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Screening of a core SNP set for the seedling identification of Saccharina japonica cultivars in northern China
Kelp is an economically important seaweed species in China. The verification of Saccharina japonica cultivars is crucial for industrial development. Four Saccharina japonica cultivars with distinctive characteristics that are widely used in China were selected. To distinguish these cultivars, a highly informative core SNP marker set was identified and validated from 441,094 SNPs. The marker set consisted of 247 core SNPs that were uniformly distributed and were abundant polymorphisms. The similarity between samples was calculated using both core and total SNPs, and a significant linear correlation (P < 0.01) was observed, with a correlation coefficient of r = 0.99. These results provide a valuable SNP set for distinguishing the germplasms of four Saccharina japonica cultivars and serve as a reference for variety differentiation.
AI tutoring outperforms in-class active learning: an RCT introducing a novel research-based design in an authentic educational setting
Biochemical and structural basis of Dicer helicase function unveiled by resurrecting ancient proteins
A fully functional Dicer helicase, present in the modern arthropod, uses energy from ATP hydrolysis to power translocation on bound dsRNA, enabling the processive dsRNA cleavage required for efficient antiviral defense. However, modern Dicer orthologs exhibit divergent helicase functions that affect their ability to contribute to antiviral defense. Moreover, mechanisms that couple ATP hydrolysis to Dicer helicase movement on dsRNA remain enigmatic. We used biochemical and structural analyses of ancestrally reconstructed Dicer helicases to map evolution of dsRNA binding affinity, ATP hydrolysis and translocation. Loss of affinity for dsRNA occurred early in Dicer evolution, coinciding with a decline in translocation activity, despite preservation of ATP hydrolysis activity. Ancestral nematode Dicer also exhibited significant decline in ATP hydrolysis and translocation, but studies of antiviral activities in the modern nematode Caenorhabditis elegans indicate Dicer retained a role in antiviral defense by recruiting a second helicase. Cryogenic electron microscopy (cryo-EM) analyses of an ancient metazoan Dicer allowed capture of multiple helicase states revealing the mechanism that connects each step of ATP hydrolysis to unidirectional movement along dsRNA. Our study rationalizes the diversity in modern Dicer helicases by connecting ancestral functions to observations in extant enzymes.
Social anxiety influences the stress-buffering potential of social presence: Evidence from cardiovascular and affective reactivity under stress
Social presence and social support are fundamental instrumental sources of interpersonal emotional regulation, playing a crucial role in mitigating the impact of stress and negative emotions. This study aims to improve our understanding of the role of relationship type and individual differences in social anxiety in the stress-buffering provided by co-presence of others during stress. A dyadic version of the Trier Social Stress Test (TSST) was employed to experimentally induce stress in a sample of 40 dyads, each comprising a target participant who was paired with a second participant, acting as a supporter. In half of the dyads the target and the supporter were in a romantic relationship (Partner Group), while in the other half they were randomly paired (Stranger Group). Heart rate and psychological stress reactivity were collected during the TSST. Results revealed that participants in the Partner Group exhibited a lower heart rate during the acute stress compared to the participants in the Stranger Group, highlighting that the buffering of the physiological stress activity is stronger within close relationships. Nonetheless, participants in the Partner Group reported more anxiety and stress during the task. Furthermore, social anxiety showed a positive correlation with subjective stress reactivity in the participants in the Partner Group, suggesting that it may hinder the perceived benefit of social support. These findings increase our understanding of stress-buffering mechanisms, emphasizing the interplay between social support, stress reactivity, and interpersonal affective processes, also highlighting the need for additional research characterizing individual differences in social regulation of stress.
