Dysfunctional BCAA degradation triggers neuronal damage through disrupted AMPK-mitochondrial axis due to enhanced PP2Ac interaction.

Metabolic and neurological disorders commonly display dysfunctional branched-chain amino acid (BCAA) metabolism, though it is poorly understood how this leads to neurological damage. We investigated this by generating Drosophila mutants lacking BCAA-catabolic activity, resulting in elevated BCAA levels and neurological dysfunction, mimicking disease-relevant symptoms. Our findings reveal a reduction in neuronal AMP-activated protein kinase (AMPK) activity, which disrupts autophagy in mutant brain tissues, linking BCAA imbalance to brain dysfunction.

Modeling of magnetic vestibular stimulation experienced during high-field clinical MRI.

Background: High-field magnetic resonance imaging (MRI) is a powerful diagnostic tool but can induce unintended physiological effects, such as nystagmus and dizziness, potentially compromising the comfort and safety of individuals undergoing imaging. These effects likely result from the Lorentz force, which arises from the interaction between the MRI's static magnetic field and electrical currents in the inner ear. Yet, the Lorentz force hypothesis fails to explain observed eye movement patterns in healthy adults fully.

Unlocking practical wisdom through the inner voice of robots.

As Artificial Intelligence and Robotics evolve, the ethical implications of autonomous systems are becoming increasingly paramount. This article explores the role of a robot's inner speech in enhancing human phronesis - the capacity for making ethical and contextually appropriate decisions. Phronesis is a complex human trait based on experience, personality, and values, and is crucial for decisions affecting others' well-being.

Molten Sn solvent expands liquid metal catalysis.

Regulating favorable assemblies of metallic atoms in the liquid state provides promise for catalyzing various chemical reactions. Expanding the selection of metallic solvents, especially those with unique properties and low cost, enables access to distinctive fluidic atomic structures on the surface of liquid alloys and offers economic feasibility. Here, Sn solvent, as a low-cost commodity, supports unique atomic assemblies at the interface of molten SnInCu, which are highly selective for H synthesis from hydrocarbons.

Taming large-scale genomic analyses via sparsified genomics.

Searching for similar genomic sequences is an essential and fundamental step in biomedical research. State-of-the-art computational methods performing such comparisons fail to cope with the exponential growth of genomic sequencing data. We introduce the concept of sparsified genomics where we systematically exclude a large number of bases from genomic sequences and enable faster and memory-efficient processing of the sparsified, shorter genomic sequences, while providing comparable accuracy to processing non-sparsified sequences.

Scaffold-enabled high-resolution cryo-EM structure determination of RNA.

Cryo-EM structure determination of protein-free RNAs has remained difficult with most attempts yielding low to moderate resolution and lacking nucleotide-level detail. These difficulties are compounded for small RNAs as cryo-EM is inherently more difficult for lower molecular weight macromolecules. Here we present a strategy for fusing small RNAs to a group II intron that yields high resolution structures of the appended RNA.

Ligand-Directed Actinide Oxo-Bond Manipulation in Actinyl Thiacalix[4]arene Complexes.

Understanding the chemistry of the inert actinide oxo bond in actinyl ions AnO22+ is important for controlling actinide behavior in the environment, during separations, and in nuclear waste (An = U, Np, Pu). The thioether calixarene TC4A (4-tert-butyltetrathiacalix[4]arene) binds equatorially to [AnO2]n+ (An = U, Np) forming a conical pocket that differentiates the two trans-oxo groups. The 'ate' complexes, [A]2[UO2(TC4A)] (A = [Li(DME)2], HNEt3) and [HNEt3]2[NpO2(TC4A)], enable selective oxo chemistry.

Inpatient Cost of Trauma Care Versus Repair of Elective Open Inguinal Hernias: Nationwide Trends Over Nearly a Decade.

Concerns exist regarding increased trauma activation fees at the expense of vulnerable patients. In contrast, elective open inguinal hernia repair (E-OIHR) has remained relatively fixed in terms of technique. This study aimed to examine health care costs for E-OIHR and trauma patients, hypothesizing trauma cost would increase from 2010 to 2018, while E-OIHR cost would remain unchanged.

