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In this study, we investigated primary school children's perspectives on their hearing and listening in classrooms with different acoustic quality levels. The sample included 213 children. The children completed a self-report questionnaire rating how well they could hear and listen in various situations in classrooms with two different acoustic conditions: "Poor acoustic quality" (long reverberation time [Long RT]) versus "Adequate acoustic quality" (short reverberation time [Short RT]) equipped with a sound-absorbing system. The results showed that auditory perception in the two conditions depends on the child's age, with only fourth- and fifth-grade children reporting benefits from classroom acoustic correction. Our study provides preliminary results on children's perspectives regarding their hearing and listening experiences during school learning, drawing out the implications for the design and implementation of school metacognitive interventions aimed at improving children's and teachers' awareness of motivational-affective, regulative, and environmental aspects favoring listening at school.

Synthetic genetic oscillators can serve as internal clocks within engineered cells to program periodic expression. However, cell-to-cell variability introduces a dispersion in the characteristics of these clocks that drives the population to complete desynchronization. Here, we introduce the optorepressilator, an optically controllable genetic clock that combines the repressilator, a three-node synthetic network in E. coli, with an optogenetic module enabling to reset, delay, or advance its phase using optical inputs. We demonstrate that a population of optorepressilators can be synchronized by transient green light exposure or entrained to oscillate indefinitely by a train of short pulses, through a mechanism reminiscent of natural circadian clocks. Furthermore, we investigate the system’s response to detuned external stimuli observing multiple regimes of global synchronization. Integrating experiments and mathematical modeling, we show that the entrainment mechanism is robust and can be understood quantitatively from single cell to population level.

Marsh terraces, constructed as a restoration and protection strategy, consist of a series of earthen berms in open water areas of the coastal wetland landscape and are being implemented across the Louisiana coast. To assess the efficacy of the marsh terraces as a nature-based solution, a small-scale, high-resolution hydrodynamic model was developed based on field sampling of vegetation and physical parameters (water level, waves, sediment, turbidity, and terrace elevation). This study tested common marsh terrace designs (e.g., chevron, linear, box, T-shape, etc.), ultimately selecting a preferred design based on the evaluation of factors such as vegetation, water depth, and sediment type on terrace stability and sediment retention under calm and storm conditions. The model results revealed that the 100 m box and the chevron designs exhibited greatest terrace stability and sediment trapping, particularly when installed perpendicular to prevailing wind and waves. The preferred terrace design was the box design due to its higher modeled resilience to wind and waves from multiple directions. Vegetation presence enhanced terrace resistance to erosion, with variations depending on vegetation type. Higher vegetation biomass, especially during the summer, contributed to the greatest stability of terraces. Greater water depth between terraces led to increased sediment retention, and terraces predominantly composed of organic-rich mud demonstrated greater stability than those with higher proportions of sand. Overall, vegetation had the greatest impact on sediment retention in the terrace field compared to water depth and sediment type. However, the potential habitat for submerged aquatic vegetation (SAV) was more influenced by water depth (i.e., 0.1 m < depth

The gut microbiota plays a crucial role in dogs’ health, influencing immune function, digestion, and protection against pathogens. This study evaluates the effects of three canine dietary supplements—Microbiotal (prebiotic), Lactobacillus reuteri (probiotic), and a combination of both—on the gut microbiota composition of a healthy canine donor using an in vitro colonic fermentation model. The SCIME™ platform, adapted to simulate the canine gastrointestinal tract, was used to monitor microbial shifts in the luminal and mucosal environments of the proximal and distal colon over a 2-week treatment period. The microbial communities were analyzed using 16S rRNA sequencing to assess changes at various taxonomic levels. Alpha- and beta-diversity indices were calculated, while LEfSe and treeclimbR were employed to identify taxa-driving microbial shifts. Results indicated that all treatments led to significant modulations in key microbial groups, with enrichment of Limosilactobacillus, Bifidobacterium, Prevotella, and Faecalibacterium. These changes suggest improved saccharolytic fermentation and butyrate production, particularly when prebiotics and probiotics were co-administered. This study highlights the promising benefits of combined prebiotic and probiotic supplementation in promoting gut health and microbial diversity, providing a basis for future studies targeting the metabolic activity of the gut microbiota using the same supplements and technology.

