A ground-breaking study conducted by researchers from McGill University, the Lady Davis Institute for Medical Research (LDI) at the Jewish General Hospital, Princess Margaret Cancer Centre and MIT has identified a novel approach to combat aggressive breast cancers by retraining neutrophils, the body’s first responders, to directly kill tumour cells. This research offers new hope for patients with breast cancers that do not respond well to existing immunotherapies.
Traditional immunotherapies primarily focus on reactivating tumour-specific T cells, which have limited effectiveness in breast cancers classified as immune cold – tumours that lack significant T cell infiltration. The new study, published in Science Advances, presents an alternative approach that harnesses the innate immune system by educating neutrophils to acquire tumoricidal properties. The researchers discovered that combining systemic Toll-like receptor (TLR) agonists with mitochondrial complex I inhibitors stimulates neutrophils to produce reactive oxygen species (ROS) and cytotoxic granules, thereby directly attacking breast cancer cells independently of cytotoxic T cell activity.
According to John Heath, former postdoctoral fellow at the LDI now at the Princess Margaret Cancer Centre in Toronto and first author of the study, “Our research has shown that by leveraging the power of innate immunity, we can develop a new class of therapies that can effectively target and kill breast cancer cells, even in the absence of T cell inflammation.”
“Our findings demonstrate that neutrophils can be reprogrammed to become potent anti-cancer agents in tumours that are otherwise resistant to current immunotherapies,” concurs Josie Ursini-Siegel, Principal Investigator and Director of the Molecular Oncology Group of the Cancer Research Axis at the LDI and lead author of the study. “This approach could open new avenues for treating aggressive breast cancers, particularly triple-negative breast cancer, which currently has limited treatment options due to the tumour’s ability to evade the immune system. This has great potential for patients who have limited treatment options and are in dire need of new and effective therapies.”
The study highlights that TLR agonists elevate NF-κB signaling in neutrophils, increasing the production of secretory granules and components of the NADPH oxidase complex, necessary for a respiratory burst that elicits cytotoxic responses. Meanwhile, complex I inhibitors amplify this effect by potentiating the capacity of neutrophils to undergo a respiratory burst, leading to oxidative damage of breast cancer cells. Importantly, neutrophil depletion in experimental models abolished the anti-tumour effects, underscoring the critical role of these immune cells in the therapy’s success. This dual treatment approach not only mobilizes neutrophils into the tumour microenvironment but also enhances their cytotoxic functions, offering a promising new therapeutic strategy for immune cold breast tumours that have so far eluded effective immune-based treatments.
The research also brings to light the importance of understanding the complex interactions between the tumour microenvironment and the immune system. By targeting key biological processes required for the survival of heterogeneous cancer cell populations, researchers can develop more effective therapies that abrogate the activation of a pro-tumorigenic immune microenvironment and instead engage novel modes of tumour immune surveillance.
“Our findings have significant implications for the development of new treatments for breast cancer, particularly for patients with limited options,” said Ursini-Siegel. “It highlights the need for a multifaceted approach to cancer treatment, one that takes into account the complex interactions between the tumour and the immune system.”
This research builds on the understanding that breast cancers often evade immune destruction through complex metabolic and inflammatory mechanisms, and it shifts the focus toward targeting innate immune cells rather than relying solely on adaptive immunity. While further research is needed to fully elucidate the mechanisms by which complex I inhibitors enhance neutrophil function, this study marks a significant step forward in precision oncology.
About the study
Heath J, Ahn R, Sabourin V, Im YK, Rezzara SR, Annett A, Mirabelli C, Worme S, Maritan SM, Mourcos C, Lazaratos AM, Maldonado E, Shen YY, White FM, Kleinman CL, Siegel PM, Ursini-Siegel J. Complex I Inhibition combined with TLR Activation in the Breast Tumor Microenvironment Educates Cytotoxic Neutrophils. Sci. Adv.11,eadu5915(2025).DOI:10.1126/sciadv.adu5915.
The James Webb Space Telescope has turned its powerful gaze on a chunk of the Cat’s Paw Nebula (NGC 6334), revealing a ‘toe bean’ of newborn stars sculpting their own cloaks of cosmic gas and dust with their fiery energy.
This image has been released to mark the Webb Telescope’s third birthday, revisiting a well-known object in a new light.
Credit: ESA/Webb, NASA & CSA, J. Lee and the PHANGS-JWST Team. Acknowledgement: J. Schmidt
4,000 light-years from Earth, the Cat’s Paw Nebula is one of the Milky Way’s most active star-forming regions.
Webb’s Near-Infrared Camera (NIRCam) enables astronomers to peer through the gas and dust to reveal secrets that would normally be invisible to the human eye.
Chaos in the Cat’s Paw
Inside the Cat’s Paw Nebula, scorching hot young stars are lighting up the surrounding dust and gas with brilliant starlight, much of it visible in Webb’s infrared image as a vibrant blue glow.
These stars emit powerful radiation and stellar winds that blast away the gas and dust – essential star-forming ingredients – stifling future star formation.
