Category: 7. Science

We can’t monitor what we can’t see. At least that’s what the latest shark science study says, pointing out that water clarity is only one factor that comes into play when observing sharks via aerial methods.

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Sharks are often imagined cruising just beneath the waves, dorsal fin protruding from the dark, ocean waters to alert people of their incoming doom. At least, that’s how Hollywood depicts them. With this in mind, you would think they would be easily visible from the air as these predators patrol coastal waters. But the reality is there are over 500 species of sharks and most of them spend very little time near the surface.

Aerial surveys are increasingly used in the New York Bight and surrounding waters to track marine animals relative to offshore wind energy sites and to conduct long-term monitoring of protected species, including cetaceans and sea turtles. Recent increases in shark bites on water users have also prompted state officials to invest heavily in visual and aerial surveillance near beaches, deploying helicopters, drones, jet skis, boats, and lifeguards. Shark bite risk for water users remains extremely low, but a combination of factors (including increasing shark abundance, shifts in predator and prey distributions, and rising human attendance at beaches) can increase encounter probabilities. The mid-Atlantic coastal waters host over two dozen shark species, many of which are highly migratory and seasonal, with varying habitat preferences and stock assessments indicate that populations of some of these predators have been increasing in recent years following decades of conservation and fisheries management. Climate change is also driving northward shifts and longer seasonal residency for many species, making encounters more likely. There are gaps in understanding how population monitoring and beach safety strategies can be optimized, and many question how effective such aerial monitoring efforts actually are.

To better understand what is happening in New York waters, NOAA Fisheries shark researcher Dr. Tobey H. Curtis and a group of scientists tracked 150 individuals across 10 species using depth-sensing tags between 2017 and 2024. These species included sand tiger (Carcharias taurus), common thresher (Alopias vulpinus), white (Carcharodon carcharias), tiger (Galeocerdo cuvier), spinner (Carcharhinus brevipinna), blacktip (Carcharhinus limbatus), dusky (Carcharhinus obscurus), sandbar (Carcharhinus plumbeus), scalloped hammerhead (Sphyrna lewini), and smooth hammerhead (Sphyrna zygaena) sharks. The tags affixed to the individuals recorded swimming depths, and the researchers then paired the data with measurements of water clarity and wave height to assess how visible sharks are to planes, drones, or helicopters.

Even when the water looks full of sharks from above, most are actually deeper and largely invisible to aerial observers.

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Despite overlapping ranges on the New York shelf, species showed distinct vertical habitat use patterns. Smooth hammerheads and blacktip sharks spent comparatively more time near the surface, whereas white sharks, spinner sharks, and dusky sharks were active throughout much of the water column. Sand tiger and sandbar sharks spent little time near the surface, staying closer to the bottom. These differences, the authors posit in their recent publication, likely reflects a combination of temperature, foraging strategy, prey availability, and distance from shore. And although many species are capable of much deeper swimming, the relatively shallow bathymetry of nearshore waters here likely constrained daytime depths. Five species (the common thresher, white, spinner, sandbar, and tiger sharks) reached maximum daytime depths exceeding 330 ft (100 m), yet mean depths remained less than 65 ft (20 m). These sharks may only occasionally explore deeper waters while spending most of their time closer to shore, where prey are concentrated. Even the most surface-oriented species, the smooth hammerhead, spent only about one-third of the time within 3 ft (1 m) of the surface. In fact, the sharks occupied the top 3 ft (1 m) of water — this is the zone where aerial detection is most feasible — only about 16 percent of the time. This means that even when you might think the water is full of visible sharks, most of the time they are actually deeper and effectively invisible to observers in the air.

Environmental conditions compound the challenge. Average summer water clarity was only 7 ft (2.1 m), and wave heights averaged 2.6 ft (0.8 m). Unlike regions such as southeast Florida or southern California, New York’s nearshore waters are frequently turbid and moderately rough, limiting the visibility of sharks from the air. Sun angle and glare can further interfere with detection, though drones with polarizing filters may partially improve observation. Even so, aerial methods alone are unlikely to provide reliable population assessments or real-time beach safety data. If anything, this new publication shines a light on a key limitation of aerial monitoring: you can’t monitor what you can’t see. The visibility of sharks is influenced not only by their depth, but various environmental factors at play. A plane flying overhead may see few, if any, sharks simply because most are swimming deeper than the camera can penetrate and the water is turbid; this creates what is called an “availability bias,” where the number of sharks detected actually underestimates the true number present. For public safety programs that rely on spotting sharks near beaches, or for scientists attempting to estimate population sizes, these biases mean aerial surveys provide only a partial and sometimes misleading picture.

Sharks can be elusive in ways that are not intuitive — afterall, their behavior is dynamic, varying by species, time of day, and environmental conditions. Tools like aerial surveys are valuable for spotting larger trends or occasional surface activity, yes, but they cannot reliably measure true abundance or guarantee timely detection for beach safety. Thus, complementary approaches such as acoustic monitoring, baited remote cameras, and tagging studies, are still needed to build an accurate understanding of shark populations and movements. Ultimately, the work of Curtis and his team shows that aerial monitoring is a limited tool in New York. And while that sounds like a negative thing, recognizing these limitations allows scientists and public safety officials to plan more effective strategies. It also reminds us that even in familiar coastal areas, much of the marine world remains hidden just below the surface, out of our reach. And to that leaves much to the imagination…

CA-G225R rescues the replication defect imposed by IP6-packaging deficiency

Cryo-electron tomography (cryoET) combined with subtomogram averaging (STA) is a cutting-edge imaging technique that reveals the 3D structure of biological specimens at near-atomic resolution in their native, frozen-hydrated state. In previous studies, we used cryoET STA to investigate the effect of mutations, namely KAKA, in the IP6 binding pocket of immature Gag hexamers in the context of the WT and 6HB-stabilizing SP1 mutations T8I and M4L/T8I^20,21. We found that immature KAKA VLPs were composed of Gag hexamers that were largely indistinguishable from those formed by WT Gag, apart from the absence of IP6 density at the top of the 6HB. To dissect further the contributions of individual single or dual mutations on the immature Gag lattice, we analysed the structures of immature K227A and KAKA/T8I VLPs produced from 293T cells and compared them to the previously reported structures of WT and KAKA immature VLPs (Fig. 1). Both K227A and KAKA/T8I assemble into immature spherical VLPs similar to those formed by WT and KAKA (Fig. 1a–d). Our cryoET STA structure of K227A at 3.82 Å resolution showed an intermediate level of IP6 compared with the WT (full) and the KAKA mutant (empty) (Fig. 1e–g, Supplementary Figs. 1a, 2, Supplementary Table 1), consistent with the previous biochemical measurements²¹. The structure of KAKA/T8I at 3.67 Å resolution displayed no IP6 density (Fig. 1h, Supplementary Fig. 1b, Supplementary Table 1), similar to the KAKA mutant, suggesting that the 6HB-stabilizing mutation SP1-T8I does not restore IP6 enrichment to KAKA. Consistent with this inability to restore IP6 enrichment, the addition of SP1-T8I does not substantially reverse the infectivity defect imposed by the KAKA mutations²¹ (Fig. 1i).

