Explore the vast range of titles available.

Apoptosis of endothelial cells prompts the release of apoptotic exosome-like vesicles (ApoExos), subtype extracellular vesicles secreted by apoptotic cells after caspase-3 activation. ApoExos are different from both apoptotic bodies and classical exosomes in their protein and nucleic acid contents and functions. In contrast to classical apoptotic bodies, ApoExos induce immunogenic responses that can be maladaptive when not tightly regulated. In the present study, we elucidated the mechanisms by which ApoExos are internalized by endothelial cells, which leads to shared specific and functional mRNAs of importance to endothelial function. Using flow cytometry and confocal microscopy, we revealed that ApoExos were actively internalized by endothelial cells. SiRNA-induced inhibition of classical endocytosis pathways with pharmacological inhibitors showed that ApoExos were internalized via phosphatidylserine-dependent macropinocytosis independently of classical endocytosis pathways. An electron microscopy analysis revealed that ApoExos increased the macropinocytosis rate in endothelial cells, setting in motion a positive feedback loop that increased the amount of internalized ApoExos. Deep sequencing of total RNA revealed that ApoExos possessed a unique protein-coding RNA profile, with PCSK5 being the most abundant mRNA. Internalization of ApoExos by cells led to the transfer of this RNA content from the ApoExos to cells. Specifically, PCSK5 mRNA was transferred to cells that had taken up ApoExos, and these cells subsequently expressed PCSK5. Collectively, our findings suggest that macropinocytosis is an effective entry pathway for the delivery of RNAs carried by ApoExos and that these RNAs are functionally expressed by the endothelial cells that internalize them. As ApoExos express a specific mRNA signature, these results suggest new avenues to understand how ApoExos produced at sites of vascular injury impact vascular function.

1. Knowing the relative contribution of vegetative propagation and sexual reproduction to the dispersal and establishment of exotic plants is crucial for devising efficient control strategies. This is particularly true for the common reed (Phragmites australis), one of the most invasive species in North America. 2. For the first time, we combined in situ field observations and genetic evidence, based on two genotyping techniques, that is microsatellite markers (SSR) and genotyping by sequencing (GBS), to determine the propagation strategies of this invader at its northern distribution limit in North America and especially in roadside ditches. 3. Field observations revealed that, in a region where the common reed is already abundant, both seeds and plant fragments contributed to the establishment of new populations. Newly established individuals originated mostly (84%) from seeds rather than fragments, but a larger proportion of individuals originating from fragments survived the second year compared to seedlings. 4. High genetic diversity among marsh and roadside common reed stands indicated the prime role of sexual reproduction for dispersal. The vast majority of genotypes were found in only one stand; such high genetic variability can only be explained by sexual reproduction. Half the surveyed stands comprised a single clone, suggesting that local expansion mainly occurred vegetatively. As the small proportion of SSR genotypes initially thought to be common between distant stands proved to be distinct (as revealed by GBS data), it is likely that all the stands examined were initially founded by genetically distinct individuals. 5. Synthesis. Our study suggests that long-distance dispersal by seeds is important for the common reed, in marshes and roadsides, while both seeds and plant fragments contribute to short-distance dispersal along roads, at least in regions where the species is already abundant. The success of this invader in North America seems to be attributable to a reproduction strategy combining the advantages of sexuality with those of vegetative propagation. Moreover, this study shows that the GBS approach strongly reduces uncertainties associated with the use of a limited number of markers. This approach is especially valuable for ecologists dealing with an ever-increasing number of invaders, of which few have identified microsatellite markers.

Apoptotic exosome-like vesicles (ApoExos) are a novel type of extracellular vesicle that contribute to the propagation of inflammation at sites of vascular injury when released by dying cells. ApoExos are characterized by the presence of the C-terminal perlecan LG3 fragment and 20S proteasome, and they are produced downstream of caspase-3 activation. In the present study, we assessed the relative roles of autophagy and caspase-3-mediated pathways in controlling the biogenesis and secretion of immunogenic ApoExos. Using electron microscopy and confocal immunofluorescence microscopy in serum-starved endothelial cells, we identified large autolysosomes resulting from the fusion of lysosomes, multivesicular bodies, and autophagosomes as a site of ApoExo biogenesis. Inhibition of autophagy with ATG7 siRNA or biochemical inhibitors (wortmannin and bafilomycin) coupled with proteomics analysis showed that autophagy regulated the processing of perlecan into LG3 and its loading onto ApoExos but was dispensable for ApoExo biogenesis. Caspase-3 activation was identified using caspase-3-deficient endothelial cells or caspase inhibitors as a pivotal regulator of fusion events between autolysosomes and the cell membrane, therefore regulating the release of immunogenic ApoExos. Collectively, these findings identified autolysosomes as a site of ApoExo biogenesis and caspase-3 as a crucial regulator of autolysosome cell membrane interactions involved in the secretion of immunogenic ApoExos.

