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Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia disorder associated with lethal arrhythmias. Most CPVT cases are caused by inherited variants in the gene encoding ryanodine receptor type 2 (RYR2)., Objective: The goal of this study was to investigate the structure-activity relationship of tetracaine derivatives and to test a lead compound in a mouse model of CPVT., Methods: We synthesized >200 tetracaine derivatives and characterized 11 of those. The effects of these compounds on Ca 2+ handling in cardiomyocytes from R176Q/+ mice was tested with confocal microscopy. The effects of lead compound MSV1302 on arrhythmia inducibility and cardiac contractility were tested by programmed electrical stimulation and echocardiography, respectively. Plasma and microsomal stability and cytotoxicity assays were also performed., Results: Ca 2+ imaging revealed that 3 of 11 compounds suppressed sarcoplasmic reticulum Ca 2+ leak through mutant RyR2. Two compounds selected for further testing exhibited a half-maximal effective concentration of 146 nM (MSV1302) and 49 nM (MSV1406). Whereas neither compound altered baseline electrocardiogram intervals, only MSV1302 suppressed stress- and pacing-induced ventricular tachycardia in vivo in R176Q/+ mice. Echocardiography revealed that the lead compound MSV1302 did not negatively affect cardiac inotropy and chronotropy. Finally, compound MSV1302 did not block I Na , I Ca,L , or I Kr ; it exhibited excellent stability in plasma and microsomes, and it was not cytotoxic., Conclusion: Structure-activity relationship studies of second-generation tetracaine derivatives identified lead compound MSV1302 with a favorable pharmacokinetic profile. MSV1302 normalized aberrant RyR2 activity in vitro and in vivo, without altering cardiac inotropy, chronotropy, or off-target effects on other ion channels. This compound may be a strong candidate for future clinical studies to determine its efficacy in CPVT patients., Competing Interests: Disclosures R.M.S. and X.H.T.W. are founding partners and M.S.-V., R.M.S., and X.H.T.W. were shareholders of Elex Biotech Inc, a start-up company that developed drug molecules that target ryanodine receptors to treat cardiac arrhythmia disorders. The other authors do not have relevant disclosures., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

We describe the geographical variation in tree species composition across Amazonian forests and show how environmental conditions are associated with species turnover. Our analyses are based on 2023 forest inventory plots (1 ha) that provide abundance data for a total of 5188 tree species. Within-plot species composition reflected both local environmental conditions (especially soil nutrients and hydrology) and geographical regions. A broader-scale view of species turnover was obtained by interpolating the relative tree species abundances over Amazonia into 47,441 0.1-degree grid cells. Two main dimensions of spatial change in tree species composition were identified. The first was a gradient between western Amazonia at the Andean forelands (with young geology and relatively nutrient-rich soils) and central-eastern Amazonia associated with the Guiana and Brazilian Shields (with more ancient geology and poor soils). The second gradient was between the wet forests of the northwest and the drier forests in southern Amazonia. Isolines linking cells of similar composition crossed major Amazonian rivers, suggesting that tree species distributions are not limited by rivers. Even though some areas of relatively sharp species turnover were identified, mostly the tree species composition changed gradually over large extents, which does not support delimiting clear discrete biogeographic regions within Amazonia., (© 2024. The Author(s).)