Pediatric Age-Prioritized Waitlisting Policy Potentially Disadvantages Adolescents on Dialysis Not Listed for Transplant Until Adulthood.

Background: Current kidney transplant (KT) policies offer advantages in waiting time and organ allocation priority to pediatric patients waitlisted before 18 years old. This study evaluates the effects of this policy for patients who are on dialysis before, but not waitlisted until after, age 18.

Methods: Patients aged 11-25 years and waitlisted between 2001 and 2022 for KT were identified in the OPTN STAR data file for analysis.

Chronic Kidney Disease-Mineral Bone Disorder (CKD-MBD) in Pediatric Kidney Transplant Recipients.

Kidney transplantation remains the gold standard treatment for end-stage kidney disease (ESKD), effectively alleviating numerous comorbidities and offering a substantial survival advantage over long-term dialysis. Despite advancements in immunosuppressive regimens and improvements in graft and patient survival rates, extended patient longevity brings an accumulating burden and complexity of bone disease in this population, which often goes underrecognized. The present study reviews the pathophysiology of CKD-MBD in pediatric KTR, focusing on the progression of bone disease before and after transplantation.

Thiamine deficiency in US veterans with obesity.

Introduction: Thiamine deficiency is common after bariatric surgery, but patients with obesity may be deficient in thiamine even before surgery. The purpose of this research was to determine the prevalence of thiamine deficiency in patients with obesity at a medical weight-management clinic and assess the relationship between recent weight loss and thiamine deficiency.

Methods: For this observational study, medical records were reviewed for patients (n = 146) at the nonsurgical obesity medicine and preoperative bariatric surgery clinic at a Veterans Affairs Medical Center between January 1, 2012, and January 31, 2019.

The Co-IMPACT Consortium: Integrating Prostate-specific Membrane Antigen Positron Emission Tomography and Radiotherapy in Prostate Cancer Care.

The Co-IMPACT consortium addresses knowledge gaps in prostate-specific membrane antigen positron emission tomography-guided radiotherapy for prostate cancer by establishing a global database (46 centres from 16 countries) to standardise and analyse data across four distinguished clinical scenarios. A collaborative model with the Advanced Prostate Cancer Consensus Conference aligns urgent clinical needs with actionable research insights.

ASRA Pain Medicine consensus practice infection control guidelines for regional anesthesia and pain medicine.

Background: To provide recommendations on risk mitigation, diagnosis and treatment of infectious complications associated with the practice of regional anesthesia, acute and chronic pain management.

Methods: Following board approval, in 2020 the American Society of Regional Anesthesia and Pain Medicine (ASRA Pain Medicine) commissioned evidence-based guidelines for best practices for infection control. More than 80 research questions were developed and literature searches undertaken by assigned working groups comprising four to five members.

The Prevalence of Septo-Optic Dysplasia in Neonates with Absent Cavum Septi Pellucidi Identified During Routine Prenatal Imaging.

Objective: To determine the prevalence of septo-optic-dysplasia (SOD) in patients with prenatally identified absent cavum septi pellucidi (CSP), agenesis of the corpus callosum (ACC) or dysgenesis of the corpus callosum (DCC).

Study Design: This retrospective chart review investigated neonates prenatally diagnosed with an absent CSP, ACC, or DCC who were admitted to a single quaternary academic medical center in the Pacific Northwest between 2016-2023. This prenatal diagnosis prompted a routine and protocolized postnatal workup for SOD including laboratory evaluation, imaging, and specialty consultation.

Long-term increases in wing length occur independently of changes in climate and climate-driven shifts in body size.

Recent widespread reductions in body size across species have been linked to increasing temperatures; simultaneous increases in wing length relative to body size have been broadly observed but remain unexplained. Size and shape may change independently of one another, or these morphological shifts may be linked, with body size mediating or directly driving the degree to which shape changes. Using hierarchical Bayesian models and a morphological time series of 27 366 specimens from five North American migratory passerine bird species, we tested the roles that climate and body size have played in shifting wing length allometry over four decades.

