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Duchenne muscular dystrophy (DMD) is a debilitating and fatal genetic disease affecting 1/5000 boys globally, characterized by progressive muscle breakdown and eventual death, with an average lifespan in the mid–late twenties. While no cure yet exists for DMD, gene and antisense therapies have been heavily explored in recent years to better treat this disease. Four antisense therapies have received conditional FDA approval, and many more exist in varying stages of clinical trials. These upcoming therapies often utilize novel drug chemistries to address limitations of existing therapies, and their development could herald the next generation of antisense therapy. This review article aims to summarize the current state of development for antisense-based therapies for the treatment of Duchenne muscular dystrophy, exploring candidates designed for both exon skipping and gene knockdown.

Grid firing fields have been proposed as a neural substrate for spatial localisation in general or for path integration in particular. To distinguish these possibilities, we investigate firing of grid and non-grid cells in the mouse medial entorhinal cortex during a location memory task. We find that grid firing can either be anchored to the task environment, or can encode distance travelled independently of the task reference frame. Anchoring varied between and within sessions, while spatial firing of non-grid cells was either coherent with the grid population, or was stably anchored to the task environment. We took advantage of the variability in task-anchoring to evaluate whether and when encoding of location by grid cells might contribute to behaviour. We find that when reward location is indicated by a visual cue, performance is similar regardless of whether grid cells are task-anchored or not, arguing against a role for grid representations when location cues are available. By contrast, in the absence of the visual cue, performance was enhanced when grid cells were anchored to the task environment. Our results suggest that anchoring of grid cells to task reference frames selectively enhances performance when path integration is required.

In this work, the detailed studies of surface polymerization stabilizing liquid crystal formed on an azodye sublayer are presented. The surface localized stabilization is obtained by free-radical polymerization of a dilute solution of a bi-functional reactive monomer (RM) in a liquid crystal (LC) solvent. To optimize the process for surface localized stabilization, we investigate the effects of several process parameters including RM concentration in LC hosts, the types of materials (either RM or LC), the photo-initiator (PI) concentration, ultra-violet (UV) polymerization intensity, and the UV curing temperature. The quality of surface localized stabilization is characterized and/or evaluated by optical microscopy, electro-optical behavior (transmission/voltage curve), the life test, and photo-bleaching. Our results show that, by carefully selecting materials, formulating mixtures, and controlling the polymerizing variables, the RM polymerization can be realized either at the surface or through the bulk. Overall, the combination of surface localized stabilization and photo-alignment offers an elegant and dynamic solution for controlling the alignment for LC, which could play a profound role in almost all liquid crystal optical devices.

The feasibility of using unoccupied aerial vehicles (UAVs, ‘drones’) to collect high-resolution still and video imagery of dugongs ( Dugong dugon ) for photo-identification (photo-ID) in the Sindalah Archipelago, NEOM (area ~ 84 km 2 ), within the northeast Red Sea, Saudi Arabia, was evaluated during opportunistic marine megafauna searches. Drone searches were conducted whenever possible over one year (January 2024 to January 2025). A total of 48 dugong observations were made during 91 days of drone flights, covering a cumulative distance of 5,962 km of flying. Of these, 35 (72.9%) were repeat sightings (range = 2 to 8 resights) of nine individuals, identified using tail-fluke notches, scars on the dorsum, or both. The time between first and last sightings ranged from 12 days to 10.5 months, with maximum linear distances between all sightings of individuals ranging 0.71 to 5.12 km (mean = 2.4 km; SD = 1.8 km). The ranges of individuals appeared relatively small, suggesting potential site fidelity. To our knowledge, this represents the first drone-based photo-ID study for dugongs using a combination of fluke markings and scarring, and suggests this technique can yield important data for dugong populations, at least over small spatial and temporal scales. Given the relatively small, low-density population of dugongs in the northeast Red Sea, and threats posed by coastal development in the region, a better understanding of spatial and temporal habitat use of individuals is required. This study will support species management decisions, contributing to conservation of dugongs in the region.

Duchenne muscular dystrophy (DMD) is a severe neuromuscular disorder caused by DMD gene mutations, leading to the loss of functional dystrophin. While antisense oligonucleotide (ASO)-mediated exon skipping offers therapeutic potential, its efficacy in cardiac muscle remains limited. Here, we investigate DG9, a cell-penetrating peptide derived from human polyhomeotic 1 homolog (Hph-1) transcription factor, as an enhancer of phosphorodiamidate morpholino oligomer (PMO)-based therapy targeting exon 44. In a humanized DMD mouse model (h DMD del45; mdx ), DG9-PMO significantly increases exon skipping, restores dystrophin expression, and improves muscle function, particularly in the heart. Mechanistically, DG9-PMO enhances intracellular uptake through multiple endocytic pathways and achieves superior nuclear localization. Compared to the benchmark R6G peptide, DG9-PMO exhibits greater efficacy in cardiac tissue with no detectable toxicity. These findings highlight DG9-PMO as a promising next-generation exon-skipping therapy with potential clinical relevance for improving both skeletal and cardiac outcomes in DMD patients. The authors show that the cell-penetrating peptide DG9 enhances PMO delivery to skeletal and cardiac muscles via multiple endocytic pathways. DG9-PMO significantly boosts dystrophin restoration and cardioprotection, addressing a key challenge in the therapy of Duchenne muscular dystrophy.