The Opera House in close-up detail
Zoom in on the ‘toe bean’ at the top centre of the image and you’ll see a striking structure: a tiered, circular feature nicknamed the ‘Opera House’.
Glowing blue clouds swirl above bright yellow stars and dense ribbons of dark dust.
One standout star, marked by Webb’s distinctive diffraction spikes, is carving out a shell-like pocket in the nebula, but hasn’t yet pushed all the surrounding gas away.
Nearby, odd formations, including a patch shaped like a tuning fork, hint at areas where dust is so thick it blocks the light behind it.
These dark spots aren’t empty, but are instead hiding stars still in the earliest stages of formation.
Credit: NASA, ESA, CSA, STScI
Seeing star formation
The central region of the image reveals glowing red clumps nestled in brown dust: telltale signs of star formation in action.
These regions are still shrouded in dense material, making them difficult to spot without infrared instruments like Webb’s.
The toe bean in the lower left shows off a few bright, sharply defined stars, their clarity hinting that they’ve already blown away much of the surrounding dust.
But just below them, dusty filaments remain, likely shielding baby stars still in the making.
A particularly bright yellow patch on the right is another giveaway: a massive star trying to shine through its dusty cocoon.
A nebula in motion
In the top right of the image is an eyecatching red-orange oval. Scientists believe this is a pocket of dust just beginning its star-forming journey.
There are hints of activity here: subtle signs of veiled stars and a dynamic bow shock (a wave of gas and dust pushed by a high-speed stellar wind), pointing to a bright, energetic source buried within.
Even in this one small region of the Cat’s Paw Nebula, the James Webb Space Telescope reveals a dynamic, evolving environment, where stars are being born and shaping their surroundings.
Proteins are typically viewed as molecular machines. When properly folded, a protein can perform its desired function. However, many proteins are modified during production to carry carbohydrate side chains known as glycans. These sugar structures rarely appear in textbook protein depictions but play decisive roles in health and disease. The ABO blood-group system offers an intuitive example: the A, B and O types differ only in the terminal sugars decorating red blood cell membrane glycoproteins, and that small change alone determines transfusion compatibility. Similar glycan codes also guide other phenomena in biology, such as immune surveillance, viral attachment and cell migration throughout the body.
What are glycans?
Glycans can enhance, dampen or redirect protein activity. Glycan modification can alter size, charge and geometry, shield an enzyme from degradation, help a hormone find its receptor or steer an antibody toward a specific immune response. Yet the production of glycans on proteins is poorly understood, as the glycan attachment (glycosylation) process is not template-driven. Unlike DNA replication or protein synthesis, which follow a strict nucleotide or amino acid sequence, glycan assembly relies on a network of enzymes in the endoplasmic reticulum and Golgi apparatus that add or trim sugars stepwise. As a result, glycan patterns are heterogeneous and sensitive to their environment and cell environmental stresses.
Nearly every secreted or membrane-bound human protein carries glycans as a post-translational modification. Many therapeutic proteins are manufactured with carefully tuned glycosylation to ensure potency and safety. For example, cancer-fighting monoclonal antibodies depend on their attached sugars to efficiently recruit immune cells, and recombinant clotting factors rely on complex branching to achieve proper half-life in circulation.
Because glycans influence so many facets of protein behavior, the ability to analyze and control them has become important in modern biopharmaceutical development. Here, we explain glycans, their structure, their contribution to disease and the analytical techniques used to study them.
A quick glyco-history
The story of glycans begins in classic chemistry. Emil Fischer’s 1891 stereochemical proof of glucose and subsequent findings of its isomers gave scientists the blueprint of how sugars can vary in three-dimensional space, establishing the nomenclature of the carbohydrate building blocks we still use today.1 Fischer also showed that sugars can react with alcohols to produce sugar alcohol conjugates known as glycosides, laying the foundation for understanding glycosylation.
A decade later, Karl Landsteiner’s 1901 paper on blood-cell agglutination revealed that terminal sugars on red blood cell glycoproteins generate the A, B and O blood groups, proof that carbohydrates can dictate life-or-death compatibility in humans.2 The first clear glimpse of sugar bonded to a protein came in 1938 when Hans Neuberger reported hexosamines and mannose attached to ovalbumin, coining the term glycoprotein.3 That finding transformed our understanding of proteins from simple amino-acid-based structures into composite molecules whose sugar attachments matter as much as the peptide backbone.
Fast-forward to biopharma’s early years, by the 1980s, researchers knew that extra sialic acid on recombinant human erythropoietin prolonged the hormone’s serum half-life and boosted in vivo potency.4 This concept led to the long-acting drug darbepoetin alfa. This was a historic moment. Change one sugar, and you change a drug.
Over the past 120 years, glycans have moved from ambiguity to a critical quality attribute (CQA) for modern biologics. They are covalent sugar chains, most commonly N-linked, O-linked or, less often, lipid-anchored, producing families of glycans with different variations known as “glycoforms” with distinct biological effects.