Coronary heart disease (CHD) is a prevalent cardiac disease that causes over 370,000 deaths annually in the USA. In CHD, occlusion of a coronary artery causes ischemia of the cardiac muscle, which results in myocardial infarction (MI). Junctophilin-2 (JPH2) is a membrane protein that ensures efficient calcium handling and proper excitation-contraction coupling. Studies have identified loss of JPH2 due to calpain-mediated proteolysis as a key pathogenic event in ischemia-induced heart failure (HF). Our findings show that calpain-2-mediated JPH2 cleavage yields increased levels of a C-terminal cleaved peptide (JPH2-CTP) in patients with ischemic cardiomyopathy and mice with experimental MI. We created a novel knock-in mouse model by removing residues 479-SPAGTPPQ-486 to prevent calpain-2-mediated cleavage at this site. Functional and molecular assessment of cardiac function post-MI in cleavage site deletion (CSD) mice showed preserved cardiac contractility and reduced dilation, reduced JPH2-CTP levels, attenuated adverse remodeling, improved T-tubular structure, and normalized SR Ca 2+ -handling. Adenovirus mediated calpain-2 knockdown in mice exhibited similar findings. Pulldown of CTP followed by proteomic analysis revealed valosin-containing protein (VCP) and BAG family molecular chaperone regulator 3 (BAG3) as novel binding partners of JPH2. Together, our findings suggest that blocking calpain-2-mediated JPH2 cleavage may be a promising new strategy for delaying the development of HF following MI., Competing Interests: Declaration of competing interest XHTW is a consultant for Pfizer and Rocket Pharmaceuticals, and a founding partner and board member of Elex Biotech Inc., a start-up company that developed drug molecules that target ryanodine receptors to treat cardiac arrhythmia disorders. LZ is the co-founder and consultant for Pelagos Pharma Inc., a start-up company that develop drug molecules that target nuclear receptors to treat heart failure and neurodegenerative disorders. Other authors have no potential conflicts to disclose. AI-assisted technology is not used in the preparation of this work (except checking grammar and spelling)., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Trees structure the Earth's most biodiverse ecosystem, tropical forests. The vast number of tree species presents a formidable challenge to understanding these forests, including their response to environmental change, as very little is known about most tropical tree species. A focus on the common species may circumvent this challenge. Here we investigate abundance patterns of common tree species using inventory data on 1,003,805 trees with trunk diameters of at least 10 cm across 1,568 locations 1-6 in closed-canopy, structurally intact old-growth tropical forests in Africa, Amazonia and Southeast Asia. We estimate that 2.2%, 2.2% and 2.3% of species comprise 50% of the tropical trees in these regions, respectively. Extrapolating across all closed-canopy tropical forests, we estimate that just 1,053 species comprise half of Earth's 800 billion tropical trees with trunk diameters of at least 10 cm. Despite differing biogeographic, climatic and anthropogenic histories 7 , we find notably consistent patterns of common species and species abundance distributions across the continents. This suggests that fundamental mechanisms of tree community assembly may apply to all tropical forests. Resampling analyses show that the most common species are likely to belong to a manageable list of known species, enabling targeted efforts to understand their ecology. Although they do not detract from the importance of rare species, our results open new opportunities to understand the world's most diverse forests, including modelling their response to environmental change, by focusing on the common species that constitute the majority of their trees., (© 2024. The Author(s).)

The purpose of this study is to explore the process through which institutional trust influences individuals' vaccination intentions for a coronavirus vaccine. We collected data from a national representative sample of the Spanish population (N = 500) from an online research panel to test the proposed conceptual model. Results revealed a positive association of institutional trust with coronavirus vaccination intentions. This effect was mediated by perceived vaccine safety and positive attitude toward the vaccine. Furthermore, findings corroborate the moderating effect of interdependent self-construal on the indirect relationship between institutional trust and vaccination intention, implying that this effect was stronger for individuals with higher levels of interdependent orientation. Findings have implications for the development of evidence-based health communication strategies for encouraging COVID-19 vaccination.

In a time of rapid global change, the question of what determines patterns in species abundance distribution remains a priority for understanding the complex dynamics of ecosystems. The constrained maximization of information entropy provides a framework for the understanding of such complex systems dynamics by a quantitative analysis of important constraints via predictions using least biased probability distributions. We apply it to over two thousand hectares of Amazonian tree inventories across seven forest types and thirteen functional traits, representing major global axes of plant strategies. Results show that constraints formed by regional relative abundances of genera explain eight times more of local relative abundances than constraints based on directional selection for specific functional traits, although the latter does show clear signals of environmental dependency. These results provide a quantitative insight by inference from large-scale data using cross-disciplinary methods, furthering our understanding of ecological dynamics., (© 2023. The Author(s).)

Objective: This study provides a first approach to the use of the Multiple-Choice Procedure in social media networks use, as well as empirical evidence for the application of the Behavioral Perspective Model to digital consumption behavior in young users in conjunction with a methodology based on behavioral economics., Participants/methods: The participants were part of a large university in Bogotá, Colombia, and they received an academic credit once they completed the online questionnaire. A total of 311 participants completed the experiment. Of the participants, 49% were men with a mean age of 20.6 years (SD = 3.10, Range = 15-30); 51% were women with a mean age of 20.2 years (SD = 2.84, Range = 15-29)., Results: Among the total participants, 40% reported that they used social networks between 1 and 2 h a day, 38% between 2 and 3 h, 16% for 4 h or more, and the remaining 9% used them for 1 h or less per day. The factorial analysis of variance (ANOVA) allowed us to identify a statistically significant effect of the delay of the alternative reinforcer, that is, the average crossover points were higher when the monetary reinforcer was delayed 1 week, compared to the immediate delivery of the monetary reinforcer. There was no statistically significant effect of the interaction between the magnitude of the reinforcer and the delay time of the alternative reinforcer., Conclusions: This study supports the relative reinforcing value of an informational reinforcement consequence such as social media use, which is sensitive to both the magnitude of reinforcement and the delay in delivery as individual factors. The findings on reinforcer magnitude and delay effects are consistent with previous research that have applied behavioral economics to the study of non-substance-related addictions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Robayo-Pinzon, Rojas-Berrío, Paredes and Foxall.)