The monitoring of body condition, reflecting the state of individuals' energetic reserves, can provide early warning signals of population decline, facilitating prompt conservation actions. However, environmental and anthropogenic drivers of body condition are poorly known for rare and elusive marine mammal species over their entire ranges. We assessed the global patterns and drivers of body condition for the endangered dugong (Dugong dugon) across its Indo‐Pacific range. To do so, we applied the body condition index (BCI) developed for the related manatee based on the ratio of umbilical girth (approximated as maximum width times π), to straight body length measured in drone images. To cover the entire dugong's range, we took advantage of drone footage published on social media. Combined with footage from scientific surveys, social media footage provided body condition estimates for 272 individual dugongs across 18 countries. Despite small sample sizes relative to local population sizes, we found that dugong BCI was better, that is, individuals were ‘plumper’, in New Caledonia, the United Arab Emirates, Australia and Qatar where populations are the largest globally. Dugong BCI was comparatively poorer in countries hosting very small dugong populations such as Mozambique, suggesting a link between body condition and population size. Using statistical models, we then investigated potential environmental and anthropogenic drivers of dugong BCI, while controlling for seasonal and individual effects. The BCI decreased with human gravity, a variable integrating human pressures on tropical reefs, but increased with GDP per capita, indicating that economic wealth positively affects dugong energetic state. The BCI also showed a dome‐shaped relationship with marine protected area coverage, suggesting that extensive spatial protection is not sufficient to maintain dugongs in good state. Our study provides the first assessment of dugong body condition through drone photogrammetry, underlining the value of this non‐invasive, fast and low‐cost approach for monitoring elusive marine mammals. The monitoring of body condition has gained traction as a way to provide early warning signals of population decline, prompting conservation actions. However, the environmental and anthropogenic drivers of body condition variations are rarely investigated. We conduct the first drone‐based assessment of the body condition of the dugong—one of the most elusive and endangered species of marine mammals. Drone footage collected from scientific surveys and social media allowed us to assess the body condition of 272 individual dugongs in 18 countries across the species' Indo‐Pacific range. We show that dugong body condition is influenced by marine protected area coverage, human gravity and gross domestic product per capita. Our study underlines the value of drone photogrammetry as a non‐invasive, fast and low‐cost approach for monitoring the state of dugong populations and investigating the pressures affecting them.

Duchenne muscular dystrophy (DMD) is a fatal genetic disease affecting children that is caused by a mutation in the gene encoding for dystrophin. In the absence of functional dystrophin, patients experience progressive muscle deterioration, leaving them wheelchair-bound by age 12 and with few patients surviving beyond their third decade of life as the disease advances and causes cardiac and respiratory difficulties. In recent years, an increasing number of antisense and gene therapies have been studied for the treatment of muscular dystrophy; however, few of these therapies focus on treating mutations arising in the N-terminal encoding region of the dystrophin gene. This review summarizes the current state of development of N-terminal antisense and gene therapies for DMD, mainly focusing on exon-skipping therapy for duplications and deletions, as well as microdystrophin therapy.

Dystrophin is a 427 kDa protein that stabilizes muscle cell membranes through interactions with the cytoskeleton and various membrane-associated proteins. Loss of dystrophin as in Duchenne muscular dystrophy (DMD) causes progressive skeletal muscle weakness and cardiac dysfunction. Multiple promoters along the dystrophin gene (DMD) give rise to a number of shorter isoforms. Of interest is Dp71, a 71 kDa isoform implicated in DMD pathology by various animal and patient studies. Strong evidence supporting such a role for Dp71, however, is lacking. Here, we use del52;WT mice to understand how Dp71 overexpression affects skeletal and cardiac muscle phenotypes. Apart from the mouse Dmd gene, del52;WT mice are heterozygous for a full-length, exon 52-deleted human DMD transgene expected to only permit Dp71 expression in muscle. Thus, del52;WT mice overexpress Dp71 through both the human and murine dystrophin genes. We observed elevated Dp71 protein in del52;WT mice, significantly higher than wild-type in the heart but not the tibialis anterior. Moreover, del52;WT mice had generally normal skeletal muscle but impaired cardiac function, exhibiting significant systolic dysfunction as early as 3 months. No histological abnormalities were found in the tibialis anterior and heart. Our results suggest that Dp71 overexpression may have more detrimental effects on the heart than on skeletal muscles, providing insight into the role of Dp71 in DMD pathogenesis.