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IntroductionPiscirickettsia salmonis, the causative agent of Piscirickettsiosis, poses a significant threat to the Chilean aquaculture industry, resulting in substantial economic losses annually. The pathogen, first identified as specie in 1992, this pathogen was divided into two genogroups: LF-89 and EM-90, associated with different phenotypic mortality and pathogenicity. Traditional genotyping methods, such as multiplex PCR, are effective but limited by their cost, equipment requirements, and the need for specialized expertise.MethodsThis study validates Loop-mediated Isothermal Amplification (LAMP) as a rapid and specific alternative for diagnosing P. salmonis infections. We developed the first qPCR and LAMP assay targeting the species-conserved tonB receptor gene (tonB-r, WP_016210144.1) for the specific species-level identification of P. salmonis. Additionally, we designed two genotyping LAMP assays to differentiate between the LF-89 and EM-90 genogroups, utilizing the unique coding sequences Nitronate monooxygenase (WP_144420689.1) for LF-89 and Acid phosphatase (WP_016210154.1) for EM-90.ResultsThe LAMP assays demonstrated sensitivity and specificity comparable to real-time PCR, with additional benefits including rapid results, lower costs, and simplified operation, making them particularly suitable for field use. Specificity was confirmed by testing against other salmonid pathogens, such as Renibacterium salmoninarum, Vibrio ordalii, Flavobacterium psychrophilum, Tenacibaculum maritimum, and Aeromonas salmonicida, with no cross-reactivity observed.DiscussionThe visual detection method and precise differentiation between genogroups underscore LAMP's potential as a robust diagnostic tool for aquaculture. This advancement in the specie detection (qPCR and LAMP) and genotyping of P. salmonis represents a significant step forward in disease management within the aquaculture industry. The implementation of LAMP promises enhanced disease surveillance, early detection, and improved management strategies, ultimately benefiting the salmonid aquaculture sector.

Sensory-specific satiety (SSS) could negatively affect pigs’ feed intake, even when diets satisfy their nutritional requirements. We evaluated the short-term effects of SSS on feed intake and palatability. Thirty-two nursery pigs (tested in pairs) were exposed to short-term feeding trials for 6 days. In Trial 1, animals received for 90 min over three consecutive days three feeders: with different flavours (VAR); the same flavour (MON); or a mixture of the three flavours (MIX) in a 3 × 3 Latin square design. In Trial 2, with the same animals and different flavours, the three feeders were delivered successively (1 feeder every 30 min). In Trial 1, there was a day-by-diet interaction (F 4,36 = 2.98; p = 0.032), where the VAR diet was least consumed on the first day but most consumed subsequently. In Trial 2 a triple interaction between diet, day and delivery order modified pig’s intake (F 12,15 = 3.33; p = 0.015), and consumption patterns (F 12,15 = 3.52; p = 0.012); where VAR diet presented the highest values in the last delivery order on the third experimental day. Flavour variety may decrease the effect of SSS, increasing feed intake and hedonic value in nursery pigs when there was a previous experience with those flavours.

Piscirickettsia salmonis is a bacterial pathogen that severely impact the aquaculture in several countries as Canada, Scotland, Ireland, Norway, and Chile. It provokes Piscirickettsiosis outbreaks in the marine phase of salmonid farming, resulting in economic losses. The monophyletic genogroup LF-89 and a divergent genogroup EM-90 are responsible for the most severe Piscirickettsiosis outbreaks in Chile. Therefore, the development of methods for quick genotyping of P. salmonis genogroups in field samples is vital for veterinary diagnoses and understanding the population structure of this pathogen. The present study reports the development of a multiplex PCR for genotyping LF-89 and EM-90 genogroups based on comparative genomics of 73 fully sequenced P. salmonis genomes. The results revealed 2,322 sequences shared between 35 LF-89 genomes, 2,280 sequences in the core-genome of 38 EM-90 genomes, and 331 and 534 accessory coding sequences each genogroup, respectively. A total of 1,801 clusters of coding sequences were shared among all tested genomes of P. salmonis (LF-89 and EM-90), with 253 and 291 unique sequences for LF-89 and EM-90 genogroups, respectively. The Multiplex-1 prototype was chosen for reliable genotyping because of differences in annealing temperatures and respective reaction efficiencies. This method also identified the pathogen in field samples infected with LF-89 or EM-90 strains, which is not possible with other methods currently available. Finally, the genome-based multiplex PCR protocol presented in this study is a rapid and affordable alternative to classical sequencing of PCR products and analyzing the length of restriction fragment polymorphisms.

