Antagonistic Relationship Research Articles

‘Sympathy for the devil’: The strategic use of the populist repertoire in Viktor Orbán’s politics

Populist politicians such as Viktor Orbán are masters at harnessing intense and polarizing moral emotions: they stigmatize the enemies of the people, offer their community protection as self-proclaimed heroes, and at the same time, othering and moral transgressing trigger emotional overreactions from opponents. This article draws on a new analytical framework that incorporates theories of social labeling (moral panic and euphoria, moral entrepreneurship) and heroic/charismatic leadership to explore this multifaceted and antagonistic emotional relationship associated with populists. The theoretical reasoning suggests that these emotional dynamics define the moral cornerstones and boundaries of populist identity politics. Based on an analysis of four illustrative Hungarian cases – the migration crisis, anti-gender politics, the Authorisation Act during the coronavirus pandemic, and Fidesz’s expulsion from the European People’s Party – the article shows that populists can follow different paths to become charismatic heroes in the eyes of his supporters, while others still see them as folk devils due to their controversial moral entrepreneurship.

Resolving the Intricate Effects of Multiple Global Change Drivers on Root Litter Decomposition.

Plant roots represent about a quarter of global plant biomass and constitute a primary source of soil organic carbon (C). Yet, considerable uncertainty persists regarding root litter decomposition and their responses to global change factors (GCFs). Much of this uncertainty stems from a limited understanding of the multifactorial effects of GCFs and it remains unclear how these effects are mediated by litter quality, soil conditions and microbial functionality. Using complementary field decomposition and laboratory incubation approaches, we assessed the relative controls of GCF-mediated changes in root litter traits and soil and microbial properties on fine-root decomposition under warming, nitrogen (N) enrichment, and precipitation alteration. We found that warming and N enrichment accelerated fine-root decomposition by over 10%, and their combination showed an additive effect, while precipitation reduction suppressed decomposition overall by 12%, with the suppressive effect being most significant under warming-alone and N enrichment-alone conditions. Significantly, changes in litter quality played a dominant role and accelerated fine-root decomposition by 15% ~ 18% under warming and N enrichment, while changes in soil and microbial properties were predominant and reduced decomposition by 7% ~ 10% under precipitation reduction and the combined warming and N enrichment. Examining only the decomposition environment or litter properties in isolation can distort global change effects on root decomposition, underestimating precipitation reduction impacts by 38% and overstating warming and N effects by up to 73%. These findings highlight that the net impact of GCFs on root litter decomposition hinges on the interplay between GCF-modulated root decomposability and decomposition environment, as well as on the synergistic or antagonistic relationships among GCFs themselves. Our study emphasizes that integrating the legacy effects of multiple GCFs on root traits, soil conditions and microbial functionality would improve our prediction of C and nutrient cycling under interactive global change scenarios.

Correlation Analysis of the Transcriptome and Gut Microbiota in Salmo trutta Resistance to Aeromonas salmonicida

Aeromonas salmonicida is a major pathogenic bacterium that poses a significant threat to salmonid fish. Yadong County, located in the Xizang Autonomous Region, is renowned for its characteristic industry of Salmo trutta aquaculture. In recent years, the outbreak of Bacterial Gill Disease (BGD) has led to substantial economic losses for S. trutta farmers. Our prior research identified A. salmonicida as one of the primary culprits behind BGD. To mitigate the impact of A. salmonicida on S. trutta, we conducted a comprehensive study aimed at identifying genes associated with resistance to A. salmonicida. This involved transcriptome sequencing and 16S rRNA sequencing of intestinal flora, providing valuable insights for the study of disease resistance in S. trutta. In this study, we identified 324 genera with 5171 ASVs in the susceptible group and 293 genera with 5669 ASVs in the resistant group. Notably, Methylobacterium and Sphingomonas were common bacteria present in the salmon’s gut, and their proportions remained relatively stable before and after infection. Shewanella, with its antagonistic relationship with Aeromonas, may play a crucial role in the salmon’s defense against A. salmonicida. Several related genes were identified, including angptl4, cipcb, grasp, ccr9a, sulf1, mtmr11, B3GNT3, mt2, PLXDC1, and ank1b.