We discuss a microswimmer model made of three spheres actuated by an internal active time-periodic force, tied by an elastic potential, and submitted to hydrodynamic interactions with thermal noise. The dynamical approach we use, replacing the more common kinematic one, shows the instability of the original model and the need of a confining potential to prevent the evaporation of the swimmer. We investigate the effect of the main parameters of the model, such as the frequency and phase difference of the periodic active force, the stiffness of the confining potential, the length of the swimmer and the temperature and viscosity of the fluid. Our observables of interest are the averages of the swim velocity, the energy consumption rate, the diffusion coefficient, and the swimming precision, which is limited by the energy consumption through the celebrated thermodynamic uncertainty relations. An optimum for velocity and precision is found for an intermediate frequency. Reducing the potential stiffness, the viscosity, or the length is also beneficial for the swimming performance, but these parameters are limited by the consistency of the model. Analytical approximation for many of the relevant observables is obtained for small deformations of the swimmer. We also discuss the efficiency of the swimmer in terms of its maximum precision and of the hydrodynamic, or Lighthill, criterion, and how they are connected.

In Louisiana's Capital Area Groundwater Conservation District (CAGWCD), extensive groundwater withdrawals from the Southern Hills Aquifer System have begun to accelerate the infiltration of saltwater into the aquifer's freshwater sands. This accelerated saltwater intrusion has the potential to reduce the amount of groundwater available for public consumption and other industrial and agricultural uses throughout the region. In response to this threat, the Capital Area Ground Water Conservation Commission has begun development of a long-term strategic plan to achieve and maintain sustainable and resilient groundwater withdrawals from the aquifer system. The development of the strategic plan includes an assessment of public attitudes regarding groundwater and groundwater management in the CAGWCD. This paper presents the results of mixed methods public participatory research to evaluate current and historical views and attitudes around groundwater quality, quantity, and cost in the CAGWCD. The mixed methods approach used in this research employed a sequential explanatory design model consisting of two phases. The first phase involved the implementation of an internet-based survey, followed by a qualitative phase aimed at explaining and enhancing the quantitative results. The qualitative phase employed a combination of one-on-one interviews and focus groups. The research found that the primary governance obstacle that decision-makers may face in managing groundwater is a broad lack of public awareness of groundwater and groundwater issues in the CAGWCD. Despite the criticality of over-pumping and saltwater intrusion into the aquifer system, survey research and subsequent interviews and focus groups have shown that the public is largely unaware of these issues. This research also found a general lack of trust in both industry and government to manage groundwater issues and highlighted the need for groundwater management efforts to be led by unbiased, trusted institutions.

Engineered bacteria have the potential to deliver therapeutic payloads directly to tumors, with synthetic biology enabling precise control over therapeutic release in space and time. However, it remains unclear how to optimize therapeutic bacteria for durable colonization and sustained payload release. Here, we characterize nonpathogenic Escherichia coli expressing the bacterial toxin Perfringolysin O (PFO) and dynamic strategies that optimize therapeutic efficacy. While PFO is known for its potent cancer cell cytotoxicity, we present experimental evidence that expression of PFO causes lysis of bacteria in both batch culture and microfluidic systems, facilitating its efficient release. However, prolonged expression of PFO leads to the emergence of a mutant population that limits therapeutic-releasing bacteria in a PFO expression level-dependent manner. We present sequencing data revealing the mutant takeover and employ molecular dynamics to confirm that the observed mutations inhibit the lysis efficiency of PFO. To analyze this further, we developed a mathematical model describing the evolution of therapeutic-releasing and mutant bacteria populations revealing trade-offs between therapeutic load delivered and fraction of mutants that arise. We demonstrate that a dynamic strategy employing short and repeated inductions of the pfo gene better preserves the original population of therapeutic bacteria by mitigating the effects of mutational escape. Altogether, we demonstrate how dynamic modulation of gene expression can address mutant takeovers giving rise to limitations in engineered bacteria for therapeutic applications.

Light can be used to precisely modulate the speed of active particles in space and time. Here, the authors rectify and confine bacteria using an optical feedback loop that couples bacteria topast configurations.