Next, we sought to determine how HIV-1 might adapt to an inability to enrich IP6 during particle assembly. We propagated KAKA and KAKA/T8I in the highly permissive MT-4 T cell line. Briefly, MT-4 cells were initially transfected with the WT NL4-3 infectious molecular clone or derivatives harboring the KAKA or KAKA/T8I mutations. Consistent with the drastic decrease in KAKA and KAKA/T8I infectivity, each mutant demonstrated a significant delay in replication compared to WT virus (Fig. 1j). Upon propagation of virus collected from the peak of replication, both KAKA and KAKA/T8I replicated with a substantially reduced delay relative to WT (Fig. 1k). This observation is suggestive of the acquisition of mutations that compensate for the defects induced by the KAKA and KAKA/T8I mutations. To confirm the acquisition of compensatory mutations, we isolated genomic DNA from infected cells at the peak of replication and PCR amplified the Gag coding region. Gag amplicons were sequenced, and potential compensatory mutations were cloned into the KAKA and KAKA/T8I NL4-3 molecular clones. This process was performed iteratively using mutant viruses selected in initial experiments to initiate downstream propagation experiments. We also performed these in vitro selection experiments in the C8166 T cell line and with additional mutant viruses containing a K158T mutation in place of K158A (KTKA) and/or an SP1-M4L mutation in place of T8I. Compensatory mutations selected in these experiments were found throughout CA and SP1 (Supplementary Table 2). Interestingly, several selected mutations were identified at amino acid positions associated with resistance to capsid inhibitors (e.g., CA-Thr-107, His-87, Ala-105, Thr-58, Gly-208, Thr-216)^22,23,24,25, altered capsid assembly and stability (e.g., CA-H12Y, N21S, T216I)^11,24,26, and host factor dependence (e.g., CA-Ala-77, His-87, Gly-94D, Gly-208, Thr-210, Glu-187, Pro-207)^27,28,29,30. We also observed mutations at amino acid positions located at critical interfaces within the mature CA lattice including the β-hairpin (Val-11 and His-12), the central pore (Asn-21 and Ala-22), the Thr-Val-Gly-Gly (TVGG) motif that controls CA hexamer/pentamer assembly (Thr-58, Gly-61), the NTD/CTD interface between adjacent CA protomers (Met-68, Ala-105, Thr-107), and the trimer interface between neighboring CA hexamers/pentamers (Pro-207, Gly-208, Thr-210, Thr-216).

To determine whether the mutations selected in these experiments could restore fitness to KAKA and KAKA/T8I, we quantified the effect of these mutations on the single-cycle infectivity of KAKA and KAKA/T8I. Most of the mutations that we observed were unable to significantly restore infectivity to KAKA or KAKA/T8I (Supplementary Fig. 3), including two mutations–N21S and T216I–that were recently reported to restore infectivity to K25A, a mutant unable to bind IP6 in the context of the mature CA lattice¹¹. However, we did observe a mutation at position 225 in CA that significantly restored infectivity to KAKA/T8I. Initially, we observed a Gly-to-Ser substitution at residue 225 upon propagation of KAKA in MT-4 cells. After introducing the G225S mutation into multiple KAKA- and KTKA-containing clones, we observed a Ser-to-Arg substitution at CA position 225 (G225R) upon propagation of KTKA/T8I/G225S. We then introduced the G225R mutation into KAKA and KAKA/T8I to determine its effect on particle infectivity. We found that G225R conferred an ~8-fold increase in single-cycle infectivity to KAKA/T8I (from ~2% of WT to 16%) (Fig. 1i). Further propagation of KAKA/T8I/G225R resulted in the acquisition of an additional mutation, A77V, that doubled the infectivity of KAKA/T8I/G225R (Fig. 1i). Curiously, we also found that G225R conferred an opposing phenotype to KAKA, decreasing its infectivity to nearly undetectable levels (Fig. 1i). Thus, T8I, which stabilizes the immature Gag lattice, restores KAKA/G225R single-cycle infectivity by ~100 fold. Furthermore, the G225R mutation alone imposes an infectivity defect comparable to that of KAKA/T8I/G225R, demonstrating that G225R is insensitive to the defect imposed by KAKA/T8I (Fig. 1i).

G225R does not restore IP6 enrichment to the KAKA or KAKA/T8I mutants

We next sought to determine the mechanism by which G225R restores infectivity to KAKA/T8I. Because G225 is close to the mutated IP6-binding residue K227 at the top of the 6HB, the change of the Gly to a positively charged Arg at this position could introduce a new positively charged ring capable of restoring IP6 recruitment during particle assembly, thereby rescuing particle infectivity. To investigate this possibility, we produced immature KAKA/G225R, KAKA/T8I/G225R, A77V/KAKA/T8I/G225R, and G225R VLPs and solved their Gag hexamer structures by cryoET with STA (Fig. 2a–d, Supplementary Figs. 1, 2, Supplementary Table 1). The structure of KAKA/T8I/G225R at 4.05 Å resolution revealed no IP6 density atop the 6HB (Fig. 2a, Supplementary Fig. 1c, Supplementary Table 1). The bulky Arg sidechain, which is clearly resolved in the density map, points away from the central channel of the 6HB, unlike K227 in WT Gag, and is therefore not available for IP6 coordination (Fig. 2a). Indeed, no IP6 density was observed in cryoET STA maps in any of the KAKA-containing Gag mutants analysed, including KAKA/G225R and A77V/KAKA/T8I/G225R (Fig. 2b, c, Supplementary Fig. 1d, e, Supplementary Table 1). In contrast, the G225R Gag hexamer structure showed a clear IP6 density atop the 6HB (Fig. 2d, Supplementary Fig. 1f, Supplementary Table 1). Each of the Gag mutants evaluated is capable of assembling an immature Gag lattice similar to that present in WT immature VLPs (Fig. 2a–d). These structural data suggest that the recovery of KAKA/T8I infectivity upon introduction of the compensatory mutation G225R cannot be attributed to increased IP6 packaging.

G225R does not affect the production of KAKA/T8I virions from IP6-depleted cells

To confirm that the KAKA-containing mutants rescued by G225R remain IP6-independent during particle assembly, we conducted experiments to investigate the effect of IP6 depletion in virus-producing cells on virus production efficiency and particle infectivity. Briefly, we produced virus in HEK 293T knockout (KO) cell lines lacking either inositol polyphosphate multikinase (IPMK), which phosphorylates IP3 and IP4 to generate IP4 and IP5, or inositol pentakisphosphate 2-kinase (IPPK), which phosphorylates IP5 to generate IP6¹³. To further decrease IP6 levels in IPMK or IPPK KO cells, we simultaneously overexpressed multiple inositol-polyphosphate 1 (MINPP1), which removes phosphates from IP6, IP5, and IP4. After transfecting NL4-3 infectious molecular clones, we measured the efficiency of virus production in these IP6-depleted cells by quantifying the levels of p24 (CA) present in the supernatant relative to total Gag present in the cells and supernatant. Consistent with previous reports^20,21,31, we observed a significant reduction in the efficiency of WT virus production from IPMK KO and IPPK KO HEK 293T cells overexpressing MINPP1 relative to parental 293T cells co-transfected with an empty vector (Fig. 2e, Supplementary Fig. 4). In agreement with our structural data, G225R exhibited an IP6-dependent assembly phenotype similar to WT. In contrast, virus production efficiency of all KAKA-containing mutants was unaffected by producer-cell IP6 depletion, confirming that G225R does not rescue KAKA/T8I infectivity by restoring IP6 enrichment. Again, these data are in agreement with our cryo-ET/STA results and demonstrate that irrespective of the presence of G225R, KAKA mutants assemble in an IP6-independent manner.