Refocusing social work education on community work in Hong Kong: an urgent call

Abstract A dominant discourse in social work literature and textbooks is that community workers should take a proactive stance to pressure government officials to reform policy. Without any mission to downplay the political role of social work in the first place, the author of this paper argues that activist discourses from the 1970s are too old to inform contemporary struggles. In light of the neo-liberal, neo-managerial, post-colonial, and pan-political realities, antagonistic relationships between stakeholders in the community, politicians, opinion leaders, and the establishment have ushered in new-look community work in Hong Kong. Social work education on community development should undergo a transformation to help social work students reposition themselves in these chaotic times.

Dynamic interplay of cortisol and BDNF in males under acute and chronic psychosocial stress – A randomized controlled study

The neurotrophic protein brain-derived neurotrophic factor (BDNF) plays a pivotal role in brain function and is affected by acute and chronic stress. We here investigate the patterns of BDNF and cortisol stress reactivity and recovery under the standardized stress protocol of the TSST and the effect of perceived chronic stress on the basal BDNF levels in healthy young men. Twenty-nine lean young men underwent the Trier Social Stress Test (TSST) and a resting condition. Serum BDNF and cortisol were measured before and repeatedly after both conditions. The perception of chronic stress was assessed by the Trier Inventory for Chronic Stress (TICS). After the TSST, there was a significant increase over time for BDNF and cortisol. Stronger increase in cortisol in response to stress was linked to an accelerated BDNF decline after stress. Basal resting levels of BDNF was significantly predicted by chronic stress perception. The increased BDNF level following psychosocial stress suggest a stress-induced neuroprotective mechanism. The presumed interplay between BDNF and the HPA-axis indicates an antagonistic relationship of cortisol on BDNF recovery post-stress. Chronically elevated high cortisol levels, as present in chronic stress, could thereby contribute to reduced neurogenesis, and an increased risk of neurodegenerative conditions in persons suffering from chronic stress.

Ultrasound-Assisted Synthesis of Pyrazoline Derivatives as Potential Antagonists of RAGE-Mediated Pathologies: Insights from SAR Studies and Biological Evaluations.

In the context of age-related disorders, the receptor of advanced glycation end products (RAGE), plays a pivotal role in the pathogenesis of these conditions by triggering downstream signaling pathways associated with chronic inflammation and oxidative stress. Targeting this inflammaging phenomenon with RAGE antagonists holds promise for interventions with broad implications in healthy aging and the management of age-related conditions. This study explores the structure-activity relationship (SAR) of pyrazoline-based RAGE antagonists synthesized using an ultrasound-assisted green one-pot two-steps methodology. Our investigation identifies phenylurenyl-pyrazoline 2g as a promising candidate, demonstrating superior efficiency compared to the reference antagonist Azeliragon (IC50 = 13 µM). Compound 2g exhibits potent inhibition of the AGE2-BSA/sRAGE interaction (IC50 = 22 µM) and favorable affinity in Microscale Thermophoresis (MST) assays (Kd = 17.1 µM), along with a favorable safety profile, with no apparent cytotoxicity observed in vitro in the MTS assay. These findings underscore the potential of pyrazoline-derived RAGE antagonists as therapeutic agents for addressing age-related disorders.

Antagonism between H3K27me3 and genome-lamina association drives atypical spatial genome organization in the totipotent embryo.

In mammals, early embryonic development exhibits highly unusual spatial positioning of genomic regions at the nuclear lamina, but the mechanisms underpinning this atypical genome organization remain elusive. Here, we generated single-cell profiles of lamina-associated domains (LADs) coupled with transcriptomics, which revealed a striking overlap between preimplantation-specific LAD dissociation and noncanonical broad domains of H3K27me3. Loss of H3K27me3 resulted in a restoration of canonical LAD profiles, suggesting an antagonistic relationship between lamina association and H3K27me3. Tethering of H3K27me3 to the nuclear periphery showed that the resultant relocalization is partially dependent on the underlying DNA sequence. Collectively, our results suggest that the atypical organization of LADs in early developmental stages is the result of a tug-of-war between intrinsic affinity for the nuclear lamina and H3K27me3, constrained by the available space at the nuclear periphery. This study provides detailed insight into the molecular mechanisms regulating nuclear organization during early mammalian development.

