash is suggested to adopt in the extended mixing processes of cement systems.
Contrastive learning-based pretraining improves representation and transferability of diabetic retinopathy classification models
Authors: Alam Minhaj Nur , Yamashita Rikiya , Ramesh Vignav , Prabhune Tejas , Lim Jennifer I. , Chan R. V. P. , Hallak Joelle , Leng Theodore , Rubin Daniel
Published: April 2023

Diabetic retinopathy (DR) is a major cause of vision impairment in diabetic patients worldwide. Due to its prevalence, early clinical diagnosis is essential to improve treatment management of DR patients. Despite recent demonstration of successful machine learning (ML) models for automated DR detection, there is a significant clinical need for robust models that can be trained with smaller cohorts of dataset and still perform with high diagnostic accuracy in independent clinical datasets (i.e., high model generalizability). Towards this need, we have developed a self-supervised contrastive learning (CL) based pipeline for classification of referable vs non-referable DR. Self-supervised CL based pretraining allows enhanced data representation, therefore, the development of robust and generalized deep learning (DL) models, even with small, labeled datasets. We have integrated a neural style transfer (NST) augmentation in the CL pipeline to produce models with better representations and initializations for the detection of DR in color fundus images. We compare our CL pretrained model performance with two state of the art baseline models pretrained with Imagenet weights. We further investigate the model performance with reduced labeled training data (down to 10 percent) to test the robustness of the model when trained with small, labeled datasets. The model is trained and validated on the EyePACS dataset and tested independently on clinical datasets from the University of Illinois, Chicago (UIC). Compared to baseline models, our CL pretrained FundusNet model had higher area under the receiver operating characteristics (ROC) curve (AUC) (CI) values (0.91 (0.898 to 0.930) vs 0.80 (0.783 to 0.820) and 0.83 (0.801 to 0.853) on UIC data). At 10 percent labeled training data, the FundusNet AUC was 0.81 (0.78 to 0.84) vs 0.58 (0.56 to 0.64) and 0.63 (0.60 to 0.66) in baseline models, when tested on the UIC dataset. CL based pretraining with NST significantly improves DL classification performance, helps the model generalize well (transferable from EyePACS to UIC data), and allows training with small, annotated datasets, therefore reducing ground truth annotation burden of the clinicians.
Socio-economic status and trajectories of a novel multidimensional metric of Active and Healthy Ageing: the English Longitudinal Study of Ageing
Authors: Malkowski Olivia S. , Kanabar Ricky , Western Max J.
Published: April 2023

Healthy ageing research largely has a unidimensional focus on physical health, negating the importance of psychosocial factors in the maintenance of a good quality-of-life. In this cohort study, we aimed to identify trajectories of a new multidimensional metric of Active and Healthy Ageing (AHA), including their associations with socio-economic variables. A latent AHA metric was created for 14,755 participants across eight waves of data (collected between 2004 and 2019) from the English Longitudinal Study of Ageing (ELSA), using Bayesian Multilevel Item Response Theory (MLIRT). Then, Growth Mixture Modelling (GMM) was employed to identify sub-groups of individuals with similar trajectories of AHA, and multinomial logistic regression examined associations of these trajectories with socio-economic variables: education, occupational class, and wealth. Three latent classes of AHA trajectories were suggested. Participants in higher quintiles of the wealth distribution had decreased odds of being in the groups with consistently moderate AHA scores (i.e., ‘moderate-stable’), or the steepest deterioration (i.e., ‘decliners’), compared to the ‘high-stable’ group. Education and occupational class were not consistently associated with AHA trajectories. Our findings reiterate the need for more holistic measures of AHA and prevention strategies targeted at limiting socio-economic disparities in older adults’ quality-of-life.
Study on upper bound limit analysis of horizontal layers slope stability based on optimization method
Authors: Yao Yong , Wang Zhen
Published: April 2023

Slope stability is an important problem in the field of geotechnical engineering. In order to widen the application range of upper bound limit analysis in engineering practice, this paper analyzes layered distribution characteristics of slope soil and establishes horizontal layers slope failure mechanism which satisfies the separation of velocity, then proposes calculation method for external force power and internal energy dissipation power using discrete algorithm. On this basic, this paper prepares cycle flow of slope stability analysis by upper bound limit principle and strength reduction principle, and develops stability analysis system by computer programming technology. Taking typical mine excavation slope as engineering background and calculates stability coefficient corresponding to different slope angles and evaluate analysis results accuracy by combining with limit equilibrium method. The results show that the stability coefficient error rate of two methods is between 3 and 5%, which can satisfy requirements of engineering practice. Moreover, stability coefficient obtained by upper bound limit analysis is an upper limit solution, and calculation errors are easy to eliminate, so it has certain applicability in slope engineering practice.
Phobia-specific patterns of cognitive emotion regulation strategies
Authors: Zsido Andras N. , Lang Andras , Labadi Beatrix , Deak Anita
Published: April 2023