Animal models suggest a protective role of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin-II receptor blockers (ARBs) in reducing renal and cardiac ischemia-reperfusion injury. Our aim was to determine the association between pre-transplant ACEi/ARBs use and the occurrence of delayed graft function (DGF) in patients who received a kidney transplantation from a deceased donor. Consecutive recipients between 2008 and 2021 in 2 Canadian university-affiliated centers were included in this retrospective cohort study. The main outcome was the occurrence of DGF and the exposure was use of ACEi or ARBs at the time of admission for transplantation. Mixed models were fit. A total of 897 patients were included, of which 160 (18%) experienced DGF. At admission, 337 (38%) patients were exposed to ACEi/ARBs. In the multivariable analysis, pre-transplant ACEi/ARBs use was associated with a reduced risk of DGF (odds ratio: 0.60, 95% confidence interval: 0.40, 0.92). Other factors associated with DGF were recipient obesity, donor type, ethnicity, age, hypertension, and total ischemia time. Pre-transplant use of ACEi/ARBs is associated with a lower risk of DGF in early postoperative period, which may be due to a protective effect of these agents on renal ischemia-reperfusion injury.

Adaptive evolution is currently accepted as playing a significant role in biological invasions. Adaptations relevant to invasions are typically thought to occur either recently within the introduced range, as an evolutionary response to novel selection regimes, or within the native range, because of long-term adaptation to the local environment. We propose that recent adaptation within the native range, in particular adaptations to human-altered habitat, could also contribute to the evolution of invasive populations. Populations adapted to human-altered habitats in the native range are likely to increase in abundance within areas frequented by humans and associated with human transport mechanisms, thus enhancing the likelihood of transport to a novel range. Given that habitats are altered by humans in similar ways worldwide, as evidenced by global environmental homogenization, propagules from populations adapted to human-altered habitats in the native range should perform well within similarly human-altered habitats in the novel range. We label this scenario ‘Anthropogenically Induced Adaptation to Invade’. We illustrate how it differs from other evolutionary processes that may occur during invasions, and how it can help explain accelerating rates of invasions.

The diversity of Laurentian Great Lakes ciscoes (Coregonus artedi, sensu lato) arose via repeated local adaptive divergence including deepwater ciscoes that are now extirpated or threatened. The nigripinnis form, or Blackfin Cisco, is extirpated from the Great Lakes and remains only in Lake Nipigon. Putative nigripinnis populations were recently discovered in sympatry with artedi in a historical drainage system of glacial Lake Algonquin, the precursor of lakes Michigan and Huron. Given the apparent convergence on Great Lakes form, we labeled this form blackfin. Here, we test the hypothesis that nigripinnis may have colonized this area from the Great Lakes as a distinct lineage. It would then represent a relict occurrence of the historical diversity of Great Lakes ciscoes. Alternatively, blackfin could have evolved in situ in several lakes. We captured more than 600 individuals in the benthic or pelagic habitat in 14 lakes in or near Algonquin Provincial Park (Ontario, Canada). Fish were compared based on habitat, morphology, and genetic variation at 6,676 SNPs. Contrary to our expectations, both cisco and blackfin belonged to an Atlantic lineage that colonized the area from the east, not from the Great Lakes. Sympatric cisco and blackfin were closely related while fish from different lakes were genetically differentiated, strongly suggesting the repeated in situ origin of each form. Across lakes, there was a continuum of ecological, morphological, and genetic differentiation that could be associated with alternative resources and lake characteristics. This study uncovers a new component of cisco diversity in inland lakes of Canada that evolved independently from ciscoes of the Laurentian Great lakes. The diversity of cisco revealed in this study and across their Canadian range presents a challenge for designating conservation units at the intraspecific level within the framework of the Committee on the Status of Endangered Wildlife in Canada (COSEWIC).

Post‐glacial colonization of lakes in Algonquin Park, Ontario, Canada resulted in food webs with cisco (Coregonus artedi sensu lato) and either Mysis diluviana or Chaoborus spp. as the dominant diel migrator. Mysis as prey, its diel movements and benthic occupancy, are hypothesized to be key elements of ecological opportunity for cisco diversity in the Laurentian Great Lakes. If correct, the hypothesis strongly implies that lakes with Mysis would have greater trophic niche size and drive greater adaptive radiation of cisco forms relative to lakes without Mysis. The dichotomy in diel migrator in Algonquin Park lakes was an opportunity to assess the isotopic niche size of cisco (δ15N and δ13C) and determine if niche size expands with Mysis presence. We found the presence of Mysis is necessary to expand isotopic niche size in our study lakes. The use of habitats not typically associated with the ancestral form of cisco (e.g., benthic habitats) and phenotypic diversity (blackfin and cisco) also continue to expand niche size in Mysis‐based food webs. Partial ecological speciation based on a large niche space appears to be present in one lake (Cauchon Lake) where use of alternative habitats is the only real difference in cisco. The presence of blackfin expands niche space in Cedar and Radiant Lakes. This was not matched in Hogan Lake where niche space was relatively smaller with similar forms. Possible reasons for this discrepancy may be related to the asymmetric basin of Hogan Lake and whether the two forms overlap during cool and cold‐water periods of the annual temperature cycle. By comparing trophic niche size among lakes with and without Mysis, we conclude that Mysis provides a key ecological opportunity for cisco diversity in our study lakes and likely more widely. Mysis are thought to provide an ecological opportunity in the ecology and evolution of cisco diversity. We show that in lakes with Mysis, cisco increase isotopic niche size and further increase niche size with expanded habitat use and phenotypic diversity. This finding has important considerations for the evolution of cisco diversity broadly.