Are UV filters better together? A comparison of the toxicity of individual ultraviolet filters and off-the-shelf sunscreens to Daphnia magna

Organic ultraviolet filters (UVFs) are known to contaminate many aquatic ecosystems, with much environmental contamination attributed to the use of UVF-containing skin care products such as sunscreens during aquatic recreation. Most studies addressing the impact of sunscreen contamination have focused on the effects of UVFs under the assumption that they are the primary contaminants of concern from sunscreen pollution; however, the extent to which the toxicity of UVFs is representative of the environmental impacts of the whole sunscreen mixture is unknown. To address this knowledge gap, this study compared the mixture toxicity of five off-the-shelf sunscreen spray products containing the UVFs avobenzone, homosalate, octisalate, octocrylene and oxybenzone to the toxicity of each UVF in isolation to the freshwater invertebrate Daphnia magna. It was found that sunscreen toxicity was not proportional to their total UVF content, as the sunscreen containing the fewest UVFs was approximately equivalent to the sunscreen with the most UVFs, causing ≥90 % mortality and inhibiting all daphnid reproduction over 21 d exposures. Sunscreen toxicity was typically lower than expected when compared to the toxicity of each individual UVF within the mixture, as some sunscreens causing ≤20 % mortality contained octocrylene and/or oxybenzone at concentrations exceeding those which caused 90 % mortality during exposure to the UVF alone. Despite sunscreens causing large impairments in reproduction, growth and metabolism, poor correlations existed between the severity of most sublethal endpoints with respect to the measured UVF content of each sunscreen. Overall, these results indicate that potential antagonistic relationships between sunscreen ingredients can greatly reduce the toxicity of UVFs, creating more uncertainty regarding the level of threat that UVFs pose to the environment as a result of sunscreen contamination.

341 Impact of genomic selection for growth on feet and leg structure in Angus cattle

Abstract Historically fitness and production traits have shown an antagonistic relationship at the genetic level. Genetic selection mainly focused on growth traits (GT) might have influenced feet and leg structure traits (FT; recently added trait), causing changes over time. We aimed to examine genetic parameter changes in FT and GT over time in Angus cattle. Currently, genetic parameters are estimated using Variance Components Estimation (VCE), which has limitations in handling large datasets and is time demanding. To address these limitations, we explored the use of predictivity-based formulas to estimate heritability and genetic correlations in GT. The analysis was conducted using the blupf90+ family of programs. To estimate variance components (VCE), sampled data (2011-2022) from the American Angus population included 311K GT records [birth (BW), weaning weight (WW), and post-weaning gain (PWG)], ~70K FT records [foot claw set (CS) and foot angle (FA)], and 142K genotypes. FT are taken on the worst foot of the animal and can be scored multiple times throughout the life of the animal, but in this study, we did not include repeated records. The dataset was split into 5-yr intervals. Since FT ranged from 5 to 9, and 5 is ideal, a negative correlation is desired between FT and GT. The correlation FA-PWG, changed in an undesirable way over time, as it changed from -0.10 to 0.02 in the last interval. The correlation FA-WW is becoming more favorable over time, shifting from 0.05 to -0.15. The GT selection process shifted the correlations between CS and GT in the desired direction, changing from positive (~0.1) to almost zero in the more recent two intervals. To test the predictivity-based formulas, Genomic Estimated Breeding Values (GEBV) were estimated using GT data from 6.3M animals born from 2000 to 2022, and 900K genotyped animals. The data were divided into four slices, with a 2-yr validation period. Over time, heritabilities remained constant: ~0.3 for BW and WW, and ~0.2 for PWG. Correlations between GT also remained constant, approximately at 0.45 for BW-WW, 0.30 for BW-PWG, and 0.75 for WW-PWG. Although the formulas show promising results for heritabilities, interpreting the outcomes of genetic correlation estimation remains unclear, needing further tests. While certain correlations between FT and GT suggest a positive impact of genetic selection, some undesirable outcomes are realized. Probably due to the early FT genetic selection implementation (2019). This emphasizes the need for a multi-trait genomic selection approach to mitigate genetic antagonism. Adopting predictivity-based formulas reduces the time for genetic parameter estimation and allows the use of complete data instead of sampled data, as currently done in VCE.

Potential Trypanocidal Activity of Glycerol Analogues.