Although fear plays a vital role in survival, an overly active threat detection system could be maladaptive due to its negative health consequences. Putatively maladaptive emotion regulation (ER) strategies are a core problem in phobias. In contrast, adaptive ER strategies could help downregulate the emotion elicited by a threatening stimulus and decrease anxiety. Yet, the number of studies directly examining the pattern of ER strategies linked to various phobias is still scarce. Thus, this study sought to map the patterns of adaptive and maladaptive ER strategies linked to the three most common phobias (social, animal, and blood-injection-injury [BII]). A total of 856 healthy participants filled out our survey including self-reported measures of social anxiety, snake-, spider-, BII phobia, and cognitive ER strategies. Structural equation modeling was used to test the effects between the variables. The results show that social anxiety and animal phobia were linked to both adaptive and maladaptive ER strategies, while BII was only associated with maladaptive ones. Further analyses showed that the most prominent ER strategies differed by subtype. This is in line with previous neuroimaging studies claiming that the neurocognitive mechanisms underlying phobias are also different. Theoretical as well as practical implications are discussed.
Label-free, multi-parametric assessments of cell metabolism and matrix remodeling within human and early-stage murine osteoarthritic articular cartilage
Authors: Liu Zhiyi , Hui Mingalone Carrie K. , Gnanatheepam Einstein , Hollander Judith M. , Zhang Yang , Meng Jia , Zeng Li , Georgakoudi Irene
Published: April 2023

Osteoarthritis (OA) is characterized by the progressive deterioration of articular cartilage, involving complicated cell-matrix interactions. Systematic investigations of dynamic cellular and matrix changes during OA progression are lacking. In this study, we use label-free two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) imaging to assess cellular and extracellular matrix features of murine articular cartilage during several time points at early stages of OA development following destabilization of medial meniscus surgery. We detect significant changes in the organization of collagen fibers and crosslink-associated fluorescence of the superficial zone as early as one week following surgery. Such changes become significant within the deeper transitional and radial zones at later time-points, highlighting the importance of high spatial resolution. Cellular metabolic changes exhibit a highly dynamic behavior, and indicate metabolic reprogramming from enhanced oxidative phosphorylation to enhanced glycolysis or fatty acid oxidation over the ten-week observation period. The optical metabolic and matrix changes detected within this mouse model are consistent with differences identified in excised human cartilage specimens from OA and healthy cartilage specimens. Thus, our studies reveal important cell-matrix interactions at the onset of OA that may enable improved understanding of OA development and identification of new potential treatment targets.
Development of pathway-oriented screening to identify compounds to control 2-methylglyoxal metabolism in tumor cells
Authors: Yanagi Kouichi , Komatsu Toru , Fujikawa Yuuta , Kojima Hirotatsu , Okabe Takayoshi , Nagano Tetsuo , Ueno Tasuku , Hanaoka Kenjiro , Urano Yasuteru
Published: April 2023

Controlling tumor-specific alterations in metabolic pathways is a useful strategy for treating tumors. The glyoxalase pathway, which metabolizes the toxic electrophile 2-methylglyoxal (MG), is thought to contribute to tumor pathology. We developed a live cell-based high-throughput screening system that monitors the metabolism of MG to generate d-lactate by glyoxalase I and II (GLO1 and GLO2). It utilizes an extracellular coupled assay that uses d-lactate to generate NAD(P)H, which is detected by a selective fluorogenic probe designed to respond exclusively to extracellular NAD(P)H. This metabolic pathway-oriented screening is able to identify compounds that control MG metabolism in live cells, and we have discovered compounds that can directly or indirectly inhibit glyoxalase activities in small cell lung carcinoma cells.
A rapid and highly sensitive immunosorbent assay to monitor helicases unwinding diverse nucleic acid structures
Authors: Wang Jia-En , Zhou Ying-Chen , Wu Bi-Han , Chen Xiu-Cai , Zhai Junqiu , Tan Jia-Heng , Huang Zhi-Shu , Chen Shuo-Bin
Published: April 2023