An effective and economical vaccine against the Piscirickettsia salmonis pathogen is needed for sustainable salmon farming and to reduce disease-related economic losses. Consequently, the aquaculture industry urgently needs to investigate efficient prophylactic measures. Three protein-based vaccine prototypes against Piscirickettsia salmonis were prepared from a highly pathogenic Chilean isolate. Only one vaccine effectively protected Atlantic salmon (Salmo salar), in correlation with the induction of Piscirickettsia-specific IgM antibodies and a high induction of transcripts encoding pro-inflammatory cytokines (i.e., Il-1β and TNF-α). In addition, we studied the proteome fraction protein of P. salmonis strain Austral-005 using multidimensional protein identification technology. The analyzes identified 87 proteins of different subcellular origins, such as the cytoplasmic and membrane compartment, where many of them have virulence functions. The other two prototypes activated only the innate immune responses, but did not protect Salmo salar against P. salmonis. These results suggest that the knowledge of the formulation of vaccines based on P. salmonis proteins is useful as an effective therapy, this demonstrates the importance of the different research tools to improve the study of the different immune responses, resistance to diseases in the Atlantic salmon. We suggest that this vaccine can help prevent widespread infection by P. salmonis, in addition to being able to be used as a booster after a primary vaccine to maintain high levels of circulating protective antibodies, greatly helping to reduce the economic losses caused by the pathogen.

Pigs display an innate preference for sweet taste compounds such as sucrose. However, the influence of sucrose supplementation into maternal diets has not been examined in pigs. We tested the hypothesis that sucrose inclusion into sows’ diets would modify the feeding behavior of post-weaning pigs for sweet and umami solutions. Twenty-two sows (85 days of gestation) were used. They randomly received a gestational and lactating diet with or without 50 g/kg of sucrose. Different sucrose and monosodium glutamate solutions were offered to the progeny to analyze different intake behavior measurements during nursery. Pigs born from treated sows presented a higher sucrose threshold than control animals (15 mM vs. 0.1 mM, p = 0.032) and displayed decreased sensory-motivated intake for this disaccharide (p < 0.023). Sucrose consumption decreased (p < 0.021) in pigs born from treated sows, as well as the consumption patterns for the less concentrated solutions (p < 0.014). The inclusion of sucrose into maternal diets (gestation and lactation) could modified pigs’ feeding behavior after weaning when offered sweet solutions, which speaks against the practicality of this supplementation in pig production systems.

Shellfish farming is a relevant economic activity in Chile, where the inner sea in Chiloé island concentrates 99% of the production of the mussel Mytilus chilensis. This area is characterized by the presence of numerous human activities, which could harm the quality of seawater. Additionally, the presence of potentially pathogenic microorganisms can influence the health status of mussels, which must be constantly monitored. To have a clear viewpoint of the health status of M. chilensis and to study its potential as a host species for exotic diseases, microbiological, molecular, and histological analyses were performed. This study was carried out in October 2018, where M. chilensis gut were studied for: presence of food-borne bacteria (Vibrio parahaemolyticus, Escherichia coli, Salmonella spp.), exotic bacteria (“Candidatus Xenohaliotis californiensis”), viruses (abalone and Ostreid herpes virus), and protozoa (Marteilia spp., Perkinsus spp. and Bonamia spp.). Additionally, 18S rDNA metabarcoding and histology analyses were included to have a complete evaluation of the health status of M. chilensis. Overall, despite the presence of risk factors, abnormal mortality rates were not reported during the monitoring period and the histological examination did not reveal significant lesions. Pathogens of mandatory notification to World Organization for Animal Health (OIE) and the Chilean National Fisheries and Aquaculture Service (SERNAPESCA) were not detected, which confirms that M. chilensis have a good health status, highlighting the importance of an integrated vision of different disciplines to ensure the sustainability of this important mussel industry in Chile.