Glycerol, a versatile and ubiquitous compound, plays a vital role in a plethora of metabolic pathways in both prokaryotes and eukarotyes. Relatively few glycerol analogues have previously been explored for their use as glycerol kinase inhibitors, in addition to their therapeutic potential, however their use as (pro)-drugs in the context of parasitic diseases such as trypanosomiasis is unreported. The literature on glycerol metabolism and particular its synergic anti-profilation behaviour with salicylhydroxamic acid (SHAM) in Trypanosoma brucei is extensive. However, utiliation of glycerol analogues has not been explored as possible superior combinatory compounds. This report describes the synthesis of various glycerol analogues and their subsequent biochemical pheotypic analysis for their effect on lipid metabolism and their possible synergic activity with SHAM on Trypanosoma brucei. The glycerol analogues caused morphological changes;, including detached flagella, cytokinesis defects and 'big-eye' phenotype. All four compounds either matched or marginally increased the toxicity of SHAM when used in combination against Trypanosoma brucei. However, the compounds exhibited mostly an antagonistic relationship with SHAM rather than synergistic. This research highlights the potential of small molecule glycerol analogues for their combination use with SHAM for the treatment of parasitic disease, such as trypanosomiasis.

Virulence-Related Genes Expression in Planktonic Mixed Cultures of Candida albicans and Non-Albicans Candida Species

Introduction: Candida albicans is the most common opportunistic pathogen causing fungal infections worldwide, especially in high-risk patients. Its pathogenicity is related to virulence factors gene expression, such as hyphal growth (HWP1), cell adhesion (ALS3), and protease secretion (SAP1) during infection spreading mechanisms. In recent years, an increase in non-albicans Candida infections has been reported, which may present coinfection or competitive interactions with C. albicans, potentially aggravating the patient’s condition. This study aims to evaluate the expression of genes related to virulence factors of C. albicans and non-albicans Candida during planktonic stage. Methods: C. albicans (ATCC MYA-3573) as well as with three clinical strains (C. albicans DCA53, C. tropicalis DCT6, and C. parapsilosis DCP1) isolated from blood samples, were grown in 24-well plates at 37°C for 20 h, either in monocultures or mixed cultures. Quantitative real-time polymerase chain reaction was used to evaluate the expression levels of the genes HWP1, ALS3, and SAP1 in cells collected during the planktonic stage. In addition, hyphal filamentation was observed using a Scanning Electron Microscope. Results: The overexpression of HWP1 and ASL3 genes in mixed growth conditions between C. albicans and non-albicans Candida species suggests a synergistic relationship as well as an increased capacity for hyphal growth and adhesion. In contrast, C. parapsilosis versus C. tropicalis interaction shows an antagonistic relationship during mixed culture, suggesting a decreased virulence profile of C. parapsilosis during initial coinfection with C. tropicalis. Conclusion: The expression of HWP1, ALS3, and SAP1 genes associated with virulence factors varies under competitive conditions among species of the genus Candida during planktonic stage.

IMPACT OF DIFFERENT ZINC APPLICATION METHODS AND PHOSPHORUS DOSES ON GROWTH, YIELD AND GRAIN ZINC CONTENTS OF WHEAT

Wheat is a staple crop of around half of the world's population. About 30 percent of the world’s population is suffering from Zn deficiency. Zn deficiency problems can be encountered by agronomic and genetic biofortification. Phosphorus (P) is an important plant macronutrient and has an antagonistic relationship with Zn. A field study was performed to evaluate the impact of different Zn application methods and P doses on growth, yield, and grain Zn contents of wheat at the Agronomic Research Farm, University of Agriculture Faisalabad, Pakistan, using a high accumulation wheat variety Zincol-2016. Three doses of P (100, 150, and 200% of recommended P) along with three Zn application methods (seed priming, soil mixing, and foliar application) were applied to wheat using randomized complete block design (RCBD) with three replicates under split-plot arrangement. All agronomic practices were kept normal and uniform for all treatments. Parameters including growth, yield, and Zn content in wheat grains were monitored using standard protocols. The results were evaluated using Fisher’s analysis of variance at a 5% probability level. A comparison of means of treatments was performed using the least significant difference (LSD) test. The highest value of SPAD reading (56.38) was noted in treatment where Zn was applied as priming and P was applied at 200%. Maximum crop growth rate (63.17) was observed in P3 where Zn was applied as mix in soil. Maximum spike length (14.25), spikelets per spike (17.67), and Zn concentration were observed in P3 as a result of foliar application of Zn. Highest grain weight per spike (1.89g), no. of tillers (691.01), grain yield (4.09 t ha-1), biological yield (11.01 t ha-1), harvest index (36.54%) and NDVI (0.42 were observed in P3 where Zn was applied as soil mix.

