Antagonistic Relationship Research Articles

Methane, growth and carcase considerations when breeding for more efficient Merino sheep production

Feed intake, methane and feed efficiency have important genetic correlations with growth, carcase weights and mature size that need to be considered when breeding for production whilst reducing feed requirements and methane production in the Australian sheep industry. Live weight, growth, fat and muscle have significant antagonistic relationships with feed intake, which may make simultaneous selection for efficiency traits and, growth and meat quality slower. For example, selecting animals that grow faster is known to reduce meat-eating quality. Therefore, we estimated the genetic and phenotypic correlations between feed intake, residual feed intake, methane, carbon dioxide, oxygen, live weight, growth, fat and muscle depth traits. Fat and muscle depth were corrected for live weight. Traits were recorded on Merino sheep (n = 2 717) in Western Australia between 2010 and 2016. Sheep were measured at postweaning (range 753–2 717 records across traits), hogget (∼18 months old; range 602–1 046) and adult ages (>2 years old; range 269–443). Live weight and growth rate had significant moderate to high positive genetic correlations with feed intake, residual feed intake, methane and carbon dioxide at postweaning, hogget and adult ages. Fat and muscle depth measured at the start and finish of the feed intake measurement period generally had negative genetic correlations with residual feed intake, feed intake and methane. These genetic correlations with feed intake and residual feed intake were more negative with fat and muscle measured at the start of the measurement period than at the end. Furthermore, in young sheep, selecting for lower feed intake and residual feed intake will mean a lower change in fat between the start and finish of the intake period. Fat and muscle had significant correlations with feed efficiency and greenhouse gas traits and should therefore be considered when estimating residual feed intake, particularly in young animals.

DNA hypomethylation-associated transcriptional rewiring enables resistance to heavy metal mercury (Hg) stress in rice

Mercury (Hg) is an important hazardous pollutant that can cause phytotoxicity and harm human health through the food chain. Recently, rice (Oryza sativa L.) has been confirmed as a potential Hg bioaccumulator. Although the genetic and molecular mechanisms involved in heavy metal absorption and translocation in rice have been investigated for several heavy metals, Hg is largely neglected. Here, we analyzed one Hg-resistant line in rice (RHg) derived from a DNA methyltransferase-coding gene, OsMET1–2 heterozygous mutant. Compared with its isogenic wild-type (WT), RHg exhibited a significantly higher survival rate after Hg treatment, ameliorated oxidative damage, and lower Hg uptake and translocation. RNAseq-based comparative transcriptomic analysis identified 34 potential Hg resistance-related genes involved in phytohormone signaling, abiotic stress response, and zinc (Zn) transport. Importantly, the elevated expression of Hg resistance-related genes in RHg was highly correlated with DNA hypomethylation in their putative promoter regions. An ionomic analysis unraveled a negative correlation between Zn and Hg in roots. Moreover, Hg concentration was effectively decreased by exogenous application of Zn in Hg-stressed rice plants. Our findings indicate an epigenetic basis of Hg resistance and reveal an antagonistic relationship between Hg and Zn, providing new hints towards Hg detoxification in plants. Environmental implicationMercury (Hg) as an important hazardous pollutant adversely impacts the environment and jeopardizes human health, due to its chronicity, transferability, persistence, bioaccumulation and toxicity. In this paper, we identified 34 potential genes that may significantly contribute to Hg resistance in rice. We find the expression of Hg resistance-related genes was highly correlated with DNA hypomethylation in their putative promoter regions. Our results also revealed an antagonistic relationship between Hg and Zinc (Zn), providing new hints towards Hg detoxification in plants. Together, findings of this study extend our current understanding of Hg tolerance in rice and are informative to breed seed non–accumulating rice cultivars.