Although mammalian cells employ only a small alphabet of sugars, namely glucose, galactose, mannose, fucose, N-acetyl-glucosamine (GlcNAc), N-acetyl-galactosamine (GalNAc) and the sialic acid N-acetyl-neuraminic acid, they arrange these units into a remarkable variety of carbohydrate chains (Figure 1). A glycosidic bond links the anomeric carbon of one sugar to a hydroxyl group of the next. Its stereochemistry (α or β) describes the bond and the participating carbon atoms. For example, Galβ1-4GlcNAc tells us that galactose is in the beta configuration and attached from its C1 to the C4 of GlcNAc. Branch points arise when a monosaccharide forms two glycosidic bonds, creating antennae from a common core.
Two attachment chemistries dominate biologics: N-linked and O-linked glycans. N-linked glycans are attached to the side-chain nitrogen of an asparagine that sits within the amino acid consensus Asn-X-Ser/Thr motif, where X is any amino acid except proline.5 During translation, a lipid-linked pentasaccharide core, Man₃GlcNAc₂, is transferred en bloc to the growing polypeptide in the endoplasmic reticulum. Subsequent trimming and rebuilding in the Golgi sorts this core into three architectural families. High-mannose structures retain several extra mannoses and lack outer-arm GlcNAc. Hybrid glycans remodel only one antenna, leaving the other mannose rich. Complex glycans remodel both arms with GlcNAc, add β-linked galactose and often cap with a terminal sialic acid; nearly all human N-glycans carry a single core fucose off the innermost GlcNAc. The degree of branching can reach two, three or four antennae, and each extra branch can increase solubility, adjust receptor affinity or prolong serum half-life.6 For antibodies, deleting the core fucose alone can double antibody-dependent cellular cytotoxicity by increasing the affinity of IgG Fc for FcγRIIIa,7 a principle that underpins several next-generation antibodies.
O-linked glycans follow a different logic. Once a protein reaches the Golgi, a GalNAc transferase primes the hydroxyl oxygen of serine or threonine, after which various glycosyl-transferases extend the chain one sugar at a time. Early glycochemists grouped these mucin-type O-glycans into a handful of core motifs. Core 1 consists of Galβ1-3GalNAc and is the most widespread. Core 2 branches the primer by adding GlcNAcβ1-6 to the GalNAc, creating a scaffold that can accept repeating Gal-GlcNAc disaccharides. Cores 3 and 4, found mainly in the gut epithelium, invert the branching order with GlcNAc and create linear or branched chains contributing to the protective mucus barrier. Depending on the protein context, an O-glycan may remain a simple sialylated disaccharide, as seen on many circulating hormones, or extend into the densely packed sugar brush that shields mucins from proteases. Site selection relies more on local protein conformation than on a fixed amino acid motif, explaining the patchy clusters of O-glycans that appear in intrinsically disordered regions of proteins such as mucin 1.8
N-linked and O-linked glycans share the same sugar alphabet but diverge in their core scaffolds, branching logic and biosynthetic timing. N-glycans expand from a conserved base and are diversified broadly by antenna length and terminal capping. In contrast, O-glycans begin with several small cores that may remain concise or polymerize into extended chains. Even minute deviations in glycan profiles serve as red flags during process development. For example, Afucosylated Fc N-glycans sharpen the tumor-killing power of therapeutic IgG,9 controlled α2-6 sialylation extends the circulating half-life of clotting factors10 and deliberate exposure of the truncated Core 1 T antigen on tumor mucins supplies a neo-epitope for glycopeptide vaccines.11
Figure 1. The monosaccharide building blocks involved in glycosylation andexample structures of O-linked vs N-linked glycans. Credit: Technology Networks.
The role of glycosylation in disease and biotherapeutic development
Glycans guide nascent proteins toward correct folding, protect them from proteolysis and serve as recognition motifs for lectins and other carbohydrate‑binding receptors on neighboring cells. Because glycosylation depends on the local activities of glycosyltransferases and glycosidases, the resulting patterns are exquisitely sensitive to cell type, nutrient availability and environmental stress.
In healthy tissues, this dynamic regulation ensures proper cell-cell adhesion, immune surveillance and receptor signaling; in the bloodstream,12 terminal sialic acids prevent rapid clearance by liver asialoglycoprotein receptors, extending a glycoprotein’s half‑life.
In disease, cells often hijack glycosylation to their advantage. Cancer cells universally display aberrant glycans: they over‑branch N‑linked structures, elevate core fucosylation and hypersialylate their surfaces.13 Branched N‑glycans on adhesion molecules weaken cell-cell contacts and promote invasion. At the same time, excess sialic acid engages inhibitory Siglec receptors on natural killer cells and macrophages, suppressing anti‑tumor immunity. Fucosylated Lewis antigens facilitate tumor arrest on endothelium and metastasis. In neurodegenerative conditions, age‑related shifts toward bisected and branched N‑glycans have been detected in cerebrospinal fluid, and altered O‑GlcNAcylation of Tau and amyloid precursor protein influences aggregation and clearance in Alzheimer’s disease.14 Autoimmune disorders also carry distinct glycan signatures: patients produce IgG with reduced galactosylation and sialylation on the Fc N‑glycan, exposing pro‑inflammatory epitopes that amplify complement activation and Fcγ receptor‑mediated cytotoxicity.15
These mechanistic insights have inspired glycoengineering strategies in biopharmaceutical development. Recombinant erythropoietin was modified with additional N‑glycosylation sites and enhanced sialylation to slow renal filtration and avoid hepatic clearance, extending its half‑life.16 Monoclonal antibodies routinely exploit afucosylated Fc glycans to boost antibody‑dependent cellular cytotoxicity against cancer targets without altering antigen specificity. Enzyme replacement therapies for lysosomal storage diseases are produced with exposed mannose or mannose‑6‑phosphate termini, ensuring efficient uptake via macrophage mannose receptors.17 Biologics can be designed with optimized stability, targeting and immune‑modulating properties by harnessing the sugar codes underlying the disease.
