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Diabetic hearts are susceptible to damage from inappropriate activation of the renin angiotensin system (RAS) and hyperglycemic events both of which contribute to increased oxidant production. Prolonged elevation of oxidants impairs mitochondrial enzyme function, further contributing to metabolic derangement. Nuclear factor erythriod-2-related factor 2 (Nrf2) induces antioxidant genes including those for glutathione (GSH) synthesis following translocation to the nucleus. We hypothesized that an acute elevation in glucose impairs Nrf2-related gene expression in diabetic hearts, while AT1 antagonism would aid in Nrf2-mediated antioxidant production and energy replenishment. We used four groups (n = 6-8/group) of 25-week-old rats: 1) LETO (lean strain-control), 2) type II diabetic OLETF, 3) OLETF + angiotensin receptor blocker (ARB; 10 mg olmesartan/kg/d × 8 wks), and 4) ARBM (4 weeks on ARB, 4 weeks off) to study the effects of acutely elevated glucose on cardiac mitochondrial function and Nrf2 signaling in the diabetic heart. Animals were gavaged with a glucose bolus (2 g/kg) and groups were dissected at T0, T180, and T360 minutes. Nrf2 mRNA was 32% lower in OLETF rats compared to LETO and remained suppressed in response to glucose. LETO Nrf2 mRNA increased 25% at T360 in response to glucose while no changes were observed in diabetic hearts. GCLC and GCLM mRNA decreased in diabetic hearts 33% and 44% respectively and remained suppressed in response to glucose while ARB treatment increased GCLM transcripts 90% at T180. These data illustrate that during T2DM and in response to glucose, cardiac Nrf2's adaptive response to environmental stressors such as glucose is impaired in diabetic hearts and that ARB treatment may aid Nrf2's impaired dynamic response.

Effective conservation requires that species recovery measures are informed by rigorous scientific research. For imperilled freshwater fishes and mussels in Canada, numerous research gaps exist, in part owing to the need for specialized research methods. The Canadian Freshwater Species at Risk Research Network (SARNET) was formed and identified or implemented approaches to address current research gaps, including (1) captive experimental research populations, (2) nonlethal methods for estimating abundance and distribution, (3) nonlethal field methods to measure life-history parameters, (4) species distribution models informed by co-occurring species, (5) conservation physiology to inform habitat and threat science, (6) evidence syntheses to evaluate threats and recovery measures, (7) disease-transmission models to understand mussel-host relationships, (8) experimental mesocosms and manipulative experiments to evaluate key habitat stressors, (9) threat and hazard models for predictive applications, and (10) rigorous evaluation of surrogate species. Over a dozen threat- and recovery-focused SARNET research applications are summarized, demonstrating the value of a coordinated research program between academics and government to advance scientific research on, and to support the recovery of, imperilled freshwater species. Des mesures de retablissement reposant sur des travaux de recherche scientifique rigoureux sont necessaires a une conservation efficace. Pour les especes de poissons d'eau douce et mulettes en peril au Canada, il existe de nombreuses lacunes dans la recherche, dues partiellement a la necessite de methodes de recherche specialisees. Le reseau canadien de recherche sur les especes d'eau douce en peril (SARNET) a ete cree et il a cerne ou applique differentes approches visant a combler ces lacunes, dont les suivantes : (1) des populations experimentales captives de recherche, (2) des methodes non letales d'estimation de l'abondance et de la repartition, (3) des methodes de terrain non letales de mesure de parametres du cycle biologique, (4) des modeles de repartition des especes integrant des donnees sur les especes cooccurrentes, (5) la physiologie de la conservation pour soutenir les travaux scientifiques sur les habitats et les menaces, (6) des syntheses de donnees probantes pour evaluer les menaces et measures de retablissement, (7) des modeles de transmission des maladies pour comprendre les relations mulettes-hotes, (8) des mesocosmes experimentaux et des experiences de manipulation pour evaluer des facteurs de stress cles des habitats, (9) des modeles de menaces et de dangers pour des applications predictives et (10) Revaluation rigoureuse d'especes substitutives. Un resume de plus d'une douzaine d'applications des travaux de recherche du SARNET axees sur les menaces et le retablissement est presente, qui demontre l'utilite d'un programme de recherche au sein duquel les travaux de chercheurs universitaires et gouvernementaux sont coordonnes afin de faire avancer la recherche scientifique sur les especes d'eau douce en peril et soutenir leur retablissement. [Traduit par la Redaction], Introduction An important goal of conservation biology is to prevent species extinctions caused by human activity (Soule 1985). When populations decline and become imperilled, various recovery measures are often enacted [...]

