Breeding for resilience in finishing pigs can decrease tail biting, lameness and mortality.

BACKGROUND: Previous research showed that deviations in longitudinal data are heritable and can be used as a proxy for pigs' general resilience. However, only a few studies investigated the relationship between these resilience traits and other traits related to resilience and welfare. Therefore, this study investigated the relationship between resilience traits derived from deviations in longitudinal data and traits related to animal resilience, health and welfare, such as tail and ear biting wounds, lameness and mortality. RESULTS: In our experiment, 1919 finishing pigs with known pedigree (133 Piétrain sires and 266 crossbred dams) were weighed every 2 weeks and scored for physical abnormalities, such as lameness and ear and tail biting wounds (17,066 records). Resilience was assessed via deviations in body weight, deviations in weighing order and deviations in observed activity during weighing. The association between these resilience traits and physical abnormality traits was investigated and genetic parameters were estimated. Deviations in body weight had moderate heritability estimates (h2 = 25.2 to 36.3%), whereas deviations in weighing order (h2 = 4.2%) and deviations in activity during weighing (h2 = 12.0%) had low heritability estimates. Moreover, deviations in body weight were positively associated and genetically correlated with tail biting wounds (rg = 0.22 to 0.30), lameness (rg = 0.15 to 0.31) and mortality (rg = 0.19 to 0.33). These results indicate that events of tail biting, lameness and mortality are associated with deviations in pigs' body weight evolution. This relationship was not found for deviations in weighing order and activity during weighing. Furthermore, individual body weight deviations were positively correlated with uniformity at the pen level, providing evidence that breeding for these resilience traits might increase both pigs' resilience and within-family uniformity. CONCLUSIONS: In summary, our findings show that breeding for resilience traits based on deviations in longitudinal weight data can decrease pigs' tail biting wounds, lameness and mortality while improving uniformity at the pen level. These findings are valuable for pig breeders, as they offer evidence that these resilience traits are an indication of animals' general health, welfare and resilience. Moreover, these results will stimulate the quantification of resilience via longitudinal body weights in other species.

miRNa signature in small extracellular vesicles and their association with platinum resistance and cancer recurrence in ovarian cancer.

Carboplatin, administered as a single drug or in combination with paclitaxel, is the standard chemotherapy treatment for patients with ovarian cancer (OVCA). Recent evidence suggests that miRNAs associated with small extracellular vesicles (sEVs) participate in the development of chemoresistance. We studied the effect of carboplatin in a heterogeneity population of OVCA cells and their derived sEVs to identify mechanisms associated with chemoresistance. sEVs were quantified using an engineered superparamagnetic material, gold-loaded ferric oxide nanotubes and a screen-printed electrode. miR-21-3p, miR-21-5p, and miR-891-5p are enriched in sEVs, and they contribute to carboplatin resistance in OVCA. Using a quantitative MS/MS, miR-21-5p activates glycolysis and increases the expression of ATP-binding cassette family and a detoxification enzyme. miR-21-3p and miR-891-5p increase the expression of proteins involved in DNA repair mechanisms. Interestingly, the levels of miR-891-5p within sEVs are significantly higher in patients at risk of ovarian cancer relapse. Identification of miRNAs in sEVs also provides the opportunity to track them in biological fluids to potentially determine patient response to chemotherapy.

Burkitt Lymphoma With Aberrant Expression of Cytoplasmic Terminal Deoxynucleotidyl Transferase: A Case Report.

This study describes a rare case of Burkitt lymphoma with aberrant expression of cytoplasmic terminal deoxynucleotidyl transferase (TdT). Flow cytometry demonstrated a predominantly mature B cell immunophenotype as expected for Burkitt lymphoma, however, the immature marker TdT was also expressed. Immunohistochemistry showed that TdT was localized to the cytoplasm, with absent nuclear localization. The patient received standard intensive chemotherapy for Burkitt lymphoma and has remained in remission for nine years. Pathologists should be aware of this unusual phenomenon of aberrant cytoplasmic TdT expression to avoid confusing Burkitt lymphoma with B cell lymphoblastic leukemia/lymphoma.