What is glycan analysis?
Glycan analysis is the process of characterizing carbohydrate chains attached to proteins and lipids. In practice, this involves many techniques, including sample workup and interpretation through analytical methods such as high-performance liquid chromatography (HPLC) and mass spectrometry (MS). In biologic development, glycan analysis is indispensable. Regulatory agencies treat glycosylation as a CQA since glycan composition influences a drug’s stability, efficacy and immunogenicity. Consistent glycosylation profiles are required to ensure batch‑to‑batch reproducibility.
Glycan analysis of biopharmaceuticals
No single method can capture every aspect of glycosylation. Combined, complementary techniques are used to get a holistic understanding of glycans, including their detection, structures, site specificity, monosaccharide composition and linkage positions (Figure 2). Below are a few methods to help decipher key methodologies to analyze glycosylation.
Figure 2. Examples of some of the methods used for glycan analysis, including intact analysis, glycopeptide analysis and labeled glycan analysis. Credit: Technology Networks.
Detection of glycans
straightforward methodology to capture and understand glycans is to use carbohydrate-binding proteins, called lectins, that bind to the terminal sugar of the protein. A typical workflow uses a lectin array in which a panel of lectins is immobilized on a slide or biosensor surface, and fluorescently labeled glycoproteins are applied. Each lectin spot captures glycoproteins displaying its cognate sugar, and fluorescence intensity at each spot indicates the presence and relative abundance of the terminal sugar. Glycosylation also alters protein size and hydrodynamic radius. Hence, on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, heavily sialylated or branched glycoforms migrate more slowly, and on size‑exclusion chromatography, they elute earlier. Even marginal changes, such as adding or removing core fucose, can produce detectable electrophoretic mobility or retention shifts, providing an orthogonal method for altered glycosylation determination.
Glycan structure determination
The process of glycan structure determination typically involves the following:
Glycan structures are usually identified after enzymatic or chemical release from their protein backbone. N-glycans are commonly released using an enzyme called Peptide:N-glycosidase F (PNGase F). O-glycans typically are removed chemically by β-elimination.
The released glycans are labeled with a fluorescent tag, like 2-aminobenzamide, for improved chromatographic separation and detection.
For detection, HPLC equipped with a hydrophilic interaction chromatography column separates labeled glycans based on polarity and branching.
For further determination, matrix-assisted laser desorption/ionization time of flight mass spectrometry can be used to identify glycan compositions by mass.
Typically, a workflow would use the methodologies in steps 3 and 4 together to gain more insight into the glycan structure by liquid chromatography-mass spectrometry (LC-MS). For further structural resolution, tandem MS (MS/MS) fragmentation or enzymatic treatments (exoglycosidase sequencing) can be used for branching and sequence details.
Intact glycoprotein analysis
Analyzing glycoproteins in their intact form provides a broad overview of their glycosylation profiles, albeit less sensitively. Electrospray ionization-mass spectrometry is frequently used to distinguish glycoforms. Intact analysis quickly identifies major glycan variants without prior enzymatic treatment, which is helpful for rapid screening and quality control. For large proteins like antibodies, enzymatic fragmentation using proteases such as IdeS simplifies mass analysis by cleaving the antibody at the hinge region, isolating smaller glycopeptide fragments more amenable to accurate glycan profiling by LC-MS. Other techniques for intact glycoprotein analysis include isoelectric focusing or capillary electrophoresis, which can identify glycoform distributions based on charge difference. These are particularly useful for sialylated proteins, as sialic acid contains charge.
Glycopeptide profiling
This method combines peptide sequencing and glycan identification to pinpoint exactly where glycans attach to the protein backbone. Proteins are enzymatically digested, often by trypsin, and analyzed by LC-MS/MS. This site-specific profiling reveals both macro-heterogeneity (which sites carry glycans) and micro-heterogeneity (glycan structures at each site). Identifying glycopeptides is challenging because glycans preferentially fragment during MS analysis. Advanced methods like electron-transfer dissociation or hybrid fragmentation techniques preserve glycan–peptide linkages, enabling accurate site identification and structural assignment.
