Hemodynamic response of the aortic valve during dobutamine onset then progressive aortic banding.

An increasing number of procedures over the past two decades for aortic stenosis (AS) reflects the combination of an aging population and less invasive transcatheter options. As a result, the hemodynamics of the aortic valve (AV) have gained renewed interest to understand its behavior and to optimize patient selection. We studied the hemodynamic relationship between pressure loss (ΔP) and transvalvular flow (Q) of the normal AV as well as the impact of a variable supravalvular stenosis.

Antagonistic systemin receptors integrate the activation and attenuation of systemic wound signaling in tomato.

Pattern recognition receptor (PRR)-mediated perception of damage-associated molecular patterns (DAMPs) triggers the first line of inducible defenses in both plants and animals. Compared with animals, plants are sessile and regularly encounter physical damage by biotic and abiotic factors. A longstanding problem concerns how plants achieve a balance between wound defense response and normal growth, avoiding overcommitment to catastrophic defense.

Targeted Genome Mining Facilitates the Discovery of a Promiscuous, Hyperthermostable Amidase from Thermovenabulum Gondwanense with Notable Nylon-Degrading Capacity.

Plastics are ubiquitous in our ecosystems, and microplastic accumulation in the environment is an emerging global health concern. Since available recycling technologies are not economically competitive with primary plastic production, global use is expected to reach 1231 megatons by 2060, with 493 megatons leeching into the environment each year. To identify new nylon-recycling biotechnologies, targeted genome mining was used to identify thermostable enzymes capable of degrading polyamides.

An autonucleolytic suspension HEK293F host cell line for high-titer serum-free AAV5 and AAV9 production with reduced levels of DNA impurity.

We sought to engineer mammalian cells to secrete nuclease activity as a step toward removing the need to purchase commercial nucleases as process additions in bioprocessing of AAV5 and AAV9 as gene therapy vectors. Engineering HeLa cells with a serratial nuclease transgene did not bring about nuclease activity in surrounding media whereas engineering serum-free, suspension-adapted HEK293F cells with a staphylococcal nuclease transgene did result in detectable nuclease activity in surrounding media of the resultant stable transfectant cell line, "NuPro-1S." When cultivated in serum-free media, NuPro-1S cells yielded 3.

Genetically Encoded Trensor Circuits Report HeLa Cell Treatment with Polyplexed Plasmid DNA and Small-Molecule Transfection Modulators.

HeLa cell transfection with plasmid DNA (pDNA) is widely used to materialize biologicals and as a preclinical test of nucleic acid-based vaccine efficacy. We sought to genetically encode mammalian transfection sensor (Trensor) circuits and test their utility in HeLa cells for detecting molecules and methods for their propensity to influence transfection. We intended these Trensor circuits to be triggered if their host cell was treated with polyplexed pDNA or certain small-molecule modulators of transfection.

The frequency and chemical phenotype of neighboring plants determine the effects of intraspecific plant diversity.

Associational effects, whereby plants influence the biotic interactions of their neighbors, are an important component of plant-insect interactions. Plant chemistry has been hypothesized to mediate these interactions. The role of chemistry in associational effects, however, has been unclear in part because the diversity of plant chemistry makes it difficult to tease apart the importance and roles of particular classes of compounds.

The Impact of Sparse Datasets When Harmonizing Data from Studies with Different Measures of the Same Construct.

Prevention science has increasingly turned to integrative data analysis (IDA) to combine individual participant-level data from multiple studies of the same topic, allowing us to evaluate overall effect size, test and model heterogeneity, and examine mediation. Studies included in IDA often use different measures for the same construct, leading to sparse datasets. We introduce a graph theory method for summarizing patterns of sparseness and use simulations to explore the impact of different patterns on measurement bias within three different measurement models: a single common factor, a hierarchical model, and a bifactor model.

Heat waves induce milkweed resistance to a specialist herbivore via increased toxicity and reduced nutrient content.

