Phosphorus Stress Alters Bacterial Quorum Sensing

Fluorescence micrograph of a Brachypodium distachyon root colonized by Pseudomonas synxantha bacterial cells. The root surface provides a structured, nutrient-variable habitat where bacterial populations grow in spatially heterogeneous patches. This image relates to the major findings of our study by highlighting the rhizosphere context in which phosphorus limitation, local cell density, and spatial structure influence quorum-sensing-regulated phenazine production. Our work shows that phosphorus stress lowers the quorum-sensing threshold for phenazine induction, allowing this plant-associated bacterium to activate quorum-regulated behaviors at lower cell densities in root-associated, nutrient-limited environments.
Image Credit: Reinaldo E. Alcalde and Hannah Jeckel

Scientific Frontline: Extended "At a Glance" Summary: Bacterial Quorum Sensing Under Environmental Stress

The Core Concept: Soil bacteria, specifically Pseudomonas synxantha, can adapt to environmental stress—such as a scarcity of bioavailable phosphorus—by lowering the molecular thresholds required to activate collective behaviors.

Key Distinction/Mechanism: Quorum sensing typically requires a high bacterial cell density to accumulate sufficient signaling molecules before triggering a response. However, under phosphorus limitation, bacteria become highly sensitive to chemical signals, allowing them to initiate protective behaviors and produce survival compounds at significantly lower population densities.

Major Frameworks/Components:

• Quorum Sensing: A density-dependent molecular communication system that allows bacteria to coordinate collective actions based on local cell populations.
• Phenazines: Multi-functional, quorum-sensing-regulated secondary metabolites that assist bacteria in nutrient acquisition, neighbor competition, and stress survival.
• Phosphorus Scarcity: A pervasive ecological constraint in natural soils, where phosphorus frequently exists in forms unavailable to plants and microbes.
• Soil-Mimetic Modeling: The utilization of microfluidic reactors and custom light-sheet fluorescence microscopy to replicate and observe the physical complexity of natural root systems (the rhizosphere).

Neuronal DNA Repair During Brain Cortex Formation

Neurons migrating through dense tissue in the developing brain (green) frequently undergo DNA damage (magenta).
Image Credit: courtesy of Institute for Integrated Cell-Material Sciences

Scientific Frontline: Extended "At a Glance" Summary: Neuronal DNA Damage and Repair

The Core Concept: Developing neurons routinely experience double-strand DNA breaks while migrating through dense brain tissue, a process that is effectively managed by a rapid, specialized cellular repair system. This mechanism ensures that structural DNA damage occurs without compromising neuronal function or viability during the formation of the brain cortex.

Key Distinction/Mechanism: Unlike the random, lethal DNA damage observed in migrating cancer cells, the breaks in neurons are primarily mediated by Topoisomerase IIβ. This enzyme, which usually relieves torsional strain, becomes trapped under mechanical stress during migration; the resulting breaks are subsequently repaired via the non-homologous end joining pathway.

Major Frameworks/Components:

• Mechanical Stress-Induced Breaks: DNA double-strand breaks caused by the physical confinement of neurons navigating narrow tissue spaces.
• Topoisomerase IIβ Involvement: The enzymatic driver of the breaks, which becomes stuck during routine DNA untangling under stress.
• Non-Homologous End Joining (NHEJ): The primary repair pathway responsible for stitching the severed DNA strands back together.
• Ligase 4 Dependency: A critical enzyme in the repair process; experiments with mice lacking this enzyme revealed that failed repair leads to progressive neurological impairments.

CellTrap: Lab-on-a-Chip Tracks Immune vs. Cancer Cells

Lead author Muhammad Zia Ullah Khan examines a Petri dish containing a cell suspension. Fluorescence and bright-field images of cells in microchannels, displayed on the monitor, visualize immune cell communication
Photo Credit: Technische Universität München

Scientific Frontline: Extended "At a Glance" Summary: CellTrap Microfluidic Platform

The Core Concept: CellTrap is an instrument-free, microfluidic lab-on-a-chip system designed to isolate and observe interactions between individual immune cells and cancer cells at the single-cell level.

Key Distinction/Mechanism: While conventional laboratory tests measure average values across large cell populations, CellTrap utilizes a continuously branching main channel terminating in 1,024 microscopic trapping chambers. These chambers spatially fix individual cells, allowing researchers to use standard fluorescence time-lapse microscopy to track precise interaction timing, activation signals, and cell death over 14-hour periods.