Monosaccharide composition analysis
Glycans are built from basic sugar building blocks, so monosaccharide analysis provides a compositional understanding of the molar concentration of each sugar within the glycan. For this, the glycoprotein is chemically hydrolyzed with strong acids, breaking glycans into their individual sugars. For quantitation, high-performance anion-exchange chromatography with pulsed amperometric detection is used. This method rapidly assesses glycoprotein quality changes in sugar ratios. Changes during bioprocessing might indicate manufacturing variations or protein degradation. It also ensures the absence of immunogenic non-human sugars (such as Neu5Gc or α-galactose) within the biologic.
Determination of linkage position
A classical approach for linkage determination is methylation analysis. Here, free hydroxyl groups on a released glycan are fully methylated (known as permethylation), then the glycan is hydrolyzed, reduced and acetylated. The resulting partially methylated alditol acetates are analyzed by gas chromatography-mass spectrometry, and fragment patterns reveal which hydroxyls were initially involved in glycosidic bonds. Permethylation stabilizes sialic acids and enhances ionization, making low‑abundance glycans more detectable. Alternatively, tandem MS fragmentation techniques can generate characteristic cross‑ring cleavages that distinguish linkage details, such as differentiating α2‑3 from α2‑6 sialic acid attachments when analyzed under suitable collision conditions. While a powerful technique, some isomers may remain ambiguous, so nuclear magnetic resonance spectroscopy is used for definitive linkage and anomeric configuration assignments. However, larger amounts of purified glycan are required.
Fischer E. Ueber die glucoside der alkohole. Ber Dtsch Chem Ges. 1893;26(3):2400-2412. doi:10.1002/cber.18930260327
Landsteiner K. [Agglutination phenomena of normal human blood]. Wien Klin Wochenschr. 2001;113(20-21):768-769.
Neuberger A. Carbohydrates in protein: The carbohydrate component of crystalline egg albumin. Biochem J. 1938;32(9):1435-1451. doi:10.1042/bj0321435
Fukuda MN, Sasaki H, Lopez L, Fukuda M. Survival of recombinant erythropoietin in the circulation: the role of carbohydrates. Blood. 1989;73(1):84-89. doi:10.1182/blood.V73.1.84.84
Schjoldager KT, Narimatsu Y, Joshi HJ, Clausen H. Global view of human protein glycosylation pathways and functions. Nat Rev Mol Cell Biol. 2020;21(12):729-749. doi:10.1038/s41580-020-00294-x
Dicker M, Strasser R. Using glyco-engineering to produce therapeutic proteins. Expert Opin Biol Ther. 2015;15(10):1501-1516. doi:10.1517/14712598.2015.1069271
Li T, DiLillo DJ, Bournazos S, Giddens JP, Ravetch JV, Wang L-X. Modulating IgG effector function by Fc glycan engineering. Proc Natl Acad Sci USA. 2017;114(13):3485-3490. doi:10.1073/pnas.1702173114
Coelho H, Rivas M de L, Grosso AS, et al. Atomic and Specificity Details of Mucin 1 O-Glycosylation Process by Multiple Polypeptide GalNAc-Transferase Isoforms Unveiled by NMR and Molecular Modeling. JACS Au. 2022;2(3):631-645. doi:10.1021/jacsau.1c00529
Liu SD, Chalouni C, Young JC, Junttila TT, Sliwkowski MX, Lowe JB. Afucosylated antibodies increase activation of FcγRIIIa-dependent signaling components to intensify processes promoting ADCC. Cancer Immunol Res. 2015;3(2):173-183. doi:10.1158/2326-6066.CIR-14-0125
Elm T, Karpf DM, Øvlisen K, et al. Pharmacokinetics and pharmacodynamics of a new recombinant FVIII (N8) in haemophilia A mice. Haemophilia. 2012;18(1):139-145. doi:10.1111/j.1365-2516.2011.02608.x
Ryan SO, Turner MS, Gariépy J, Finn OJ. Tumor antigen epitopes interpreted by the immune system as self or abnormal-self differentially affect cancer vaccine responses. Cancer Res. 2010;70(14):5788-5796. doi:10.1158/0008-5472.CAN-09-4519
Varki A. Biological roles of glycans. Glycobiology. 2017;27(1):3-49. doi:http://doi.org/10.1093/glycob/cww086
Pinho SS, Reis CA. Glycosylation in cancer: mechanisms and clinical implications. Nat Rev Cancer. 2015;15(9):540-555. doi:10.1038/nrc3982
Park J, Ha H-J, Chung ES, et al. O-GlcNAcylation ameliorates the pathological manifestations of Alzheimer’s disease by inhibiting necroptosis. Sci Adv. 2021;7(3). doi:10.1126/sciadv.abd3207
Haslund-Gourley BS, Wigdahl B, Comunale MA. IgG N-glycan Signatures as Potential Diagnostic and Prognostic Biomarkers. Diagnostics. 2023;13(6):1016. doi:10.3390/diagnostics13061016
Egrie JC, Dwyer E, Browne JK, Hitz A, Lykos MA. Darbepoetin alfa has a longer circulating half-life and greater in vivo potency than recombinant human erythropoietin. Exp Hematol. 2003;31(4):290-299. doi:10.1016/S0301-472X(03)00006-7
Shaaltiel Y, Bartfeld D, Hashmueli S, et al. Production of glucocerebrosidase with terminal mannose glycans for enzyme replacement therapy of Gaucher’s disease using a plant cell system. Plant Biotechnol J. 2007;5(5):579-590. doi:10.1111/j.1467-7652.2007.00263.x
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These are the sorts of discoveries we stand to lose if New Horizons is canceled. Shutting down the spacecraft would mean abandoning our best window into the outer Solar System — one already built, paid for, and working smoothly. Worlds would go unexplored, and mysteries would remain unsolved.