Growth and metabolism of halophilic Candida versatilis and Tetragenococcus halophilus in simultaneous and sequential fermentation of salted soy whey

This study investigated various strategies: mono-, simultaneous and sequential fermentation of halophilic Candida versatilis and Tetragenococcus halophilus to valorize salted whey, a side stream of salted tofu (pressed beancurd) production, with an ultimate goal of creating a soy sauce-like condiment. Growth, glucose, organic acids were monitored throughout fermentation, while free amino acids and volatile compounds were analyzed on the final days. In monoculture fermentation, both C. versatilis and T. halophilus thrived in salted soy whey. However, in co-culture fermentation, an antagonistic relationship was observed, wherein C. versatilis growth was slightly suppressed and T. halophilus was significantly inhibited. In C. versatilis-involved fermentations, no significant (p > 0.05) differences in key volatile and non-volatile chemical components were found among various fermentation modes. Key soy sauce-like volatile compounds, such as 4-ethylguaiacol and 4-ethylphenol, were detected in all C. versatilis-fermented salted soy whey, while T. halophilus primarily functioned as a lactic and acetic acids producer. This study highlights the potential of mixed culture fermentation involving soy sauce yeast and lactic acid bacteria for eventually developing a soy sauce-like condiment from salted soy whey, with C. versatilis playing a crucial role in flavour development. The findings suggest that fermenting of a single culture of C. versatilis in lactic acid-adjusted salted soy whey could be a viable and efficient choice for future production of soy sauce-like condiment.

LEP Gene Promotes Milk Fat Synthesis via the JAK2-STAT3 and mTOR Signaling Pathways in Buffalo Mammary Epithelial Cells.

Leptin (LEP), a protein hormone well-known for its role in metabolic regulation, has recently been linked to lipid metabolism in cattle. However, its function in buffalo mammary glands remains unclear. To address this issue, we isolated and identified the LEP gene and conducted experiments to investigate its function in buffalo mammary epithelial cells (BuMECs). In this study, two transcript variants of LEP, designated as LEP_X1 and LEP_X2, were identified. The coding sequences (CDS) of LEP_X1 and LEP_X2 are 504 bp and 579 bp in length, encoding 167 and 192 amino acid residues, respectively. Bioinformatics analysis revealed that LEP_X2 is a hydrophobic protein with an isoelectric point below 7 and contains a signal peptide, while LEP_X1 is hydrophilic and lacks a signal peptide. Our study found that LEP gene expression in lactating BuMECs was significantly higher than in non-lactating cells, with LEP_X2 expression remarkably higher than LEP_X1 in lactating BuMECs. Overexpression of both LEP_X1 and LEP_X2 significantly promoted the expression of genes related to milk fat synthesis in lactating BuMECs, including STAT3, PI3K, mTOR, SCD, and SREBF1, accompanied by an increase in cellular triglycerides (TG). Interestingly, LEP_X2 overexpression significantly suppressed LEP_X1 expression while increasing intracellular TG concentration by 12.10-fold compared to LEP_X1 overexpression, suggesting an antagonistic relationship between the two variants and supposing LEP_X2 plays a dominant role in milk fat synthesis in lactating BuMECs. Additionally, four nucleotide substitutions were identified in the buffalo LEP CDS, including a nonsynonymous substitution c.148C>T (p.Arg50Cys), which was predicted to decrease the stability of the LEP protein without affecting its function. These results collectively underscore the significant role of LEP in milk fat synthesis and can provide a basis for molecular breeding strategies of buffalo.

Nonequilibrium phases of a biomolecular condensate facilitated by enzyme activity.