Major Frameworks/Components:

• Microfluidic Trapping Array: A branching chip architecture containing 1,024 isolated chambers designed to draw in and spatially fix living cells.
• Stochastic Effector-to-Target Observation: The capability to randomly generate and study varying ratios of immune cells to cancer cells within individual chambers.
• Time-Lapse Fluorescence Microscopy: An affordable, standard laboratory imaging method used to track cell-cell interactions over extended observation windows.

Glycobiology: In-Depth Description

Glycobiology is the comprehensive study of the structure, biosynthesis, biology, and evolution of saccharides (sugars or glycans) that are widely distributed in nature. The primary goal of this field is to elucidate the vital roles these complex carbohydrates play in living organisms, particularly how they mediate cellular communication, influence protein stability, and contribute to both health and disease pathogenesis.

ST8Sia5L Enzyme: A Novel Autopolysialylation Discovery

The three enzymes shown here build polysialic acid (orange), a long sugar chain important for brain development and function. ST8Sia5L (left) builds the chain only on itself, a newly discovered activity. The four labeled amino acids on ST8Sia5L (R289, R333, and K380 in red; Y286 in green) are important for its polysialic acid synthesis. The resulting polysialic acid silences enzyme activity and triggers its secretion from the cell. ST8Sia2 (center) and ST8Sia4 (right) mainly add polysialic acid to other molecules.
Image Credit: Credit: Sakamoto et al., 2026

Scientific Frontline: Extended "At a Glance" Summary: Autopolysialylation of ST8Sia5L

The Core Concept: ST8Sia5L is a brain enzyme that regulates its own activity by synthesizing a polysialic acid chain directly onto its own molecular structure, triggering its deactivation and subsequent secretion from the cell.

Key Distinction/Mechanism: Unlike typical enzymatic regulation that requires external regulatory molecules, ST8Sia5L utilizes self-modification (autopolysialylation) as a built-in "off switch." The attached sugar chain completely suppresses the enzyme's primary ganglioside-building function and initiates its release into extracellular fluid. The enzyme reactivates outside the cell only when the polysialic acid is removed, such as by sialidases during periods of cellular stress or inflammation.

Origin/History: The ST8Sia5 enzyme was initially discovered in 1996 and recognized solely as a builder of gangliosides. The unique autopolysialylation capability of its long form, ST8Sia5L, was published in the Journal of Biological Chemistry in 2026 by researchers at Nagoya University’s Institute for Glyco-core Research, following an unexpected laboratory observation.

Virtual 3-D Tissue Staining Explained

Goran Lovric from the PSI Center for Photon Science is combining artificial intelligence with synchrotron imaging to create three-dimensional virtual staining of tissue samples.
Photo Credit: © Paul Scherrer Institute PSI/Mahir Dzambegovic

Scientific Frontline: Extended "At a Glance" Summary: Virtual Tissue Staining in 3-D

The Core Concept: Virtual tissue staining in 3-D, pioneered through the VISTACT platform, is an AI-driven technique that applies traditional histological color markers to high-resolution, greyscale micro-computed tomography (µCT) scans. This enables the non-destructive, three-dimensional analysis of pathological tissue changes without the need to physically slice and chemically stain delicate samples.

Key Distinction/Mechanism: Traditional pathology relies on cutting tissue into ultra-thin, two-dimensional sections for manual staining and microscopic examination. In contrast, VISTACT utilizes high-resolution phase-contrast micro-CT paired with a conditional generative adversarial network. The AI automatically translates 3-D greyscale structural density data into the familiar diagnostic color contrasts used by pathologists (such as blue-violet for cell nuclei and pink for collagen).

Major Frameworks/Components: 

• Phase-Contrast Micro-CT (PCµCT): An advanced imaging technique that captures highly detailed, three-dimensional structural data of soft tissues using X-ray phase shifts rather than simple density.
• Conditional Generative Adversarial Network: A specialized image-to-image machine learning model trained to link microscopic X-ray patterns with specific histological color profiles.
• Spatial Mapping Protocol: A multi-stage algorithmic process used to perfectly align delicate 2-D histological training sections within the comprehensive 3-D CT datasets to ensure accurate AI training.