Hsa-miR-21-5p is induced by interleukin-6 and affects multiple pathogenic factors associated with fibroblast-like synoviocytes in rheumatoid arthritis
Abstract Fibroblast-like synoviocytes (FLS) contribute significantly to the pathogenesis of rheumatoid arthritis (RA), particularly through their roles in synovitis and joint destruction. The microRNAs (miRNAs) are short non-coding RNA that regulate gene expression post-transcriptionally. Although more than 2000 human miRNAs are registered, comprehensive analyses of miRNA expression in FLS are limited. Herein, we investigated the relationship between miRNAs and FLS. Next-generation sequencing (small RNA-seq) was performed on primary cultured FLS derived from patients with RA to analyze the mature miRNA expression pattern. To assess inflammation-induced changes in miRNA levels, FLS were cultured with cytokines and evaluated by RT-qPCR. MiRNA mimics were transfected into FLS and an immortalized synovial fibroblast cell line (MH7A cells), and validated using conventional RNA-seq. Out of 2861 mature miRNAs, 297 mature miRNAs were detected and intronic miRNAs were predominated. Notably, hsa-miR-21-5p was abundantly expressed and its expression was enhanced by IL-6 stimulation. The induction of miR-21-5p mimic decreased the expression of Programmed Cell Death 4 (PDCD4) and Osteoprotegerin (OPG), while upregulating Semaphorin 5A (SEMA5A). MiR-21-5p mimic led to enhanced cell proliferation. These data suggest that hsa-miR-21-5p in FLS may exacerbate the pathophysiology of rheumatoid synovitis by promoting FLS proliferation, highlighting its potential as a therapeutic target in RA.
Lynn Landmesser (1943–2024): A pioneer in developmental neurobiology
Lynn Landmesser, whose studies transformed our view of how neurons find the proper partners on which to form synapses, died at the age of 80 in November 2024. Using elegant electrophysiological methods, she showed that specificity is apparent from the earliest times that connections are established in both autonomic and motor systems. Her work overturned the idea that synaptic connectivity arises by gradual refinement of initially nonspecific patterns and thereby laid the groundwork for molecular analysis of the factors that guide axons to and connect them with their targets.
Examining oxyhydrogen gas generation experimentally using wet cell design
Oxyhydrogen (HHO) gas, which is created when water is electrolyzed using a dry cell electrolyzer, is becoming more and more popular as a new energy source because of its improved combustion properties. The creation of HHO wet cell is the primary goal of the current study in order to maximize gas flow rate and improve electrolyzer efficiency compared to dry cell. An inexpensive electrolyzer made of local obtainable parts was used to create HHO. Stainless steel 316L electrodes having a surface area of 136.5 cm 2 and 4 mm distance between plates were used to generate HHO gas. Various concentrations of KOH and NaOH electrolytes were used. The rate of HHO generation was influenced by the electrolyte ratio, operation time, cell connection, electric current, electrolyte temperature, and voltage. Different plate arrangements were looked at. It had been discovered that raising the voltage, electrolyte temperature, electrolyte concentration, and applied current all contributed to higher gas generation. At 90 min. operation time, the wet cell showed continuous output peak values of 975, 1160, 1325, and 1375 ml/min at 5, 10, 15, and 20 g/L NaOH, respectively, along with supply currents of 17.8, 23.5, 26, and 27 A. At 5, 10, 15, and 20 g/L catalyst percentage, the temperatures were increased to 35, 44, 50, and 58°C, respectively. With a production efficiency of 69.3%, the HHO wet cell generated 1160 ml per minute at 18 amps and 10 g/litre of NaOH. Wet cell electrolyzers overheating has drawback for practical applications due to higher current supply about dry cell.
A topological approach to understanding crack initiation and propagation in carbon fiber reinforced polymer composites under an opening load
Cardiolipin membranes drive Myosin VI activation, oligomerization, and processive cargo transport
Mitochondrial damage determines cell fate, leading to mitochondrial autophagy or cellular apoptosis in health and disease. The molecular mechanisms and role of the acto-myosin cytoskeleton regulating mitochondrial clearance and membrane remodeling are critical in neurodegenerative disease progression including Alzheimer, but remain unclear. To investigate the potential link between full-length Myosin VI (FL-Myo6) recruitment and exposure of the mitochondria-specific lipid cardiolipin (CL), here we adapted a combination of molecular biology, biochemical, high-resolution fluorescence and interferometric light-scattering techniques. We developed analysis tools to reveal the structural Myo6–CL interaction sites, Myo6-oligomerization interfaces and mechanical properties. We found that CL activates backfolded FL-Myo6 and induces Myo6-oligomerization. Myo6 bound to CL cargo-vesicles in vitro mediates processive runs over >500 nm at >90 nm s −1 . We propose a model how CL-interaction regulates backfolded Myo6 activation into a highly processive cargo-bound motor.