“We’re the only spacecraft out there,” Stern said. “There’s nothing else planned to come this way.”
But the cost of cancellation would not just be scientific. All the labor that went into designing the mission and building the spacecraft, the years spent wringing meaningful measurements and beautiful images out of it, all the people who dedicated their careers to New Horizons, all those who were inspired by it, everyone who stood up and spoke out again and again to say that this mission mattered to them — all would feel the loss.
Now, as ever, The Planetary Society is standing by New Horizons. We are encouraging Congress to reject the White House’s plan and organizing ways you can show elected officials that space science and exploration matter. Whether we are sending postcards, petitions, or Bill Nye himself to the Capitol, The Planetary Society will advocate for this mission and all other science projects facing pointless termination.
If enough people take action, there is still time to save NASA science.
While humans can regularly replace certain cells, like those in our blood and gut, we cannot naturally regrow most other parts of the body. For example, when the tiny sensory hair cells in our inner ears are damaged, the result is often permanent hearing loss, deafness, or balance problems. In contrast, animals like fish, frogs, and chicks regenerate sensory hair cells effortlessly.
Now, scientists at the Stowers Institute for Medical Research have identified how two distinct genes guide the regeneration of sensory cells in zebrafish. The discovery improves our understanding of how regeneration works in zebrafish and may guide future studies on hearing loss and regenerative medicine in mammals, including humans.
“Mammals such as ourselves cannot regenerate hair cells in the inner ear,” said Stowers Investigator Tatjana Piotrowski, Ph.D., the study’s co-author. “As we age or are subjected to prolonged noise exposure, we lose our hearing and balance.”
New research from the Piotrowski Lab, published in Nature Communications on July 14, 2025, seeks to understand how cell division is regulated to both promote regeneration of hair cells and to also maintain a steady supply of stem cells. Led by former Stowers Researcher Mark Lush, Ph.D., the team discovered that two different genes regulating cell division each control the growth of two key types of sensory support cells in zebrafish. The finding may help scientists study whether similar processes could be triggered in human cells in the future.
“During normal tissue maintenance and regeneration, cells need to proliferate to replace the cells that are dying or being shed — however, this only works if there are existing cells that can divide to replace them,” said Piotrowski. “To understand how proliferation is regulated, we need to understand how stem cells and their offspring know when to divide and at what point to differentiate.”
Zebrafish are an excellent system for studying regeneration. Dotted in a straight line from their head to tailfin are sensory organs called neuromasts. Each neuromast resembles a garlic bulb with “hair cells” sprouting from its top. A variety of supporting cells encompass the neuromast to give rise to new hair cells. These sensory cells, which help zebrafish detect water motion, closely resemble those in the human inner ear.
Because zebrafish are transparent during development and have accessible sensory organ systems, scientists can visualize, as well as genetically sequence and modify, each neuromast cell. This allows them to investigate the mechanisms of stem cell renewal, the proliferation of progenitor cells — direct precursors to hair cells — and hair cell regeneration.
“We can manipulate genes and test which ones are important for regeneration,” said Piotrowski. “By understanding how these cells regenerate in zebrafish, we hope to identify why similar regeneration does not occur in mammals and whether it might be possible to encourage this process in the future.”
Two key populations of support cells contribute to regeneration within neuromasts: active stem cells at the neuromast’s edge and progenitor cells near the center. These cells divide symmetrically, which allows the neuromast to continuously make new hair cells while not depleting its stem cells. The team used a sequencing technique to determine which genes were active in each type and found two distinct cyclinD genes present in only one or the other population.
The researchers then genetically altered each gene in the stem and progenitor populations. They discovered that the different cyclinD genes were independently regulating cell division of the two types of cells.
“When we rendered one of these genes non-functional, only one population stopped dividing,” said Piotrowski. “This finding shows that different groups of cells within an organ can be controlled separately, which may help scientists understand cell growth in other tissues, such as the intestine or blood.”
Progenitor cells lacking their cell type-specific cyclinD gene did not proliferate; however, they did form a hair cell, uncoupling cell division with differentiation. Notably, when the stem cell-specific cyclinD gene was engineered to work in progenitor cells, progenitor cell division was restored.
David Raible, Ph.D., a professor at the University of Washington who studies the zebrafish lateral line sensory system, commented on the significance of the new study. “This work illuminates an elegant mechanism for maintaining neuromast stem cells while promoting hair cell regeneration. It may help us investigate whether similar processes exist or could be activated in mammals.”