Methylation of cytosine in CpG dinucleotides is an epigenetic modification carried out by DNA-methyltransferases (DNMTs) that contributes to chromatin condensation and structure and, thus, to gene transcription regulation and chromosome stability. DNMT1 maintains the DNA methylation pattern of the genome at each cell cycle by copying it to the newly synthesized DNA strand during the S-phase. DNMT1 pharmacological inhibition as well as genetic knockout and knockdown, leads to passive DNA methylation loss. However, these strategies have been associated with different cell fates, even in the same cell background, suggesting that they can question the interpretation of the obtained results. Using a cell system in which endogenous DNMT1 is fused with an inducible degron and can be rapidly degraded, we found that in non-tumoral RPE-1 cells, DNMT1 loss progressively induced cell proliferation slowing-down and cell cycle arrest at the G1/S transition. The latter is due to p21 activation, which is partly mediated by p53 and leads to a global reduction in DNA methylation. DNMT1 restoration rescues cell proliferation, indicating that its deregulation is sensed as tunable cellular stress. [ABSTRACT FROM AUTHOR]

In this study, we investigated primary school children's perspectives on their hearing and listening in classrooms with different acoustic quality levels. The sample included 213 children. The children completed a self-report questionnaire rating how well they could hear and listen in various situations in classrooms with two different acoustic conditions: Poor acoustic quality (long reverberation time [Long RT]) versus Adequate acoustic quality (short reverberation time [Short RT]) equipped with a sound-absorbing system. The results showed that auditory perception in the two conditions depends on the child's age, with only fourth- and fifth-grade children reporting benefits from classroom acoustic correction. Our study provides preliminary results on children's perspectives regarding their hearing and listening experiences during school learning, drawing out the implications for the design and implementation of school metacognitive interventions aimed at improving children's and teachers' awareness of motivational-affective, regulative, and environmental aspects favoring listening at school. [ABSTRACT FROM AUTHOR]

Simple Summary: Gut microbiota significantly influences dogs' well-being, and several researchers have made strides in characterizing canine gut microbiota composition. Recent research has revealed that the canine gut microbiota is highly impacted by the type of diet. Prebiotics (non-digestible oligosaccharides able to promote the growth of beneficial bacteria) and probiotics (live microorganisms that confer a health benefit by enhancing microbial diversity) can modulate the gut microbiota and promote gastrointestinal health. A growing interest has recently been in combining prebiotics and probiotics (synbiotics) to achieve synergistic effects. The present study aimed to investigate the effects of supplementation with a prebiotic (Microbiotal) and a probiotic (L. reuteri) using the fecal microbiota of a healthy canine donor. The investigators used a novel in vitro fermentation platform (SCIME™), which closely mimics the canine gastrointestinal tract, allowing long-term experiments. This study demonstrates the promising modulatory effects of prebiotics and probiotics, especially when combined. The gut microbiota plays a crucial role in dogs' health, influencing immune function, digestion, and protection against pathogens. This study evaluates the effects of three canine dietary supplements—Microbiotal (prebiotic), Lactobacillus reuteri (probiotic), and a combination of both—on the gut microbiota composition of a healthy canine donor using an in vitro colonic fermentation model. The SCIME™ platform, adapted to simulate the canine gastrointestinal tract, was used to monitor microbial shifts in the luminal and mucosal environments of the proximal and distal colon over a 2-week treatment period. The microbial communities were analyzed using 16S rRNA sequencing to assess changes at various taxonomic levels. Alpha- and beta-diversity indices were calculated, while LEfSe and treeclimbR were employed to identify taxa-driving microbial shifts. Results indicated that all treatments led to significant modulations in key microbial groups, with enrichment of Limosilactobacillus, Bifidobacterium, Prevotella, and Faecalibacterium. These changes suggest improved saccharolytic fermentation and butyrate production, particularly when prebiotics and probiotics were co-administered. This study highlights the promising benefits of combined prebiotic and probiotic supplementation in promoting gut health and microbial diversity, providing a basis for future studies targeting the metabolic activity of the gut microbiota using the same supplements and technology. [ABSTRACT FROM AUTHOR]

