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Despite antiretroviral therapy (ART), people living with HIV (PLWH) are at increased risk of developing cardiovascular disease (CVD) and HIV-associated neurocognitive disorder (HAND), among other comorbidities. Studies from ART-treated individuals identified galectin-3 (gal-3) and interleukin (IL)-18 as CVD biomarkers, galectin-9 (gal-9) as a HAND biomarker, and sCD163, a marker of monocyte/macrophage activation, as a biomarker of both. We asked if plasma gal-3, gal-9, and IL-18 are associated with an individual comorbidity or increase in both with animals that develop AIDS with both pathologies versus (CVD-path) alone or simian immunodeficiency virus encephalitis (SIVE) alone. We found that no biomarkers were selective between individual pathologies, and all biomarkers increased with co-development of CVD-path and SIVE (gal-3, p = 0.11; gal-9, p = 0.001; IL-18, p = 0.007; sCD163, p < 0.001; %BrdU p = 0.02). Although gal-3, gal-9, and IL-18 did not distinguish between pathologies, they correlated strongly with one another, with sCD163, a marker of monocyte/macrophage activation, and the %BrdU monocytes, a marker of monocyte turnover. Compared to animals with CVD-path or SIVE alone, animals that co-developed both pathologies had consistently elevated IL-18 throughout infection (p = 0.02) and increased sCD163 in late infection (p = 0.01). These data indicate that gal-3, gal-9, and IL-18 are associated with monocyte/macrophage activation by sCD163 and monocyte turnover by the %BrdU+ monocytes more so than CVD-path or SIVE. [ABSTRACT FROM AUTHOR]

RationaleThe relative actions and synergism between distinct myocardial-derived stem cell populations remain obscure. Ongoing debates on optimal cell population(s) for treatment of heart failure prompted implementation of a protocol for isolation of multiple stem cell populations from a single myocardial tissue sample to develop new insights for achieving myocardial regeneration.ObjectiveEstablish a robust cardiac stem cell isolation and culture protocol to consistently generate 3 distinct stem cell populations from a single human heart biopsy.Methods and resultsIsolation of 3 endogenous cardiac stem cell populations was performed from human heart samples routinely discarded during implantation of a left ventricular assist device. Tissue explants were mechanically minced into 1 mm3 pieces to minimize time exposure to collagenase digestion and preserve cell viability. Centrifugation removes large cardiomyocytes and tissue debris producing a single cell suspension that is sorted using magnetic-activated cell sorting technology. Initial sorting is based on tyrosine-protein kinase Kit (c-Kit) expression that enriches for 2 c-Kit+ cell populations yielding a mixture of cardiac progenitor cells and endothelial progenitor cells. Flowthrough c-Kit- mesenchymal stem cells are positively selected by surface expression of markers CD90 and CD105. After 1 week of culture, the c-Kit+ population is further enriched by selection for a CD133+ endothelial progenitor cell population. Persistence of respective cell surface markers in vitro is confirmed both by flow cytometry and immunocytochemistry.ConclusionsThree distinct cardiac cell populations with individualized phenotypic properties consistent with cardiac progenitor cells, endothelial progenitor cells, and mesenchymal stem cells can be successfully concurrently isolated and expanded from a single tissue sample derived from human heart failure patients.

Elucidating patterns of adult survival rates is key to understanding population dynamics of large mammals. We used data from 7 separate studies of mountain goats (Oreamnos americanus) conducted from 2002 through 2022 in western Washington, USA, to quantify survival rates in relation to key biotic and abiotic factors using known fate models implemented in program MARK. We monitored 324 (206 females, 118 males) radio‐marked mountain goats for 178,339 days. A substantial number of mountain goats in our sample (n = 217) had been translocated from the Olympic Peninsula to the Cascade Mountains on Washington's mainland, providing an added opportunity to examine translocation effects. We adopted a sequential modeling approach, first building a set of models to examine fundamental survival patterns by age, sex, season, study area, and translocated status. We used variables retained from the top model in a second set to investigate relationships between annual survival and local weather covariates hypothesized by previous studies to influence mountain goat behavior, habitat selection, and vital rates. Survival among adult females in spring was slightly lower than other sex and age categories, but seasonal patterns were otherwise not evident. There were significant negative relationships between survival and winter snow depth, an index of the previous year's drought, and mean daily temperature during the previous May, and a positive relationship with previous year's precipitation. Weather effects were similar among resident and translocated animals. By the end of the study period, weather effects had evidently contributed to reductions in mountain goat survival to a level low enough that population stability was unlikely. Because the frequency of droughts and warm spring temperatures are expected to increase with climate change, mountain goat populations in Washington will likely be increasingly challenged as the atmosphere warms. [ABSTRACT FROM AUTHOR]