Monovalent mRNA XBB.1.5 vaccine effectiveness against COVID-19 hospitalization in Quebec, Canada: Impact of variant replacement and waning protection during 10-month follow-up
Background Vaccine formulations targeting contemporaneous subvariants have been developed to respond to SARS-CoV-2 virus evolution. Updated monovalent COVID-19 vaccines targeting the Omicron XBB.1.5 variant (XBB-vaccines) were administered in the province of Quebec, Canada, during 2023 autumn and 2024 spring vaccination campaigns. Our objective was to evaluate mRNA XBB-vaccine effectiveness (VE) against COVID-19 hospitalizations among adults aged ≥60 years overall during a ten-month follow-up period, by subvariant predominant period, and by time since vaccination. Methods We conducted a test-negative case-control study using Quebec population-based administrative data. Specimens collected from individuals aged ≥60 years tested at an acute-care hospital from October 2023 to August 2024 were considered test-positive cases if hospitalized for COVID-19, or controls if test-negative for SARS-CoV-2. Vaccination was defined by receipt of at least one mRNA XBB-vaccine (autumn or spring) dose. Subvariant predominant periods were defined according to whole-genome sequencing data from provincial laboratories: XBB or EG.5 and subvariants (XBB period), BA.2.86, JN.1 or subvariants (JN period), and KP.2 or KP.3 and subvariants (KP period). Multivariable logistic regression analyses estimated VE relative to several comparator groups, primarily those last-vaccinated in 2022, by subvariant period, by time since XBB-vaccination and by number of XBB-vaccine doses (KP period). Results Participants overall and by XBB, JN and KP periods included: 5532 (4.9%) test-positive cases (1321, 1838 and 1372, respectively) and 108473 (95.1%) test-negative controls (12881, 53414 and 28595, respectively); 14584 specimens were collected during periods of subvariant cocirculation. By subvariant period, 3322 (25.8%), 27041 (50.6%) and 15401 (53.9%) controls, respectively, were considered XBB-vaccinated. Overall VE was 30% (95%CI:24–35) and by XBB, JN or KP period: 54% (95%CI:46–62), 23% (95%CI:13–32) and 0% (95%CI:-18–15), respectively. During each subvariant period, the hospitalization risk was reduced only during the first four months post-vaccination. Conclusions Among individuals aged 60 years or older, mRNA XBB-vaccination provided meaningful, albeit limited to first four months post-vaccination, protection against COVID-19 hospitalization due to XBB, JN and KP subvariants. Better vaccines are needed to effectively protect older adults against COVID-19 hospitalizations.
Comparative evaluation of nano ocular delivery systems loaded pH and thermosensitive in situ gels for Acanthamoeba keratitis treatment
Abstract Acanthamoeba keratitis is the most dangerous ocular-infection that can cause blindness. The propamidine-isethionate (PI) 0.1% eye-drops are used in the treatment, but they have low-bioavailability due to precorneal loss parameters. In-situ-gels are administered as drops into the eye and changed into gel in the cul-de-sac, which may be able to solve these issues. In this study, we demonstrate different nano-ocular delivery-systems formulations of 0.1%PI loaded in-situ-gels using the ideas of pH & temperature-stimulated in-situ-gelation. Pluronic F-127 a thermosensitive-polymer with chitosan as a pH-sensitive polymer that also enhances permeability was utilized as a gelling-agent. Several in-vitro pharmaceutical and antiprotozoal assessments on Acanthamoeba keratitis were assessed for the developed formulations. It was observed that the created PI-chitosan nanoparticles in-situ-gel formulation showed smaller particle-size, higher zeta with a higher %inhibition of amoebae after 24-h incubation compared to other formulations with continuous drug release for 24-h. The PI-CSNPs in-situ-gel formulation offers an effective substitute for traditional BROLENE eye-drops in the management of Acanthamebae, around double the effect based on % amebae inhibition, reached 92%. It can reach the clinical-stage & is appropriate for sustained-ocular-administration for the treatment of Acanthamoeba keratitis.
