The mechanisms of frequency tuning in gecko auditory hair cells.

We developed an isolated auditory papilla of the crested gecko to record from the hair cells and explore the origins of frequency tuning. Low-frequency cells displayed electrical tuning, dependent on Ca-activated K channels; high-frequency cells, overlain with sallets, showed a variation in hair bundle stiffness which when combined with sallet mass could provide a mechanical resonance of 1 to 6 kHz. Sinusoidal electrical currents injected extracellularly evoked hair bundle oscillations at twice the stimulation frequency, consistent with fast electromechanical responses from hair bundles of two opposing orientations, as occur in the sallets.

Uncovering the substrate of olefin synthase loading domains in cyanobacteria sp. strain PCC 7002.

Cyanobacteria are widespread, photosynthetic, gram-negative bacteria that generate numerous bioactive secondary metabolites complex biosynthetic enzymatic machinery. The model cyanobacterium sp. strain PCC 7002, hereafter referred to as PCC 7002, contains a type I polyketide synthase (PKS), termed olefin synthase (OlsWT), that synthesizes 1-nonadecene and 1,14-nonadecadiene: α-olefins that are important for growth at low temperatures.

Virus-free CRISPR knock-in of a chimeric antigen receptor into KLRC1 generates potent GD2-specific natural killer cells.

Natural killer (NK) cells are an appealing off-the-shelf, allogeneic cellular therapy due to their cytotoxic profile. However, their activity against solid tumors remains suboptimal in part due to the upregulation of NK-inhibitory ligands, such as HLA-E, within the tumor microenvironment. Here, we utilize CRISPR-Cas9 to disrupt the KLRC1 gene (encoding the HLA-E-binding NKG2A receptor) and perform non-viral insertion of a GD2-targeting chimeric antigen receptor (CAR) within NK cells isolated from human peripheral blood.

OPTO: Automated Optimization for Solid-State NMR Spectroscopy.

NMR spectroscopy presents boundless opportunities for understanding the structure, dynamics, and function for a broad range of scientific applications. Solid-state NMR (SSNMR), in particular, provides novel insights into biological and material systems that are not amenable to other approaches. However, a major bottleneck is the extent of user training and the difficulty of obtaining reproducible, high-quality experimental results, especially for the sophisticated multidimensional pulse sequences that are essential to provide site-resolved measurements in large biomolecules.

Fully biodegradable hierarchically designed high-performance nanocellulose piezo-arrays.

While piezoelectric sensing and energy-harvesting devices still largely rely on inorganic components, biocompatible and biodegradable piezoelectric materials, such as cellulose nanocrystals, might constitute optimal and sustainable building blocks for a variety of applications in electronics and transient implants. To this aim, however, effective methods are needed to position cellulose nanocrystals in large and high-performance architectures. Here, we report on scalable assemblies of cellulose nanocrystals in multilayered piezoelectric systems with exceptional response, for various application scopes.

Combining Top-Down and Bottom-Up: An Open Microfluidic Microtumor Model for Investigating Tumor Cell-ECM Interaction and Anti-Metastasis.

Using a combined top-down (i.e., operator-directed) and bottom-up (i.

Cocaine-Induced Remodeling of the Rat Brain Peptidome: Quantitative Mass Spectrometry Reveals Anatomically Specific Patterns of Cocaine-Regulated Peptide Changes.

Addiction to psychostimulants, including cocaine, causes widespread morbidity and mortality and is a major threat to global public health. Currently, no pharmacotherapies can successfully treat psychostimulant addiction. The neuroactive effects of cocaine and other psychostimulants have been studied extensively with respect to their modulation of monoamine systems (particularly dopamine); effects on neuropeptide systems have received less attention.

Dual Activation Modes Enable Bifunctional Catalysis of Aldol Reactions by Flexible Dihydrazides.

Hydrazides are known to catalyze reactions of α,β-unsaturated aldehydes via transient iminium formation. The iminium intermediate displays enhanced electrophilicity, which facilitates conjugate additions and cycloadditions. We observed that a hydrazide embedded in a seven-membered ring catalyzes homoaldol condensation of a simple aldehyde in a process that displays an approximate second-order dependence on the hydrazide.

Creation of Piezoelectricity in Quadruple Perovskite Oxides by Harnessing Cation Defects and Their Application in Piezo-Photocatalysis.

