Surgical castration with pain relief affects the health and productive performance of pigs in the suckling period

peer-reviewedBackground Surgical castration is still practiced in many EU countries to avoid undesirable aggressive behavior and boar taint in male pigs. However, evidence shows that castration is painful and has a detrimental influence on pig health. This study investigated the clinical and productive effects of surgical castration in the suckling period. A total of 3696 male pigs, 3 to 6 days old, comprising of 721 litters from two different farms were included in the study. Within each litter, half of the males were kept as intact males (IM) and half were surgically castrated (CM). Surgical castration was conducted by a trained farmer. Average daily gain (ADG), body weight at weaning (BWW), percentage of pre-weaning mortality (PWM) and antibiotic usage were measured. Pig major acute phase protein (PigMAP) serum concentrations were analyzed prior to castration, and on days 1 and 10 after castration. Productive performance data were analyzed using a linear mixed model. Mortality and percentage of pigs treated with antibiotics were analyzed using the Fisher’s exact test. Results No overall differences in BWW and ADG were observed between the two groups. However, differences were observed when the same effects were analyzed in the 25% lightest, 50% medium and 25% heaviest pigs at birth. PWM was higher in CM than in IM groups (6.3% vs 3.6%; p < 0.001), especially in the light (12.2% vs 6.2%; p = 0.02) and in the medium (5.5% vs 2.7%; p = 0.04) weight groups. In the heaviest pigs group PWM was not affected by castration, but IM tended to show higher ADG (p = 0.06) and showed higher BWW (8.0 kg vs 7.8 kg; p = 0.05) than CM. There were no differences in percentage of pigs treated with antibiotics between the two groups (5.8% vs 5.8%; p = 0.98) in this study. Furthermore, PigMAP was increased in CM the day after castration (0.944 mg/ml vs 0.847 mg/ml; p = 0.025), but there was no difference between CM and IM groups at day 10. Conclusions Surgical castration has a negative impact on production in the suckling period because it causes an increase in PWM, especially in pigs in the three lower quartiles for body weight, and negatively affects the BWW in pigs born in the highest quartile for body weight

Oligodendroglia-derived extracellular vesicles activate autophagy via LC3B/BAG3 to protect against oxidative stress with an enhanced effect for HSPB8 enriched vesicles

BACKGROUND: The contribution of native or modified oligodendroglia-derived extracellular vesicles (OL-EVs) in controlling chronic inflammation is poorly understood. In activated microglia, OL-EVs contribute to the removal of cytotoxic proteins following a proteotoxic stress. Intracellular small heat shock protein B8 (HSPB8) sustain this function by facilitating autophagy and protecting cells against oxidative stress mediated cell death. Therefore, secretion of HSPB8 in OL-EVs could be beneficial for neurons during chronic inflammation. However, how secreted HSPB8 contribute to cellular proteostasis remains to be elucidated. METHODS: We produced oligodendroglia-derived EVs, either native (OL-EVs) or HSPB8 modified (OL-HSPB8-EVs), to investigate their effects in controlling chronic inflammation and cellular homeostasis. We analyzed the impact of both EV subsets on either a resting or activated microglial cell line and on primary mixed neural cell culture cells. Cells were activated by stimulating with either tumor necrosis factor-alpha and interleukin 1-beta or with phorbol-12-myristate-13-acetate. RESULTS: We show that OL-EVs and modified OL-HSPB8-EVs are internalized by C20 microglia and by primary mixed neural cells. The cellular uptake of OL-HSPB8-EVs increases the endogenous HSPB8 mRNA expression. Consistently, our results revealed that both EV subsets maintained cellular homeostasis during chronic inflammation with an increase in the formation of autophagic vesicles. Both EV subsets conveyed LC3B-II and BAG3 autophagy markers with an enhanced effect observed for OL-HSPB8-EVs. Moreover, stimulation with either native or modified OL-HSPB8-EVs showed a significant reduction in ubiquitinated protein, reactive oxygen species and mitochondrial depolarization, with OL-HSPB8-EVs exhibiting a more protective effect. Both EV subsets did not induce cell death in the C20 microglia cell line or the primary mixed neural cultures. CONCLUSION: We demonstrate that the functions of oligodendroglia secreted EVs enriched with HSPB8 have a supportive role, comparable to the native OL-EVs. Further development of engineered oligodendroglia derived EVs could be a novel therapeutic strategy in countering chronic inflammation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12964-022-00863-x

Translocations disrupting PHF21A in the Potocki-Shaffer-syndrome region are associated with intellectual disability and craniofacial anomalies

Contains fulltext : 110038.pdf (publisher's version ) (Closed access)Potocki-Shaffer syndrome (PSS) is a contiguous gene disorder due to the interstitial deletion of band p11.2 of chromosome 11 and is characterized by multiple exostoses, parietal foramina, intellectual disability (ID), and craniofacial anomalies (CFAs). Despite the identification of individual genes responsible for multiple exostoses and parietal foramina in PSS, the identity of the gene(s) associated with the ID and CFA phenotypes has remained elusive. Through characterization of independent subjects with balanced translocations and supportive comparative deletion mapping of PSS subjects, we have uncovered evidence that the ID and CFA phenotypes are both caused by haploinsufficiency of a single gene, PHF21A, at 11p11.2. PHF21A encodes a plant homeodomain finger protein whose murine and zebrafish orthologs are both expressed in a manner consistent with a function in neurofacial and craniofacial development, and suppression of the latter led to both craniofacial abnormalities and neuronal apoptosis. Along with lysine-specific demethylase 1 (LSD1), PHF21A, also known as BHC80, is a component of the BRAF-histone deacetylase complex that represses target-gene transcription. In lymphoblastoid cell lines from two translocation subjects in whom PHF21A was directly disrupted by the respective breakpoints, we observed derepression of the neuronal gene SCN3A and reduced LSD1 occupancy at the SCN3A promoter, supporting a direct functional consequence of PHF21A haploinsufficiency on transcriptional regulation. Our finding that disruption of PHF21A by translocations in the PSS region is associated with ID adds to the growing list of ID-associated genes that emphasize the critical role of transcriptional regulation and chromatin remodeling in normal brain development and cognitive function