Tourism in a post-pandemic era will likely be oriented toward nature because contact with nature has restorative health benefits. The purpose of this study was to analyze the antecedents of tourists' intentions to visit nature-based resorts during a pandemic. A nationally representative sample of the Spanish population (n = 500) was recruited by an online commercial panel to test and empirically validate the proposed conceptual framework. The findings confirmed a direct relationship between negative perceptions of wearing face masks during the COVID-19 pandemic and tourists' intentions to visit nature-based resorts. The relationship between the perceived negative effects of wearing face masks and the intention to visit nature-based resorts was positively mediated by the need for escapism. This impact was less pronounced for anxious travelers, as shown by results corroborating the moderating effect of travel anxiety. The findings of this study contribute to research on tourism crises and provide future insights into the recovery of the industry during COVID-19., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Paredes et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The objective of this study was to investigate the relationship between influencer worship and consumers' self-connection with the brands promoted by the influencer in social media contexts. Data from 698 active social media users who follow influencers were collected to test the conceptual framework. The findings support the positive link between influencer worship and consumers' self-connection with the brands promoted by the influencer on social media and suggest that this relationship is mediated by the activation of benign envy. The results also confirm the positive moderating effect of trait competitiveness on this relationship. Specifically, the effect is stronger for individuals with a higher level of competitive orientation. The findings contribute to the understanding of the relationship between influencers and their followers through computer-mediated environments. Theoretical contributions and managerial implications are presented.

This study proposes a novel theoretical model on the negative effect of the perceived cognitive threat and fear of COVID-19 on full board hotel booking intentions, which includes the moderating effects of perceived coping efficacy and present-hedonism orientation. The model was tested with a representative online sample (N = 400) of the Spanish population older than 35 years. The results confirmed negative effects of threat and fear of COVID-19 on hotel booking intentions, as well as a negative moderating effect of perceived coping efficacy on the influence of fear of COVID-19. However, coping efficacy did not moderate the effect of perceived cognitive threat on hotel booking intentions. The present-hedonism orientation positively affected full board hotel booking intentions, but did not, however, reduce the negative effect of threat or fear on those intentions. The findings provide new insights for hospitality managers that can contribute to accelerate the recovery of the hospitality industry., (© 2022 The Authors.)

The COVID-19 pandemic has potentially a serious impact on many people's mental well-being. This study analyses the influence of the perceived threat of COVID-19 on subjective mental well-being with an online survey (n = 711). Findings confirmed the hypothesized model that provides a process explanation for this effect through the mediating influence of the activation of future anxiety. In addition, results confirmed that this influence via future anxiety is moderated by resilience, a personality trait that enables individuals to cope better with stressful or traumatic events. Individuals with higher levels of resilience compared to those with lower levels registered a lower impact of perceived Covid threat on future anxiety and, in turn, on subjective well-being. This study contributes theoretically to a better understanding of the factors that determine the impact of traumatic events such as a pandemic on people's mental health. The implications of this study indicate interventions that may be carried out to minimize the pandemic's negative psychological consequences., (© 2020 Elsevier Ltd. All rights reserved.)

Amazonian forests are extraordinarily diverse, but the estimated species richness is very much debated. Here, we apply an ensemble of parametric estimators and a novel technique that includes conspecific spatial aggregation to an extended database of forest plots with up-to-date taxonomy. We show that the species abundance distribution of Amazonia is best approximated by a logseries with aggregated individuals, where aggregation increases with rarity. By averaging several methods to estimate total richness, we confirm that over 15,000 tree species are expected to occur in Amazonia. We also show that using ten times the number of plots would result in an increase to just ~50% of those 15,000 estimated species. To get a more complete sample of all tree species, rigorous field campaigns may be needed but the number of trees in Amazonia will remain an estimate for years to come.

