Biology subjects

Dewar, M.

Publications and source records attributed to Dewar, M..

7 recordsLinked to original sources

bioRxiv2026

Latent Transforming Growth Factor Binding Protein ? 2 promotes microfibrillar TGF-? bioavailability to drive pathologic fibrosis in remote regions of infarcted hearts

Myocardial infarction (MI) initiates ventricular remodeling that extends beyond the infarct into remote, viable myocardium, where diffuse extracellular matrix (ECM) remodeling and stiffening contribute to progressive dysfunction and heart failure. Latent transforming growth factor binding protein 2 (LTBP2) is an injury-induced, microfibril-associated ECM glycoprotein that, among the LTBP family, does not covalently bind latent TGF-{beta}. We asked whether LTBP2 regulates remote remodeling after MI, and how a protein lacking latent TGF-{beta}-binding capacity could influence TGF-{beta}-dependent fibrosis. Wild-type and Ltbp2-null mice underwent permanent coronary ligation or sham surgery and were followed for 28 days by echocardiography and speckle-tracking strain analysis. Remote myocardium was assessed by histology, atomic force microscopy, and quantitative proteomics. Mechanism was interrogated in primary cardiac fibroblasts using a TGF-{beta} reporter assay. Sufficiency was tested with a fibrillin-1?binding module of LTBP2 delivered as purified protein or by lentiviral expression. LTBP2 was induced in injury-activated cardiac fibroblasts and localized to infarct and remote myocardium by 7 days post-MI. Ltbp2 deletion improved 28-day survival (P=0.0272) where Ltbp2-null hearts showed preserved ejection fraction and faster diastolic strain rates, with protection concentrated in segments remote from the infarct. Remote myocardium contained less interstitial collagen and was significantly less stiff. Proteomic profiling showed enrichment of ECM organization and TGF-{beta}-responsive programs in wild-type hearts that was attenuated in knockouts. In fibroblasts, loss of LTBP2 increased LTBP1 matrix incorporation and shifted TGF-{beta} from the soluble to the matrix-bound compartment; conversely, the minimal LTBP2 module bound fibrillin-1 directly and mobilized latent TGF-{beta} from established matrix within 20 minutes. LTBP2 drives maladaptive remodeling of remote myocardium after MI by limiting matrix sequestration of latent TGF-{beta} and expanding the activatable pool, resolving how an LTBP that does not bind latent TGF-{beta} amplifies TGF-{beta}- dependent fibrosis. LTBP2 and its fibrillin-1 interaction surface may be tractable targets.

physiology↗

bioRxiv2026

Skuas as sentinels of high pathogenicity avian influenza H5N1 on the Antarctic Peninsula in the 2024/2025 austral summer

Despite Antarcticas geographic isolation, the first incursion of high pathogenicity avian influenza (HPAI) H5N1 was detected in the 2023/24 austral summer. Surveillance for HPAI H5N1 in Antarctica remains patchy due to logistical, financial, and infrastructure challenges, with many suspected cases remaining unconfirmed, and few viral genomes sequences available to date. Through the 2024/25 austral summer we undertook five sampling expeditions to the South Shetland Islands and Antarctic Peninsula facilitated by cruise ships/operators. Across more than 500 faecal environmental samples collected from apparently healthy penguins and marine mammals, we found no detectable evidence of HPAI H5N1. However, HPAI H5N1 was detected in all but one of the skua carcasses sampled, which, in most cases, were found within meters of penguin sub-colonies. All HPAI H5N1 viral genomes sequences from skuas on the Antarctic Peninsula fell within a single lineage, which included those genomes from skuas sampled in the 2024/25 season from the South Shetland Islands. Genomes were in a different clade to those from the Antarctic Peninsula collected in the 2023/24 austral summer. Our results confirm although the prevalence may be low, HPAI H5N1 is established in Antarctica, emphasizing the need for ongoing surveillance to monitor and mitigate threats to wildlife, even in the planets most isolated regions.

microbiology↗

bioRxiv2025

Mass mortality at penguin mega-colonies due to avian cholera confounds H5N1 HPAIV surveillance in Antarctica