We then investigated the effects of producer-cell IP6 depletion on particle infectivity. Consistent with previous results^20,21,31 producer-cell IP6 depletion drastically reduces WT particle infectivity, while KAKA and KAKA/T8I infectivity is more mildly reduced (Fig. 2f). Our assay was unable to detect KAKA/G225R infectivity under any condition. The rescued mutants KAKA/T8I/G225R and A77V/KAKA/T8I/G225R also showed only mild reductions in infectivity when produced from IP6-depleted cells. However, KAKA/T8I/G225R virions produced from IP6-depleted cells remained ~10–fold more infectious than KAKA/T8I virions produced under the same conditions (Fig. 2f). Since neither mutant is able to enrich IP6 into virions, this suggests that G225R may rescue KAKA/T8I infectivity by mitigating the consequences of reduced IP6 during particle maturation, perhaps by facilitating capsid formation at low IP6 concentrations.

G225R increases the efficiency of KAKA/T8I capsid formation in virions and in vitro

To test the hypothesis that G225R facilitates capsid formation in the absence of enriched IP6, we next examined the effects of G225R on the morphology of mature, Env(-) viral particles by cryoET (Fig. 2g, h). CryoET reconstructions revealed a variety of distinct morphologies of mature WT HIV-1 particles produced from HEK 293T cells, which we categorized into Mature, Mature (eccentric), Mature (abnormal), and Immature (Fig. 2g). All the mutants tested displayed reduced numbers of viral particles containing normal mature conical cores relative to the WT. The revertant mutants KAKA/T8I/G225R and A77V/KAKA/T8I/G225R exhibited higher numbers of viral particles containing normal mature conical cores than KAKA/T8I (Fig. 2h). The occurrence of normal mature cores (Fig. 2h, light blue) correlates well with the observed infectivity measurements for these mutants (Fig. 1i). These analyses demonstrate that G225R increases the formation of normal mature cores in the absence of IP6 enrichment into viral particles.

The findings that the G225R mutation improves mature particle formation without IP6 enrichment led us to hypothesize that this mutation may increase the efficiency of mature capsid assembly under low-IP6 conditions. To test this, we expressed and purified recombinant CA protein carrying KAKA and G225R mutations and conducted in vitro assembly assays at IP6 concentrations ranging from 0 µM to 5 mM (Fig. 3a–d). Assembly properties of each mutant were evaluated by determining the amount of pelletable CA in each reaction. While WT and KAKA CA require high IP6 concentrations to assemble (Fig. 3a, b), the CA proteins carrying the G225R mutation assemble at low IP6 concentrations (Fig. 3c–e). Negative stain transmission EM images show that the KAKA/G225R CA starts forming tubes and cones at an IP6 concentration as low as 5 µM and the G225R CA at 50 µM, whereas no such structures were observed with WT and KAKA CA at 150 µM IP6 (Fig. 3f). Further statistical analyses on the number of assembled tubes and cones for each variant indicate that KAKA/G225R and G225R CA form significantly more tubes and cones than WT and KAKA CA at low IP6 concentrations (Fig. 3g–i). The data suggest that the G225R mutation reduces IP6 dependency for mature capsid assembly.

CryoEM structure of KAKA/G225R CLP reveals previously unresolved CA C-terminus stabilizing the dimer interface

To understand the molecular mechanism by which the G225R mutation promotes the assembly of stable mature capsids under low-IP6 conditions, we prepared KAKA/G225R CLPs in the presence of 100 µM IP6 to optimize the sample for cryoEM structural analysis, noting that WT CA shows no assembly at this IP6 concentration (Fig. 3f–i). The in vitro assembled KAKA/G225R CLPs are highly ordered (Fig. 4a), from which we determined the structure of KAKA/G225R CA hexamer at 2.7 Å resolution and built an atomic model (PDB 9I8I) using single-particle cryoEM (Fig. 4b, c, Supplementary Fig. 5, Supplementary Table 3).

The structure reveals two IP6 densities in the hexamer center, coordinated by R18 at the top density and K25 at the bottom density (Fig. 4d), consistent with previous studies^{4,6,7,9,32,33}. It is worth noting that the IP6 densities are rather weak compared to those in WT CA CLPs assembled with 2.5–5 mM IP6^9,32,33 and in native mature cores within perforated virions with 1 mM IP6⁷, suggesting a low IP6 occupancy in KAKA/G225R CLPs. This is expected, as our KAKA/G225R CLPs were assembled in the presence of 25 to 50–fold lower IP6 concentrations than WT CLPs. In the hexamer structure, the β-hairpin exhibits an open conformation similar to those observed in previous cryoEM structures derived from CLPs as well as the crystal structure from the non-pandemic strain HIV-1 (O) at pH 6, distinct from the closed conformation in cryoEM structures determined from tubular assemblies and the crystal structure of the WT CA hexamer at pH 7^{8,9,32,33,34,35} (Fig. 4e, f). The reduced pH in the CLP assemblies was suggested to affect the β-hairpin conformation^{4,6,8,9,10,11,12}. The NTD-CTD interface around the binding pocket for Lenacapavir and FG-motif-containing host factors appears preserved (Fig. 4g, h). The linker that connects CA-NTD to CA-CTD resembles that of the WT CA (Fig. 4i). The CypA binding loop is very well ordered (Fig. 4i), in contrast to the majority of CA hexamer structures determined previously. Intriguingly, the density of KAKA/G225R CA C-terminus extends to G223 which can be unambiguously modeled (Fig. 4i, inset), along with additional densities further extending to the inter-hexamer interfaces but not well-resolved. Interestingly, this C-terminal extension adopts the same configuration as our previous CA-CTD NMR solution structure (PDB 2KOD, the 2nd conformer) (Fig. 4i inset, grey)³⁶. These results suggest that the otherwise flexible C-terminus could adopt a structured conformation to mediate intermolecular interactions, thus strengthening the capsid stability when required.

To further clarify the inter-hexamer densities, cryoEM density maps of the tri-hexamer interface were obtained (Fig. 5a). The dimer and trimer interfaces of KAKA/G225R are very similar to those of WT (PDB 8G6M), with an RMSD of 0.27 Å and 0.44 Å, respectively (Fig. 5b, c). A further 3D classification and refinement resulted in two major classes, one without extra density (Fig. 5d) and another with an extra density extending from the end of H11, reaching below the dimer interface (Fig. 5e, red density). This density most likely corresponds to the previously unresolved CA C-terminal fragment (220–231), which was too flexible to be resolved in all previous crystal or cryoEM structures.