Over the last decade, a large effort has been made to understand how extreme climate events disrupt species interactions. Yet, it is unclear how these events affect plants and herbivores directly, via metabolic changes, and indirectly, via their subsequent altered interaction. We exposed common milkweed (Asclepias syriaca) and monarch caterpillars (Danaus plexippus) to control (26:14°C, day:night) or heat wave (HW) conditions (36:24°C, day:night) for 4 days and then moved each organism to a new control or HW partner to disentangle the direct and indirect effects of heat exposure on each organism.

Intramolecular Cyclization and a Retro-Ene Reaction Enable the Rapid Fragmentation of a Vitamin B-Derived Breslow Intermediate.

In solution, analogues of the Breslow intermediate formed during catalysis by benzoylformate decarboxylase (BFDC) undergo rapid, irreversible fragmentation. The ability of BFDC to prevent this reaction and preserve its cofactor is a striking example of an enzyme 'steering' a reactive intermediate towards a productive pathway. To understand how BFDC suppresses the off-pathway reactivity of this Breslow intermediate, a clear mechanistic understanding of the fragmentation reaction is required.

Genome Mining Leads to the Identification of a Stable and Promiscuous Baeyer-Villiger Monooxygenase from a Thermophilic Microorganism.

Baeyer-Villiger monooxygenases (BVMOs) are NAD(P)H-dependent flavoproteins that convert ketones to esters and lactones. While these enzymes offer an appealing alternative to traditional Baeyer-Villiger oxidations, these proteins tend to be either too unstable or exhibit too narrow of a substrate scope for implementation as industrial biocatalysts. Here, sequence similarity networks were used to search for novel BVMOs that are both stable and promiscuous.

Are gel blasters a safe toy? A study into their kinetic energy per unit area.

Gel blasters are currently imported and marketed as children's toys in Australia. Gel blasters closely imitate the appearance of many genuine firearms of all types and are designed to propel small hydrated gel balls of approximately 7-8 mm in diameter, by means of compressed air or gas. They are considered illegal in all states of Australia except Queensland but these items aren't specifically written into most state firearms legislation.

Energetics of a World-Tour Female Road Cyclist During a Multistage Race (Tour de France Femmes).

Despite the increased popularity of female elite road cycling, research to inform the fueling requirements of these endurance athletes is lacking. In this case study, we report for the first time the energetics of a female world-tour cyclist competing in the 2023 Tour de France Femmes, an 8-day race of the Union Cycliste Internationale. The 29-year-old athlete presented with oligomenorrhea and low T3 before the race.

Analysis of unknown (unlabeled/mislabeled) drug products for active pharmaceutical ingredients and related substances by an international mail facility satellite laboratory equipped with rapid screening devices.

Two chemists employed a three-device rapid screening "toolkit" consisting of a handheld Raman spectrometer, transportable mass spectrometer, and portable Fourier transform infrared (FT-IR) spectrometer at an international mail facility (IMF) satellite laboratory to examine unknown (unlabeled/mislabeled) products for the presence of active pharmaceutical ingredients (APIs). Phase I of this project previously demonstrated that this toolkit was the most effective collection of instruments for identifying APIs in product types collected at IMFs during a nationwide mail blitz and Phase II of this project previously demonstrated that results generated using the toolkit during a satellite laboratory pilot program were as reliable as those generated by a full-service library when two or more of these instruments identify an API. This study (Phase III) described the results of the satellite laboratory toolkit during production mode and encompassed the period ranging from June 2021 through December 2022.

Tailored photoacoustic apertures with superimposed optical holograms.

A new method of generating potentially arbitrary photoacoustic wavefronts with optical holograms is presented. This method uses nanosecond laser pulses at 1064 nm that are split into four time-delayed components by means of a configurable multipass optical delay apparatus, which serves to map the pulses onto phase-delayed regions of a given acoustic wavefront. A single spatial light modulator generates separate holograms for each component, which are imaged onto a photoacoustic transducer comprised of a thermoelastic polymer.

Phytohormones in a universe of regulatory metabolites: lessons from jasmonate.

