The mTORC1/4E-BP pathway coordinates hemoglobin production with L-leucine availability

In multicellular organisms, the mechanisms by which diverse cell types acquire distinct amino acids and how cellular function adapts to their availability are fundamental questions in biology. We found that increased neutral essential amino acid (NEAA) uptake was a critical component of erythropoiesis. As red blood cells matured, expression of the amino acid transporter gene Lat3 increased, which increased NEAA import. Inadequate NEAA uptake by pharmacologic inhibition or RNAi-mediated knockdown of LAT3 triggered a specific reduction in hemoglobin production in zebrafish embryos and murine erythroid cells through the mTORC1 (mammalian target of rapamycin complex 1)/4E-BP (eukaryotic translation initiation factor 4E–binding protein) pathway. CRISPR-mediated deletion of members of the 4E-BP family in murine erythroid cells rendered them resistant to mTORC1 and LAT3 inhibition and restored hemoglobin production. These results identify a developmental role for LAT3 in red blood cells and demonstrate that mTORC1 serves as a homeostatic sensor that couples hemoglobin production at the translational level to sufficient uptake of NEAAs, particularly L-leucine.National Institutes of Health (U.S.) (P01 HL032262

The mTORC1/4E-BP pathway coordinates hemoglobin production with L-leucine availability

In multicellular organisms, the mechanisms by which diverse cell types acquire distinct amino acids and how cellular function adapts to their availability are fundamental questions in biology. We found that increased neutral essential amino acid (NEAA) uptake was a critical component of erythropoiesis. As red blood cells matured, expression of the amino acid transporter gene Lat3 increased, which increased NEAA import. Inadequate NEAA uptake by pharmacologic inhibition or RNAi-mediated knockdown of LAT3 triggered a specific reduction in hemoglobin production in zebrafish embryos and murine erythroid cells through the mTORC1 (mammalian target of rapamycin complex 1)/4E-BP (eukaryotic translation initiation factor 4E–binding protein) pathway. CRISPR-mediated deletion of members of the 4E-BP family in murine erythroid cells rendered them resistant to mTORC1 and LAT3 inhibition and restored hemoglobin production. These results identify a developmental role for LAT3 in red blood cells and demonstrate that mTORC1 serves as a homeostatic sensor that couples hemoglobin production at the translational level to sufficient uptake of NEAAs, particularly L-leucine

Monitoring individual behaviours and the social hierarchy of dairy cows using electronic drinkers

International audienceFreedom from thirst is a key criterion for dairy cattle welfare but little is known about how competition at the drinker influences the water access of different individuals in a group. Recently, automated methods had been validated to record the individual drinking behaviour of cows and competition at the drinker. However, it is not known if competition at the drinker provides suitable data for identifying the dominance hierarchy in cow groups. We monitored agonistic interactions and drinking behaviour in a group of 22 lactating Holstein dairy cows for 9 consecutive days by video recording and with 6 electronic drinkers. 691 agonistic interactions were identified by video observation during this period, including 299 events at the drinkers. We used the Normalized David’s Score to calculate the dominance score of each cow based on all observed agonistic interactions (Complete DS) and then based on those only at the drinker (Drinker DS). The social ranks of individuals were highly correlated between hierarchies (Pearson’s r=0.82), suggesting that the social hierarchy can be identified using agonistic interactions at drinkers. We further categorized agonistic interactions at drinkers that can potentially be detected based on automated drinker data (i.e. replacements; aggressive contact from the actor cow that resulted in the recipient leaving the drinker and the actor occupying the place within 60s). Replacements (n=235) were used to determine each cow’s social rank (Replacement DS) and found that it was highly correlated with the Drinker DS (Pearson’s r=0.75). Our results indicate that drinkers can be used to identify the dominance position of cows, allowing for the monitoring of the drinking behaviour of cows with a low social rank

Alexithymia partly predicts pain, poor health and social difficulties in patients with temporomandibular disorders

Temporomandibular disorders (TMD) are functional diseases of the masticatory system; their symptoms are clicking, difficulty opening the mouth wide, ear pain, facial pain and headaches. The relationships among distress, emotional factors and TMD are well known. It was shown that patients with TMD have little awareness of their inner states and emotions, and it was found that those reporting oro-facial pain presented higher alexithymia than did asymptomatic people. Other authors confirmed that alexithymia was higher in the painful TMD group than controls. This study was aimed to evaluate whether alexithymia and its components can be considered as predisposing factors for pain severity, poor health and greater social difficulties in patients with TMD. One hundred thirty-three patients received a diagnosis of TMD and completed the 20-item Toronto Alexithymia Scale. Multiple stepwise regressions showed that alexithymia and age explained 10% of the pain and 31% of poor health and also that alexithymia explained 7% of social difficulty. A direct comparison of patients with TMD based on alexithymia revealed a higher presence of pain in alexithymic patients with TMD than in those characterised by moderate or no alexithymia. In conclusion, alexithymia partly predicts pain, poor health and social difficulties in patients with TMD. Furthermore, alexithymic patients have more pain than those with moderate or low alexithymia

Effects of Bovine Somatotropin and Revalor-S® on Growth Performance and Carcass Leanness in Beef Cattle

Twenty crossbred steers were used to evaluate bovine somatotropin (bST) and an anabolic steroid implant, Revalor-S® (REV), to improve growth and increase carcass leanness. During the first 70 days on feed, bST-treated steers tended to improve live weight gains, consume more feed, and numerically improve feed utilization for growth. The implanted steers grew faster and utilized feed better than steers not implanted with REV. The improvement in gain and feed utilization for growth was maintained throughout the feeding period for REV-implanted steers. At slaughter, REV steers had heavier carcasses which resulted in more pounds of muscle, bone, and fat. When adjusted for hot carcass weight, bST increased leanness of the carcass as evident by the increased weight of the semitendinosus muscle, more pounds of dissected lean, and fewer pounds of dissected fat. Thus, REV and bST can be used to improve growth performance and increase carcass leanness