Calcium carbonate-actuated ion homeostasis perturbator for oxidative damage-augmented Ca2+/Mg2+ interference therapy

Ion homeostasis distortion through exogenous overload or underload of intracellular ion species has become an arresting therapeutic approach against malignant tumor. Nevertheless, treatment outcomes of such ion interference are always compromised by the intrinsic ion homeostasis maintenance systems in cancer cells. Herein, an ion homeostasis perturbator (CTC) is facilely designed by co-encapsulation of carvacrol (CAR) and meso-tetra-(4-carboxyphenyl)porphine (TCPP) into pH-sensitive nano-CaCO3, aiming to disrupt the self-defense mechanism during the process of ion imbalance. Upon the endocytosis of CTC into tumor cells, lysosomal acidity can render the decomposition of CaCO3, resulting in the instant Ca2+ overload and CO2 generation in cytoplasm. Simultaneously, CaCO3 disintegration triggers the release of CAR and TCPP, which are devoted to TRPM7 inhibition and sonosensitization, respectively. The malfunction of TRPM7 can impede the influx of Mg2+ and allow unrestricted influx of Ca2+ based on the antagonism relationship between Mg2+ and Ca2+, leading to an aggravated Ca2+/Mg2+ dyshomeostasis through ion channel deactivation. In another aspect, US-triggered cavitation can be significantly enhanced by the presence of inert CO2 microbubbles, further amplifying the generation of reactive oxygen species. Such oxidative damage-augmented Ca2+/Mg2+ interference therapy effectively impairs the mitochondrial function of tumor, which may provide useful insights in cancer therapy.

Enhancing Centelloside Production in Centella asiatica Hairy Root Lines through Metabolic Engineering of Triterpene Biosynthetic Pathway Early Genes.

Centella asiatica is a medicinal plant with a rich tradition of use for its therapeutic properties. Among its bioactive compounds are centellosides, a group of triterpenoid secondary metabolites whose potent pharmacological activities have attracted significant attention. Metabolic engineering has emerged as a powerful biotechnological tool to enhance the production of target compounds. In this study, we explored the effects of overexpressing the squalene synthase (SQS) gene and transcription factor TSAR2 on various aspects of C. asiatica hairy root lines: the expression level of centelloside biosynthetic genes, morphological traits, as well as squalene, phytosterol, and centelloside content. Three distinct categories of transformed lines were obtained: LS, harboring At-SQS; LT, overexpressing TSAR2; and LST, simultaneously carrying both transgenes. These lines displayed noticeable alterations in morphological traits, including changes in branching rate and biomass production. Furthermore, we observed that the expression of T-DNA genes, particularly aux2 and rolC genes, significantly modulated the expression of pivotal genes involved in centelloside biosynthesis. Notably, the LS lines boasted an elevated centelloside content but concurrently displayed reduced phytosterol content, a finding that underscores the intriguing antagonistic relationship between phytosterol and triterpene pathways. Additionally, the inverse correlation between the centelloside content and morphological growth values observed in LS lines was countered by the action of TSAR2 in the LST and LT lines. This difference could be attributed to the simultaneous increase in the phytosterol content in the TSAR2-expressing lines, as these compounds are closely linked to root development. Overall, these discoveries offer valuable information for the biotechnological application of C. asiatica hairy roots and their potential to increase centelloside production.

A clash on the Toll pathway: competitive action between pesticides and zymosan A on components of innate immunity in Apis mellifera.

The immune system of honeybees includes multiple pathways that may be affected by pesticide exposure decreasing the immune competencies of bees and increasing their susceptibility to diseases like the fungal Nosema spp. infection, which is detected in collapsed colonies. To better understand the effect of the co-presence of multiple pesticides that interact with bees like imidacloprid and amitraz, we evaluated the expression of immune-related genes in honeybee hemocytes. Imidacloprid, amitraz, and the immune activator, zymosan A, mainly affect the gene expression in the Toll pathway. Imidacloprid, amitraz, and zymosan A have a synergistic or an antagonistic relationship on gene expression depending on the level of immune signaling. The presence of multiple risk factors like pesticides and pathogens requires the assessment of their complex interaction, which has differential effects on the innate immunity of honeybees as seen in this study.

Exploring the relationship between bats (Mammalia, Chiroptera) and ectoparasitic flies (Diptera, Hippoboscoidea) of the Orinoquia Region in South America.