In the austral summer 2023/2024, H5N1 high pathogenicity avian influenza virus (HPAIV) was reported for the first time in Antarctica. Concerns of HPAIV causing high mortality of seabirds and mammals prompted immediate efforts to track its spread and impact on endemic wildlife. In March 2024, we visited the Danger Islands archipelago, that hosts two mega-colonies of Adelie penguins, and observed an unusual mortality estimated in thousands of Adelie penguins and other species. Swabs and tissues were collected for molecular detection of infectious agents from 49 carcasses, and additional tissues for histology from a selection of 9 carcasses. We unexpectedly detected Pasteurella multocida DNA in 46 of 49 individuals, and diagnosed avian cholera, and not HPAI, as the cause of death of most of these animals. By metagenomics, we retrieved the genomic sequences of the Pasteurella multocida strain which caused the epizootic, and the phylogenetic analysis showed a close relation with strains previously reported in the Southern Ocean area. This study confirms avian cholera as a relevant cause of mortality in the Antarctic region, and overall highlights the importance of considering avian cholera in the differential diagnoses during mortality events in Antarctica, even with the concurrent circulation of HPAIV.

microbiology↗

bioRxiv2025

Surveillance of migratory shorebirds and seabirds in 2024 in Australia reveals incursions of a diversity of low pathogenicity avian influenza viruses, but not high pathogenicity avian influenza H5N1

The current panzootic of high pathogenicity avian influenza (HPAI) H5N1 has been catastrophic for wildlife, and following a significant sweep, clade 2.3.4.4b is found in every region aside from Oceania. Herein, we report the results of our third year of targeted surveillance of incoming migratory seabirds and shorebirds into Australia. We did not find evidence of HPAI H5N1 in any of the birds tested, and there were no reports of HPAI H5N1 in wildlife tested through other surveillance schemes in 2024. Unlike previous years, we detected a diversity of low pathogenicity avian influenza (LPAI) viruses in shorebirds. Through phylogenetic analysis we revealed that the H3N7 and H4N7 viruses recovered from Red-necked Stints were complex mosaic viruses, comprising segments of Eurasian, Australian shorebird, and Australian waterfowl segments. A H1N7 virus detected comprised a wholly Eurasian introduction, confirming this route for avian influenza viruses into Australian ecosystems. These results provide further evidence for the key role of long-distance migratory shorebirds in introducing novel LPAI viruses into Oceania. While our focus on northern migration routes remained appropriate for HPAI H5N1 surveillance in 2024, the continued spread of HPAI H5N1 to sub-Antarctic Islands demands consideration of a potential southern incursion route for Oceania in future.

microbiology↗

bioRxiv2025

The expanding avian influenza panzootic: skua die-off in Antarctica

High pathogenicity avian influenza virus of subtype H5 (H5 HPAIV), clade 2.3.4.4b, invaded Antarctica in 2023. Here we show that H5 HPAIV caused high mortality in a breeding colony of skuas at one of ten sites we visited in March 2024. By combined virological and pathological analyses, we found that H5 HPAIV caused multi-organ necrosis and rapid death in skuas. Taken together with recent data, skuas in Antarctica are at risk of continued mortality from H5 HPAIV infection, threatening their already small populations. Conversely, because of their wide distribution and ecological relevance, skuas may play a substantial role in spread of the virus across Antarctica. Transdisciplinary surveillance is needed in coming years to monitor the impact of this poultry-origin disease on Antarcticas unique wildlife.

microbiology↗

bioRxiv2024

Long distance avian migrants fail to bring 2.3.4.4b HPAI H5N1 into Australia for a second year in a row

There is an ongoing and profound burden of lineage 2.3.4.4b high pathogenicity avian influenza (HPAI) H5N1 on wildlife and poultry, globally. Herein we report the continued absence of HPAI and antibodies against lineage 2.3.4.4b HPAI from October - December 2023, in migratory birds shortly after their arrival in Australia. Given the ever-changing phenotype of this virus, worldwide studies on the occurrence, or here absence of the virus, are of critical importance to understand the virus dispersal and incursion risk and development of response strategies.

microbiology↗

bioRxiv2023

No evidence for highly pathogenic avian influenza virus H5N1 (clade 2.3.4.4b) in the Antarctic region during the austral summer 2022/23

The current highly pathogenic avian influenza H5N1 panzootic has substantial impacts on wild birds and marine mammals. Although major outbreaks occurred in South America, incursion to Antarctica emerged late in the breeding season of 2023/2024 and was confined the wider region of the Antarctic Peninsula. To infer potential underlying processes, we compiled H5N1 surveillance from Antarctica and Sub-Antarctic Islands prior to the first confirmed cases.

microbiology↗