Microvascular rarefaction substantially contributes to renal dysfunction following ischemia-reperfusion injury (IRI). We characterized the microRNA signature of extracellular vesicles (EVs) released during endothelial apoptosis to identify biomarkers and regulators of microvascular rarefaction and renal dysfunction. Using in vitro models and RNA-Seq, we found miR-423-5p, let-7b-5p, and let-7c-5p enriched in small EVs from apoptotic endothelial cells. In mouse models of renal IRI and a cohort of 51 patients who have undergone renal transplant with delayed graft function, serum miR-423-5p correlated with circulating EVs, while let-7b-5p and let-7c-5p were also present in free form. Early acute kidney injury saw increased serum miR-423-5p levels linked to small EVs with endothelial markers. Over time, higher serum miR-423-5p levels were associated with large EVs and correlated with greater renal microvascular density and reduced fibrosis. Microvascular density and fibrosis predicted renal function 3 years after transplantation. We explored miR-423-5p’s role in renal homeostasis, finding that its injection during renal IRI preserved microvascular density and inhibited fibrosis. Endothelial cells transfected with miR-423-5p showed enhanced resistance to apoptosis, increased migration, and angiogenesis. Localized miR-423-5p injection in hindlimb ischemia model accelerated revascularization. These findings position miR-423-5p as a predictor of renal microvascular rarefaction and fibrosis, highlighting potential strategies for preserving renal function.

Aging is associated with increased oxidative stress levels and impaired neovascularization following ischemia. CuZnSOD has an important role to limit oxidative stress in the vasculature. Here we investigated the role of CuZnSOD for the modulation of ischemia-induced neovascularisation during aging. Hindlimb ischemia was surgically induced in young (2- month-old) or older (8-month-old) wild type (WT) and CuZnSOD(-/-) mice. We found that blood flow recovery after ischemia and vascular density in ischemic muscles were significantly reduced in older compared to young WT mice. Both in young and older mice, CuZnSOD deficiency led to a further reduction of neovascularization. Accordingly, the resulting neovascularisation potential in a young CuZnSOD(-/-) mouse was similar to that of an older WT mouse. Oxidative stress levels were also increased to similar levels in the ischemic muscles of young CuZnSOD(-/-) and older WT mice. To identify potential mechanisms involved, we investigated the effect of aging and CuZnSOD deficiency on the number and the function of endothelial progenitor cells (EPCs). Both aging and CuZnSOD deficiency were associated with reduced number of bone marrow and peripheral EPCs. The effect of moderate aging alone on specific functional activities of EPCs (migration, integration into tubules) was modest. However, CuZnSOD deficiency was associated with severe age-dependent defects in EPC functional activities. CuZnSOD deficiency is associated with accelerated vascular aging and impaired ischemia-induced neovascularization. Our results suggest that in the context of aging, CuZnSOD has an essential role to protect against excessive oxidative stress in ischemic tissues and preserve the function of EPCs.

The North-east American Rainbow smelt (Osmerus mordax) is composed of two glacial races first identified through the spatial distribution of two distinct mtDNA lineages. Contemporary breeding populations of smelt in the St. Lawrence estuary comprise contrasting mixtures of both lineages, suggesting that the two races came into secondary contact in this estuary. The overall objective of this study was to assess the role of intraspecific genetic admixture in the morphological diversification of the estuarine rainbow smelt population complex. The morphology of mixed-ancestry populations varied as a function of the relative contribution of the two races to estuarine populations, supporting the hypothesis of genetic admixture. Populations comprising both ancestral mtDNA races did not exhibit intermediate morphologies relative to pure populations but rather exhibited many traits that exceeded the parental trait values, consistent with the hypothesis of transgressive segregation. Evidence for genetic admixture at the level of the nuclear gene pool, however, provided only partial support for this hypothesis. Variation at nuclear AFLP markers revealed clear evidence of the two corresponding mtDNA glacial races. The admixture of the two races at the nuclear level is only pronounced in mixed-ancestry populations dominated by one of the mtDNA lineages, the same populations showing the greatest degree of morphological diversification and population structure. In contrast, mixed-ancestry populations dominated by the alternate mtDNA lineage showed little evidence of introgression of the nuclear genome, little morphological diversification and little contemporary population genetic structure. These results only partially support the hypothesis of transgressive segregation and may be the result of the differential effects of natural selection acting on admixed genomes from different sources.