Bat flies (Nycteribiidae and Streblidae) have been used to study co-evolutionary patterns between ectoparasites and bats. In the world, Nycteribiidae and Streblidae are represented by approximately 276 and 237 species, respectively. In regions such as the Orinoquia located in the north of South America (Colombia and Venezuela), the richness of bats is high (more than 100 documented species), but studies on Nycteribiidae and Streblidae are scarce and discontinuous. To contribute to the knowledge of ectoparasitic flies in the Orinoquia, records of flies and their interactions with bats were reviewed, including new records and associations using interaction networks. We documented 124 species of Streblidae and only 12 of Nycteribiidae for the Orinoquia in approximately 102 bat species reported in Colombia and Venezuela. New records for six species of bat flies in Colombia were found (Mastopteraguimaraesi, Noctiliostreblamaai, Paradyschiriaparvuloides, Trichobiusjubatus, Trichobiusparasiticus, and Basiliaferrisi) associated with six species of bats (Cynomopsplanirostris, Desmodusrotundus, Myotishandleyi, Molossusrufus, Noctilioalbiventris, and Phyllostomushastatus). The bat-ectoparasite interaction networks in the Orinoquia revealed a pattern of antagonistic relationships, with high specialization, modularity, and low connectivity and nesting. The identified networks are between bat fly species belonging to different ecomorphological groups with unique host species. This supports the idea of ecological niche partitioning among ectoparasitic bat flies and hosts. Our study expanded the knowledge of the distribution of some fly species and the associations with bat hosts in Colombia, by presenting morphological descriptions and new observations, which are key to understanding the ecology, diversity, and distribution of these species.

Plastoquinone synthesis inhibition by tetrabromo biphenyldiol as a widespread algicidal mechanism of marine bacteria

Algae and bacteria have complex and intimate interactions in the ocean. Besides mutualism, bacteria have evolved a variety of molecular-based anti-algal strategies. However, limited by the unknown mechanism of synthesis and action of these molecules, these strategies and their global prevalence remain unknown. Here we identify a novel strategy through which a marine representative of the Gammaproteobacteria produced 3,3’,5,5’-tetrabromo-2,2’-biphenyldiol (4-BP), that kills or inhibits diverse phytoplankton by inhibiting plastoquinone synthesis and its effect cascades to many other key metabolic processes of the algae. Through comparative genomic analysis between the 4-BP-producing bacterium and its algicidally inactive mutant, combined with gene function verification, we identified the gene cluster responsible for 4-BP synthesis, which contains genes encoding chorismate lyase, flavin-dependent halogenase and cytochrome P450. We demonstrated that in near in situ simulated algal blooming seawater, even low concentrations of 4-BP can cause changes in overall phytoplankton community structure with a decline in dinoflagellates and diatoms. Further analyses of the gene sequences from the Tara Oceans expeditions and 2750 whole genome sequences confirmed the ubiquitous presence of 4-BP synthetic genes in diverse bacterial members in the global ocean, suggesting that it is a bacterial tool potentially widely used in global oceans to mediate bacteria-algae antagonistic relationships.

Multi-Species Host Use by the Parasitoid Fly Ormia lineifrons.

Antagonistic species relationships such as parasitoid/host interactions lead to evolutionary arms races between species. Many parasitoids use more than one host species, requiring the parasitoid to adapt to multiple hosts, sometimes being the leader or the follower in the evolutionary back-and-forth between species. Thus, multi-species interactions are dynamic and show temporary evolutionary outcomes at a given point in time. We investigated the interactions of the multivoltine parasitoid fly Ormia lineifrons that uses different katydid hosts for each of its fly generations sequentially over time. We hypothesized that this fly is adapted to utilizing all hosts equally well for the population to persist. We quantified and compared the fly's development in each of the four Neoconocephalus hosts. Cumulative parasitism rates ranged between ~14% and 73%, but parasitoid load and development time did not differ across host species. Yet, pupal size was lowest for flies using N. velox as a host compared to N. triops and other host species. Successful development from pupa to adult fly differed across host species, with flies emerging from N. triops displaying a significantly lower development success rate than those emerging from N. velox and the other two hosts. Interestingly, N. triops and N. velox did not differ in size and were smaller than N. robustus and N. nebrascensis hosts. Thus, O. lineifrons utilized all hosts but displayed especially low ability to develop in N. triops, potentially due to differences in the nutritional status of the host. In the multi-species interactions between the fly and its hosts, the poor use of N. triops may currently affect the fly's evolution the most. Similarities and differences across host utilization and their evolutionary background are discussed.

Evaluation of a Standardized Extract Obtained from Cashew Apple (Anacardium occidentale L.) Bagasse in DSS-Induced Mouse Colitis.

