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TRANSPIRATION COOLING IN GAS TURBINE TRAILING EDGE USING STAINLESS STEEL AND TITANIUM...
Md Tarif Raihan

Md Tarif Raihan

January 10, 2025
This paper investigates the transpiration cooling performance of porous media, comparing SS316L and Titanium in a rectangular channel. The experimental setup involved heating the porous materials using a hot air blower and cooling with controlled airflow at varying Reynolds numbers (Re = 39,000, Re = 63,000, and Re = 70,000). Temperature distributions and cooling effectiveness were recorded and analyzed. Simulation studies were conducted parallel to validate the experimental results and provide further insights into the flow and thermal characteristics. The findings reveal that both materials exhibit increased cooling effectiveness with higher Reynolds numbers. SEM imaging shows that Titanium demonstrated superior cooling performance due to its higher thermal conductivity and a well-structured, finely distributed porous network. This uniformity facilitated enhanced airflow interaction, particularly at higher Reynolds numbers. SS316L, while exhibiting lower cooling effectiveness, provided more consistent thermal performance across the surface, highlighting its suitability for applications requiring uniform heat dissipation. Comparative analysis of experimental and simulation results showed reasonable agreement, with simulations capturing the overall trends of the cooling behavior. However, discrepancies were observed at localized points, particularly for SS316L at lower Reynolds numbers and Titanium at higher Reynolds numbers. These differences emphasize the influence of realworld flow dynamics, boundary layer effects, and porosity distribution on cooling performance. This study underscores the importance of combining experimental and simulation approaches to evaluate transpiration cooling systems comprehensively. The results provide critical insights for material selection and design optimization in applications requiring efficient thermal management, such as aerospace and high-performance cooling systems. Future work should focus on refining simulation models and exploring long-term durability under extreme operating conditions to enhance the applicability of these materials.
Clinical Profile and Referral Pathways in Late Radiation-Associated Dysphagia (Late-R...
Diane Sellstrom
James O'Hara

Diane Sellstrom

and 4 more

January 10, 2025
Dysphagia as a late side-effect of radiotherapy (RT) for head and neck cancer (HNC) may not manifest until many years post-treatment (1). Insidious deterioration in swallowing function can significantly impact emotional and physical health. Patients may need enteral feeding support and experience chest co-morbidities which can be fatal (2). Not all patients will develop late-RAD and there is variation in the literature regarding actual prevalence due to heterogeneity in study populations and designs (3). There is also a lack of consensus regarding the definition of ‘late’ but growing acknowledgement that a latency period occurs, where swallowing function is stable before a progressive decline is seen (4). Discharge from surveillance at five years post-treatment has been standard in published recommendations (5). However, there is increasing recognition that this should be extended to allow for appropriate monitoring for the development of delayed side effects (6).
Preferences for ‘Gender-typed’ Toys in Brazilian Boys and Girls Aged 9 to 32 Months
Samara Oliveira Rocha
Isabele Tenório dos Santos

Samara Oliveira Rocha

and 2 more

January 10, 2025
International literature recognizes gender-related differences in children's toy preferences. However, to date, no study has assessed how these differences in play are expressed in the Brazilian children at an early age. This study used a selection of gender-typed toys to compare the time spent by children playing with them. It also assessed the effect of age and parents' judgments on the desirability and level of typing of distinct types of toys for their children. Similarly to previous research, the Brazilian children also showed gender-typed preferences. Boys played more with trucks than girls, while girls spent more time with feminine toys than with masculine and neutral toys. There was evidence of age effects and that parents' desire for neutral toys encouraged boys' play with kitchen sets. The implications considered were related to biological predispositions, cognitive development, and environmental influences on toy preferences.
Children’s Peer Conflicts: A Participatory Science Observational Study
Gouri A. Kallambella
Fiona Prestemon

