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Our understanding of the complex pathophysiology of Heart failure with preserved ejection fraction (HFpEF) is limited by the lack of a robust in vivo model. Existing in-vivo models attempt to reproduce the four main phenotypes of HFpEF; ageing, obesity, diabetes mellitus and hypertension. To date, there is no in vivo model that represents all the haemodynamic characteristics of HFpEF, and only a few have proven to be reliable for the preclinical evaluation of potentially new therapeutic targets. HFpEF accounts for 50% of all the heart failure cases and its incidence is on the rise, posing a huge economic burden on the health system. Patients with HFpEF have limited therapeutic options available. The inadequate effectiveness of current pharmaceutical therapeutics for HFpEF has prompted the development of device-based treatments that target the hemodynamic changes to reduce the symptoms of HFpEF. However, despite the potential of device-based solutions to treat HFpEF, most of these therapies are still in the developmental stage and a relevant HFpEF in vivo model will surely expedite their development process. This review article outlines the major limitations of the current large in-vivo models in use while discussing how these designs have helped in the development of therapy devices for the treatment of HFpEF. [ABSTRACT FROM AUTHOR]

Recaptures of white seabass Atractoscion nobilis from a marine stock enhancement program were analyzed to understand long-term movement patterns within the Southern California Bight, USA. Between 1999 and 2020, white seabass at liberty for 1–20 years were recaptured as legal-sized (≥ 711 mm TL) adults recruited to California commercial and recreational fisheries. Movement metrics were quantified for 190 recaptures that had been released as juveniles (91–466 mm TL) from a large offshore island, Santa Catalina Island, or from coastal areas. Santa Catalina Island-released white seabass tended to be recaptured in the vicinity of the island up to 7 years post-release (minimum displacement distance = 18.0 ± 4.9 km (mean ± SE)). In contrast, white seabass released from coastal areas were at liberty for up to 20 years and moved significantly farther (145.0 ± 9.2 km and 82.9 ± 5.5 km for southern and northern coastal release areas, respectively), to areas of habitat continuous to (i.e., elsewhere along the coast) and disconnected from (i.e., islands and other offshore areas) the point of release. Minimum displacement distance distributions for 2-year time at liberty intervals (and fitted Weibull curves) further demonstrated the heterogeneous movement patterns associated with Santa Catalina Island and coastal release areas. White seabass released from coastal areas were predominantly recaptured in a west to north west direction from the point of release. Divergent movement metrics were not detected between male and female white seabass. This study provides much needed information on the long-term movement and dispersal of hatchery-reared white seabass, which will help guide stock enhancement management strategies of this highly mobile marine fish species. [ABSTRACT FROM AUTHOR]

Aims: Contrasting nutrient-acquisition strategies would explain why species differ in their distribution in relation to soil phosphorus (P) availability, promoting diversity. However, what drives the differential distribution of plant species with the same P-acquisition strategy remains poorly understood. Methods: We selected two Haemodoraceae species, Anigozanthos flavidus and Macropidia fuliginosa, to investigate physiological responses in non-mycorrhizal monocots adapted to different edaphic habitats that vary in P availability. Plants were grown in nutrient solution in large tanks at a range of P concentrations (0, 0.1, 1, 10 µM P). After seven months, we measured growth, photosynthetic rate, net P-uptake capacity, and leaf [P]. Results: Fresh weights of A. flavidus plants were highest at 1 µM P and lowest at 0 µM P. Fresh weights of M. fuliginosa plants were lowest at 10 µM P compared with those at other P levels. Rates of P uptake by A. flavidus showed a steady decline with increasing P level during growth from 0 to 1 µM P, and then a sharp decline from 1 to 10 µM P. Rates of P uptake in M. fuliginosa did not differ among growth P levels, except between 0 and 1 µM P. Both species showed a drastic increase in the concentration of both total P and inorganic P at 10 µM P. Conclusions: The results support our hypothesis that A. flavidus is efficient in down-regulating its P-uptake capacity, while M. fuliginosa is not. Thus, partly explaining the narrower and wider distribution of these species. [ABSTRACT FROM AUTHOR]