Inflammatory bowel diseases (IBD) include Crohn's disease and ulcerative colitis. Several studies relate eating habits to different aspects of IBD, such as progression and worsening of the clinical condition. Therefore, many natural products (NPs) such as polyphenols and carotenoids have been identified as promising agents in supporting IBD. An interesting source for obtaining bioactive NPs is the by-products of the food industry. The present study evaluated the potential beneficial effect of a standardized extract (CAE) obtained from cashew apple bagasse in the dextran sulfate sodium (DSS)-induced ulcerative colitis model in mice. This was the first time that CAE had been evaluated in this experimental model. Chemical evaluation of CAE identified carotenoids (96.28 ± 0.15 mg/100 g), phenolic compounds (37.49 ± 0.64 mg/100 g), and a mixture of anacardic acids (C15:3 = 94.2 ± 0.6 mg/100 g; C15:2 = 108.4 ± 0.1 mg/100 g; C15:1 = 214.8 ± 0.2 mg/100 g). Administration of CAE (500 mg/kg, 4 days, p.o.) after DSS challenge was more effective in delaying disease progression compared with prior treatment (500 mg/kg, 30 days, p.o.), according to the disease activity index. However, no treatment strategy with CAE was able to prevent or inhibit disease progression, since all parameters evaluated (macroscopic, biochemical, and histopathological) in CAE-treated animals were similar to those observed in DSS-challenged animals. Despite the high dose (500 mg/kg), the standardized extract (CAE) did not result in an effective concentration of carotenoids. Furthermore, as some anacardic acids have been reported as histone acetyltransferases inhibitors, there could be a possible antagonistic relationship between carotenoids and anacardic acids. Complementary research will be necessary to test the hypothesis of antagonism. Thus, an optimized extract, with an even higher concentration of carotenoids, obtained from cashew apple bagasse, can be developed as a possible adjuvant food supplement for inflammatory bowel diseases.

Rewriting the Economic Growth History of Korea in the 1970s: Focusing on the Pollution Imports and the Shadow People of Economic Growth

During the period of rapid economic growth since the 1970s, Korea imported many polluting industrial facilities from Japan, resulting in the generation of huge amounts of hazardous waste. While the problems of environmental degradation such as these were an integral part of Korea’s development process, they have received only scant attention in the official history of the country’s economic development, often being dismissed as peripheral issues. This paper aims to go beyond this tendency by rewriting the history of economic growth that underlay the disputes caused by the importation of polluting industries from Japan in the 1970s. Its features can be summarized as follows.</br>First, Japan was the most damaging pollution exporter to Korea in the 1970s, and it was also the direct channel to import the knowledge of pollution, and alternative logic against the pollution issues.</br>Second, discussions over industrial pollution in the 1970s occurred in the antagonistic relationship between four groups: the government, media, opposition party, and scholars.</br>Third, a group of experts played various roles, including bureaucrats, researchers, and policy makers, leading the discussion of pollution in Korean society in the 1970s.</br>It has been well over 50 years since 1970. Nevertheless, Korean society still does not hesitate to create areas and people that become shadows in the wake of development. This explains why we should focus on the “sick body” rather than the “numbers” in this age of science and technology.

Indazole as a Phenol Bioisostere: Structure-Affinity Relationships of GluN2B-Selective NMDA Receptor Antagonists.

Negative allosteric modulation of GluN2B subunit-containing NMDA receptors prevents overstimulation, resulting in neuroprotective effects. Since the phenol of prominent negative allosteric modulators is prone to rapid glucuronidation, its bioisosteric replacement by an indazole was envisaged. The key step in the synthesis was a Sonogashira reaction of non-protected iodoindazoles with propargylpiperidine derivatives. Modification of the alkynyl moiety allowed the introduction of several functional groups. The synthesized indazoles showed very high GluN2B affinity but limited selectivity over σ receptors. Molecular dynamics simulations revealed the same molecular interactions with the ifenprodil binding site as the analogous phenols. In two-electrode voltage-clamp experiments, enantiomeric 3-(4-benzylpiperidin-1-yl)-1-(1H-indazol-5-yl)propan-1-ols (S)-10a and (R)-10a displayed higher inhibitory activity than ifenprodil. In contrast to phenolic GluN2B antagonists, the indazoles were not conjugated with glucuronic acid. It can be concluded that the phenol of potent GluN2B antagonists can be replaced bioisosterically by an indazole, retaining the high GluN2B affinity and activity but inhibiting glucuronidation.