Gouri A. Kallambella

and 2 more

January 10, 2025
Prior research shows that children negotiate conflicts with their peers through prosocial and peaceful resolution (Spivak, 2017). However, there are limited studies on parental responses to children’s conflicts (Kramer, Chung, & Perozynski, 2003). The current study used participatory science approaches, in which introductory psychology students with basic training collected observational data on parent-child conflicts in public spaces. The aim of the study is to understand how conflicts between children are related to the parental response time and the type of resolution. Findings demonstrated that parents responded more quickly to conflicts involving potential physical harm, such as hitting, than conflicts surrounding gameplay. Additionally, resolutions differed depending on the type of conflict observed, the participants’ ages, and gender. Analyses also revealed differences in the type of conflict based on the gender and age of the children. Findings contribute to the literature on conflicts between children.
A constant TNT equivalence fit for blast wave position versus time data
caio

Caio Barbosa Amorim

and 2 more

January 10, 2025
Caio Barbosa Amorim1, Anselmo da Silva Augusto1, Rene Francisco Boschi Gonçalves1
Persistence of CD8+ skin-resident memory T cells in mice requires TCR signaling
Anders Funch
Julie Weber

Anders Funch

and 13 more

January 10, 2025
Background: Epidermal-resident memory CD8 + T (T RM) cells play a significant role in fighting off pathogens. However, CD8 + T RM cells are also central in the pathogenesis of a variety of inflammatory skin diseases. It is unclear whether the generation and persistence of CD8 + T RM cells are dependent on the presence of cognate antigen and T cell receptor (TCR) signaling. Methods: We determined the generation and persistence of epidermal CD8 + T RM cells by flow cytometry and single-cell TCR sequencing in a well-characterized mouse model for allergic contact dermatitis. We examined the responses to four different contact allergens in combination with adoptive transfer and prime-pull experiments. We determined the presence of contact allergens in the skin by Western blot analysis. Results: We found that epidermal CD8 + T RM cells can develop in the absence of the cognate antigen and TCR signaling as determined by Nur77 induction, whereas persistence of epidermal CD8 + T RM cells requires presence of the cognate antigen and correlates with Nur77 expression. In the presence of contact allergen, a selective expansion of specific TCR clonotypes was seen. Conclusion: This study demonstrates that cognate antigen and TCR signaling are required for the persistence of allergen-specific CD8 + T RM cells in the skin.
Wind Tunnel Test of Counter-Rotating Dual Rotor Wind Turbine with Double Rotational A...
Niels (N.C.) Adema
Wouter (W.F.J.) Swart Ranshuysen

Niels (N.C.) Adema

and 3 more

January 10, 2025
This study evaluates the performance of a Counter-Rotating Dual Rotor Wind Turbine (CR-DRWT) equipped with a double rotational armature, aimed at enhancing energy capture and efficiency in small-scale wind turbine (SWT) applications. Through wind tunnel testing, the CR-DRWT confirmed earlier findings in literature and achieved a 15 to 50% increase in power output and a 10% increase in efficiency (CP) compared to a single rotor configuration at higher wind speeds (> 7 m/s). Though these gains were not observed at lower wind speeds (4-7m/s). The simplified mechanics of a double rotational armature demonstrated promise for application in SWT’s. The design’s maximum CP values were below those achieved in previous field tests at larger scale highlighting potential for improvement for smaller sized turbines. To further explore the aerodynamics of CR-DRWT’s, computational fluid dynamics (CFD) simulations are recommended, as they could provide insights into optimizing flow dynamics around both rotors. Finally, the study emphasizes the need for precise pitch angle and rotational speed measurements to improve the value of future measurements.
Land values and agricultural expansion into dry regions of Argentina
Ana Laura Llanes

Ana Laura Llanes

and 3 more

January 10, 2025
Over the past two decades, agricultural demand has driven significant increases in food and land values. This study examined land value trends in Argentina's expanding agricultural belt, focusing on the dry periphery and its correlation with the more humid core. Analyzing real estate data (2000-2020), we found that core land values tripled, reaching levels comparable to the agricultural cores of the US and Brazil at 15-18 thousand USD/ha by 2018-2020, while the periphery's value ended up appreciated first but stabilized afterwards at levels of 35-40% from the core, convergent whit those observed in the dry peripheries of the US and Brazil. The stagnation of agricultural land values in Argentina´s periphery under a rising productivity context did not respond to increasing costs or declining grain prices and could be the result of perceived long-term limitations to agricultural production coming from climate risks and/or regulations. The fact that the periphery-core land valuation is lower than the periphery-core productive profit suggests that Argentina's agricultural frontier is advancing mainly driven by the incentives of immediate profit rather than longer-term speculation.
RoBERTa-BiLSTM-Multihead Attention Model for Network Public Opinion Sentiment Analysi...
Kai Yu
Zhaoxiang Mu