Small-molecule phytohormones exert control over plant growth, development, and stress responses by coordinating the patterns of gene expression within and between cells. Increasing evidence indicates that currently recognized plant hormones are part of a larger group of regulatory metabolites that have acquired signaling properties during the evolution of land plants. This rich assortment of chemical signals reflects the tremendous diversity of plant secondary metabolism, which offers evolutionary solutions to the daunting challenges of sessility and other unique aspects of plant biology.

Transmembrane stem factor nanodiscs enhanced revascularization in a hind limb ischemia model in diabetic, hyperlipidemic rabbits.

Therapies to revascularize ischemic tissue have long been a goal for the treatment of vascular disease and other disorders. Therapies using stem cell factor (SCF), also known as a c-Kit ligand, had great promise for treating ischemia for myocardial infarct and stroke, however clinical development for SCF was stopped due to toxic side effects including mast cell activation in patients. We recently developed a novel therapy using a transmembrane form of SCF (tmSCF) delivered in lipid nanodiscs.

Engineering an Autonucleolytic Mammalian Suspension Host Cell Line to Reduce DNA Impurity Levels in Serum-Free Lentiviral Process Streams.

We engineered HEK293T cells with a transgene encoding tetracycline-inducible expression of a nuclease incorporating a translocation signal. We adapted the unmodified and nuclease-engineered cell lines to grow in suspension in serum-free media, generating the HEK293TS and NuPro-2S cell lines, respectively. Transient transfection yielded 1.

Examining insomnia disorder and stress generation among individuals who have experienced involuntary job loss.

Objective: Depressed individuals generate more stressful life events than non-depressed individuals. Like depressive symptoms, the symptoms of insomnia disorder may lead to impaired decision-making, daytime sleepiness, fatigue, and emotion dysregulation, yet the prospective relationship with insomnia disorder and stress generation has not previously been investigated. We hypothesized that insomnia disorder within the first three months of involuntary job loss would lead to an increased number of stressful life events three-months later.

Retrospective Psychometrics and Effect Heterogeneity in Integrated Data Analysis: Commentary on the Special Issue.

The current special issue of Prevention Science indicates that momentum in using individual participant data (IPD) and integrative data analysis (IDA) to combine and synthesize findings in prevention science has accelerated over the past decade. In this commentary, we focus on two general themes involving methods for harmonizing measures and findings of effect heterogeneity. We describe methods for harmonization as retrospective psychometrics, requiring that we attend to the assumptions necessary for accurate measurement, but adjust our methods given the constraints of working with existing datasets that often involve different measures in different studies.

Interleukin-6 is not involved in appetite regulation following moderate-intensity exercise in males with normal weight and obesity.

Objective: In obesogenic states and after exercise, interleukin (IL)-6 elevations are established, and IL-6 is speculated to be an appetite-regulating mechanism. This study examined the role of IL-6 on exercise-induced appetite regulation in sedentary normal weight (NW) males and those with obesity (OB).

Methods: Nine NW participants and eight participants with OB completed one non-exercise control (CTRL) and one moderate-intensity continuous training (MICT; 60 minutes, 65% V̇O ) session.

Diversification of JAZ-MYC signaling function in immune metabolism.

Jasmonate (JA) re-programs metabolism to confer resistance to diverse environmental threats. Jasmonate stimulates the degradation of JASMONATE ZIM-DOMAIN (JAZ) proteins that repress the activity of MYC transcription factors. In Arabidopsis thaliana, MYC and JAZ are encoded by 4 and 13 genes, respectively.

Transmembrane Stem Factor Nanodiscs Enhanced Revascularization in a Hind Limb Ischemia Model in Diabetic, Hyperlipidemic Rabbits.

Therapies to revascularize ischemic tissue have long been a goal for the treatment of vascular disease and other disorders. Therapies using stem cell factor (SCF), also known as a c-Kit ligand, had great promise for treating ischemia for myocardial infarct and stroke, however clinical development for SCF was stopped due to toxic side effects including mast cell activation in patients. We recently developed a novel therapy using a transmembrane form of SCF (tmSCF) delivered in lipid nanodiscs.