Molecular dynamics simulation of interactions involving the CA C-terminal segment

To explore the interactions between the C-terminal fragment with the neighboring CA monomers, we used Rosetta^37,38,39 to derive density-guided models of a KAKA/G225R CA trimer of dimers with an extended C-terminus. Furthermore, we performed molecular dynamics simulations of the KAKA/G225R CA trimer of dimers, as well as a KAKA CA and WT CA trimer of dimers, to assess the stability of the C-terminal fragment in the CA dimer interface. Across 7 independent replicates of 400 ns long unrestrained equilibration MD simulations, we observed that the C-terminal region (residues 220–231) is highly flexible and transiently occupies the CA dimer interface. In the KAKA/G225R CA trimer of dimers simulations, C-terminal tail occupancies at the dimer interface ranged from 1 to 90%, with an average occupancy of 20.7%, consistent with the multiple 3D classes observed in the cryoEM analysis. In contrast, for KAKA CA and WT CA, the dimer interface occupancies were consistently lower, with average occupancies of 6.9% and 10.4%, respectively (Supplementary Fig. 6a, b).

Additionally, we analysed the residence times of C-terminal segment contacts in all simulations. While C-terminal interactions at the dimer interface generally have short residence times (<5 ns) across all CA variants, contact events for KAKA/G225R CA exhibited a broader distribution of residence times, with several events lasting over 20 ns and up to 150 ns (Supplementary Fig. 6c). Interestingly, across all simulation replicas we also observed one high residence time event for WT CA, where the C-terminal tail was stabilized via salt bridge interactions involving R229 and L231 with charged residues at the dimer interface. This suggests that, although C-terminal tail interactions with the dimer interface can occur in WT CA, these events are rare and more prevalent in KAKA/G225R CA.

We then performed a residue-level contact analysis of the C-terminal segment and CA dimer interactions to identify the specific interactions that stabilize the C-terminal tail at the dimer interface. Notably, we observed that residues L231 (the C-terminal residue), R229 and G225R form salt bridges with high occupancies with residues K199, R154 and D152 at the dimer interface (Fig. 5f, Supplementary Table 4). These interactions increase the stability of conformations where the C-terminal segment resides at the dimer interface. In contrast, interactions with those residues have significantly reduced occupancies in the KAKA CA and WT CA simulations (Supplementary Table 4).

Thus, the extra density observed in the cryoEM map of KAKA/G225R CA tri-hexamer likely stems from the transient interactions of the C-terminal segment at the dimer interface, which are facilitated by the added charge of the G225R mutation on the C-terminal segment. The presence of the C-terminal segment at the dimer interface, along with the formation of salt bridge interactions therein, might explain why the KAKA/G225R CA mutation stabilizes the mature capsid even with minimal IP6 present.

KAKA/G225R CA forms compact assembly interfaces

To further evaluate the effect of the KAKA/G225R CA mutation in capsid interfaces, we extracted all possible capsomer-capsomer interfaces (hexamer-hexamer-hexamer, hexamer-hexamer-pentamer and hexamer-pentamer-pentamer) from a full capsid cone⁷ and compared them with the KAKA/G225R CA trimer of dimers assembly (Fig. 6). For each capsomer-capsomer dimer interface, we measured the center of mass distances and tilt angles between alpha helices 9 and 10 and the 3–10 helix. Compared to all WT dimer interfaces, the helices 9 and 10 in KAKA/G225R CA are packed closer, resembling the distance for pentamer-pentamer-hexamer interfaces. However, these helices are oriented at a more acute angle (for helix 9), or closer to a right angle (for helix 10). In conclusion, the KAKA/G225R CA dimer interfaces are more tightly packed than those measured in a WT CA cone, likely due to the interactions with the C-terminal flexible tail described above.

Infectivity of the KAKA and G225R mutants is insensitive to target-cell IP6 depletion

We further investigated whether an inability to enrich IP6 into viral particles results in sensitivity to depletion of IP6 in target cells, and whether G225R could reverse this sensitivity. Consistent with previous reports⁴⁰, we found that the infectivity of the hypostable CA mutant P38A was severely reduced in HEK 293T IPPK KO target cells relative to its infectivity in parental HEK 293T cells (Supplementary Fig. 7). In contrast, WT and KAKA/T8I infectivity was unaffected in HEK 293T IPPK KO cells relative to parental cells, and the addition of G225R to KAKA/T8I did not alter this phenotype. We did observe a statistically significant decrease in G225R infectivity in HEK 293T IPPK KO cells relative to parental cells. However, the effect size was much smaller than that of P38A. These data demonstrate that the addition of G225R to KAKA/T8I did not eliminate insensitivity to target cell IP6 depletion.

How did lifeless chemistry on early Earth transform into biology? For decades, scientists have wrestled with this chicken-or-egg riddle: proteins are essential to cells, but they can only be made inside cells with the help of other proteins. Now, a new study in Nature suggests that this paradox may not be as impossible as once thought.

A team of researchers from University College London has shown that RNA molecules and amino acids can spontaneously join forces in water under neutral conditions, without the need for complex enzymes. They demonstrated that aminoacyl-thiols—a class of sulfur-based compounds—can selectively attach amino acids to RNA, effectively mimicking the first stage of modern protein production inside ribosomes.

“We have achieved the first part of that complex process, using very simple chemistry in water at neutral pH,” said Matthew Powner, one of the study’s authors, in a statement quoted by Futurism. “The chemistry is spontaneous, selective, and could have occurred on early Earth.”

Life’s molecular matchmaking

The research team explained that thioesters, molecules central to metabolism even today, might have been the original matchmakers of life. Instead of leading to uncontrolled chaos, these sulfur-linked compounds nudged amino acids to pair with RNA strands in a tidy, selective way. This step is critical, because life depends on order—random peptides would never sustain the genetic coding system required for evolution.

Interestingly, the experiments revealed that RNA duplexes (double-stranded forms) played a special role in directing amino acids to attach at precise spots, setting the stage for what could later evolve into coding and protein synthesis.

Clues hidden in ice and freshwater pools

Another quirky finding: freezing conditions amplified these reactions, even at very low concentrations of molecules. This means icy lakes and ponds on early Earth might have been quiet cradles of life, where primitive chemistry ticked along for millennia. Nick Lane, a UCL chemist not involved in the research, told Science that while the study is a breakthrough, it doesn’t yet fully explain how life’s tidy protein sequences emerged from random chemistry. Still, he noted that these insights bring us closer to understanding how amino acids could have first been organized.

From space rocks to living cells

Adding to the cosmic curiosity, scientists have also discovered amino acids and nucleotides—the raw ingredients of life—on meteorites and asteroid samples. This makes the scenario even more plausible: early Earth may have received an extraterrestrial delivery, with thioesters and RNA molecules teaming up to spark the first whispers of biology.

The study, “Thioester-mediated RNA aminoacylation and peptidyl-RNA synthesis in water” published in Nature, doesn’t just address a long-standing scientific puzzle. It adds weight to the idea of a “thioester world,” where sulfur chemistry provided the spark for life long before enzymes existed.