In this study, we addressed the social attentiveness, as well as the phenomenon of social facilitation and inhibition in the context of a positive human–pig relationship. Specifically, we investigated whether the social rank of an experienced pig (termed “demonstrator”) has an effect on the attentiveness of the remaining pen mates (N = 40) when they observe the demonstrator being gently handled by a stockperson from behind an acrylic panel. We found that pigs preferentially attended to dominant demonstrators rather than subordinate demonstrators during their gentle handling sessions with the stockperson. Additionally, we also examined whether the presence of a demonstrator pig of different social rank, who previously established a positive relationship with the stockperson in presence of conspecifics, affects the behavior and motivation of their pen mates to positively interact with the stockperson. To test for the effect of the presence and demonstrator’s social rank on pen mate interactions with the stockperson, we evaluated the behavior of domestic pigs (N = 65) toward the stockperson using a human-approach test in their home-pen. Pigs showed a decrease in their motivation to positively interact with the stockperson when a socially dominant demonstrator was present, behaving similarly to animals receiving minimal human contact (control group). Overall, they exhibited a greater latency to physical contact, a lower acceptance of stroking, and spent more time looking at the stockperson compared to pigs exposed to subordinate demonstrators. Taken together, these findings expand our current understanding of pigs’ cognition and social behavior, and the nature of social attention bias in farm animals. Our findings indicate that positive handling of previously selected subordinate demonstrators seems to be the best strategy to reduce the level of fear in large groups of pigs.

Farm animals can perceive humans positively by observing another animal being positively handled. This study evaluated whether pigs acquire a positive perception of humans after observing either a high or low socially ranked conspecific receiving gentle handling. Seventy-five 21-week-old pigs were housed in 15 nursery pens (five pigs/pen) and randomly assigned to one of three pen treatments: Dominant Demonstrator Group (DDG), Subordinate Demonstrator Group (SDG) and Control Group (CG). Pigs from DDG and SDG observed a high and low socially ranked conspecific (“demonstrator”), respectively, while the demonstrator received gentle stroking and a sucrose solution for 10 min, twice a day for 5 weeks. Control group pigs received minimal human contact. Following treatment, the behavior and heart rate variability of non-demonstrator pigs were evaluated in response to a stockperson in an open-field test. Pigs from the DDG and SDG contacted the stockperson sooner (p < 0.001), spent more time investigating the stockperson (p < 0.05), accepted more stroking (p < 0.001) and exhibited a lower low/high frequency ratio (p = 0.015) compared to the CG. No differences in learning between the pigs from the DDG and SDG were found. These results suggest that pigs can learn to perceive humans positively through observational social learning, regardless of the demonstrator conspecific’s social rank.

Kennelled dogs are at risk of suffering chronic stress due to long-term spatial, social and feeding restrictions. Chronic stress may decrease the dogs’ capacity to feel pleasure when facing hedonic experiences, modifying their perception for palatable ingredients. However, different abilities to cope with environmental stressors could prevent the onset of anhedonia. Fourteen kennelled Beagle dogs were used to study the acceptability and preference for different dilute sucrose and monosodium glutamate (MSG) solutions. Coping style of animals was previously evaluated through a human approach test (HAT) and classified as close dogs (CD; proactive) or distant dogs (DD; reactive) according to whether or not they approached an unfamiliar human when a feeding opportunity was presented. Consumption results were analysed taking into account the sucrose/MSG concentrations, HAT (CD or DD), age, and weight of the animals. DD presented a lower intake of sucrose (p = 0.041) and MSG (p = 0.069) solutions compared with CD. However, DD exhibited a higher consumption of MSG than CD at its highest concentrations, supporting that their intake depends on solution palatability. Finally, DD did not prefer sucrose or MSG solutions over water at any dilute solution offered. Together, these results suggest that dogs that are categorized as reactive animals could diminish their ability to perceive dilute palatable solutions, reflecting depressive-like behaviours as anhedonia.

Piscirickettsia salmonis is the causative agent of Piscirickettsiosis, an infectious disease with a high economic impact on the Chilean salmonid aquaculture industry. This bacterium produces biofilm as a potential resistance and persistence strategy against stressful environmental stimuli. However, the in vitro culture conditions that modulate biofilm formation as well as the effect of sessile bacteria on virulence and immune gene expression in host cells have not been described for P. salmonis. Therefore, this study aimed to analyze the biofilm formation by P. salmonis isolates under several NaCl and iron concentrations and to evaluate the virulence of planktonic and sessile bacteria, together with the immune gene expression induced by these bacterial conditions in an Atlantic salmon macrophage cell line. Our results showed that NaCl and Fe significantly increased biofilm production in the LF-89 type strain and EM-90-like isolates. Additionally, the planktonic EM-90 isolate and sessile LF-89 generated the highest virulence levels, associated with differential expression of il-1β, il-8, nf-κb, and iκb-α genes in SHK-1 cells. These results suggest that there is no single virulence pattern or gene expression profile induced by the planktonic or sessile condition of P. salmonis, which are dependent on each strain and bacterial condition used.