Genetic evaluation of heat tolerance in Holsteins using test-day production records and NASA POWER weather data

Heat stress is a prominent issue in livestock production, even for intensively housed dairy herds in Canada. Production records and meteorological data can be combined to assess heat tolerance in dairy cattle. The overall aim of this study was to evaluate the possibility of genetic evaluation for heat tolerance in Canadian dairy cattle. The 2 specific objectives were: 1) to estimate the genetic parameters for milk, fat, and protein yield for Holsteins while accounting for high environmental heat loads, and 2) to determine if a genotype-by-environment interaction causes re-ranking of top-ranked sires between environments with low and high heat loads. A repeatability test-day model with a heat stress function was used to evaluate the genetic merit for milk, fat, and protein yield under heat stress and at thermal comfort for first parity in 5 regions in Canada. The heat stress function for each trait was defined using a specific temperature-humidity index (THI) threshold. The purpose of this function was to quantify the level of heat stress that was experienced by the dairy cattle. The estimated genetic correlation between the general additive genetic effect and the additive effect on the slope of the change in the trait phenotype for milk, fat, and protein yield ranged from -0.16 to -0.30, -0.20 to -0.44, and -0.28 to -0.42, respectively. These negative correlations imply that there is an antagonistic relationship between sensitivity to heat stress and level of production. The heritabilities for milk, fat, and protein yield at 15 units above the THI threshold ranged from 0.15 to 0.27, 0.11 to 0.15, and 0.11 to 0.15, respectively. Finally, the rank correlations between the breeding values from a repeatability model with no heat stress effect and the breeding values accounting for heat stress for the 100 top-ranked bulls indicated possible interaction between milk production traits and THI, resulting in substantial re-ranking of the top-ranked sires in Canada, especially for milk yield. This is the first study to implement NASA POWER weather data in a genetic evaluation of heat tolerance in dairy cattle. NASA POWER is a novel alternative meteorological resource that is potentially more reliable and consistent and with broader coverage than weather station data increasing the number of animals that could be included in a heat stress evaluation.

Conflicted Identities: Negotiating Belonging among Young People from the Lebanese Diasporas in Montreal

To elucidate the reproduction of antagonist relationships between diasporic populations, conflict transportation theories tend to focus on societal and transnational contexts. This approach often neglects the complexity of people’s lived experiences and risks essentializing diasporic identities. Based on ethnographic fieldwork among young people of the Lebanese diasporas in Montreal, this contribution reconsiders the interplay between diasporas and conflict by pondering the shifting nature of existence. It argues that everyday encounters and life trajectories play a critical role in how the diasporic youth relate to identity categories, inspiring them to continuously renegotiate and transform what being Lebanese means in their existence.

Research Note: Analysis of body weight and walking ability in turkeys and the prediction of categorical responses across systematic effect classes using a linear threshold model

Heavy selection for growth in turkeys has led to a decay in leg soundness and walking ability. In this study, different models and traits were used to investigate the genetic relationships between body weight (BW) and walking ability (WA) in a turkey population. The data consisted of BW and WA traits collected on 276,059 male birds. Body weight was measured at 12 and 20 wk and WA at 20 wk of age. For WA, birds were scored based on a 1 (bad) to 6 (good) grading system. Due to the small number of records with scores 5 and 6, birds with WA scores of 4, 5, and 6 were grouped together resulting in only 4 classes. Additionally, a binary classification of WA (scores 1 and 2=Similarly, an estimate of the genetic correlation between WA and BW at 20 wk was -0.45, indicating a more pronounced class 1; scores 3, 4, 5, and 6=class 2) was evaluated. The inheritability estimates of WA ranged between 0.25 and 0.27 depending on the number of classes. The Heritability of BW at 12 and 20 wk was 0.44 and 0.51, respectively. The genetic correlation between WA and BW at 12 wk was around -0.35, indicating that heavy birds tend to have poor WA. antagonistic relationship between BW and WA. The genetic correlation between BW at 12 and 20 wk was positive and high (0.80). The residual correlation between WA and BW at 12 and 20 wk of age was -0.07 and -0.02, respectively. The residual correlation between body weight traits was 0.57. Similar results were observed when a binary classification was adopted for WA. The probability of an individual with a given genetic merit expressing a certain class of WA was determined for different fixed effect designations. Predictive probabilities clearly showed that birds when hatched in the winter would have a small chance to exhibit good WA phenotypes.