Because cyclinD genes also regulate proliferation in many human cells, like those in the gut and blood, the team’s findings may have implications beyond hair cell regeneration.
“Insights from zebrafish hair cell regeneration could eventually inform research on other organs and tissues, both those that naturally regenerate and those that do not,” said Piotrowski.
Additional authors include Ya-Yin Tsai, Shiyuan Chen, Daniela Münch, Julia Peloggia, Ph.D., and Jeremy Sandler, Ph.D.
This work was funded by the National Institute on Deafness and Other Communication Disorders of the National Institutes of Health (NIH) (award: 1R01DC015488-01A1), the Hearing Health Foundation, and with institutional support from the Stowers Institute for Medical Research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Astronomers have spotted a monster-sized planet that could be up to ten times the size of Jupiter emerging from the stellar fog surrounding a young star.
Prior observations of the roughly 13 million-year-old star MP Mus (also known as PDS 66) located around 280 light-years away had failed to distinguish features in the swirling cloud of gas and dust, or protoplanetary disk, that surrounds it.
However, when astronomers reexamined the apparently featureless protoplanetary disk of this star using combined data from the Atacama Large Millimeter/submillimeter Array (ALMA) and the European Space Agency (ESA) Gaia mission, they found it may not be quite so lonely after all.
The team detected a huge gas giant dwelling in the protoplanetary disk of MP Mus, which had been previously hidden. This represents the first time Gaia has spotted an extrasolar planet or “exoplanet” sitting in a protoplanetary disk, the disks of material around young stars that birth planets.
Such detections have typically been tough due to interference from the gas and dust of the protoplanetary disk. Until now, astronomers have only made three strong detections of planets within protoplanetary disks.
This new finding could help astronomers hunt more recently formed planets around infant stars.
Young exoplanets get into the groove
Planets form within protoplanetary disks through a process called core accretion, when larger and larger particles stick together via gravity, forming planetesimals, asteroids, and eventually planets.
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As material from the protoplanetary disk is swallowed up by this process, the planets created begin to carve channels in the disk, akin to the grooves in a vinyl record.
When this team initially observed the protoplanetary disk around MP Mus in 2023 with ALMA, these were the kind of structures they had expected to see. Structures that were missing.
“We first observed this star at the time when we learned that most discs have rings and gaps, and I was hoping to find features around MP Mus that could hint at the presence of a planet or planets,” team leader Álvaro Ribas from Cambridge’s Institute of Astronomy said in a statement.
The protoplanetary disk of the young star MP Mus as seen by ALMA with ring structures that reveal a lurking monster exoplanet. (Image credit: ALMA(ESO/NAOJ/NRAO)/A. Ribas et al.)
What the team found instead was a seemingly lonely star surrounded by a featureless disk of gas and dust that had none of the hallmarks of forming planets.
“Our earlier observations showed a boring, flat disc,” Ribas said. “But this seemed odd to us, since the disc is between seven and ten million years old.
“In a disc of that age, we would expect to see some evidence of planet formation.”
With their curiosity piqued, the team set about relooking at MP Mus again using ALMA, but in longer wavelengths of light. This allowed them to probe deeper into the disk, revealing a cavity in the disk close to the young star and two further “holes” further out, all of which were absent in the prior observations.
Further evidence of a planetary companion to MP Mus was about to be delivered.
More than just a first for Gaia
As Ribas and colleagues were examining MP Mus with ALMA, European Southern Observatory (ESO) researcher Miguel Vioque was looking at the young star using the now-retired star tracking spacecraft Gaia.
What Vioque discovered was that this young star is “wobbling.” This is something that would usually be the effect of a planet in orbit gravitationally tugging on a star, but Vioque was aware that MP Mus’ protoplanetary disk had, until that point, come up empty in terms of planets.
“My first reaction was that I must have made a mistake in my calculations, because MP Mus was known to have a featureless disc,” Vioque explained. “I was revising my calculations when I saw Álvaro give a talk presenting preliminary results of a newly-discovered inner cavity in the disc, which meant the wobbling I was detecting was real and had a good chance of being caused by a forming planet.”
Artist impression of ESA’s Gaia satellite observing the Milky Way. (Image credit: Spacecraft: ESA/ATG medialab; Milky Way: ESA/Gaia/DPAC; CC BY-SA 3.0 IGO. Acknowledgement: A. Moitinho.)
The researchers came together, combining the Gaia and ALMA data with some computer modeling assistance to determine that the wobbling is likely caused by a gas giant with a mass between three and ten times that of Jupiter.
This giant planet appears to orbit MP Mus at a distance of between one and three times the distance between Earth and the sun.
“Our modelling work showed that if you put a giant planet inside the newfound cavity, you can also explain the Gaia signal,” Ribas said. “And using the longer ALMA wavelengths allowed us to see structures we couldn’t see before.”
As well as being the first time Gaia has spotted a planet within a protoplanetary disk, this is the first time an embedded exoplanet has been indirectly discovered by combining precise star movement data from Gaia with deep observations of the disk courtesy of ALMA.