Brassica forage may be included in pigs’ diet as a dietary fiber ingredient to reduce feeding costs, benefit gut health, immune system, reproductive traits, and welfare. However, they contain antinutritional factors which may affect feeding behavior. This study evaluated feeding behavior of growing pigs offered winter (kale and swede) and summer (turnip and forage rape) brassicas incorporated on their diets as dried ground meal. Two consecutive experiments with six growing castrated male pigs were conducted. Experiment 1 evaluated the inclusion of turnip bulbs and forage rape, while experiment 2 studied inclusion of kale and swede bulbs. Brassica meal was included at 15% of the diet by replacing wheat middlings (control diet). In each experiment, pigs were offered experimental diets over six consecutive days for 10 min to test their acceptability (day 1–3) and preferences (day 4–6). No differences were found between diets that included brassicas and control diet in pigs’ acceptability or palatability (p > 0.05). However, during preference tests of winter brassicas, swede presented a higher consumption than control and kale (p < 0.05). This suggest that brassicas may be incorporated in growing pigs’ diets without negative effects in animals’ oral perception during short term feeding tests. Nevertheless, the long-term effects need to be explored.

Pesticides cause severe environmental damage to marine ecosystems. In the last ten years, cypermethrin has been extensively used as an antiparasitic pesticide in the salmon farming industry located in Northern Patagonia. The objective of this study was the biochemical and genomic characterization of cypermethrin-degrading and biosurfactant-producing bacterial strains isolated from cypermethrin-contaminated marine sediment samples collected in southern Chile (MS). Eleven strains were isolated by cypermethrin enrichment culture techniques and were identified by 16S rDNA gene sequencing analyses. The highest growth rate on cypermethrin was observed in four isolates (MS13, MS15a, MS16, and MS19) that also exhibited high levels of biosurfactant production. Genome sequence analyses of these isolates revealed the presence of genes encoding components of bacterial secondary metabolism, and the enzymes esterase, pyrethroid hydrolase, and laccase, which have been associated with different biodegradation pathways of cypermethrin. These novel cypermethrin-degrading and biosurfactant-producing bacterial isolates have a biotechnological potential for biodegradation of cypermethrin-contaminated marine sediments, and their genomes contribute to the understanding of microbial lifestyles in these extreme environments.

Piglets can prefer flavors that are presented to pregnant sows, hence this study intended to estimate the effect of prenatal exposure of piglets to flavors on the intake of flavored creep feed and performance. Gestational sows were fed either a flavored (garlic or aniseed; n24) or an unflavored diet (n24) from days 90 to 114 of gestation. Their litters were offered either garlic, aniseed, or unflavored creep feed during the suckling period, and its intake was measured as well as animal’s final body weight (BW) and average daily gain (ADG). Data was analyzed taking into account the diet offered to both sows and piglets, as well as the interaction between these variables. As previous experiments have shown, flavor learning did not affect a piglet’s performance during the suckling period, finding no differences for creep feed intake, ADG, or BW according to diets (p > 0.05). Repeated exposure of piglets to previously learned flavors without clear post-ingestive benefits could nullify the strategies proposed. Moreover, milk and creep feed diets show a great reward contrast that may accelerate learning extinction. Results of the present and previous experiments suggest that current flavor continuity strategies that are proposed for pig production systems need to be reconsidered.