Biomolecular condensates represent a frontier in cellular organization, existing as dynamic materials driven out of equilibrium by active cellular processes. Here we explore active mechanisms of condensate regulation by examining the interplay between DEAD-box helicase activity and RNA base-pairing interactions within ribonucleoprotein condensates. We demonstrate how the ATP-dependent activity of DEAD-box helicases-a key class of enzymes in condensate regulation-acts as a nonequilibrium driver of condensate properties through the continuous remodeling of RNA interactions. By combining the LAF-1 DEAD-box helicase with a designer RNA hairpin concatemer, we unveil a complex landscape of dynamic behaviors, including time-dependent alterations in RNA partitioning, evolving condensate morphologies, and shifting condensate dynamics. Importantly, we reveal an antagonistic relationship between RNA secondary structure and helicase activity which promotes condensate homogeneity via a nonequilibrium steady state. By elucidating these nonequilibrium mechanisms, we gain a deeper understanding of cellular organization and expand the potential for active synthetic condensate systems.

The Relationship of Physical Activity with Restless Legs Syndrome in Chronic Kidney Disease Patients in the Hemodialysis Room of Subang District Hospital

Restless legs syndrome (RLS) is a sensorimotor disorder that affects a person's desire to move the legs. Physical activity is considered to be one way to reduce RLS symptoms. The purpose of this study was to analyze the relationship of physical activity with RLS in patients with chronic kidney disease (CKD) in the hemodialysis room of RSUD Kab Subang. This research is a type of quantitative research, correlational descriptive research design using cross-sectional. The sample in this study was 62 respondents, with purposive sampling techniques. Data collection using the Global Physical Activity Questionaire (GPAQ) and International Restless Legs Syndrome Group (IRLS) questionnaires, and data analysis using the spearmen rank test. The results showed that most respondents had a low level of physical activity, with a prevalence of 64.5%, and most respondents experienced severe symptoms of RLS, with a prevalence of 40.3%. Statistical tests show that there is a relationship between the physical activity variable and RLS (p-value 0.001), with the coefficient value is -0.741. It can be concluded that there is a solid relationship between physical activity and RLS in CKD patients in the hemodialysis room of RSUD Kab Subang with an antagonistic relationship direction. It is expected that nurses can intervene in chronic kidney disease patients to perform physical activity in accordance with their ability to reduce RLS.

Abstract We090: Antagonistic and Cooperative Dynamics of Irx3 and Irx4 in Ventricular Compaction

Left ventricular non-compaction cardiomyopathy (LVNC) is a rare heart condition characterized by excessive trabeculae and intertrabecular recesses in the left ventricle of the heart. It is believed to be caused by abnormal trabecular compaction process, which involves trabecular remodelling to form a thick myocardial wall. Embryonic trabeculae consist of bipotent progenitors that differentiate into the ventricular conduction system (VCS) and contractile cardiomyocytes, yet it remains to be further understood how the pathways involved in trabecular cell specifications play a role in the compaction process. Here we present two transcription factors, Iroquois homeobox 3 ( Irx3 ) and Irx4 , playing antagonistic and cooperative roles during trabecular specification and maturation, thereby facilitating proper ventricular compaction. Our single-cell RNA sequencing analysis revealed that the differentiation of trabecular cells into VCS cells was accompanied by increased Irx3 but decreased Irx4 expression. In addition, we found that the loss of Irx4 led to both an increased expression level of Irx3 and an expansion in the number of Irx3 -expressing cells. Conversely, the loss of Irx3 resulted in an upregulation of Irx4 expression within VCS cells. Next, to investigate the functional importance of the antagonistic relationship between Irx3 and Irx4 in trabecular differentiation, we generated Irx3 and Irx4 compound knockout (KO) mice and examined the structure and function of their hearts. Notably, unlike Irx3 KO hearts showing normal ventricular myocardium, Irx4 KO hearts exhibited mild LVNC, and Irx3 and Irx4 double knockouts ( Irx3 /4dKO) hearts displayed severe LVNC. Multiome sequencing of E14.5 ventricles revealed that Irx3 /4dKO ventricles contained an increased number of trabecular cells, expressing higher levels of cell proliferation markers and altered trabecular identity genes, compared to littermate controls. Collectively, our results demonstrate that balanced antagonism between Irx3 and Irx4 is crucial for establishing trabecular identity. This highlights the importance of proper differentiation of trabeculae into the VCS and non-VCS contractile cells during ventricular compaction, thereby preventing noncompaction cardiomyopathy.