BAMBI: A new method for automated assessment of bidirectional early-life interaction between maternal behavior and pup vocalization in mouse dam-pup dyads.

Vital early-life dyadic interaction in mice requires a pup to signal its needs adequately, and a dam to recognize and respond to the pup's cues accurately and timely. Previous research might have missed important biological and/or environmental elements of this complex bidirectional interaction, because it often focused on one dyadic member only. In laboratory rodents, the Pup Retrieval Test (PRT) is the leading procedure to assess pup-directed maternal care. The present study describes BAMBI (Bidirectional Automated Mother-pup Behavioral Interaction test), a novel automated PRT methodology based on synchronous video recording of maternal behavior and audio recording of pup vocalizations, which allows to assess bidirectional dam-pup dyadic interaction. We were able to estimate pup retrieval and pup vocalization parameters accurately in 156 pups from 29 dams on postnatal days (PND) 5, 7, 9, 11, and 13. Moreover, we showed an association between number of emitted USVs and retrieval success, indicating dyadic interdependency and bidirectionality. BAMBI is a promising new automated home-cage behavioral method that can be applied to both basic and preclinical studies investigating complex phenotypes related to early-life social development.

A promising resilience parameter for breeding: the use of weight and feed trajectories in growing pigs.

BACKGROUND: Increasing resilience is a priority in modern pig breeding. Recent research shows that general resilience can be quantified via variability in longitudinal data. The collection of such longitudinal data on weight, feed intake and feeding behaviour in pigs has been facilitated by the development of technologies such as automated feeding stations. The goal of this study was to investigate resilience traits, which were estimated as deviations from longitudinal weight, feed intake and feeding behaviour data during the finishing phase. A dataset with 324,207 records between the age of 95 and 155 days on 5,939 Piétrain pigs with known pedigree and genomic information was used. We provided guidelines for a rigid quality control of longitudinal body weight data, as we found that outliers can significantly affect results. Gompertz growth curve analysis, linear modelling and trajectory analyses were used for quantifying resilience traits. RESULTS: To our knowledge, this is the first study comparing resilience traits from longitudinal body weight, feed intake and feeding behaviour data in pigs. We demonstrated that the resilience traits are lowly to moderately heritable for deviations in body weight (h2 = 2.9%-20.2%), in feed intake (9.4%-23.3%) and in feeding behaviour (16.2%-28.3%). Additionally, these traits have good predictive abilities in cross-validation analyses. Deviations in individual body weight and feed intake trajectories are highly correlated (rg = 0.78) with low to moderate favourable genetic correlations with feed conversion ratio (rg = 0.39-0.49). Lastly, we showed that some resilience traits, such as the natural logarithm of variances of observed versus predicted body weights (lnvarweight), are more robust to lower observation frequencies and are repeatable over three different time periods of the finishing phase. CONCLUSIONS: Our results will help future studies investigating resilience traits and resilience-related traits. Moreover, our study provides first results on standardization of quality control and efficient data sampling from automated feeding station data. Our findings will be valuable for breeding organizations as they offer evidence that pigs' general resilience can be selected on with good accuracy. Moreover, this methodology might be extended to other species to quantify resilience based on longitudinal data.

Automated procedure to assess pup retrieval in laboratory mice.

All mammalian mothers form some sort of caring bond with their infants that is crucial to the development of their offspring. The Pup Retrieval Test (PRT) is the leading procedure to assess pup-directed maternal care in laboratory rodents, used in a wide range of basic and preclinical research applications. Most PRT protocols require manual scoring, which is prone to bias and spatial and temporal inaccuracies. This study proposes a novel procedure using machine learning algorithms to enable reliable assessment of PRT performance. Automated tracking of a dam and one pup was established in DeepLabCut and was combined with automated behavioral classification of "maternal approach", "carrying" and "digging" in Simple Behavioral Analysis (SimBA). Our automated procedure estimated retrieval success with an accuracy of 86.7%, whereas accuracies of "approach", "carry" and "digging" were estimated at respectively 99.3%, 98.6% and 85.0%. We provide an open-source, step-by-step protocol for automated PRT assessment, which aims to increase reproducibility and reliability, and can be easily shared and distributed.