Quadruple perovskite oxides have received extensive attention in electronics and catalysis, owing to their cation-ordering structure and intriguing physical properties. However, their repertoires still remain limited. In particular, piezoelectricity from quadruple perovskites has been rarely reported due to the frustrated symmetry-breaking transition in A-site-ordered perovskite structures, disabling their piezoelectric applications.

Design and implementation of optics for the experiment for cryogenic large-aperture intensity mapping (EXCLAIM).

This work describes the design and implementation of optics for EXCLAIM, the EXperiment for Cryogenic Large-Aperture Intensity Mapping. EXCLAIM is a balloon-borne telescope that will measure integrated line emission from carbon monoxide at redshifts z < 1 and ionized carbon ([CII]) at redshifts z = 2.5 - 3.

State shifts in the deep Critical Zone drive landscape evolution in volcanic terrains.

Volcanic provinces are among the most active but least well understood landscapes on Earth. Here, we show that the central Cascade arc, USA, exhibits systematic spatial covariation of topography and hydrology that are linked to aging volcanic bedrock, suggesting systematic controls on landscape evolution. At the Cascade crest, a locus of Quaternary volcanism, water circulates deeply through the upper [Formula: see text]1 km of crust but transitions to shallow and dominantly horizontal flow as rocks age away from the arc front.

A data-driven modeling framework for mapping genotypes to synthetic microbial community functions.

Microbial communities play a central role in transforming environments across Earth, driving both physical and chemical changes. By harnessing these capabilities, synthetic microbial communities, assembled from the bottom up, offer valuable insights into the mechanisms that govern community functions. These communities can also be tailored to produce desired outcomes, such as the synthesis of health-related metabolites or nitrogen fixation to improve plant productivity.

Evaluating the physiological benefits of behavioral flexibility in chacma baboons (Papio ursinus) using a biophysical model.

As opportunistic generalists occupying a range of ecological niches, chacma baboons (Papio ursinus) are considered a highly flexible species of relatively low conservation priority. Underlying their ecological flexibility is a repertoire of behavioral strategies observed in response to ecological stressors. Although these strategies are relatively well-documented, we know very little about how they impact upon an individual's thermal and energetic physiology, which can influence population-level reproductive potential in the face of climatic warming.

Nutrient Intake and Dietary Adequacy Among Rural Tanzanian Infants Enrolled in the Mycotoxin Mitigation Trial.

Background: The Mycotoxin Mitigation Trial (MMT) was a community-based cluster-randomized trial designed to assess the effect of dietary aflatoxin (AF) on linear growth. Similar dietary intake between arms was an important component of the trial's program theory and essential for the trial's internal validity and interpretation.

Objective: This analysis assessed and compared dietary intake by arm within a sub-sample of infants enrolled in the MMT.

Dereplication of Natural Product Antifungals via Liquid Chromatography-Tandem Mass Spectrometry and Chemical Genomics.

Recently expanded reports of multidrug-resistant fungal infections underscore the need to develop new and more efficient methods for antifungal drug discovery. A ubiquitous problem in natural product drug discovery campaigns is the rediscovery of known compounds or their relatives; accordingly, we have integrated Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) for structural dereplication and Yeast Chemical Genomics for bioprocess evaluation into a screening platform to identify such compounds early in the screening process. We identified 450 fractions inhibiting and the resistant strains of and among more than 40,000 natural product fractions.

Nickel-Catalyzed Cross-Electrophile Coupling of Aryl Triflates with Alkyl Halides: Mechanism-Informed Design of More General Conditions.

Aryl triflates make up a class of aryl electrophiles that are available in a single step from the corresponding phenol. Despite the known reactivity of nickel complexes for aryl C-O bond activation of phenol derivatives, nickel-catalyzed cross-electrophile coupling using aryl triflates has proven challenging. Herein, we report a method to form C(sp)-C(sp) bonds by coupling aryl triflates with alkyl bromides and chlorides using phenanthroline (phen) or pyridine-2,6-bis(-cyanocarboxamidine) (PyBCam)-ligated nickel catalysts.

Drivers of forest productivity in two regions of the United States: Relative impacts of management and environmental variables.

Climate, environmental conditions, and management strategies are key factors affecting forest net ecosystem production (NEP). However, little is known about the relationship between management approaches and regional to continental-scale forest productivity. In this study, we utilized forests of the U.

Characterization of Bifidobacterium bifidum growth and metabolism on whey protein phospholipid concentrate.