A ten-year database of food preference tests (n = 1021; period 2007−2017) was used to explore the feeding behavior of domestic cats. Principal component (PC) analysis and linear regression between food nutrients and preferences (for the most preferred diet of each test; Diet A) were performed. Intake and preference for Diet A were analyzed by intrinsic cats’ variables and climate season. The PC1 (calcium (Ca), phosphorus (P), and ash), PC2 (lipids and ether extract) and PC4 (crude fiber; CF) had borderline significance (p < 0.06; β = −1.42, β = −1.56, and β = 2.68, respectively). Ash and CF contents presented negative correlations with food preference (rho = −0.269, p = 0.031; rho = −0.338, p = 0.006, respectively), and Ca had borderline significance and negative correlation with food preference (rho = −0.241, p = 0.054). Body weight and sex influenced the intake of Diet A, being lower for females (β = 11.758; p = 0.014) and heaviest cats (β = −5.490; p < 0.001). However, only body weight affected food preferences, where the heaviest cats had greater preferences for Diet A. Hot season decreased food intake (β = −2,117; p = 0.032), mostly in females (rho = −3.537; p = 0.002). Males had greater preferences for Diet A during hot seasons (β = 10.216; p = 0.023) and females presented similar preferences throughout the year (p = 0.950). Mineral contents, body weight and sex affected food intake and preferences of cats under the influence of climate season, probably explained by adaptive changes in food detection.

Pigs show an innate preference for umami (monosodium glutamate, MSG) taste. Nevertheless, the influence of a pre and postnatal umami exposure remains unclear. An experiment was conducted to test the hypothesis that MSG inclusion into maternal diets would modify the feeding behavior of post-weaning pigs. A total of 22 sows were selected on day 85 of gestation and randomly assigned to one of two gestating and lactating programs (standard commercial diets without or with 50 g/kg of MSG). Later, 208 pigs born from these sows were selected to evaluate their preference thresholds, sensory-motivated intake, total consumption, and consumption patterns for MSG and sucrose solutions. Pigs born from MSG-fed sows showed lower (p < 0.045) preference thresholds for MSG and sucrose than did animals born from control sows, and displayed an increased (p < 0.050) sensory-motivated intake for sucrose and decreased for MSG. Conversely, no differences (p > 0.05) were observed in the total consumption or consumption patterns of MSG or sucrose solutions among pigs born from control and MSG-fed sows. It is concluded that the feeding behavior of nursery pigs can be influenced by pre and postnatal inclusion of a taste active compound into maternal diets. It would appear that a compensatory mechanism to balance dietary nutrients might be in place.

A ten-year food preference database (2007−2017) was used to relate food selection in dogs to the nutritional components of diets by doing a principal component analysis (PCA) and a linear regression between components obtained and dogs’ preferences. Intake and preference of preferred diets were analyzed by dogs’ sex, breed, age, body weight, and the season of the year (hot or cold). The fourth component after PCA presented a relation with food preferences (OR = −2.699, p = 0.026), showing negative correlations with crude fiber (rho = −0.196; P = 0.038) and dry matter (rho = −0.184; p = 0.049). Weight (OR = −1.35; p < 0.001), breed, both Boxer (OR = 10.62; p = 0.003) and Labrador Retriever (OR = 26.30; p < 0.001), and season (hot season) (OR = −5.27; p < 0.001) all influenced animals’ intake. Boxers presented a lower food preference compared to the other breeds (OR = −44.3; p < 0.001), while animals’ weight influenced preferences only in Boxers (OR = 2.02; p < 0.001). Finally, age and sex did not affect dogs’ preference or intake of preferred diets. Thus dry matter and fiber content have a negative impact on dogs’ food choices. Dogs’ weight, breed, and season affected food intake, but only breed affected dogs’ preferences, which is probably explained by adaptive changes in the detection, metabolization, and learning of nutritive food cues.

Here we show the cloning and characterization of a novel homolog of prepro C-RFa cDNA from Cyprinus carpió. The deduced preprohormone precursor of 115 amino acids leads to a mature bioactive peptide of 20 amino acids with identical sequence to other teleost C-RFa. Modeling of the mature C-RFa peptide highlighted significant similarity to homologous human PrRP20, specifically the conserved amphipathic system defined by the C-terminal alpha-helix. Clearly, the synthetic C-RFa peptide stimulated prolactin release from primary cultured fish pituitary cells. For the first time, significant variation was shown in C-RFa mRNA and protein levels in the hypothalamus and pituitary between summer- and winter-acclimatized carp. Furthermore, C-RFa protein distribution in carp central nervous tissue was visualized by immunodetection in fibers and cells in hypothalamus, olfactory tract, cerebellum and pituitary stalk. In conclusion, we demonstrated the structure conservation of C-RFa in teleosts and mammals and immunopositive cells and fibers for C-RFa in brain areas. Finally, the increase of C-RFa expression suggests the participation of this hypothalamic factor in the mechanism of modulation in PRL expression in carp.