Marsh and mangrove forest habitats are productive at capturing and storing carbon, thus actions to protect and create coastal blue carbon sinks could help mitigate global warming. Dredged material is often used to create coastal habitats and evaluating the carbon impact of placement alternatives (PA) could help inform restoration and climate policies. Output from a Delft3D‐FM morphodynamics and hydrodynamics model informed a Coastal Wetlands Carbon Model at years 2020, 2025, 2030, and 2050. Three model simulations were used and included (1) no restoration (PA1), (2) restoration dominated with mangroves (PA2), and (3) restoration dominated with marshes (PA3) at a different location. Habitats of brackish marsh, saline marsh, mangrove forest, and saline open water that surround Port Fourchon, Louisiana, U.S.A., were evaluated to estimate the net greenhouse gas (GHG) flux of the study area with and without restoration. In years 2020 and 2025, the study area was estimated to be a net GHG sink (−1.1 ± 0.2 MMT CO2e) with or without mangrove and marsh‐dominated restoration. At years 2030 and 2050, even with habitat loss due to sea‐level rise, the study area for all simulations was projected to remain a net GHG sink. At year 2050, +0.1 ± 0.04 MMT CO2e could be avoided with restoration. At the restoration project scale, mangrove‐dominated restoration (PA2) had net GHG sinks (−0.07 to −0.09 MMT CO2e) near the marsh‐dominated restoration (PA3, −0.09 to −0.13 MMT CO2e). Thus, these modeled results could help inform future restoration planning and climate policies. [ABSTRACT FROM AUTHOR]

Port Fourchon is a vital staging area for Gulf of Mexico energy production and is strategically located in the Barataria-Terrebonne Estuary System, a biologically and economically productive ecosystem bounded by the Atchafalaya and Mississippi Rivers. This is also one of the most fragile and rapidly evolving landscapes in the United States, making the port and surrounding communities highly vulnerable to natural hazards and the impacts of climate change. Building resilience to climate-based disruptions is vital to Port Fourchon and other businesses operating in this dynamic landscape. The port plans to deepen its channel to 50 feet (15 m) to service larger vessels, generating millions of cubic yards of sediment and seeks to beneficially utilize this sediment to develop natural and nature-based solutions to help prepare for future challenges. To accomplish this goal, an Environmental Competency Group consisting of residents, coastal scientists, and key stakeholders was convened to co-develop and evaluate a series of marsh creation projects utilizing this sediment that will maximize social and ecological co-benefits and enhance the resilience of Port Fourchon and the surrounding communities. The group utilized participatory modeling and social return on investment methods to model long-term changes to the landscape and wetland vegetation communities resulting from the co-developed restoration strategies and assess the social value of these strategies. Residents who live and work around Port Fourchon were included in all stages of this research, including development and prioritization of potential restoration areas, identifying important physical and ecological parameters that should be modeled, evaluation of model results, and assessment of the social values expected to be generated by each restoration alternative under consideration. The transdisciplinary approach used in this research highlights the effectiveness of a community-informed, systematic approach to coastal restoration planning in building community resilience and ecosystem sustainability. This study provides approaches and tools that can be adapted for use elsewhere to develop holistic solutions that maximize the social, ecological, and economic co-benefits of coastal restoration.

Abstract Inflammation is a physiological process whose deregulation causes some diseases including cancer. Nuclear Factor kB (NF-kB) is a family of ubiquitous and inducible transcription factors, in which the p65/p50 heterodimer is the most abundant complex, that play critical roles mainly in inflammation. Glucocorticoid Receptor (GR) is a ligand-activated transcription factor and acts as an anti-inflammatory agent and immunosuppressant. Thus, NF-kB and GR are physiological antagonists in the inflammation process. Here we show that in mice and humans there is a spliced variant of p65, named p65 iso5, which binds the corticosteroid hormone dexamethasone amplifying the effect of the glucocorticoid receptor and is expressed in the liver of patients with hepatic cirrhosis and hepatocellular carcinoma (HCC). Furthermore, we have quantified the gene expression level of p65 and p65 iso5 in the PBMC of patients affected by SARS-CoV-2 disease. The results showed that in these patients the p65 and p65 iso5 mRNA levels are higher than in healthy subjects. The ability of p65 iso5 to bind dexamethasone and the regulation of the glucocorticoid (GC) response in the opposite way of the wild type improves our knowledge and understanding of the anti-inflammatory response and identifies it as a new therapeutic target to control inflammation and related diseases.