Whey protein phospholipid concentrate (WPPC) is a co-product generated during the manufacture of whey protein isolate. WPPC is depleted of simple sugars but contains numerous glycoconjugates embedded in the milk fat globule membrane, suggesting this fraction may serve as a carbon source for growth of bifidobacteria commonly enriched in breast fed infants. In this work, we demonstrate that WPPC can serve as a sole carbon source for the growth of Bifidobacterium bifidum, a species common to the breastfed infant and routinely used as a probiotic.

Comparing the efficacy of serotonin and EGTA on postpartum hypocalcemia.

Inducing a transient state of hypocalcemia prepartum mobilizes stored calcium (Ca) before the abrupt demand for Ca at parturition thus more tightly regulating postpartum hypocalcemia. Prepartum transient hypocalcemia can be achieved through intravenous infusions of either the precursor to serotonin, 5-hydroxy-tryptophan (5HTP) or a Ca chelating agent, ethylene-glycol-tetraacetic acid (EGTA). This study aimed to compare the ability of 5HTP and EGTA treatments to prevent postpartum hypocalcemia.

Flood-driven survival and growth of dominant C grasses helps set their distributions along tallgrass prairie moisture gradients.

Premise: Five C grasses (Bouteloua curtipendula, Schizachyrium scoparium, Andropogon gerardii, Sorghastrum nutans, Spartina pectinata) dominate different portions of a moisture gradient from dry to wet tallgrass prairies in the Upper Midwest of the United States. We hypothesized that their distributions may partly reflect differences in flooding tolerance and context-specific growth relative to each other.

Methods: We tested these ideas with greenhouse flooding and drought experiments, outdoor mesocosm experiments, and a natural experiment involving a month-long flood in two wet-mesic prairies.

The importance of peripheral populations in the face of novel environmental change.

Anthropogenically driven environmental change has imposed substantial threats on biodiversity, including the emergence of infectious diseases that have resulted in declines of wildlife globally. In response to pathogen invasion, maintaining diversity within host populations across heterogenous environments is essential to facilitating species persistence. White-nose syndrome is an emerging fungal pathogen that has caused mass mortalities of hibernating bats across North America.

Constrained Nuclear-Electronic Orbital Transition State Theory Using Energy Surfaces with Nuclear Quantum Effects.

Hydrogen-atom transfer is crucial in a myriad of chemical and biological processes, yet the accurate and efficient description of hydrogen-atom transfer reactions and kinetic isotope effects remains challenging due to significant quantum effects on hydrogenic motion, especially tunneling and zero-point energy. In this paper, we combine transition state theory (TST) with the recently developed constrained nuclear-electronic orbital (CNEO) theory to propose a new transition state theory denoted CNEO-TST. We use CNEO-TST with CNEO density functional theory (CNEO-DFT) to predict reaction rate constants for two prototypical gas-phase hydrogen-atom transfer reactions and their deuterated isotopologic reactions.

Spectroscopic and Computational Insights into the Mechanism of Cofactor Cobalt-Carbon Bond Homolysis by the Adenosylcobalamin-Dependent Enzyme Ethanolamine Ammonia-Lyase.

The adenosylcobalamin (AdoCbl)-dependent enzyme ethanolamine ammonia-lyase (EAL) catalyzes the conversion of ethanolamine to acetaldehyde and ammonia. As is the case for all AdoCbl-dependent isomerases, the catalytic cycle of EAL is initiated by homolytic cleavage of the cofactor's Co-C bond, producing Cocobalamin (CoCbl) and an adenosyl radical that serves to abstract a hydrogen atom from the substrate. Remarkably, in the presence of substrate, the rate of Co-C bond homolysis of enzyme-bound AdoCbl is increased by 12 orders of magnitude.

Use of Haloperidol in Companion Psittacine Birds: 19 Cases (2012-2022).

The antipsychotic medication haloperidol has been used for many years in avian medicine as a pharmacologic therapy for refractory feather destructive behavior in pet parrots. However, despite its common use, there are no published studies evaluating its efficacy and adverse effects in psittacine birds. The goal of this study was to report the signalment, clinical presentation, dosing regimen, response to therapy, and adverse effects of companion psittacine birds prescribed oral haloperidol therapy at a single veterinary referral hospital.

Genotypic Clustering of H5N1 Avian Influenza Viruses in North America Evaluated by Ordination Analysis.

The introduction of HPAI H5N1 clade 2.3.4.