Billions of years later, the fact that our own cells still rely on thioesters to fuel essential reactions may be nature’s way of reminding us where it all began.

Group Captain Shubhanshu Shukla has shared a fascinating video of his training inside the Multi Axis Trainer (MAT) at NASA’s Marshall Space Flight Center for the Ax-4 mission. The video offers a rare peek into the intense preparation astronauts undergo to handle the challenges of spaceflight, showcasing Shukla strapped into a device that spins wildly to simulate the disorienting motions of a spacecraft.

The Multi Axis Trainer, also called the Mercury Astronaut Trainer, was originally designed to prepare America’s early astronauts for the possibility of their capsule spinning out of control in orbit.

Let’s get spinning.
I am in a MAT (Multi Axis Trainer or Mercury Astronaut
Trainer) at the Marshall Space Flight Center. This trainer was used to expose the Mercury astronauts to excessive rates in roll, pitch and yaw should the capsule experience the same in orbit. The aim was… pic.twitter.com/E1QN2ZsXEC
— Shubhanshu Shukla (@gagan_shux) August 31, 2025

“This trainer was used to expose the Mercury astronauts to excessive rates in roll, pitch, and yaw should the capsule experience the same in orbit,” Shukla explained. “The aim was to expose the astronauts to such rates so that they can control the space capsule in spite of being under such extreme rates,” he added. The device mimics the chaotic tumbling an astronaut might face, helping them learn to stay focused and in control under extreme conditions.

ALSO SEE: Shubhanshu Shukla Reunites With His Family After Ax-4 Mission; Shares Pics

Although the Mercury astronauts never faced such extreme spins during their missions, the training proved its worth later. Shukla shared a gripping story about legendary astronaut Neil Armstrong during the Gemini 8 mission in 1966. When a faulty thruster caused Armstrong’s spacecraft to spin dangerously while attempting to dock with the Agena target vehicle, he relied on his training to take manual control and stabilize the craft. This quick thinking saved the mission and remains a celebrated moment in space history.

Shukla’s video also gave a glimpse into what it feels like to train in the MAT. Despite its dizzying appearance, the trainer is designed to keep trainees’ stomachs at the center of the motion, which helps prevent motion sickness. “Incidentally, you don’t feel sick in this trainer as your stomach is at the center always,” Shukla noted. However, he warned that closing one’s eyes during the training could cause nausea due to sensory confusion, adding, “not ready to try” that himself.

ALSO SEE: Welcome Home Shubhanshu Shukla! SpaceX Dragon Splashes Down With Ax-4 Mission Crew

Canada is developing its first lunar rover as part of NASA’s Artemis program, designed to locate water ice and measure radiation on the Moon’s south pole while surviving extreme temperature swings between -200°C and 100°C.

The 35-kg vehicle, set for launch in 2029, represents Canada’s latest contribution to space exploration following its legacy of the Canadarm and satellite technology.

Christian Sallaberger, CEO of Canadensys Aerospace revealed: “Temperature is one of the biggest engineering challenges, It is not just surviving cold but swinging between very cold and very hot.”

Despite recent lunar landing failures by private companies, Sallaberger acknowledged that the team remains confident. We try to mitigate those things goes wrong.

Chief scientist Dr. Gordon Osinski confirmed: “Water molecules can be broken down to obtain hydrogen for rocket fuel, making the Moon a potential petrol station for spacecraft.”

The first lunar rover project continues Canada’s space legacy that includes astronauts like Chris Hadfield and Jeremy Hansen, who will orbit the Moon on Artemis II next year.

Rover builder mission scientifically directs treacherous regolith, jagged lunar soil described as Velcro dirt that gums up mechanisms.

In addition to that, the U.S. even passed laws to protect Apollo sites from potential interference with over 50 countries signing the Artemis Accords.

The Canadian Space Agency held an online competition to name the unnamed vehicle and asked the public to pitch names and the agency will select one, and is expected to announce the winner in the future.

Plant materials and growth

The B. napus accessions in this study were planted in Zhijiang (30° 48’ N, 111° 77’ E) and Taiping (29° 71’ N, 118° 29’ E), spanning three growing seasons (2016–2018). The edited B. napus plants were planted in Hubei (30° 54’ N, 113° 81’ E) and Gansu (38° 43’ N and 100° 81’ E) in 2023. All B. napus materials were maintained by self-pollination. Crop management of field experiments for agronomic trait tests followed the standard protocol of the China National Rapeseed Variety Field Test.

All A. thaliana and Nicotiana benthamiana plants were grown under controlled conditions at 21–24°C and with a 16 h photoperiod. The Arabidopsis materials used in this study include pmr4-1 (gsl5)²³, sid2-1 (ref. ³⁹), jar1-1 (ref. ⁴⁰), ein2-1 (ref. ⁴¹), ald1 (ref. ⁴²), pad4 (ref. ⁴³) and the transgenic line NahG⁴⁴. The homozygosity of T-DNA insertion mutants was genotyped by PCR with both gene-specific and T-DNA border primers. The point mutation lines were genotyped by sequencing the PCR products after amplification with gene-specific primers. The resultant homozygous double mutants were used for the clubroot resistance test. The primers used in this study are listed in Supplementary Table 5.

Phenotyping for field traits

All field experiments for phenotyping the field traits were carried out in a randomized block design with three replicates. Each replicate contained at least 60 plants with a space of about 30 cm between rows, and each row was 2 m in length with a space between plants of approximately 10 cm. The seeds of each accession were sown in late September (26–30), which is the beginning of the growing season for winter canola plantation areas in China. In early December (about 70 days after sowing), the roots of the susceptible control (Westar) became severely clubbed, and the growth of the plants, as well as the P. brassicae infection, was almost terminated in the clubroot disease fields owing to the lower temperature in winter (usually below 8 °C). All tested B. napus accessions in the clubroot disease fields were harvested to score clubroot disease severity. Disease scales 0, 1, 2 and 3 were used to score each plant of each replicate of 244 B. napus accessions and to generate the DI to quantify the disease severity of each accession based on a previously described method⁷: 0, no clubs; 1, a few small clubs present on less than one-third of the lateral roots or on the main root; 2, moderate clubs present on one-third to two-thirds of the lateral roots or the main root; and 3, severe clubs on the main root or present on more than two-thirds of the lateral roots. In early May of the next year—the end of the growing season for winter canola plantation areas in China—the B. napus plants were harvested for scoring of the key agronomic traits.

To evaluate the key agronomic traits, each replicate comprised 15 rows with 20 plants in each row. The sampling method depended on specific traits: (1) plant height (the length (cm) from the cotyledon node to the tip of a plant); (2) branch number (the number of primary branches per plant); (3) the 1,000-seed weight (in g) per plant; (4) silique number per plant (all siliques in each plant); (5) seed number per silique (the average seed number of the bottom 20 siliques from the main inflorescence of each plant); (6) yield (the seed weight of all plants within each block); and (7) seed oil content. Data from the first five key agronomic traits were determined based on three replicates, each of which comprised ten randomized plants. A Foss NIR Systems 5000 Near-Infrared Reflectance Spectroscope was used to measure the oil content of seeds collected at the maturity period⁴⁵.