Kai Yu

and 2 more

January 10, 2025
With the rapid development of the internet and social media, network public opinion has become an essential channel for expressing public opinions and sentiments. Governments and enterprises need to quickly understand public sentiment when responding to emergencies, policy releases, and social hotspots, in order to adjust response strategies promptly. This paper proposes a hybrid model based on RoBERTa, BiLSTM, and multi-head attention mechanisms (RBMA), aiming to enhance the accuracy and efficiency of sentiment analysis in network public opinion. The model utilizes the RoBERTa pre-trained model to capture the deep semantic features of text, incorporates BiLSTM to learn semantic dependencies, and applies multi-head attention to focus on critical sentiment information, thus handling complex emotional transitions more precisely. The study conducts model construction and comparison research and validates the model’s effectiveness in practical applications through case studies. Experimental results demonstrate that the RBMA model significantly outperforms traditional models in terms of accuracy, precision, recall, and F1-score, particularly excelling in handling sudden public opinion events and the spread of negative sentiments. By applying this model, public opinion managers can monitor sentiment dynamics more promptly and effectively, reducing the potential risks of negative sentiment for society and organizations, and improving the overall response efficiency in public opinion management.
Bacterial Reverse Mutation test of 1-[[(3-hydroxy-1- adamantyl) amino] acetyl] pyrali...
T. Pavan Pradeep
Debiprasad Padhy

T. Pavan Pradeep

and 1 more

January 10, 2025
The purpose of the Ames short-term bacterial reverse mutation experiment is to identify a variety of chemicals that can cause genetic harm that results in gene mutations. In this study, we investigated the mutagenic potential of 1-[[(3-hydroxy-1-adamantyl) amino] acetyl] pyralidine-(S)-2-carboxamide (Vildagliptin amide impurity) using Salmonella typhimurium and Escherichia coli tester strains. The evaluation utilized plate incorporation methods to assess point mutations at the histidine locus in four strains of Salmonella and at the tryptophan locus in E. coli WP2uvrA, both with and without a metabolic activation system (S9). A series of concentrations (15.8 to 5000 µg/plate) were tested, revealing no significant decreases in revertant colony counts or cytotoxicity, as evidenced by the integrity of the bacterial lawn and lack of precipitation. Confirmatory assays at varying concentrations indicated that treatment did not induce notable increases in revertant counts across the tester strains, further supporting the absence of mutagenic activity. Positive controls demonstrated expected responses, confirming the reliability of the test conditions and the functionality of the metabolic activation system. Overall, the findings suggest that Vildagliptin amide impurity does not exhibit mutagenic properties under the tested conditions.
Facilitation thinking for coexistence theory
Aubre James
Margaret Mayfield

Aubrie James

and 2 more

January 10, 2025
Species interactions are foundational to biodiversity maintenance. Facilitation, a common outcome of species interactions, occurs among and between a wide variety of organisms yet its treatment in the theory and models used to predict species coexistence is underdeveloped. We ask why this is and speculate about how to address this apparent discrepancy. We first evaluate a persistent ambivalence to facilitation in the context of population and community ecology, particularly in contemporary coexistence theory. We then propose “facilitation thinking” to remedy the gap between empirical evidence of facilitation and mathematical theory of coexistence. We briefly discuss how a holistic treatment of facilitation in theory has the potential to reconfigure our basic understanding and definition of coexistence. Ultimately, we argue for an expanded theory of coexistence that accounts for a diversity of species interaction outcomes, allowing for the study of interactions and diversity maintenance beyond the war of all against all.
Druggability studies of diarylamide E3 as a novel diuretic
Hang Zhang
Shuyuan Wang