Quantifying the responses of rare and vulnerable species to environmental stressors poses special challenges. This study examined the responses of vulnerable fish species listed under the Species at Risk Act to environmental stressors in lakes, streams, and wetlands of the Canadian Great Lakes basin. We used a joint species distribution model (JSDM) to improve the estimates of responses of vulnerable species to environmental stressors, and the effects of functional traits on those responses, by 'borrowing information' from abundant species for which we have more information. We measured abundance, functional traits, and taxonomic relationships for 115 freshwater fish species (including 12 vulnerable species), and environmental features, at 1972 sites. The JSDM yielded more precise estimates of responses than single-species models fitted to each vulnerable species. Habitat associations inferred from the JSDM showed substantial overlap with those provided in COSEWIC status reports. Model-derived responses to environmental stressors can provide a management-friendly basis for species classification in terms of species' tolerances to various forms of environmental change, and supplement the qualitative criteria for habitat requirements currently used in assessments of species vulnerability. La quantification des reactions d'especes vulnerables rares a des agents de stress ambiants presente des defis particuliers. L'objectif de l'etude etait de comprendre les reactions de poissons vulnerables designes en vertu de la Loi sur les especes en peril a des agents de stress ambiants dans des lacs, cours d'eau et milieux humides du bassin des Grands Lacs canadiens. Nous avons utilise un modele de repartition conjointe d'especes (MRCE) afin d'ameliorer les estimations des reactions d'especes vulnerables a des agents de stress ambiants et les effets de caracteres fonctionnels sur ces reactions, en << empruntant de l'information >> sur des especes abondantes pour lesquelles la quantite d'information est plus grande. Nous avons mesure l'abondance, des caracteres fonctionnels et des relations taxonomiques pour 115 especes de poissons d'eau douce, dont 12 especes vulnerables, ainsi que des elements du milieu ambiant dans 1972 sites. Le MRCE produit des estimations plus precises de reactions que des modeles a espece unique cales sur les donnees de chaque espece vulnerable. Les associations d'habitat inferees a partir des resultats du MRCE montrent un important chevauchement avec les associations fournies par les rapports de situation du COSEPAC. Les reactions derivees du modele a des agents de stress ambiants peuvent constituer une base utile aux gestionnaires pour la classification d'especes selon leur tolerance a differentes formes de changement ambiant et complementer les criteres qualitatifs concernant les exigences en matiere d'habitat actuellement utilises dans les evaluations de la vulnerabilite d'especes. [Traduit par la Redaction], Introduction Anthropogenic changes to the environment are a major threat to aquatic species worldwide (Darwall and Freyhof 2016; Myers et al. 2017; Reid et al. 2019). In the Canadian Great [...]

Hydromorphological descriptors such as substrate type, water depth, and velocity are commonly used to describe fish habitat, but few studies have focused on how underwater sounds affect habitat use by freshwater fish. We evaluated the influence of the underwater soundscape and other habitat descriptors on the spatial distribution of brook trout (Salvelinus fontinalis) in a small stream in eastern Canada. Habitat measurements were made at high spatial resolution (2.5 m intervals). High acoustical heterogeneity of stream habitats (40-150 dB re 1 [micro]Pa) was related to differences in water velocity and depth as expected from theory. Brook trout densities were positively related to broadband sound pressure levels (SPL), irrespective of water velocity and depth, but in interaction with habitat type. The positive relationship between brook trout densities and SPL could be related to the high auditory threshold of salmonid fishes. Alternatively, brook trout may use the underwater soundscape to select favourable feeding habitats. Underwater sounds integrate the many environmental dimensions of a stream and may be used by fish as cues for habitat selection. Si des descripteurs hydromorphologiques comme le type de substrat et la profondeur et la vitesse de l'eau sont communement utilises pour decrire l'habitat des poissons, peu d'etudes se sont interessees a l'incidence des sons subaquatiques sur l'utilisation de l'habitat par les poissons d'eau douce. Nous avons evalue l'influence du paysage sonore subaquatique et d'autres descripteurs de l'habitat sur la repartition spatiale des ombles de fontaine (Salvelinus fontinalis) dans un petit cours d'eau de l'est du Canada. Les mesures de parametres de l'habitat ont ete prises a haute resolution spatiale (intervalles de 2,5 m). Une forte heterogeneite acoustique des habitats du cours d'eau (40-150 dB, niveau de reference : 1 [micro]Pa) etait reliee a des variations de la vitesse et de la profondeur de l'eau, comme permettent de la predire des considerations theoriques. Les densites d'ombles de fontaine etaient positivement reliees aux niveaux de pression acoustique (NPA) de large bande, independamment de la vitesse et de la profondeur de l'eau, mais en interaction avec le type d'habitat. La relation positive entre les densites d'ombles de fontaine et les NPA pourrait etre associee au seuil d'audition eleve des salmonides. Par ailleurs, les ombles de fontaine pourraient utiliser le paysage sonore subaquatique pour selectionner des habitats d'alimentation favorables. Les sons subaquatiques integrent les nombreuses dimensions environnementales d'un cours d'eau et pourraient etre utilises par les poissons comme indices pour la selection d'habitats. [Traduit par la Redaction], Introduction Under natural conditions, underwater habitats that range from quiet shallow lakes to fast-flowing cascades show a rich mosaic of sounds (Amoser and Ladich 2005; Wysocki et al. 2007a). Lotic [...]

Hepatocellular carcinoma (HCC) is a malignant and deadly form of liver cancer with limited treatment options. Transcatheter arterial chemoembolization, a procedure that delivers embolic and chemotherapeutic agents through blood vessels, is a promising cancer treatment strategy. However, it still faces limitations, such as inefficient agent delivery and the inability to address tumor‐induced immunosuppression. Here, a drug‐eluting shear‐thinning hydrogel (DESTH) loaded with chemotherapeutic and immunotherapeutic agents in nanocomposite hydrogels composed of gelatin and nanoclays is presented as a therapeutic strategy for a catheter‐based endovascular anticancer approach. DESTH is manually deliverable using a conventional needle and catheter. In addition, drug release studies show a sustained and pH‐dependent co‐delivery of the chemotherapy doxorubicin (acidic pH) and the immune‐checkpoint inhibitor aPD‐1 (neutral pH). In a mouse liver tumor model, the DESTH‐based chemo/immunotherapy combination has the highest survival rate and smallest residual tumor size. Finally, immunofluorescence analysis confirms that DESTH application enhances cell death and increases intratumoral infiltration of cytotoxic T‐cells. In conclusion, the results show that DESTH, which enables efficient ischemic tumor cell death and effective co‐delivery of chemo‐ and immunotherapeutic agents, may have the potential to be an effective therapeutic modality in the treatment of HCC. [ABSTRACT FROM AUTHOR]