Alternative cGAS signaling promotes herpes simplex encephalitis
During infection, foreign DNA is sensed by cyclic GMP-AMP synthase (cGAS) leading to the production of cGAMP, STING-dependent type I interferon and proinflammatory cytokine expression, and autophagy. To prevent a response to self-DNA, cGAS activity is tightly regulated. Dysregulation of cGAS underpins interferonopathies, such as Aicardi–Goutières syndrome, as well as Lupus and neurodegenerative diseases like Parkinson’s disease. Thus, cGAS and its product cGAMP are therapeutic targets. However, if cGAS functions independently of cGAMP signaling is undefined. Here, we identified an alternative signaling pathway that cGAS engages independent of cGAMP synthesis. We demonstrate that alternative cGAS signaling promotes hyperexpression of CXCL1 and enhanced neutrophil recruitment that facilitates viral dissemination during herpes simplex encephalitis. Our study reports of an alternative cGAS response independent of cGAMP, highlighting a previously uncharacterized scaffold function for cGAS.
Investigation of the effects of benznidazole on the salivary glands: A biochemical, morphological, and functional approach
This study aimed to evaluate the possible biochemical effects of the administration of benznidazole on the parotid and submandibular salivary glands and saliva of rats, as well as on salivary components for the first time. Male Wistar rats (Rattus norvegicus), 66-days-old, weighing approximately 250 g were randomized into two groups: control, administered distilled water by gavage and benznidazole, administered benznidazole at a dose of 19.6 mg/kg daily by gavage over 15 days. On the 16th day, the animals were anaesthetized and the parotid and submandibular salivary glands and saliva were collected for oxidative biochemistry and morphometric analyses, and the biochemical composition of the saliva was also assessed. On the 16th day, the animals were anesthetized and their pilocarpine-induced saliva was collected. They were then euthanized to collect the parotid and submandibular salivary glands for oxidative biochemical and morphometric analyses, and the biochemical composition of the saliva was also assessed. Shapiro–Wilk normality analysis and Student’s t-test was used for parametric data and non-parametric data, respectively, with a significance of p < 0.05. The oxidative biochemical results revealed a reduction in the antioxidant capacity of the parotid and submandibular glands in benznidazole group. Morphometric analyses revealed an increase in the average area of the acini in both glands and a reduction in the stromal area of the parotid gland in the benznidazole group. Salivary analyses demonstrated a decrease in antioxidant levels and an increase in pro-oxidant levels in the group exposed to benznidazole. Total proteins, amylase, and mucin levels reduced in the exposed group. Thus, administration of benznidazole conclusively caused biochemical alterations in the antioxidant and morphological capacities of the salivary glands, followed by biochemical and protein alterations in the saliva, highlighting the possible damage caused by the drug in patients during the treatment of Chagas disease.
Deciphering the dynamics of enzymes associated with the synthesis of cryoprotectants during cold acclimation in contrasting chickpea genotypes
Dynamic early recruitment of GAK–Hsc70 regulates coated pit maturation
Clathrin-mediated endocytosis (CME) begins with the assembly of clathrin onto the plasma membrane. These structures grow and stabilize to form clathrin-coated pits (CCPs), which invaginate and accumulate cargo. Finally, through membrane fission, CCPs detach to form clathrin-coated vesicles (CCVs). Mechanisms governing the transition of CCPs from flat-to-curved structures have been a matter of debate. GAK and its chaperone protein, Hsc70, are well known to mediate clathrin release from CCVs, and several studies have observed a late burst of GAK recruitment as CCVs form. Other studies have proposed that early recruitment of GAK–Hsc70 could function to provide the necessary energy source to remodel nascent flat clathrin lattices, replacing hexagons with pentagons and enabling a gain of curvature and invagination of the growing CCP; however, direct functional evidence is lacking. Here, we show that GAK knockdown inhibits CCP stabilization and invagination. Furthermore, mutations in the J domain of GAK that abolish Hsc70 recruitment to and activation at CCPs lead to the accumulation of GAK at CCPs, hinder CCP stabilization and invagination, and result in a striking increase in the proportion of highly transient, abortive CCPs. These findings support the hypothesis that GAK–Hsc70 promotes the turnover and remodeling of nascent clathrin assemblies required for curvature development during CME.