GWAS and favorable allele identification

A total of 244 B. napus accessions were genome-resequenced with at least tenfold genome coverage, and a total of 2,797,642 filtered SNPs with a missing rate of ≤0.1 and minor allele frequency of ≥0.05 were obtained²⁰. The clubroot DI of each B. napus accession was investigated in three consecutive years (2016–2018) and used to generate the best linear unbiased prediction using the R script lme4 (https://cran.r-project.org/web/packages/lme4) and lsmeans²¹. Three models, including a general linear model, mixed linear model and fixed and random model Circulating Probability Unification (FarmCPU), were used for genome-wide association analysis. The significant P value threshold of the GWAS was set to 1.8 × 10⁻⁸ (−log₁₀P = 7.74, calculated as 0.05 / total number of SNPs). Haplotype block estimation was based on the confidence interval method⁴⁶. The linkage disequilibrium of the whole genome and the significantly associated regions were analyzed using PopLDdecay and LDBlockShow software^47,48.

The SNPs of the gene-related regions were extracted from the genomic variation files. A phylogenetic tree was constructed using PHYLIP (v.3.696) with the neighbor-joining method and default parameters and was visualized by FigTree (v.1.4.3)⁴⁹. PCA analysis was performed using PLINK (v.1.90b4.6), and the first two principal components of the PCA analysis were illustrated by the ggplot2 package in R (v.4.1)⁵⁰. Population structure was analyzed by ADMIXTURE (v.1.3.0) with the following parameters: the number of subgroups, K, ranged from two to eight, and the cross-validation error was calculated for each K value⁵¹.

Gene complementation and expression, RNA interference assay and genome editing

For complementation experiments with the gsl5 mutant, a full-length genomic DNA fragment of GSL5 including approximately 3.0 kb of the upstream sequence of the start codon and the open reading frame was amplified from Arabidopsis, B. napus, B. rapa, B. oleracea and R. sativus using gene-specific primers (Supplementary Table 5). All fragments were respectively cloned into the pBI121 vector, generating the recombinant plasmids proAtGSL5^Col-0:AtGSL5^Col-0 (GSL5), proBnaA09.GSL5^Westar:BnaA09.GSL5^Westar(Hap_1), proBnaA09.GSL5^ZS11:BnaA09.GSL5^ZS11(Hap_2), proBnaC09.GSL5^ZS11:BnaC09.GSL5^ZS11 (BnaC09.GSL5), proBraGSL5^Chiifu:BraGSL5^Chiifu (BraGSL5), proBolGSL5^ZG11:BolGSL5^ZG11 (BolGSL5) and proRsaGSL5^MTH:RsaGSL5^MTH (RsaGSL5) for Agrobacterium-mediated transfection of Arabidopsis gsl5 plants.

To overexpress AtGSL5 in Arabidopsis, the GSL5 genomic region was cloned into pBI121 driven by the cauliflower mosaic virus 35S promoter, generating the recombinant plasmid 35S:AtGSL5 (GSL5-OE) for Agrobacterium-mediated transfection of wild-type plants.

For the RNA interference assay, a 385 bp coding sequence of PbPDIa was cloned into a pBI121-RNAi vector driven by the cauliflower mosaic virus 35S promoter, generating the recombinant plasmid for Agrobacterium-mediated transfection of wild-type plants. The transgenic plants produced a hairpin containing a 385 bp double-stranded RNA and generated endogenous small RNA that was able to knock down the PbPDIa expression of P. brassicae⁵².

For genome editing, two single-guide RNA (sgRNA) sequences, sgRNA1 and sgRNA2, from the first exon of GSL5 were designed as the editing targets to knock out the GSL5 from A. thaliana, B. napus, B. rapa and B. oleracea (Supplementary Table 5). All sgRNAs were designed using CRISPR-P (v.2.0) (http://crispr.hzau.edu.cn/CRISPR2)⁵³. A previously developed multiplex genome editing vector, pYLCRISPR-Cas9-DB⁵⁴, was used to knock out GSL5.

All fused plasmids were confirmed by sequencing and introduced into Agrobacterium tumefaciens strain GV3101 for the following transformation of Arabidopsis, B. napus, B. rapa and B. oleracea, using previously described methods⁵⁵. All transgenic plants were genotyped by PCR amplification or DNA sequencing with the specific primers listed in Supplementary Table 5. The homozygous gsl5 mutants of A. thaliana, B. napus, B. rapa and B. oleracea were used for further phenotyping.

Pathogen maintenance and inoculation

P. brassicae isolates were collected from diseased plants of different Brassica crops across China and have been previously identified for the pathotypes¹⁷. The clubbed roots were harvested, cleaned and stored in −20 °C freezers. To isolate the resting spores, the clubbed roots were cut into small pieces and smashed in distilled water with a blender. The suspensions were filtered with six layers of gauze and adjusted to 1.0 × 10⁷ resting spores per ml. To evaluate clubroot resistance under controlled conditions (21–24 °C, 16 h light, 8 h darkness), 2-week-old seedlings of Arabidopsis or 10-day-old seedlings of B. napus, B. rapa and B. oleracea were inoculated with 1 ml of resting spore suspension (1.0 × 10⁷ spores per ml) per seedling. After 24–30 days, the inoculated plants were harvested for scoring based on disease scale and severity as described previously⁷.

Subcellular localization

For subcellular localization, the coding sequence of PbPDIa, after removing the signal peptide sequence, was cloned into pBI121-mCherry. Then, pBI121-mCherry-PbPDIa was transformed into A. tumefaciens GV3101 and injected into the leaves of 4-week-old N. benthamiana plants for transient expression. The empty vector pBI121-mCherry was used as a control. The mCherry signals were detected with a confocal microscope (Carl Zeiss) with an excitation wavelength of 561 nm and an emission wavelength of 560–620 nm.

Microscopy analysis

Fluorescent probe-based confocal microscopy was used to visualize the zoosporangia of P. brassicae during the primary infection, and the fluorescent probe HCS LipidTox Green neutral lipid stain (HLG; Thermo Fisher Scientific) was used to label the zoosporangia⁶. To detect the fluorescence of HLG, an excitation wavelength of 488 nm and an emission wavelength of 500 to 540 nm were used.

Histological technique was used to detect P. brassicae parasites during secondary infection. P. brassicae-inoculated roots of Arabidopsis were harvested at 12 dpi and 21 dpi, and the main roots adjacent to the hypocotyl were sampled for histological analysis as described previously⁵⁶. In brief, tissues were fixed overnight in a freshly prepared solution of 2% glutaraldehyde, dehydrated through a graded ethanol series, embedded in a mold in melted paraffin and trimmed to produce hemi-sections. The sections were then placed on a slide, stained with 0.05% toluidine blue O and subjected to microscopic analysis.