Estimating genetics of body dimensions and activity levels in pigs using automated pose estimation.

Pig breeding is changing rapidly due to technological progress and socio-ecological factors. New precision livestock farming technologies such as computer vision systems are crucial for automated phenotyping on a large scale for novel traits, as pigs' robustness and behavior are gaining importance in breeding goals. However, individual identification, data processing and the availability of adequate (open source) software currently pose the main hurdles. The overall goal of this study was to expand pig weighing with automated measurements of body dimensions and activity levels using an automated video-analytic system: DeepLabCut. Furthermore, these data were coupled with pedigree information to estimate genetic parameters for breeding programs. We analyzed 7428 recordings over the fattening period of 1556 finishing pigs (Piétrain sire x crossbred dam) with two-week intervals between recordings on the same pig. We were able to accurately estimate relevant body parts with an average tracking error of 3.3 cm. Body metrics extracted from video images were highly heritable (61-74%) and significantly genetically correlated with average daily gain (rg = 0.81-0.92). Activity traits were low to moderately heritable (22-35%) and showed low genetic correlations with production traits and physical abnormalities. We demonstrated a simple and cost-efficient method to extract body dimension parameters and activity traits. These traits were estimated to be heritable, and hence, can be selected on. These findings are valuable for (pig) breeding organizations, as they offer a method to automatically phenotype new production and behavioral traits on an individual level.

Extracellular Vesicle Transmission of Chemoresistance to Ovarian Cancer Cells Is Associated with Hypoxia-Induced Expression of Glycolytic Pathway Proteins, and Prediction of Epithelial Ovarian Cancer Disease Recurrence.

Hypoxia is a key regulator of cancer progression and chemoresistance. Ambiguity remains about how cancer cells adapt to hypoxic microenvironments and transfer oncogenic factors to surrounding cells. In this study, we determined the effects of hypoxia on the bioactivity of sEVs in a panel of ovarian cancer (OvCar) cell lines. The data obtained demonstrate a varying degree of platinum resistance induced in OvCar cells when exposed to low oxygen tension (1% oxygen). Using quantitative mass spectrometry (Sequential Window Acquisition of All Theoretical Fragment Ion Mass Spectra, SWATH) and targeted multiple reaction monitoring (MRM), we identified a suite of proteins associated with glycolysis that change under hypoxic conditions in cells and sEVs. Interestingly, we identified a differential response to hypoxia in the OvCar cell lines and their secreted sEVs, highlighting the cells' heterogeneity. Proteins are involved in metabolic reprogramming such as glycolysis, including putative hexokinase (HK), UDP-glucuronosyltransferase 1-6 (UD16), and 6-phosphogluconolactonase (6 PGL), and their presence correlates with the induction of platinum resistance. Furthermore, when normoxic cells were exposed to sEVs from hypoxic cells, platinum-resistance increased significantly (p < 0.05). Altered chemoresistance was associated with changes in glycolysis and fatty acid synthesis. Finally, sEVs isolated from a clinical cohort (n = 31) were also found to be enriched in glycolysis-pathway proteins, especially in patients with recurrent disease. These data support the hypothesis that hypoxia induces changes in sEVs composition and bioactivity that confers carboplatin resistance on target cells. Furthermore, we propose that the expression of sEV-associated glycolysis-pathway proteins is predictive of ovarian cancer recurrence and is of clinical utility in disease management.

Acute promyelocytic leukemia presenting with features of metastatic osseous disease.

Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia defined by a balanced translocation between chromosomes 15 and 17 resulting in fusion of the promyelocytic leukemia gene (PML) on chromosome 15 with the retinoic acid receptor-alpha gene (RARα) on chromosome 17. APL often presents with pancytopenia and is associated with a life threatening coagulopathy making prompt diagnosis and initiation of therapy critical. We report an unusual case of APL in a 59 year old female without peripheral blood abnormalities or diffuse marrow involvement. Clinical and radiographic findings were initially interpreted as metastatic osseous disease but ultimately found to be APL.