What Is: Enteric Nervous System: The Second Brain

Scientific Frontline: Extended "At a Glance" Summary: The Enteric Nervous System (ENS)

The Core Concept: The Enteric Nervous System (ENS) is a highly sophisticated, autonomous network of approximately 500 million neurons and supportive glial cells embedded within the human gastrointestinal tract. Often referred to as the body's "second brain," it operates independently of the central nervous system to govern digestion, mucosal immunity, and systemic physiological homeostasis.

Key Distinction/Mechanism: Unlike traditional peripheral nerves that passively relay brain commands, the ENS acts as an autonomous sensory-motor computing matrix. It detects local physical and chemical stimuli via Intrinsic Primary Afferent Neurons (IPANs), processes this data through complex interneuron circuits, and executes precise muscular and secretory reflexes using over 30 distinct neurotransmitters, including massive quantities of locally synthesized serotonin.

Major Frameworks/Components: 

• The Myenteric Plexus (Auerbach's Plexus): Located deep between the circular and longitudinal muscular layers of the gut, this network primarily orchestrates smooth muscle contraction and the rhythmic phenomena of the peristaltic reflex.
• The Submucosal Plexus (Meissner's Plexus): Situated in the submucosa near the gut lumen, this network regulates localized gastrointestinal secretion, mucosal blood flow, and the selective absorption of water and nutrients.
• Enteric Glial Cells (EGCs): Dynamic, non-neuronal support cells that heavily outnumber neurons. They are indispensable for maintaining the intestinal epithelial barrier, supporting the stem cell niche via WNT ligands, and actively coordinating mucosal immune responses.
• The Gut-Brain Axis (GBA): A bidirectional communication superhighway between the ENS and the central nervous system, primarily utilizing the vagus nerve—which functionally acts as a massive sensory conduit, sending 90% of its data upward to the brain.
• Braak's Hypothesis: A paradigm-shifting neurological framework suggesting that idiopathic Parkinson's disease physically originates in the ENS via misfolded alpha-synuclein proteins, which propagate in a prion-like manner retrogradely up the vagus nerve to the brain.

Biomedical Engineering: In-Depth Description

Biomedical engineering is the application of engineering principles and design concepts to medicine and biology for healthcare purposes. The primary goal of this field is to close the gap between engineering and medicine, combining the rigorous problem-solving and quantitative skills of the physical sciences with the nuanced understanding of biological systems. By doing so, biomedical engineers aim to advance healthcare treatment, from rapid diagnosis and continuous patient monitoring to complex therapeutics, artificial organ generation, and surgical interventions, ultimately improving human health, enhancing physical capabilities, and extending lifespans.

Universal Animal Communication Tempo

Gouldian finches
Photo Credit: David Clode

Scientific Frontline: Extended "At a Glance" Summary: Universal Tempo of Animal Communication

The Core Concept: Across an extraordinary variety of species, animals vocalize at a strikingly consistent rate of approximately two to three acoustic events per second (around 2.8 Hz), constrained by the brain's inherent capacity to process auditory stimuli.

Key Distinction/Mechanism: Unlike pitch or timbre, which vary based on physical traits or habitat, this universal rhythmic tempo is not determined by body weight, lung capacity, or social complexity. It functions through a dual-timescale neural mechanism where slow brain oscillations track acoustic sequences, and fast oscillations manage fine-grained temporal discrimination.

Major Frameworks/Components:

• Delta Band Oscillations (1–4 Hz): Slow neural rhythms that provide an extended integration window for mammals, birds, amphibians, and insects to identify the general structure of acoustic sequences.
• Low Gamma Bands: Faster neural processes responsible for detailed temporal discrimination, enabling animals to identify individual speakers or specific sound sources.
• Cross-Species Temporal Homogeneity: The statistical framework demonstrating that 95% of the analyzed species maintain a vocalization rate strictly between 0.45 and 4.99 Hz.

Mycology: In-Depth Description

Mycology is the scientific study of fungi, a vast and complex kingdom of organisms that includes yeasts, molds, and mushrooms. The primary goal of mycology is to comprehend the genetic, biochemical, and physiological properties of fungi, their taxonomy, and their evolutionary history. Additionally, the field seeks to elucidate their critical ecological roles and their complex relationships with humans, ranging from their utility as sources of pharmaceuticals and industrial enzymes to their devastating impacts as agricultural pathogens and infectious agents.