Aims: Non-mycorrhizal species such as Banksia (Proteaceae) that depend on root exudates to acquire phosphorus (P) are prominent in south-western Australia, a biodiversity hotspot on severely P-impoverished soils. We investigated the consequences of an exudate-releasing P-mobilising strategy related to control of iron (Fe) acquisition in two Banksia species, B. attenuata R.Br. and B. laricina C. Gardner, that differ greatly in their geographical distribution and rarity. Methods: We undertook solution culture experiments to measure root-mediated Fe reduction (FeR) in non-cluster and cluster roots at four stages of cluster-root development, and whole root systems for plants grown at 2 to 300 μM Fe (as Fe-EDTA). As a positive control, we used Pisum sativum (cv. Dunn) to validate the FeR assay. Results: Unlike typical Strategy I species, both Banksia species showed no significant variation in FeR, for either cluster or non-cluster roots, when grown at a wide range of Fe supply. For roots of different developmental stages, we measured a range for B. attenuata cluster roots of 0.13 ± 0.03 to 1.29 ± 0.14 μmol Fe3+ reduced g−1 FW h−1 and 0.56 ± 0.11 to 1.10 ± 0.24 μmol Fe3+ reduced g−1 FW h−1 in non-cluster roots. Similarly, for B. laricina cluster-roots, FeR ranged from 0.22 ± 0.07 to 1.21 ± 0.37 μmol Fe3+ reduced g−1 FW h−1, and in non-cluster roots from 0.56 ± 0.11 to 0.71 ± 0.08 μmol Fe3+ reduced g−1 FW h−1. We also observed only minor differences for whole-root system FeR, and even though B. attenuata showed signs of leaf Fe deficiency in the 2 μM Fe treatment, its FeR was the lowest of both species across all treatments at 0.079 ± 0.009 μmol Fe3+ reduced g−1 FW h−1, compared with the fastest rate of 0.20 ± 0.014 μmol Fe3+ reduced g−1 FW h−1 for B. laricina in the 28 μM Fe treatment. Taking plants through a pulse from low to high Fe, then back to low Fe supply did not elucidate any significant response in FeR. Conclusions: Although Fe acquisition is tightly controlled in the investigated Banksia species, such control is not based on regulation of FeR, which challenges the model that is commonly accepted for Strategy I species. [ABSTRACT FROM AUTHOR]

Background and aims: Root-released carboxylates enhance the availability of manganese (Mn), which enters roots through transporters with low substrate specificity. Leaf Mn concentration ([Mn]) has been proposed as a signature for phosphorus (P)-mobilising carboxylates in the rhizosphere. Here we test whether leaf [Mn] provides a signature for root functional types related to P acquisition. Methods: Across 727 species at 66 sites in Australia and New Zealand, we measured leaf [Mn] as related to root functional type, while also considering soil and climate variables. To further assess the specific situations under which leaf [Mn] is a suitable proxy for rhizosphere carboxylate concentration, we studied leaf [Mn] along a strong gradient in water availability on one representative site. In addition, we focused on two systems where a species produced unexpected results. Results: Controlling for background site-specific variation in leaf [Mn] with soil pH and mean annual precipitation, we established that mycorrhizal species have significantly lower leaf [Mn] than non-mycorrhizal species with carboxylate-releasing root structures, e.g., cluster roots. In exception to the general tendency, leaf [Mn] did not provide information about root functional types under seasonally waterlogged conditions, which increase iron availability and thereby interfere with Mn-uptake capacity. Two further exceptions were scrutinised, leading to the conclusion that they were 'anomalous' in not functioning like typical species in their families, as expected according to the literature. Conclusions: Leaf [Mn] variation provides considerable insights on differences in belowground functioning among co-occurring species. Using this approach, we concluded that, within typical mycorrhizal families, some species actually depend on a carboxylate-releasing P-mobilising strategy. Likewise, within families that are known to produce carboxylate-releasing cluster roots, some do not produce functional cluster roots when mature. An analysis of leaf [Mn] can alert us to such 'anomalous' species. [ABSTRACT FROM AUTHOR]

Microhomology-mediated end-joining (MMEJ) is an error-prone alternative double-strand break-repair pathway that uses sequence microhomology to recombine broken DNA. Although MMEJ has been implicated in cancer development, the mechanism of this pathway is unknown. We demonstrate that purified human DNA polymerase θ (Polθ) performs MMEJ of DNA containing 3′ single-strand DNA overhangs with ≥2 bp of homology, including DNA modeled after telomeres, and show that MMEJ is dependent on Polθ in human cells. Our data support a mechanism whereby Polθ facilitates end-joining and microhomology annealing, then uses the opposing overhang as a template in trans to stabilize the DNA synapse. Polθ exhibits a preference for DNA containing a 5′-terminal phosphate, similarly to polymerases involved in nonhomologous end-joining. Finally, we identify a conserved loop domain that is essential for MMEJ and higher-order structures of Polθ that probably promote DNA synapse formation. [ABSTRACT FROM AUTHOR]