Despite effective antiretroviral therapy, HIV co-morbidities remain where central nervous system (CNS) neurocognitive disorders and cardiovascular disease (CVD)-pathology that are linked with myeloid activation are most prevalent. Comorbidities such as neurocogntive dysfunction and cardiovascular disease (CVD) remain prevalent among people living with HIV. We sought to investigate if cardiac pathology (inflammation, fibrosis, cardiomyocyte damage) and CNS pathology (encephalitis) develop together during simian immunodeficiency virus (SIV) infection and if their co-development is linked with monocyte/ macrophage activation. We used a cohort of SIV-infected rhesus macaques with rapid AIDS and demonstrated that SIV encephalitis (SIVE) and CVD pathology occur together more frequently than SIVE or CVD pathology alone. Their co-development correlated more strongly with activated myeloid cells, increased numbers of CD14+CD16+ monocytes, plasma CD163 and interleukin18 (IL-18) than did SIVE or CVD pathology alone, or no pathology. Animals with both SIVE and CVD pathology had greater numbers of cardiac macrophages and increased collagen and monocyte/macrophage accumulation, which were better correlates of CVD-pathology than SIV-RNA. Animals with SIVE alone had higher levels of activated macrophage biomarkers and cardiac macrophage accumulation than SIVnoE animals. These observations were confirmed in HIV infected individuals with HIV encephalitis (HIVE) that had greater numbers of cardiac macrophages and fibrosis than HIV-infected controls without HIVE. These results underscore the notion that CNS and CVD pathologies frequently occur together in HIV and SIV infection, and demonstrate an unmet need for adjunctive therapies targeting macrophages. [ABSTRACT FROM AUTHOR]

Abstract: Climate change represents a primary threat to species persistence and biodiversity at a global scale. Cold adapted alpine species are especially sensitive to climate change and can offer key “early warning signs” about deleterious effects of predicted change. Among mountain ungulates, survival, a key determinant of demographic performance, may be influenced by future climate in complex, and possibly opposing ways. Demographic data collected from 447 mountain goats in 10 coastal Alaska, USA, populations over a 37‐year time span indicated that survival is highest during low snowfall winters and cool summers. However, general circulation models (GCMs) predict future increase in summer temperature and decline in winter snowfall. To disentangle how these opposing climate‐driven effects influence mountain goat populations, we developed an age‐structured population model to project mountain goat population trajectories for 10 different GCM/emissions scenarios relevant for coastal Alaska. Projected increases in summer temperature had stronger negative effects on population trajectories than the positive demographic effects of reduced winter snowfall. In 5 of the 10 GCM/representative concentration pathway (RCP) scenarios, the net effect of projected climate change was extinction over a 70‐year time window (2015–2085); smaller initial populations were more likely to go extinct faster than larger populations. Using a resource selection modeling approach, we determined that distributional shifts to higher elevation (i.e., “thermoneutral”) summer range was unlikely to be a viable behavioral adaptation strategy; due to the conical shape of mountains, summer range was expected to decline by 17%–86% for 7 of the 10 GCM/RCP scenarios. Projected declines of mountain goat populations are driven by climate‐linked bottom‐up mechanisms and may have wide ranging implications for alpine ecosystems. These analyses elucidate how projected climate change can negatively alter population dynamics of a sentinel alpine species and provide insight into how demographic modeling can be used to assess risk to species persistence. [ABSTRACT FROM AUTHOR]

Reports on several instances of wolf predation on mustelids in Alaska, which involved wolverines and an American marten. Details of observations on wolf predation; Analysis of the behavior of the wolves; Examination of the possible role of wolves in influencing mesocarnivore communities in northern environments.

Human disturbance and climate change can impact populations by disrupting movement corridors and reducing important habitat. Characterizing how animals respond to such environmental changes is valuable for conservation as many species can experience reduced genetic diversity when deleterious habitat change occurs, leading to an increased likelihood of extirpation. Mountain goats (Oreamnos americanus) exemplify this conservation challenge; their geographically isolated habitat can inhibit gene flow, making them susceptible to population declines in the face of anthropogenic-induced change. To facilitate biologically informed population management of mountain goats in Glacier Bay National Park, Alaska, we characterized the fine-scale genetic population structure and examined how future climate change could impact population density. Our results indicated that three genetically distinct subpopulations exist in Glacier Bay and that the genealogical history is reflective of the historic landscape patterns. Climate modeling predicted that demographic productivity was likely to be reduced for all subpopulations; additionally, we found that climate change likely degrades the suitability of movement corridors that facilitate gene flow between subpopulations, ultimately increasing the cost of travel. Understanding such fine-scale patterns are key to managing subpopulations, particularly with impending changes to the landscape. [ABSTRACT FROM AUTHOR]