Hang Zhang

and 10 more

January 10, 2025
Background and Purpose: Urea transporters (UTs) play an important role in the urine-concentrating mechanism and have been regarded as a novel drug target for developing salt-sparing diuretics. Our previous studies found that diarylamides 1H and 25a are specific UT inhibitors and have oral diuretic activity. However, these compounds necessitate further optimization and comprehensive druggability studies. Experimental Approach: The optimal compound was identified through structural optimization. Experiments were conducted to investigate its inhibitory activity and evaluate its diuretic effect. Furthermore, disease models were utilized to assess the compound’s efficacy in treating hyponatremia. Pharmacokinetic studies were performed to examine its metabolic stability, and toxicity tests were conducted to evaluate its safety. Key Results: Based on the chemical structure of compound 25a, we synthesized a novel compound, E3, by introducing a benzenesulfonamide group into its side chain. E3 exhibited dose-dependent inhibition of UT at the nanomolar level and demonstrated oral diuretic activity without causing electrolyte excretion disorders in both mice and rats. Experiments involving UT-B-/- and UT-A1-/- mice indicated that E3 enhances the diuretic effect primarily by inhibiting UT-A1 more effectively than UT-B. Furthermore, E3 displayed good metabolic stability and favorable pharmacokinetic characteristics. E3 significantly ameliorated hyponatremia through diuresis in rat model. Importantly, E3 did not induce acute oral toxicity, subacute oral toxicity, genotoxicity, or cardiotoxicity. Conclusion and Implications: Our study confirms that E3 exerts diuretic effect by specifically inhibiting UTs and has good druggability, which offers potential for E3 to be developed into a new diuretic for the treatment of hyponatremia.
Pediatric Allergy and Immunology in North America - An introduction
Bianca Olivieri
Ayobami Akenroye

Bianca Olivieri

and 3 more

January 10, 2025
Pediatric Allergy and Immunology in North America - An introductionBianca Olivieri1,2, Ayobami Akenroye3, Carmen Riggioni4,5, Philippe Eigenmann6
Strategic Integration of Melatonin to Enhance Corticosteroid Therapy in Long COVID-19...
Amine Souissi
Ismail DERGAA

Amine Souissi

and 2 more

January 10, 2025
We applaud Kakad et al. for their convincing analysis of melatonin’s potential as a treatment for long-term COVID-19 (LC19), emphasizing its pleiotropic effects. Due to oxidative stress and chronic inflammation, LC19 has caused millions of people to suffer from cardiovascular problems such myocarditis and thrombosis. Even while corticosteroids are still a mainstay of treatment, long-term usage of them can have serious adverse effects, such as disruption of metabolism and disturbed sleep. In this letter, we present a novel chronotherapeutic strategy that combines evening melatonin supplementation with morning corticosteroid delivery that is timed to coincide with natural cortisol peaks. This approach seeks to minimize side effects brought on by corticosteroids while maximizing the anti-inflammatory and cardioprotective benefits of both drugs. The cardioprotective, anti-inflammatory, and antioxidant qualities of melatonin enhance corticosteroid treatment, potentially lowering dosages and improving patient results. In order to continue this strategy through coordinated, multi-center trials and guarantee thorough assessment and application of this potential therapeutic paradigm, we also support the creation of a Global LC19 Chronotherapy Consortium.
Enhanced sampled-data model predictive control via nonlinear lifting
Nuthasith Gerdpratoom
Fumiya Matsuzaki

Nuthasith Gerdpratoom

and 3 more

January 10, 2025
This paper introduces a novel nonlinear model predictive control (NMPC) framework that incorporates a lifting technique to enhance control performance for nonlinear systems. While the lifting technique has been widely employed in linear systems to capture intersample behaviour, their application to nonlinear systems remains unexplored. We address this gap by formulating an NMPC scheme that combines fast-sample fast-hold (FSFH) approximations and numerical methods to approximate system dynamics and cost functions. The proposed approach is validated through two case studies: the Van der Pol oscillator and the inverted pendulum on a cart. Simulation results demonstrate that the lifted NMPC outperforms conventional NMPC in terms of reduced settling time and improved control accuracy. These findings underscore the potential of the lifting-based NMPC for efficient control of nonlinear systems, offering a practical solution for real-time applications.
The evolution of migration is associated with distinct climates in temperate- versus...
Emily Johns
Oscar Johnson