Transcriptome profiling and quantitative real-time PCR analysis

The roots of Arabidopsis plants with or without P. brassicae inoculation were harvested at 12 dpi and 21 dpi with three replicates and immediately frozen in liquid nitrogen. High-quality RNA was extracted using the Fast Pure Plant Total RNA Isolation Kit (VAZYME). cDNA library construction and sequencing, data quality control and gene expression calculation were performed at Novogene. In brief, clean reads were obtained by filtering raw reads and then mapped to the Arabidopsis Col-0 reference genome using HISAT2 software^57,58. The number of fragments per kilobase per million mapped fragments was calculated and used to estimate gene expression levels⁵⁹. Pearson’s correlation coefficient was calculated with the R script cor (https://search.r-project.org/R/refmans/stats/html/cor.html) to evaluate the correlation between biological replicates⁶⁰. DESeq software was used to identify the differentially expressed genes with the thresholds |log₂(fold change)| > 1 and adjusted P < 0.05 (ref. ⁶¹). A Venn diagram of differentially expressed genes between groups was plotted on the website http://jvenn.toulouse.inra.fr/app/example.html⁶².

For quantitative PCR with reverse transcription (RT–qPCR), total RNA was used for first-strand cDNA synthesis with the Hifair III 1st Strand cDNA Synthesis Kit (gDNA digester plus) following the manufacturer’s instructions (YEASEN). Quantitative PCR was performed with a CFX Connect Real-time PCR system (Bio-Rad), using Hieff UNICON Universal Blue qPCR SYBR Master Mix (YEASEN). Ubiquitin 5 (UBQ5) and Actin 7 were used as the internal control in Arabidopsis and B. napus, respectively. The relative expression level of genes was achieved using the 2^(-ΔΔCT) method⁶³. The primers for RT–qPCR are listed in Supplementary Table 5.

MeJA treatments

MeJA powder (Macklin) was dissolved in dimethylsulfoxide to prepare a 1 M stock solution. Different concentrations of working solution were prepared by diluting the stock solution of MeJA with distilled water and used to water the Arabidopsis or B. napus plants at 5 dpi and 9 dpi. The treated plants were collected at 30 dpi for scoring the disease severity.

Measurement of plant hormones, ACC, callose, lignin and reactive oxygen species

The roots of Arabidopsis plants with or without P. brassicae inoculation were harvested at 12 dpi and immediately frozen in liquid nitrogen with three biological replicates. Extraction and quantification were performed at RUIYUAN BIOTECHNOLOGY. In brief, the frozen plant tissues were ground and extracted with specialized buffers, followed by successive incubation, centrifugation, purification and condensation for the preparations. Quantification analysis was performed by ultra-performance liquid chromatography–electrospray tandem mass spectrometry using a high-performance liquid chromatograph (Agilent 1290) and a mass spectrometer (AB Qtrap 6500).

Expression and purification of GSL5 and PbPDIa

GSL5 and PbPDIa were cloned into the engineered pMlink vector with a Flag or His tag, respectively, and then transfected into Expi293F cells (A14528, ThermoFisher, cat. no. 100044202, cGMP bank) for 60 h incubation. After harvest and washing with PBS, the transfected cells were homogenized in lysis buffer (50 mM Tris-HCl pH 7.4, 150 mM NaCl), disrupted with high pressure and incubated in 1% N-dodecyl-β-d-maltoside (DDM) for 2 h at 4 °C. After centrifugation, the supernatant was incubated with anti-Flag M2 or Ni²⁺ affinity resin for 1 h. The resin was eluted for Flag-tagged GSL5 with lysis buffer containing 150 μg ml⁻¹ Flag peptide and 0.02% DDM or for His-tagged PbPDIa, with the lysis buffer containing 250 mM imidazole and 0.02% DDM. The eluted samples were concentrated to 1 ml immediately before gel filtration chromatography (Superose 6 10/300, GE Healthcare).

Pull-down assays and protein stability assay

The purified Flag-tagged GSL5, His-tagged PbPDIa and their mixture samples were incubated with anti-Flag M2 affinity resin for 1 h. The resin was washed with washing buffer containing 50 mM Tris-HCl pH 7.4, 150 mM NaCl and 0.02% DDM and then eluted with washing buffer containing 150 μg ml⁻¹ Flag peptide. The proteins were detected through immunoblots with antibodies against His or Flag.

Two equal portions of Flag-tagged GSL5 proteins were treated with the lysis buffer without or with PbPDIa at 25 °C. Samples were collected every 4 h and detected for protein stability by immunoblot with Flag antibodies.

In vitro PDI activity assay

An in vitro PDI activity assay using reduced ribonuclease A (rRNase A) as a substrate was carried out as previously described⁶⁴. RNase A (50 μg) was unfolded in unfolding buffer (100 mM Tris-HCl pH 8.0, 0.3 M DTT, 6 M guanidine-HCl) for 1 h at 37 °C and desalted with a 0.1% acetic acid-equilibrated G25 column. The resultant rRNase A fractions were collected and quantified using a molar extinction coefficient at 280 nm. The PDI activity assay was carried out in refolding buffer (36 μM rRNase A, 100 mM Tris-HCl buffer pH 8.5, 1 mM glutathione, 0.2 mM oxidized glutathione, 16 μM PbPDIa). RNase activity was measured by the A260 absorption value resulting from the cleavage of total RNAs. The relative activity was calculated as (k_treat − k_RNA) / (k_{RNase A} − k_RNA) × 100%.

Assessment of PbPDIa secretory activity

Assessment of PbPDIa secretory activity was performed with the Yeast Signal Trap Assay Kit (COOLABER). In brief, the DNA sequence of PbPDIa encoding the signal peptide was amplified, cloned into the pSUC2 vector and transformed into the sucrase-deficient yeast strain YTK12. YPRAA medium (a medium containing 1% yeast extract, 2% peptone, 2% raffinose, 2 µg ml⁻¹ antimycin A and 2% agar) was used to evaluate secretory activity, as only the strain containing the functional signal peptide can grow on the YPRAA medium. Furthermore, 2,3,5-triphenyltetrazolium chloride was also included as per the user guide and was reduced by secreted sucrase into insoluble, red-colored 1,3,5-triphenylformazan.

Cell death assay

Cell death was assessed by Evans blue (Merck) staining and by measuring cytoplasmic ion leakage from plant tissues^28,29,30. The roots of Arabidopsis plants with or without P. brassicae inoculation were collected at 12 dpi and placed in a 2% Evans blue solution for 30 min of staining. The plants were then rinsed in distilled water until the roots of the solvent-treated plants could not be stained. The Evans blue-stained plants were imaged under a stereomicroscope SZX16 (Olympus).

To measure the cytoplasmic ion leakage, P. brassicae-infected roots of Arabidopsis were collected at 12 dpi for a 3 h inoculation in ultrapure water at room temperature and the conductivity of the bathing solution was measured with a conductivity meter (STARTER 300C; OHAUS), referred to as value C₁; the conductivity of the ultrapure water is value C₀. The bathing solution containing the root tissues was incubated at 95 °C for 30 min, and conductivity was determined after cooling to room temperature, referred to as value C₂. The relative cytoplastic ion leakage was calculated with the following formula: (C₁ − C₀) / (C₂ − C₀) × 100%.