Global Map of AM Fungal Networks

An image taken in Bhutan from the research expedition.
Photo Credit: Courtesy of University of Sheffield

Scientific Frontline: Extended "At a Glance" Summary: Global Arbuscular Mycorrhizal Fungal Networks

The Core Concept: Arbuscular mycorrhizal (AM) fungal networks are vast underground systems that form symbiotic relationships with the majority of Earth's plant species, exchanging water and nutrients for plant-fixed carbon. A recent global mapping effort revealed these living infrastructures possess a total length of approximately 110 quadrillion kilometers and a mass of roughly 300 megatons of carbon.

Key Distinction/Mechanism: Unlike standard root systems, AM fungi act as ecosystem engineers that penetrate plant roots and extend extensively into the soil, functioning as a planetary circulatory system. This hyper-efficient network increases root foraging areas by up to 100 times, transporting water, nutrients, and an estimated four billion tons of carbon dioxide equivalent into soils annually.

Origin/History: While mycorrhizal fungi have shaped terrestrial life for hundreds of millions of years, the first global distribution map and mass quantification of AM networks was published in 2026 by an international team including the University of Sheffield, AMOLF, and the Society for the Protection of Underground Networks (SPUN).

Dynamic Mechanobiology Platform

Jae Park, a doctoral student in the lab of Alexandra Rutz, assistant professor of biomedical engineering, has developed a unique, dynamic platform with electricity-conducting biomaterials in which stiffness can be modulated by applying voltage. Such a platform can help researchers learn more about the potential to use conducting polymers to study mechanobiology and to study the effect of stiff environments on cells, which play a role in fibrosis and some types of cancer.
Photo Credit: Jae Park

Scientific Frontline: Extended "At a Glance" Summary: Voltage-Modulated PEDOT:PSS Platform

The Core Concept: A novel bioelectronic platform utilizes the conducting polymer PEDOT:PSS to dynamically modulate material stiffness through the application of electrical voltage. This allows researchers to subject cells to varying mechanical environments in real time.

Key Distinction/Mechanism: Unlike traditional mechanobiology tools that rely on static stiffness, this dynamic system alters its mechanical properties incrementally as applied voltage recruits ions. This enables the application of multiple, reversible stiffness states to the exact same cell or tissue sample to observe corresponding biological reactions.

Major Frameworks/Components:

• PEDOT:PSS: A bioelectronic conducting polymer capable of adopting tissue-like softness and changing mechanical properties in response to electrical stimuli.
• Ion Recruitment Mechanism: The underlying process where applied voltage draws ions into the polymer matrix, resulting in measurable, incremental changes to material stiffness.
• Dynamic Mechanical Stimulation: The methodological shift from static tissue modeling to active environmental manipulation, allowing researchers to test cellular memory and adaptability when transitioning between soft and stiff substrates.

Gut-Brain Axis: Intestinal Influence on Behavior

A plug-like structure, the Reinger’s knot (red), blocks the hindgut (blue) in fruit flies with a defective apterous gene.
Image Credit: Biozentrum, University of Basel

Scientific Frontline: Extended "At a Glance" Summary: Gut-Brain Communication and Behavioral Modification

The Core Concept: Researchers have identified a direct link between intestinal obstruction and behavior in Drosophila melanogaster, where the inability to excrete metabolic waste (meconium) prevents independent feeding and induces prolonged sleep.

Key Distinction/Mechanism: A defect in the apterous gene prevents the formation of normal rectal papillae and instead causes the formation of a "Reinger's knot"—a plug-like structure that completely blocks the hindgut. This inability to expel meconium suppresses hunger signaling and triggers lethargy, which functions as a compensatory mechanism to conserve energy and potentially stimulate gut motility through rhythmic proboscis movement..

Major Frameworks/Components:

• Gut-Brain Axis Signaling: The physiological and neurological pathways that translate localized intestinal distress into systemic behavioral changes, such as increased sleep and suppressed feeding.
• Genetic Regulation of Organogenesis: The specific function of the apterous gene in ensuring the proper morphological development of the hindgut and rectal papillae.
• Metabolic Survival Strategies: The induction of lethargy and sleep as an adaptive energy conservation response to obstruction-induced starvation.

BayesCNA: Statistical Method for Cancer Blood Analysis

Lotta Eriksson and Eszter Lakatos.
Photo Credits: Ruben Seyer and Marco Nikic.