Between-day reliability of local and global muscle-tendon unit assessments in female athletes whilst standardising menstrual cycle phase
Muscle-tendon unit (MTU) assessments can be categorised into local (e.g., tendon strain) or global (e.g., jump height) assessments. Although menstrual cycle phase may be a key consideration when implementing these assessments in female athletes, the reliability of many MTU assessments is not well defined within female populations. Therefore, the purpose of this study was to report the test-retest reliability of local and global MTU assessments during the early follicular phase of the menstrual cycle. Seventeen naturally menstruating females (age 28.5 ± 7.3 years) completed local and global MTU assessments during two testing sessions separated over 24–72 hours. Local tests included Achilles’ tendon mechanical testing and isometric strength of ankle plantar flexors and knee extensors, whereas global tests included countermovement, squat, and drop jumps, and the isometric midthigh pull. Based on intraclass correlation coefficient (ICC) statistics, poor to excellent reliability was found for local measures (ICC: 0.096–0.936). Good to excellent reliability was found for all global measures (ICC: 0.788–0.985), excluding the eccentric utilisation ratio (ICC 0.738) and most rate of force development metrics (ICC: 0.635–0.912). Isometric midthigh pull peak force displayed excellent reliability (ICC: 0.966), whereas force-time metrics ranged from moderate to excellent (ICC: 0.635–0.970). Excluding rate of force development (coefficient of variation [CV]: 10.6–35.9%), global measures (CV: 1.6–12.9%) were more reproducible than local measures (CV: 3.6–64.5%). However, local metrics directly measure specific properties of the MTU, and therefore provide valuable information despite lower reproducibility. The novel data reported here provides insight into the natural variability of MTU assessments within female athletes which can be used to enhance the interpretation of other female athlete data, especially that which aims to investigate other aspects of variability, such as the menstrual cycle.
Identification and validation of SAC3D1 as a prognostic biomarker promoting the development of osteosarcoma
Evolution of the essential gene <i>MN1</i> during the macroevolutionary transition toward patterning the vertebrate hindbrain
The tight link between brain and skull formation is a fundamental aspect of vertebrate evolution and embryogenesis. Their developmental synchronization is essential for structural and functional integration. The brain and skull shape coevolution is evident along the vertebrate phylogeny; however, the genetic basis underlying their close evolutionary and developmental relationship remains little explored. Here, we reveal the evolution and function of the MN1 gene that was previously found to be associated with significant shape variation in the mouse skull and the formation of cranial bones. We show that the vertebrate MN1 gene evolved from an ancestral deuterostome sequence. In vertebrates, the MN1 gene structure, synteny, and spatiotemporal expression pattern are remarkably conserved, indicating that the gene carries out a core function. Using a newly generated mouse knock-out model, we demonstrate in vivo that Mn1 integrated into an ancient molecular machinery and controls the expression of the Cyp26 genes in the developing hindbrain, thereby tuning the retinoic acid levels and patterning of the developing central nervous system. This study thus showcases the emergence of a novel gene function from an ancestral sequence and its role in generating a macroevolutionary innovation. The data expand our knowledge of brain and skull codevelopment and coevolution and highlight the role of this regulatory loop in craniofacial human syndromes.
Comparison of the stabilized waste soil properties and stabilization mechanism of phosphogypsum-fly ash-steel slag based cement versus Portland cement
Through physical and chemical reactions in the presence of phosphogypsum, steel slag and fly ash modify the load-bearing skeleton and fill the pores of the wasted soil, resulting in high-strength performance. Extensive experiments that compared Portland cement with phosphogypsum-fly ash-steel slag-based cement (PFS cement) revealed that the later-stage unconfined compressive strength (UCS) of PFS cement exceeded that of Portland cement by approximately 33.18%. In terms of the stress-strain curve, the maximum stress and yield strength of PFS cement-stabilized waste soil were 40% to 50% higher than those of Portland cement. In the dry-wet cycle resistance experiment, PFS cement-stabilized waste soil showed a compressive strength increase of 15.17% over Portland cement. Furthermore, during the freeze-thaw cycle test, PFS cement-stabilized waste soil demonstrated a 29.95% higher performance compared to Portland cement. When used as a solidifying agent, PFS cement exhibits significant advantages over Portland cement in backfilling for underground engineering, trenches, roadbeds, bridge abutments, and road base layers.