Statistical analysis

All statistical analyses were performed using Graphpad Prism (v.7.0; https://www.graphpad.com) or R (v.4.1.2). Detailed information, including the testing model, sample size, replicates and P values, is provided in the individual figures and figure legends.

Inclusion and ethics

The data presented in this study were derived exclusively from Arabidopsis and Brassica crops, without involving any animal experiments. The transgenic planting and artificial inoculation of P. brassicae are subject to strict regulation. All experimental data are included in the Data availability section.

Reporting summary

Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article.

An international team of researchers has announced a significant advancement in gravitational-wave astronomy, with the detection of 128 new cosmic collisions involving black holes and neutron stars.

This discovery more than doubles the number of known gravitational-wave events and marks a major milestone in our understanding of the Universe.

The findings come from the latest data release by the Laser Interferometer Gravitational-Wave Observatory (LIGO) Virgo Gravitational Wave Interferometer (Virgo) Kamioka Gravitational Wave Detector (KAGRA) collaboration, a global network of gravitational-wave observatories.

The newly published catalogue, Gravitational Wave Transient Catalog (GWTC-4.0), includes data from the first nine months of the fourth observing run, which took place between May 2023 and January 2024.

Massive cosmic events

Gravitational waves were first detected in 2015.

They are ripples in the fabric of space-time caused by massive cosmic events, such as collisions between black holes and neutron stars.

Since then, UK scientists have played a leading role in developing the technology and analysis techniques required to detect these faint signals.

UK contributions to global science

The UK has been a long-standing contributor to gravitational wave science, with support from the Science and Technology Facilities Council and institutions across the country, including:

• the University of Glasgow
• the University of Portsmouth
• Royal Holloway, University of London

Researchers have helped develop the ultra-sensitive detectors used in LIGO observatories and have led efforts to analyse the complex data they produce.

Thanks to recent upgrades, the detectors are now 25% more sensitive, allowing scientists to observe a much larger volume of the Universe and detect more distant and massive black hole mergers.

Cosmic discoveries

Dr Daniel Williams, a research fellow at the University of Glasgow’s Institute for Gravitational Research, who led the team who performed the analysis, said:

This new update really highlights the capabilities of both the international network of gravitational-wave detectors, and the analysis techniques which have been developed to dig very faint signals out of the data.

The 128 new gravitational wave events include the loudest signal ever recorded (GW230814), which is evidence of black holes formed from previous mergers.

This evidence offers clues about stellar evolution in dense environments and details of two black hole-neutron star collisions (GW230518).

Exploring the nature of the Universe

The enhanced sensitivity of the detectors has not only increased the number of observable events but also improved the clarity of the measurements.

This allows researchers to test Einstein’s theory of gravity with greater precision and explore the fundamental nature of the Universe.

Each merger provides valuable data about the Universe’s expansion rate, contributing to efforts to refine the measurement of the Hubble constant.

New gravitational wave events

Tessa Baker at the Institute of Cosmology and Gravitation, University of Portsmouth, and manager on this new Cosmology paper, said:

It’s really exciting to bring over a hundred new gravitational-wave events into the public domain, after several years of quiet.

These new events have allowed us to refine our measurements of how fast the Universe is expanding, also known as the Hubble Constant, arguably the most crucial and hotly debated number in current cosmology.

We’ve also been able to show that gravity on large scales of the Universe behaves consistently with Einstein’s theory of general relativity.

This means that the standard model of cosmology, along with its bizarre components like dark matter and dark energy, continues to be our best understanding of the Universe.

Looking ahead

With new telescopes like the Vera Rubin Observatory coming online, the chances of detecting both gravitational waves and light from cosmic collisions are increasing.

This multi-messenger approach enabling the discovery of diverse cosmic mergers could unlock even deeper insights into the nature of stars, black holes and the evolution of the cosmos.

The GWTC-4.0 catalogue is available as a preprint and represents a major achievement in international scientific collaboration.

Mosquitoes bite people in almost every country across the globe. But are there any countries that don’t have this blood-sucking pest?

The answer is “yes,” there is one country without mosquitoes: Iceland. While its neighbors — including Norway, Scotland and Greenland — are home to multiple mosquito species, Iceland remains mosquito-free. (Of note, Antarctica is also mosquito-free, but the southern continent is not a country.)

For decades, the idea of bringing dinosaurs back from extinction was confined to the realm of science fiction, popularized by films like Jurassic Park. Now, artificial intelligence (AI) is transforming this dream into a new reality, though not in the literal sense of living dinosaurs. Scientists are using AI to reconstruct fossils, generate realistic visuals, and even hypothesize genetic sequences, offering unprecedented insight into these prehistoric creatures. While true de-extinction remains impossible due to DNA degradation over millions of years, AI allows researchers to study, visualize, and interact with dinosaurs like never before, blurring the line between science and imagination.

Dinosaur reconstruction with AI

AI is helping paleontologists reconstruct dinosaurs with remarkable accuracy. By analyzing fossil records and the skeletal structures of modern relatives such as birds, AI models can generate detailed 3D reconstructions of dinosaurs. These reconstructions overcome challenges posed by incomplete fossils, damaged bones, and fragmentary specimens, producing scientifically plausible images and models that help researchers and the public visualize these ancient creatures.Although no complete dinosaur DNA exists, AI is being explored as a tool to infer missing genetic sequences from fossil fragments. By combining evolutionary data from living species with fossil analysis, researchers can generate hypotheses about dinosaur genomes. While these efforts are experimental and speculative, they open the door to future synthetic biology projects, such as creating hybrid organisms that reflect traits of long-extinct animals.

AI-generated visuals and immersive experiences

AI technologies now enable the creation of hyper-realistic dinosaur images, videos, and animations. Virtual and augmented reality platforms allow users to interact with these AI-driven dinosaurs in educational and entertainment contexts. These immersive experiences bring Jurassic Park-style encounters to life without relying on real organisms, making ancient creatures accessible to millions in entirely new ways.Machine learning algorithms are accelerating fossil identification, classification, and discovery. AI excels at recognizing subtle patterns in fossilized teeth, bones, and fragments, assisting scientists in distinguishing species and uncovering new insights. While AI enhances research efficiency, human expertise remains crucial in interpreting data and guiding hypotheses, ensuring scientific rigor in every reconstruction.

Jurassic Park: reality vs fiction

Despite impressive technological advancements, cloning actual dinosaurs remains impossible due to DNA decay over 65 million years. AI brings the Jurassic Park experience closer in terms of visualization, research, and hypothetical genetic reconstruction, but living dinosaurs roaming the Earth are still science fiction. Current projects focus on digital, hybrid, or engineered species that capture the essence of dinosaurs without replicating them authentically.

Timeline and future prospects

Over the next decade, AI is expected to revolutionize paleontology, from automated fossil reconstructions and advanced genetic analysis to fully immersive dinosaur experiences in VR and AR. Some biotech leaders have speculated on creating super exotic species resembling dinosaurs through genetic engineering, but these would be engineered approximations rather than true prehistoric animals.