Is state-owned enterprise merging private enterprise “market choice” or “space crowding” ? —Based on the motives of equity transfer of mixed-ownership enterprises

Many state-owned enterprises have mergers and acquisitions (M&A) with private enterprises, which has caused private enterprises to worry about their living space being squeezed. Based on 572 data records about equity transfers of Chinese listed companies extracted from CSMAR4.0 from 2013 to 2020, this paper categorized ownership structures into three categories: privatization of state-owned enterprises (Category 1), state-owned enterprises merging private enterprises (Category 2), and state-owned enterprises merging state-owned enterprises (Category 3). The categorical regression of ex-ante equity transfer motivation revealed that the motives for Category 1 conformed to the phenomenon of the “pretty girl gets married first” and “embezzlement view.” Category In contrast, the motives for Category 2 conformed to the “fiscal revenue view.” The categorical regression of ex-post equity transfer motivation showed that all three types significantly improved various efficiencies and represented an optimal allocation of resources. Moreover, it was revealed that the transfer of equity to state-owned enterprises by inefficient private firms in Category 2 also significantly improved enterprise efficiency. Thus, it can be considered as a rational behavior of market selection and never squeezed the space crowding. Further analysis showed that the efficiency improvement is due to the symbiotic development relationship rather than the antagonistic relationship between heterogeneous shareholders. Therefore, it is suggested to initiate market-oriented reform by actively developing ownership mixed-ownership economy and adhering to the “two unwavering” basic economic system.

Mindfulness in Persons with Mild Dementia and Their Caregivers: Exploring Trait Rumination as a Clinical Outcome Measure

ObjectivesMindfulness-based interventions (MBIs) have been successfully applied to persons with dementia (PwD) and their caregivers and may yield beneficial effects on depression and quality of life. However, due to inconsistent results, it may be beneficial to re-examine mindfulness in PwD cross-sectionally to identify further potential therapeutic target variables. Rumination, the maladaptive disposition to excessively think about causes and consequences of symptoms and negative mood, may represent such a target. The current study sought to confirm the validity of trait rumination and the antagonistic relationship between mindfulness, rumination, and depression in PwD and their caregivers, as this may qualify rumination as a potential process and outcome variable in future MBIs.MethodForty patients with mild dementia completed a neuropsychological examination and provided self-report data on trait mindfulness, depression, and rumination. Self-report measures were also obtained from 30 caregivers. Regression analyses were used to examine the relation between mindfulness, depression, and rumination. We used clinical cutoffs for depression and rumination to estimate the practical implications of the opposing relationships between these variables.ResultsFor PwD, mindfulness was significantly negatively correlated with depression and rumination, explaining 37% and 25% of variance, respectively. In PwD with low mindfulness scores, clinical depression and rumination syndromes occurred more frequently than in those with high mindfulness. Caregiver results were compatible.ConclusionMindfulness shows an antagonistic relationship with clinically relevant rumination in PwD. Rumination may represent a relevant clinical outcome variable for future MBIs that can be reliably measured in PwD through validated self-report measures.PreregistrationThis study is not preregistered.

Structure activity relationships of 5-HT2B and 5-HT2C serotonin receptor antagonists: N6, C2 and 5′-Modified (N)-methanocarba-adenosine derivatives

(N)-Methanocarba adenosine derivatives were structurally modified to target 5-HT2B serotonin receptors as antagonists, predominantly containing branched N6-alkyl groups. N6-Dicycloalkyl-methyl groups, including their asymmetric variations, as well as 2-iodo, were found to generally favor 5-HT2Rs, while only N6-dicyclohexyl-methyl derivative 35 showed weak 5-HT2AR affinity (Ki 3.6 μM). The highest 5-HT2BR affinities were Ki 11–23 nM (N6-dicyclopropyl-methyl-2-iodo 11, 2-chloro-5′-deoxy-5′-methylthio 15 and N6-((R)-cyclobuty-cyclopropyl-methyl)-2-iodo 43), and Ki 73 nM at 5-HT2CR for 36. Direct comparison of adenine ribosides and their corresponding rigid (N)-methanocarba derivatives (cf. 51 and MRS8099 45) indicated a multifold affinity enhancement with the bicyclic ring system. Compounds 43, 45 and 48 were functional 5-HT2BR (KB 2–3 nM) and 5-HT2CR (KB 79–328 nM) antagonists in a Gq-mediated calcium flux assay, with 5-HT2BR functional selectivity ranging from 45- (48) to 113-fold (43). Substantial adenosine receptor (AR) affinity (Ki, A1AR < Ki, A3AR < Ki, A2AAR) was still present in this series, suggestive of dual acting compounds: 5-HT2B antagonist and A1AR agonist, potentially useful for treating chronic conditions (fibrosis; pain). Given its affinity (17 nM) and moderate 5-HT2BR binding selectivity (32-fold vs. 5-HT2CR, 4-fold vs. A1AR), 43 (MRS7925) could potentially be useful for anti-fibrotic therapy.