Here we have developed an immunosorbent assay to accurately and sensitively monitor helicase unwinding a broad range of DNA substrate structures. This assay can be utilized to investigate diverse helicases' functions and to identify their inhibitors.
Manganese supplementation of orthopedic implants: a new strategy for enhancing integrin-mediated cellular responses
Authors: Li Kai , Liu Shiwei , Li Jieping , Yi Deliang , Shao Dandan , Hu Tao , Zheng Xuebin
Published: April 2023

Surface modification with Mn induced unfolding of fibronectin with exposure of the RGD motif and increased the ligand-binding affinity of integrin α5β1.
Exploration of the reaction mechanism of the LaFeO3 oxygen carrier for chemical-looping steam methane reforming: a DFT study
Authors: Feng Yuchuan , Hu Xiude , Guo Xin , Wang Nana
Published: April 2023

The detailed reaction mechanism of CO conversion over the LaFeO3 oxygen carrier was systematically explored.
The removal efficiency of emerging organic contaminants, heavy metals and dyes: intrinsic limits at low concentrations
Authors: Khaliha Sara , Jones Derek , Kovtun Alessandro , Navacchia Maria Luisa , Zambianchi Massimo , Melucci Manuela , Palermo Vincenzo
Published: April 2023

In this work, we exploit Langmuir adsorption isotherms to compare the performance of different materials (adsorbents) in removing contaminants (adsorbates) from water.
Metal-based-oxide nanoparticles assisted thein vitroculture growth ofPopulus albaas micronutrients: essential metabolic processes and genetic stability
Authors: Ahmed Mohamed F. , Ibrahim Mostafa A. , Mansour Ahmed S. , Emam Ahmed N. , Abd El-Razik Ashraf B. , Tawfik Eman
Published: April 2023

In vitroculture growth rate ofPopulus albaupon using nano metal-based-oxides such as hematite (Fe2O3NPs), zinc oxide (ZnO NPs), and manganese oxide (Mn2O3NPs) nanoparticles as micronutrients.
Expedient synthesis and luminescence sensing of the inositol pyrophosphate cellular messenger 5-PP-InsP5
Authors: Shipton Megan L. , Jamion Fathima A. , Wheeler Simon , Riley Andrew M. , Plasser Felix , Potter Barry V. L. , Butler Stephen J.
Published: April 2023

We report the first molecular probe for the selective detection of the most abundant cellular inositol pyrophosphate 5-PP-InsP5, supported by computational chemistry, as well as an efficient new synthesis.
Selecting the appropriate indirect viability assay for 3D paper-based cultures: a data-driven study
Authors: Sitte Zachary R. , Larson Tyler S. , McIntosh Julie C. , Sinanian Melanie , Lockett Matthew R.
Published: April 2023

Cellular viability measurements quantify decreased proliferation or increased cytotoxicity caused by drug candidates or potential environmental toxins.
Reagentless protein-based electrochemical biosensors
Authors: Silva Saimon M. , Li Miaosi , Mendes Alexandre Xavier , Moulton Simon E.
Published: April 2023

The creation of reagentless protein-based biosensors that are capable of monitoring molecular analytes directly in bodily fluids could revolutionize our understanding of biology and personalized health monitoring.
Radiolabeling and in vivo evaluation of lanmodulin with biomedically relevant lanthanide isotopes
Authors: Martin Kirsten E. , Mattocks Joseph A. , Śmiłowicz Dariusz , Aluicio-Sarduy Eduardo , Whetter Jennifer N. , Engle Jonathan W. , Cotruvo Joseph A. , Boros Eszter
Published: April 2023

This work describes successful radiochemical labeling and subsequent in vivo evaluation of radiolanthanide-tagged versions of lanmodulin (LanM), a lathanide-binding protein.
Benchmarking of commercial Cu catalysts in CO2electro-reduction using a gas-diffusion type microfluidic flow electrolyzer
Authors: Xiong Haocheng , Li Jing , Wu Donghuan , Xu Bingjun , Lu Qi
Published: April 2023

Commercial Cu could deliver a high selectivity of ∼80% for multicarbon products at an industrially relevant rate of 300 mA cm−2.
Nonaromatic naphthocorroles
Authors: Kielesiński Łukasz , Summa Francesco F. , Conradie Jeanet , Honig Hilah C. , Friedman Ariel , Monaco Gugliemo , Elbaz Lior , Ghosh Abhik , Gryko Daniel T.
Published: April 2023

Previously unknown naphthocorroles possess nonaromatic character, NIR absorption and unusually low-lying LUMO.
Assembly of split aptamers by dynamic pH-responsive covalent ligation
Authors: Aho Aapo , Virta Pasi
Published: April 2023

A dynamic pH-responsive covalent ligation of split aptamer fragments utilizing a small molecule substrate as a template is described.