Emily Johns

and 2 more

January 10, 2025
Avian migration has long captured human interest, but causes of the evolution of migration remain unclear due to limited study of the full spectrum of migratory strategies, including short-distance and intratropical movements. We examine the climatic drivers of migration across the roughly 1,300 species of suboscine birds, a group containing many intratropical migrants. Comparative analyses confirm that migratory behavior in temperate-breeding suboscines evolves in association with temperature seasonality. The evolution of migration in the tropics, however, has a more complex association with climatic variables including precipitation and greenness seasonality. Projections under future climates scenarios show that suboscines will experience average lower temperature seasonality, potentially favoring the loss of migration, but higher precipitation seasonality, potentially favoring an increase in short-distance migration. The divergent impacts of climate on the evolution of different migratory strategies highlights the complexity of climate-movement associations and the challenges of projecting responses to climate change.
Genomic correlates of disease recovery in natural populations of mountain yellow-legg...
Allison Byrne
Andrew Rothstein

Allison Byrne

and 3 more

January 10, 2025
In our rapidly changing world, evolution is likely to play an important role in facilitating the resilience of wildlife populations. The mountain yellow-legged frog (Rana muscosa/Rana sierrae) provides a rare example of recovery following severe declines caused by the amphibian chytrid fungus (Batrachochytrium dendrobatidis). However, the role of evolution in facilitating this recovery remains circumstantial. In this study, we sought to gain insights into the potential role of evolution by comparing genomes of frogs from naïve and recovering populations located in relatively close proximity. Using multiple methods to scan frog genomes for signatures of selection, our study reveals several genomic variants associated with frog recovery. Specifically, we identify gene variants in interferon-related genes and genes associated with the complement system and major histocompatibility complex (MHC). Additionally, we identify a recovery-associated variant in RIN3, a gene that may play a critical role in disease defense and wound healing. Finally, we report no differences in genetic diversity between naïve and recovering populations. We provide a rare example from natural populations that suggests that evolution can produce individuals that harbor adaptive alleles and allow population recovery in a novel environment. These findings complement recent research on amphibian immune evolution and provide mechanistic hypotheses for how individuals from populations can recover from disease.
Invasion genomics of the alpine newt in Britain reveal a complex history of introduct...
Rachel Hester
Jim Labisko

Rachel Hester

and 3 more

January 10, 2025
The spread of invasive species to regions outside of their typical, native range has been fuelled by globalization and trade, with human-facilitated introductions being a primary driver of invasion by non-native species. The alpine newt, Ichthyosaura alpestris is native to mainland Europe, and has become well-established at several locations across the UK, with a pattern of invasion in the UK suggesting both primary introductions from its native range, and secondary translocations from established sites. We sampled 95 individuals from 23 ponds in 11 sites across the UK and obtained their genomic SNP (Single Nucleotide Polymorphisms) data from ddRAD-sequencing to answer questions about the invasion history of these UK non-native amphibians. In conjunction with these genomic tools, anecdotal evidence is also used to better understand the pattern of invasion and subsequent spread of alpine newts across the country. Our results provide an insight into the genetic variation within these populations, with strong population structure among sites and ponds within a site. Population structure analyses also provide evidence for human-assisted movement of newts within the UK and the results are consistent with multiple independent introductions. Such findings support the idea that human-mediated translocation plays a central role in the movement of alpine newts around the UK. This research illustrates how genomics can be used in conjunction with historical data to better understand the invasion history of non-native organisms.
Mining Alzheimer's Interactomes, Macromolecular Complexes and Pathways for drug disco...
Kalpana Panneerselvam
Krishna Kumar Tiwari