“We think this might be one of the reasons why it’s hard to detect young planets in protoplanetary discs, because in this case, we needed the ALMA and Gaia data together,” said Ribas. “The longer ALMA wavelength is incredibly useful, but to observe at this wavelength requires more time on the telescope.”
Ribas is hopeful that future ALMA upgrades, in addition to forthcoming telescopes, could be used to probe even deeper into protoplanetary disks.
This would not only reveal a hitherto undiscovered population of young embedded exoplanets, but it could help us understand how the solar system came to be around 4.5 billion years ago.
The team’s research was published on Monday (July 14) in the journal Nature Astronomy.
The journal Space Science Reviews is publishing a collection of articles about the University of Iowa-led Tandem Reconnection And Cusp Electrodynamics Reconnaissance Satellites (TRACERS) mission. This collection presents the science objectives of the mission, descriptions of the design and calibration of the plasma instruments, and other important aspects of the mission.
Dr. David Miles, associate professor in the UI Department of Physics and Astronomy, is leading NASA-funded mission, which aims to uncover how magnetic reconnection drives dynamic processes in Earth’s cusp region—a critical gateway between the solar wind and our planet’s magnetosphere.
TRACERS will use two identical small satellites flying in tandem low-Earth orbits to collect plasma and magnetic field data over a 12-month primary mission. These measurements will help scientists understand how spatial and temporal variations in reconnection influence the coupling between the solar wind and near-Earth space.
An overview of the mission can be found in this article: The Tandem Reconnection and Cusp Electrodynamics Reconnaissance Satellites (TRACERS) Mission. Mission design is described in The Tandem Reconnection and Cusp Electrodynamics Reconnaissance Satellites (TRACERS) Mission Design, while From the TRICE-2 Investigations to the TRACERS Mission shows how a the results of 2018 sounding rocket mission guided the science objectives of the TRACERS mission.
The articles describing instrumentation include:
The article Observing Cusp High-Altitude Reconnection and Electrodynamics: The TRACERS Student Rocket describes the Observing Cusp High-altitude Reconnection and Electrodynamics (OCHRE) mission, a student/early career researcher (ECR) focused sounding rocket that will fly as a compliment to the TRACERS satellites. The launch is scheduled in Winter 2026 from Andøya, Norway.
Miles expects additional articles to be published in the collection as the mission progresses.
The TRACERS mission is a collaborative effort involving the University of Iowa, Southwest Research Institute, UCLA, UC Berkeley, and Millennium Space Systems. It is dedicated to the late Professor Craig Kletzing, the mission’s original Principal Investigator and a longtime leader in space plasma research at Iowa.
TRACERS continues the department’s legacy of leadership in space physics and instrumentation and represents a major step forward in understanding the fundamental processes that shape space weather and Earth’s near-space environment.
Interested in why the moon looks like it does tonight? Wonder no more, here’s what you need to know about tonight’s moon, as it moves through the lunar cycle.
The lunar cycle is a series of eight unique phases of the moon’s visibility. The whole cycle takes about 29.5 days, according to NASA, and these different phases happen as the Sun lights up different parts of the moon whilst it orbits Earth.
See what’s happening tonight, July 14.
What is today’s moon phase?
As of Monday, July 14, the moon phase is still in Waning Gibbous. The moon is still mostly lit up, even days after the full moon. Tonight it will be 85% visible to us, NASA’s Daily Moon Observation tells us.
It’s day 19 of the lunar cycle, and here’s what you’ll be able to see when you look up. Without any visual aids, enjoy sights of the Aristarchus Plateau, the Copernicus Crater, and the Mare Serenitatis. With binoculars, you’ll also spot the Clavius Crater, Alphonsus Crater, and the Mare Nectaris.
With a telescope, you’ll see all this and more, including the Apollo 12 and 16. The rocks collected during the Apollo 16 mission are some of the oldest brought back from the Moon, according to NASA.
When is the next full moon?
The next full moon will be on August 9. The last full moon was on July 10.
Mashable Light Speed
What are moon phases?
Moon phases are part of a 29.5-day lunar cycle, NASA tells us, caused by the angles between the sun, moon, and Earth. Moon phases are how the moon looks from Earth as it goes around us. We always see the same side of the moon, but how much of it is lit up by the Sun changes depending on where it is in its orbit. So, sometimes it looks full, sometimes half, and sometimes not there at all. There are eight main moon phases, and they follow a repeating cycle:
New Moon – The moon is between Earth and the sun, so the side we see is dark (in other words, it’s invisible to the eye).
Waxing Crescent – A small sliver of light appears on the right side (Northern Hemisphere).
First Quarter – Half of the moon is lit on the right side. It looks like a half-moon.
Waxing Gibbous – More than half is lit up, but it’s not quite full yet.
Full Moon – The whole face of the moon is illuminated and fully visible.
Waning Gibbous – The moon starts losing light on the right side.
Last Quarter (or Third Quarter) – Another half-moon, but now the left side is lit.
Waning Crescent – A thin sliver of light remains on the left side before going dark again.