Scientific Frontline: Extended "At a Glance" Summary: BayesCNA Blood Analysis Method

The Core Concept: A highly sensitive analytical blood-testing method that uses classical statistics to isolate and analyze samples containing as little as 5% cancer DNA.

Key Distinction/Mechanism: While current clinical methods require 15–20% tumor DNA to function, BayesCNA applies a classical statistical algorithm to amplify extremely weak signals from low-pass whole-genome sequencing. This allows researchers to filter out the "noise" of healthy DNA and bypass the need for machine learning models, which proved less effective for this specific data structure.

Major Frameworks/Components:

• Low-Pass Whole-Genome Sequencing: A rapid, highly cost-effective sequencing technique utilized to generate a broad structural overview of DNA, despite yielding inherently low-quality data.
• Classical Statistical Modeling: The algorithmic foundation that isolates weak pathological signals from overwhelming biological noise to reveal hidden tumor composition.
• Liquid Biopsy Pathology: The clinical framework of utilizing frequent, non-invasive blood draws to map tumor characteristics in lieu of invasive solid tissue sampling.

GluK2/GluK5 Kainate Receptor Complex Explained

Laura Moreno Wasiliewski (left) and Andreas Reiner are studying how nerve cells communicate.
Photo Credit: © RUB, Marquard

Scientific Frontline: Extended "At a Glance" Summary: GluK2/GluK5 Kainate Receptor Heteromer

The Core Concept: The GluK2/GluK5 kainate receptor heteromer is a specialized ionotropic glutamate receptor complex in the brain, composed of two GluK2 and two GluK5 subunits, that functions as a glutamate-activated ion channel to transmit excitatory neuronal signals.

Key Distinction/Mechanism: Unlike other kainate receptors, ligand binding exclusively at the two structurally less-favorably positioned GluK5 subunits forces adjacent GluK2 subunits to move, activating a persistently open channel without triggering the extensive structural restructuring required for receptor desensitization (inactivation). Additionally, a unique structural interaction between opposing GluK5 subunits results in an unusually slow deactivation process that is nearly ten times slower than related receptor complexes.

Major Frameworks/Components:

• Ionotropic Glutamate Receptors (iGluRs): Transmembrane neuronal receptor proteins consisting of four subunits that form a shared ion channel pore, with each subunit possessing an independent glutamate binding site.
• Partial Occupancy Activation: Ligand binding (such as with the agonist 5-iodowillardiine) at only the two GluK5 subunits is functionally sufficient to elicit receptor activation and produce long-lasting, non-desensitizing currents.
• Subunit Interaction Dynamics: A distinct structural interaction specifically between opposing GluK5 subunits dictates the complex's functional properties, directly driving its unusually slow deactivation rate.

Zika Virus: Hidden Infant Development Risks

The Zika virus, spread by mosquitos such as the Aedes aegypti above, is known to cause severe birth defects. A new study explored why 30% of babies born without these physical symptoms still go on to experience developmental problems including vision and hearing loss.
Photo: Jeff Miller / UW–Madison

Scientific Frontline: Extended "At a Glance" Summary: Prenatal Zika Exposure and Neurodevelopment

The Core Concept: Prenatal exposure to the Zika virus can cause subtle, long-term neurodevelopmental and sensory processing disorders in infants who are born without visible physical defects.

Key Distinction/Mechanism: Unlike severe structural anomalies directly linked to the virus (such as microcephaly), these hidden deficits stem from neurological communication disruptions—including cortical visual dysfunction—that occur independently of the mother's observable infection characteristics or immune biomarkers.

Major Frameworks/Components:

• Cortical Visual Dysfunction: A disruption in eye-to-brain communication causing early visual delays, even when the infant's eyes are structurally healthy.
• Altered Social-Emotional Development: Manifested as prolonged maternal attachment, indicating underlying challenges with sensory processing, threat assessment, and emotional regulation.
• Behavioral Disinhibition: An abnormally rapid approach to novel objects and situations, which serves as a clinical signal for early anxiety and delayed emotional learning.
• Diagnostic Biomarker Limitations: Standard maternal indicators, such as viral load, placental infection status, and antibody responses, fail to predict which infants will experience these long-term developmental differences.