Kalpana Panneerselvam

and 12 more

January 10, 2025
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that leads to dementia. Many cases are diagnosed annually and there is no currently available cure. Understanding the underlying disease biology of AD through the study of molecular networks, particularly by mapping clinical variants to tissue-specific interactomes and regulatory macromolecular assemblies, offers a promising avenue to elucidate altered disease pathways. This, in turn, could provide valuable insights for drug discovery. In this study, we leverage our manually curated AD-specific dataset from the IMEx consortium, which provides detailed interaction data, including the relationship between interacting partners, detection in specific host tissues and cell lines, and the impact of variants on interaction outcomes. By integrating these data with information on protein complex composition taken from the Complex Portal, we have identified relevant macromolecular assemblies enriched in AD networks. Further pathway enrichment analysis is conducted using Reactome, enabling a comprehensive exploration of disease mechanisms and potential therapeutic targets.
Glucagon-like Peptide 1 Receptor Agonists in Asthma Exacerbations: an Application of...
Tiansheng Wang
Jeanny Wang H

Tiansheng Wang

and 9 more

January 10, 2025
BACKGROUND: Glucagon-like Peptide 1 Receptor Agonists (GLP1RA) may reduce asthma exacerbation (AE) risk, but it is unclear which populations benefit most. Recent pharmacoepidemiologic studies have employed iterative causal forest (iCF), a machine learning (ML) algorithm to identify subgroups with heterogeneous treatment effects. While iCF do not rely on prior knowledge of treatment-variable interactions, it may be constrained by missing or misdefined variables in pharmacepidemiology studies. METHODS: We applied the high-dimensional iterative causal forest (hdiCF), a causal ML algorithm that does not reply on predefined variables, to MarketScan 2016-2020 claims data to identify populations with asthma that might benefit most from GLP1RA in reducing AE risk. We built a GLP1RA vs sulfonylurea new-user cohort with ≥ 1 inpatient or 2 outpatient asthma encounters, excluding patients with non-asthma indications for systemic steroids. Using 599 high-dimensional features from inpatient/outpatient services and pharmacy claims, patients were followed for 6 months from their second prescription. The outcome was acute AE (hospital admission or emergency department visit for asthma). RESULTS: In the overall population, GLP1RA decreased AE risk relative to sulfonylurea: aRD -1.4% (-2.0%, -0.8%). hdiCF identified 3 subgroups based on systemic steroid prescription fills (0, 1, and ≥2): patients with ≥2 systemic steroid prescriptions (GLP1RA: 34 events/1367 individuals; sulfonylurea: 53/1013) benefited most from GLP1RA: aRD -3.8% (-5.3%, -2.2%). CONCLUSIONS: This study demonstrates how automated feature identification can pinpoint clinically relevant subgroups with varying treatment effects. Systemic steroid use, as a proxy for severe asthma, may guide personalized predictions of GLP1RA’s short-term benefits on acute AE.
Plasticity of larval dispersal-related traits in the orange anemonefish
Robin Francis
Kurt Castro

Robin Francis

and 5 more

January 10, 2025
A major goal in marine ecology is to understand patterns of larval dispersal and population connectivity. Dispersal plasticity allows for adaptive variation in dispersal phenotypes in response to variation in environmental conditions and may help to explain intraspecific variation in dispersal distances. However, this phenomenon has not yet been investigated in marine fishes. Here, we test the hypothesis that parents produce larvae with different dispersal-related traits in response to variation in environmental quality using the orange anemonefish, Amphiprion percula. By experimentally manipulating food rations, we show that parents produce larger offspring on low-food rations than on high-food rations. However, there was no effect of parental diet on larval critical swimming speed. We also found an effect on larval otolith core size which, in combination with parentage analyses, may provide a way to test the dispersal plasticity hypothesis in the field. This study shows that parents can produce different larval phenotypes in response to variation in environmental conditions, demonstrating plasticity in a dispersal-related trait which may help to explain observed variation in A. percula larval dispersal distances. Incorporating dispersal plasticity into our understanding of marine dispersal patterns may enhance our understanding of marine metapopulation ecology, fisheries management, and conservation.
Development and characterization of Adeno-associated virus-loaded coaxial electrospun...
Haiguang Zhang
Bing Zhou