Species distribution models (SDMs) are widely used in ecology and conservation. Presence-only SDMs such as MaxEnt frequently use natural history collections (NHCs) as occurrence data, given their huge numbers and accessibility. NHCs are often spatially biased which may generate inaccuracies in SDMs. Here, we test how the distribution of NHCs and MaxEnt predictions relates to a spatial abundance model, based on a large plot dataset for Amazonian tree species, using inverse distance weighting (IDW). We also propose a new pipeline to deal with inconsistencies in NHCs and to limit the area of occupancy of the species. We found a significant but weak positive relationship between the distribution of NHCs and IDW for 66% of the species. The relationship between SDMs and IDW was also significant but weakly positive for 95% of the species, and sensitivity for both analyses was high. Furthermore, the pipeline removed half of the NHCs records. Presence-only SDM applications should consider this limitation, especially for large biodiversity assessments projects, when they are automatically generated without subsequent checking. Our pipeline provides a conservative estimate of a species' area of occupancy, within an area slightly larger than its extent of occurrence, compatible to e.g. IUCN red list assessments.

The extent to which pre-Columbian societies altered Amazonian landscapes is hotly debated. We performed a basin-wide analysis of pre-Columbian impacts on Amazonian forests by overlaying known archaeological sites in Amazonia with the distributions and abundances of 85 woody species domesticated by pre-Columbian peoples. Domesticated species are five times more likely than nondomesticated species to be hyperdominant. Across the basin, the relative abundance and richness of domesticated species increase in forests on and around archaeological sites. In southwestern and eastern Amazonia, distance to archaeological sites strongly influences the relative abundance and richness of domesticated species. Our analyses indicate that modern tree communities in Amazonia are structured to an important extent by a long history of plant domestication by Amazonian peoples., (Copyright © 2017, American Association for the Advancement of Science.)

Estimates of extinction risk for Amazonian plant and animal species are rare and not often incorporated into land-use policy and conservation planning. We overlay spatial distribution models with historical and projected deforestation to show that at least 36% and up to 57% of all Amazonian tree species are likely to qualify as globally threatened under International Union for Conservation of Nature (IUCN) Red List criteria. If confirmed, these results would increase the number of threatened plant species on Earth by 22%. We show that the trends observed in Amazonia apply to trees throughout the tropics, and we predict that most of the world's >40,000 tropical tree species now qualify as globally threatened. A gap analysis suggests that existing Amazonian protected areas and indigenous territories will protect viable populations of most threatened species if these areas suffer no further degradation, highlighting the key roles that protected areas, indigenous peoples, and improved governance can play in preventing large-scale extinctions in the tropics in this century.

The vast extent of the Amazon Basin has historically restricted the study of its tree communities to the local and regional scales. Here, we provide empirical data on the commonness, rarity, and richness of lowland tree species across the entire Amazon Basin and Guiana Shield (Amazonia), collected in 1170 tree plots in all major forest types. Extrapolations suggest that Amazonia harbors roughly 16,000 tree species, of which just 227 (1.4%) account for half of all trees. Most of these are habitat specialists and only dominant in one or two regions of the basin. We discuss some implications of the finding that a small group of species--less diverse than the North American tree flora--accounts for half of the world's most diverse tree community.

We report here a review of the seventh mitochondrial DNA (mtDNA) exercise undertaken by the Spanish and Portuguese working group (GEP) of the International Society for Forensic Genetics (ISFG) corresponding to the period 2003-2004. Five reference bloodstains from five donors (M1-M5), a mixed stain of saliva and semen (M6), and a hair sample (M7) were submitted to each participating laboratory for nuclear DNA (nDNA; autosomal STR and Y-STR) and mtDNA analysis. Laboratories were asked to investigate the contributors of samples M6 and M7 among the reference donors (M1-M5). A total of 34 laboratories reported total or partial mtDNA sequence data from both, the reference bloodstains (M1-M5) and the hair sample (M7) concluding a match between mtDNA profiles of M5 and M7. Autosomal STR and Y-STR profiling was the preferred strategy to investigate the contributors of the semen/saliva mixture (M6). Nuclear DNA profiles were consistent with a mixture of saliva from the donor (female) of M4 and semen from donor M5, being the semen (XY) profile the dominant component of the mixture. Strikingly, and in contradiction to the nuclear DNA analysis, mtDNA sequencing results yield a more simple result: only the saliva contribution (M4) was detected, either after preferential lysis or after complete DNA digestion. Some labs provided with several explanations for this finding and carried out additional experiments to explain this apparent contradictory result. The results pointed to the existence of different relative amounts of nuclear and mtDNAs in saliva and semen. We conclude that this circumstance could strongly influence the interpretation of the mtDNA evidence in unbalanced mixtures and in consequence lead to false exclusions. During the GEP-ISFG annual conference a validation study was planned to progress in the interpretation of mtDNA from different mixtures.