Listening to the Enemy: Challenging The National Narrative of World War II in Contemporary Norwegian Fiction

This article analyses five Norwegian novels that all incorporate German soldiers’ experiences as an important part of the Norwegian story of World War II. Abandoning the strong focus on antagonistic relationships of previous narratives, the five novels analysed in this article represent a new approach to the history of the war that aims to view the enemy through what Bull and Hansen (2016) have called agonistic memory, which includes the perspective of the perpetrator to understand conflicts.Previously, when Norwegian authors included German soldiers in narratives about World War II, it was part of a general portrait of the enemy. The individual soldier has few distinct features and no independent identity. These portraits followed the hegemonic Norwegian narrative of the occupation: The good Norwegians, who were part of the home front, versus the Germans and the morally inferior Norwegians who supported them. However, in the last ten years, several novels have revisited the war narrative through representations of previously neglected groups, one of which is the German soldier. The five novels have quite different approaches, but they all question the traditional Norwegian war narrative through complex representations of the enemy. My analysis of the five texts will identify how the texts challenge the conventional history of the occupation through an agonistic perspective that aims to revisit how the war is remembered. These representations of the German soldiers are a central part of the new examination of the long shadows cast by the memories of war in Norway.

Three-dimensional motion of the toes with simulated contraction of individual toe flexors and extensors: A cadaver study

BackgroundThe primary motion of the toes is flexion and extension. The motion results from activity of multiple muscles, and toe disorders may result from muscle dysfunction. The relationships of specific muscles related to toe function is underreported. The purpose of this study was to quantitatively evaluate three-dimensional toe motion resulting from specific muscle contraction using cadavers. MethodsThree-dimensional joint movements of the 1st, 2nd, and 5th toe were produced by applying traction of individual muscles using six Thiel-embalmed cadaver legs. The traction increments were 3 mm, 6 mm, and 9 mm, during which the angle of the distal bone with respect to the proximal bone of each toe joint was measured using a magnetic tracking system. ResultsAs tendon traction distance increased, the angular measure of the distal bone with respect to the proximal bone at each toe joint increased linearly and three-dimensionally. The flexor hallucis brevis significantly pronated and abducted the 1st toe compared to the extensor hallucis longus and brevis. The flexor digitorum brevis significantly supinated and adducted the 2nd toe compared to the flexor digitorum longus and quadratus plantae, while the extensor digitorum brevis demonstrated significant pronation and abduction compared to the extensor digitorum longus. ConclusionsThree intrinsic muscles produced significant toe motion in frontal and horizontal planes. Our results revealed that there was a proportional relationship between tendon excursion and joint angle, and an antagonistic relationship of muscles acting on the toes. These results can be considered regarding pathogenesis of toe disorders or deformity and regarding treatment such as exercise therapy or tendon transfer. Level of evidenceV, cadaveric study.

More than Gold: Embodying the Human Cost of Mining in Maroon Popular Music

Abstract Maroons (descendants of Africans who escaped enslavement) have long been locked in an antagonistic relationship with the Surinamese government over gold-mining legislation and its reinforcement. This contentious topic includes complex debates over land rights and conflicting economic and environmental priorities. This article considers how three contemporary Maroon popular musicians have gone beyond stock metaphors about gold to reference local engagements with gold and the gold-mining industry. I introduce the concept, performative figuring, as a strategy whereby a speaker or performer uses their embodied presence to assert their rights and/or self-worth against practices and policies that threaten to undermine them.