Filter feeding in devil rays is highly sensitive to morphology.

Mobulid rays (manta and devil rays) use a highly specialized filtering apparatus to separate plankton food particles from seawater. Recent studies have indicated that captive vortices form within the microscale pores of the filter, which enhance filtration efficiency through a novel mechanism referred to as ricochet separation. The high throughput and clog resistance of this filtration process have led to the development of several bioinspired engineered filtration systems.

Submarine groundwater discharge drives both direct and indirect effects on organismal and community metabolism on coral reefs.

Coral reefs experience numerous environmental gradients affecting organismal physiology and species biodiversity, which ultimately impact community metabolism. This study shows that submarine groundwater discharge (SGD), a common natural environmental gradient in coastal ecosystems associated with decreasing temperatures, salinity and pH with increasing nutrients, has both direct and indirect effects on coral reef community metabolism by altering individual growth rates and community composition. Our data revealed that SGD exposure hindered the growth of two algae, and by 67 and 200%, respectively, and one coral, by 20%.

Energetic costs of social dominance in wild male baboons.

In vertebrates, glucocorticoids can be upregulated in response to both psychosocial and energetic stressors, making it difficult to identify the cause of elevated glucocorticoid concentrations when both types of stressors are present. This problem has been particularly challenging in studies of social dominance rank in wild animals. In contrast to glucocorticoids, thyroid hormone concentrations are largely unaffected by psychosocial stressors and therefore offer a better estimate of energetic challenges.

CryoEM structure and small-angle X-ray scattering analyses of porcine retinol-binding protein 3.

The vertebrate visual cycle hinges on enzymatically converting all--retinol (at-ROL) into 11--retinal (11c-RAL), the chromophore that binds to opsins in photoreceptors, forming light-responsive pigments. When struck by a photon, these pigments activate the phototransduction pathway and initiate the process of vision. The enzymatic isomerization of at-ROL, crucial for restoring the visual pigments and preparing them to receive new light stimuli, relies on various enzymes found in both the photoreceptors and retinal pigment epithelium cells.

A minimal model of cognition based on oscillatory and current-based reinforcement processes.

Building mathematical models of brains is difficult because of the sheer complexity of the problem. One potential starting point is basal cognition, which gives an abstract representation of a range of organisms without central nervous systems, including fungi, slime moulds and bacteria. We propose one such model, demonstrating how a combination of oscillatory and current-based reinforcement processes can be used to couple resources in an efficient manner, mimicking the way these organisms function.

Autonomous learning of generative models with chemical reaction network ensembles.

Can a micron-sized sack of interacting molecules autonomously learn an internal model of a complex and fluctuating environment? We draw insights from control theory, machine learning theory, chemical reaction network theory and statistical physics to develop a general architecture whereby a broad class of chemical systems can autonomously learn complex distributions. Our construction takes the form of a chemical implementation of machine learning's optimization workhorse: gradient descent on the relative entropy cost function, which we demonstrate can be viewed as a form of integral feedback control. We show how this method can be applied to optimize any detailed balanced chemical reaction network and that the construction is capable of using hidden units to learn complex distributions.

Techniques and analytic workflow for spatial transcriptomics and its application to allergy and inflammation.

Spatial profiling, through single-cell gene level expression data paired with cell localization, offers unprecedented biological insights within the intact spatial context of cells in healthy and diseased tissue, adding a novel dimension to data interpretation. This review summarizes recent developments in this field, its application to allergy and inflammation, and recent single-cell resolution platforms designed for spatial transcriptomics with a focus on data processing and analyses for efficient biological interpretation of data. By preserving spatial context, these technologies provide critical insights into tissue architecture and cellular interactions unattainable with traditional transcriptomics methods, such as revealing localized inflammatory cell network in atopic dermatitis, and T-cell interactions in the lung in chronic obstructive pulmonary disease.