How Honeybees Crown Queens: Beyond Royal Jelly

Photo Credit: Yu Fang/UCR

Scientific Frontline: Extended "At a Glance" Summary: Environmental Engineering in Honeybee Queen Development

The Core Concept: The development of a queen honeybee relies not solely on a specialized diet of royal jelly, but on an actively engineered environment created by a dedicated class of worker bees.

Key Distinction/Mechanism: Previously, the biological divergence between queens and workers was attributed almost entirely to diet. This research reveals a complex socio-environmental mechanism: a specialized caste of young worker bees, termed "queen cell builders," alters their own physiology to raise ambient temperatures and constructs "royal cribs." These cribs are built from a highly pliable, custom-engineered wax featuring unique fatty acid profiles and chemical signals that dictate the larva's royal phenotypic trajectory.

Origin/History: For decades, the "royal jelly" hypothesis dominated biological frameworks regarding queen development. This paradigm shifted with a June 3, 2026, study published in the journal Nature by researchers at the University of California, Riverside's Center for Integrative Bee Research (CIBER), which detailed the complex architectural and social machinery behind bee royalty.

Unlocking Durable Immunotherapy with Stem Cell-Derived CD4⁺ T Cells

Image Credit: Courtesy of Center for iPS Cell Research and Application

Scientific Frontline: Extended "At a Glance" Summary: Stem Cell-Derived CD4⁺ T Cell Immunotherapy

The Core Concept: Stem cell-derived CD4⁺ T cell immunotherapy is a novel approach to cancer treatment that differentiates human induced pluripotent stem (iPS) cells into adaptive-like CD4⁺ T cells equipped with chimeric antigen receptors (CARs) to target and destroy malignancies.

Key Distinction/Mechanism: While traditional CAR-T therapies rely heavily on CD8⁺ T cells that often suffer from rapid functional exhaustion, CD4⁺ T cells uniquely resist this decline. They maintain long-term proliferation, secrete immune-coordinating cytokines, and act as direct cytotoxic effectors across repeated rounds of antigen exposure.

Major Frameworks/Components:

• Induced Pluripotent Stem (iPS) Cells: A renewable, highly scalable, and genetically malleable source material intended for "off-the-shelf" immune cell manufacturing.
• Artificial Thymic Organoid System: A specialized developmental model used to successfully differentiate iPS cells into mature, adaptive-like T cells rather than innate-like lymphocytes.
• Chimeric Antigen Receptor (CAR) Engineering: Genetic modifications (such as CD19-targeting) that enable the CD4⁺ T cells to specifically recognize and eliminate leukemia cells.
• Memory-Like Molecular Signature: An intrinsic genetic programming profile that grants the engineered CD4⁺ cells resistance to functional decline over time.

Cannabis and Male Testosterone Levels

Although cannabis appears to disrupt certain biological mechanisms related to reproduction, the exact clinical consequences on the fertility of young men are still being studied.
Photo Credit: Esteban López

Scientific Frontline: Extended "At a Glance" Summary: Cannabis Use and Male Testosterone Levels

The Core Concept: A recent study demonstrates that cannabis use in young men does not reduce testosterone levels, but instead appears to increase the testicular synthesis of the hormone by approximately 23%.

Key Distinction/Mechanism: Contrary to earlier assumptions that cannabis decreases male sex hormones, this research localized the testosterone increase specifically to the testes (Leydig cells), rather than the adrenal glands. Importantly, the study clarifies that this hormonal spike does not equate to improved sperm quality or overall fertility and may represent a compensatory physiological response.

Major Frameworks/Components:

• Extensive steroid profiling that analyzed hundreds of hormones (including androgens, progestogens, and estrogens), expanding significantly beyond isolated testosterone screening.
• Examination of the endocannabinoid system's interaction with male reproductive biology.
• The isolation of two novel metabolic biomarkers indicating regular cannabis exposure: hydroxyprogesterone (11B-OHP4) and dihydroprogesterone (5B-DHP4).

Endocrinology: In-Depth Description

Endocrinology is the branch of biology and medicine focused on the study of the endocrine system, its diseases, and its specific secretions known as hormones. The primary goal of this field is to understand how these chemical messengers coordinate and regulate complex bodily functions—ranging from metabolism and cellular growth to reproduction and circadian rhythms—and to diagnose, manage, and treat disorders that arise when hormone production or receptor signaling is disrupted.