En este artículo se revisa el caso clínico de una yegua de 60 meses de edad aproximada, la cual meses atrás según el propietario del animal estuvo perdida, encontrándose después en una zona pantanosa en el Municipio de la Montañita con una cría y en una condición corporal paupérrima.

El tricobezoar es una concreción de cabellos que se puede encontrar en el tracto digestivo humano debido a tricofagia y que puede causar una gran variedad de signos y síntomas hasta llegar a la oclusión, perforación o ulceración del tracto digestivo; su incidencia es bastante rara, y suele ocurriren pacientes con problemas siquiátricos de sexo femenino. El tratamiento de esta entidad es muy variado, desde la sola extracción o/y fragmentación endoscopica o quirúrgica hasta la reparación o resección intestinal.Se presenta el caso de una paciente femenina del Hospital Erasmo Meoz de la ciudad de San José de Cúcuta en su puerperio tardío con un tricobezoar gástrico y que aparentemente no poseía un trastorno de base ni sintomatología relacionada previa al embarazo.

We isolated and cloned a carp somatolactin SL DNA fragment, of which 78% of the nucleotides were identical to the corresponding salmon SL sequence. The results obtained upon Northern blot hybridization of carp pituitary RNA allowed the identification of two transcripts as described for other fish. When the content of SL transcripts in pituitary sections from summer- and winter- acclimatized carp was quantified by in situ hybridization assays, we found no significant differences between the two seasons. In salmonids, plasma SL reaches higher levels in summer than in winter in synchrony with the water temperature cycle; in the eurythermal carp, however, the complex adaptive responses imposed by seasonal environmental changes do not seem to include the regulation of the somatolactin detected with the probe used at the transcriptional level in pituitary glands

Introducción: Staphylococcus aureus es un importante patógeno involucrado en una serie de infecciones cuyo impacto se incrementa por sus múltiples factores de virulencia y su resistencia a los antimicrobianos. La resistencia a clindamicina inducida por eritromicina constituye un problema creciente en diversas partes del mundo. Objetivos: determinar la frecuencia de resistencia a clindamicina inducida por eritromicina en Staphylococcus aureus aislados de 3 hospitales de Lima Metropolitana, la presencia de de cepas SAMR MLSBi y su relación con el origen biológico de las cepas. Material y método: entre mayo del 2005 y septiembre del 2006, se estudiaron 272 cepas de Staphylococcus aureus procedentes del Hospital Nacional Cayetano Heredia, Instituto Nacional de Enfermedades Neoplásicas e Instituto Nacional de Salud del Niño. Se determinó la resistencia a meticilina por el método Oxacillin Agar Screen, y la resistencia inducida a clindamicina usando el ensayo de inhibición por doble disco difusión en agar (D-Test). Se determinaron los fenotipos de MLSBi Resultados: se detectaron 13 cepas D-Test positivo, de las cuales 9 (3,3%) fueron SAMS y 4 cepas fueron SAMR (1,5%). La resistencia total a clindamicina (constitutiva e inducida) representa el 48,2% del total de cepas evaluadas. Conclusiones: la frecuencia de resistencia inducida a clindamicina en cepas de Staphylococcus aureus nuestro país es aún baja tanto en cepas sensibles como resistentes a meticilina.

Brachyury is an oncogenic transcription factor whose overexpression drives chordoma growth. The downmodulation of brachyury in chordoma cells has demonstrated therapeutic potential, however, as a transcription factor it is classically deemed "undruggable". Given that direct pharmacological intervention against brachyury has proven difficult, attempts at intervention have instead targeted upstream kinases. Recently, afatinib, an FDA‐approved kinase inhibitor, has been shown to modulate brachyury levels in multiple chordoma cell lines. Herein, we use afatinib as a lead to undertake a structure‐based drug design approach, aided by mass‐spectrometry and X‐ray crystallography, to develop DHC‐156, a small molecule that more selectively binds brachyury and downmodulates it as potently as afatinib. We eliminated kinase‐inhibition from this novel scaffold while demonstrating that DHC‐156 induces the post‐translational downmodulation of brachyury that results in an irreversible impairment of chordoma tumor cell growth. In doing so, we demonstrate the feasibility of direct brachyury modulation, which may further be developed into more potent tool compounds and therapies. [ABSTRACT FROM AUTHOR]