SAMD1 suppresses epithelial-mesenchymal transition pathways in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) poses a significant threat due to its tendency to evade early detection, frequent metastasis, and the subsequent challenges in devising effective treatments. Processes that govern epithelial-mesenchymal transition (EMT) in PDAC hold promise for advancing novel therapeutic strategies. SAMD1 (SAM domain-containing protein 1) is a CpG island-binding protein that plays a pivotal role in the repression of its target genes. Here, we revealed that SAMD1 acts as a repressor of genes associated with EMT. Upon deletion of SAMD1 in PDAC cells, we observed significantly increased migration rates. SAMD1 exerts its effects by binding to specific genomic targets, including CDH2, encoding N-cadherin, which emerged as a driver of enhanced migration upon SAMD1 knockout. Furthermore, we discovered the FBXO11-containing E3 ubiquitin ligase complex as an interactor and negative regulator of SAMD1, which inhibits SAMD1 chromatin-binding genome-wide. High FBXO11 expression in PDAC is associated with poor prognosis and increased expression of EMT-related genes, underlining an antagonistic relationship between SAMD1 and FBXO11. In summary, our findings provide insights into the regulation of EMT-related genes in PDAC, shedding light on the intricate role of SAMD1 and its interplay with FBXO11 in this cancer type.

Bayesian blacksmithing: discovering thermomechanical properties and deformation mechanisms in high-entropy refractory alloys

Finding alloys with specific design properties is challenging due to the large number of possible compositions and the complex interactions between elements. This study introduces a multi-objective Bayesian optimization approach guiding molecular dynamics simulations for discovering high-performance refractory alloys with both targeted intrinsic static thermomechanical properties and also deformation mechanisms occurring during dynamic loading. The objective functions are aiming for excellent thermomechanical stability via a high bulk modulus, a low thermal expansion, a high heat capacity, and for a resilient deformation mechanism maximizing the retention of the BCC phase after shock loading. Contrasting two optimization procedures, we show that the Pareto-optimal solutions are confined to a small performance space when the property objectives display a cooperative relationship. Conversely, the Pareto front is much broader in the performance space when these properties have antagonistic relationships. Density functional theory simulations validate these findings and unveil underlying atomic-bond changes driving property improvements.

Unravelling the mechanisms underlying the social interaction effects on the feed efficiency of rabbits

The feed consumption and feeding patterns of group-housed livestock and their productive outputs can be affected by interactions among group members, such as competition for feeder access and aggression. The impact of competition is especially significant when feed restriction is implemented during the fattening stage, a common practice in rabbit farms to reduce mortality from digestive disorders during this period. The overall aim was to quantify the importance of social interaction effects at the genetic and environmental level on feed efficiency, feeding behaviour and social ranking traits in rabbit populations having access to electronic feeders whilst they were housed in groups during fattening. This was done by quantifying novel feeding behaviour (FB) and social ranking (SR) traits and by estimating the genetic parameters and genetic correlations between all combinations of direct and social effects of these traits and residual feed intake (RFI), an indicator of feed efficiency. These effects were estimated in animals fed either ad libitum (AL) or on a time-based feed restriction (R) and were selected for feed efficiency on these feeding regimes for six generations. We found that there were substantial social genetic and social litter effects on RFI and FB traits, manifesting as antagonistic relationships between direct and social genetic effects. These effects were stronger amongst the R, as opposed to the AL animals. Despite these antagonistic relationships, the large social genetic effects resulted in substantial heritable variation available for selection of these traits, and therefore feeding behaviour could be changed by genetic selection, especially for R animals. The indicators of an animal’s SR were also heritable and subject to social genetic effects and therefore may respond to selection. However, the phenotypic population mean would not change, because such traits are context−specific. The animals that took most of the feeding resources and had priority access to the feeder had a higher RFI, that is, they were less efficient, but they made their cage mates more efficient. This is the first time that the genetic correlations between direct effects of RFI and direct effects of FB and SR traits, as well as between social effects of RFI and direct effects of FB traits and SR traits, have been quantified. Results could help to understand the mechanisms by which an animal exerts its influence on the feed efficiency of its cage mates under different feeding regimes and assist in the development of breeding strategies.