β2-glycoprotein I (β2-GPI) is a serum protein widely recognized as the main target of antibodies present in patients with antiphospholipid syndrome (APS). β2-GPI binds to activated endothelial cells, platelets and leukocytes, key players in thrombus formation. We developed a new targeted thrombolytic agent consisting of nanobubbles (NB) coated with recombinant tissue plasminogen activator (rtPA) and a recombinant antibody specific for cell-bound β2-GPI. The therapeutic efficacy of targeted NB was evaluated in vitro, using platelet-rich blood clots, and in vivo in three different animal models: i) thrombosis developed in a rat model of APS; ii) ferric chloride-induced mesenteric thrombosis in rats, and iii) thrombotic microangiopathy in a mouse model of atypical hemolytic uremic syndrome (C3-gain-of-function mice). Targeted NB bound preferentially to platelets and leukocytes within thrombi and to endothelial cells through β2-GPI expressed on activated cells. In vitro, rtPA-targeted NB (rtPA-tNB) induced greater lysis of platelet-rich blood clots than untargeted NB. In a rat model of APS, administration of rtPA-tNB caused rapid dissolution of thrombi and, unlike soluble rtPA that induced transient thrombolysis, prevented new thrombus formation. In a rat model of ferric chloride triggered thrombosis, rtPA-tNB, but not untargeted NB and free rtPA, induced rapid and persistent recanalization of occluded vessels. Finally, treatment of C3-gain-of-function mice with rtPA-tNB, that target β2-GPI deposited in kidney glomeruli, decreased fibrin deposition, and improved urinalysis data with a greater efficiency than untargeted NB. Our findings suggest that targeting cell-bound β2-GPI may represent an efficient and thrombus-specific thrombolytic strategy in both APS-related and APS-unrelated thrombotic conditions.

ABSTRACT Knowledge of the organizational and functional properties of hydrogen metabolism is pivotal to the construction of a framework supportive of a hydrogen-fueled low-carbon economy. Hydrogen metabolism relies on the mechanism of action of hydrogenases. In this study, we investigated the genomes of several industrially relevant acetogens of the genus Clostridium (C. autoethanogenum, C. ljungdahlii, C. carboxidivorans, C. drakei, C. scatologenes, C. coskatii, C. ragsdalei, C. sp. AWRP) to systematically identify their intriguingly diversified hydrogenases’ repertoire. An entirely computational annotation pipeline unveiled common and strain-specific traits in the functional content of [NiFe]- and [FeFe]-hydrogenases. Hydrogenases were identified and categorized into functionally distinct classes by the combination of sequence homology, with respect to a database of curated nonredundant hydrogenases, with the analysis of sequence patterns characteristic of the mode of action of [FeFe]- and [NiFe]-hydrogenases. The inspection of the genes in the neighborhood of the catalytic subunits unveiled a wide agreement between their genomic arrangement and the gene organization templates previously developed for the predicted hydrogenase classes. Subunits’ characterization of the identified hydrogenases allowed us to glean some insights on the redox cofactor-binding determinants in the diaphorase subunits of the electron-bifurcating [FeFe]-hydrogenases. Finally, the reliability of the inferred hydrogenases was corroborated by the punctual analysis of the maturation proteins necessary for the biosynthesis of [NiFe]- and [FeFe]-hydrogenases. IMPORTANCE Mastering hydrogen metabolism can support a sustainable carbon-neutral economy. Of the many microorganisms metabolizing hydrogen, acetogens of the genus Clostridium are appealing, with some of them already in usage as industrial workhorses. Having provided detailed information on the hydrogenase content of an unprecedented number of clostridial acetogens at the gene level, our study represents a valuable knowledge base to deepen our understanding of hydrogenases’ functional specificity and/or redundancy and to develop a large array of biotechnological processes. We also believe our study could serve as a basis for future strain-engineering approaches, acting at the hydrogenases’ level or at the level of their maturation proteins. On the other side, the wealth of functional elements discussed in relation to the identified hydrogenases is worthy of further investigation by biochemical and structural studies to ultimately lead to the usage of these enzymes as valuable catalysts.