Haiguang Zhang

and 9 more

January 10, 2025
Gene therapy, which treats genetic diseases by fixing defective genes, has gained significant attention. Viral vectors show great potential for gene delivery but face limitations like low transduction efficiency and poor targeting. Loading viral vectors onto tissue engineered scaffolds presents a promising strategy to address these challenges, but their widespread application remains limited by challenges like vector stability, biomaterial selection, and high manufacturing costs. Adeno-associated virus (AAV), recognized for its safety, high efficiency, and low immunogenicity, was employed as a model virus. In this study, AAV was encapsulated within electrospun fibers (AAV/PCL-PEO@Co-ES) composed of polycaprolactone (PCL) and polyethylene oxide (PEO) via coaxial electrospinning, ensuring effective AAV protection and controlled release. The physicochemical characterization results indicated that the scaffold exhibited excellent mechanical properties (tensile strength: 3.22 ± 0.48 MPa) and wettability (WCA: 67.90 ± 8.45°). In vitro release and cell transduction assays demonstrated that the AAV-loaded scaffold effectively control viral vector release and transduction. Furthermore, the in vitro cell and in vivo animal experiments suggested that the AAV-loaded scaffolds exhibit excellent biocompatibility and efficient viral vector delivery capability. Hence, our research not only enhances the storage and delivery of viral vectors but also provides innovative solutions for viral vector delivery strategies.
Epigenetic Aging Clock for Long-Lived Fish Collected from the Wild
Ellen Weise
Cait Nemeczek

Ellen Weise

and 4 more

January 10, 2025
Age information is fundamental in population biology. In fisheries management, robust and effective stock assessment models rely on fecundity and survival rates, and other life history traits that are generally age specific. Current aging methods for most fish species are based on the number of otolith growth rings, a time intensive method that requires lethal sampling and highly specialized expertise. To supplement current otolith-based aging efforts, here we develop a DNA methylation approach for aging Atlantic Halibut. We conducted whole-genome methylation sequencing on 66 wild caught individuals with otolith-derived age estimates. The resulting 14,588 CpG sites were evaluated as predictors of age in an elastic net model. We found a strong positive linear correlation between otolith age and predictions using a subset of 87 CpG sites selected by the elastic net model that had a mean absolute error of less than one year. The enzymatic treatment required for methylation sequencing with short-read technology like Illumina is still cost-prohibitive for routine application of large numbers of individuals. Accordingly, we conducted a successful pilot test to use adaptive nanopore sequencing for rapid, large-scale aging, and developed a framework to process the data for use in an aging framework. Our technique can be used to age Atlantic halibut when non-lethal sampling is needed (e.g., tagging studies) and to supplement otolith aging data for lethally sampled fish.
Cas11 augments Cascade functions in type I-E CRISPR system but is redundant for gene...
Neha Pandey
Chitra S. Misra

Neha Pandey

and 2 more

January 10, 2025
The structural and mechanistic complexity of Escherichia coli’s type I CRISPR-Cas system compared to the multidomain, single effector protein-based type II systems, limits its application in genome editing and silencing. Despite higher prevalence of the type I endogenous systems in bacteria, significant research has focused on improving the type II systems. While the type-I CRISPR system possesses several advantages over others, it may benefit from further studies to simplify the system for ease of use. To enable this, the dispensability of the type-I Cascade components (Cas8, Cas11, Cas7, Cas5, Cas6) for genome editing and silencing applications was evaluated in vivo. We created deletion variants of each of the Cascade components and investigated their effects on gene silencing and plasmid interference in two genetically distinct Escherichia coli lineages, BW25113, a K-12 strain that bears an endogenous, albeit repressed type I-E CRISPR system and BL21, a natural mutant lacking the type I-E CRISPR-Cascade system. Cas8, Cas7 and Cas5 were found to be indispensable for gene silencing and plasmid interference. Dispensability of Cas6, which is involved in crRNA maturation, was strain-dependent. Notably, Cas11 which has no definitive function assigned to it, was found to be dispensable for gene silencing and plasmid interference.
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