While calpains have been implicated in neurogenesis for a long time, there is still little information regarding the specific contributions of various isoforms in this process. We took advantage of the availability of mutant mice with complete deletion of calpain-1 to analyze its contribution to neurogenesis. We first used the incorporation of BrdU in newly-generated cells in the subgranular zone of the dentate gyrus to determine the role of calpain-1 deletion in neuronal proliferation. Our results showed that the lack of calpain-1 decreased the rate of cell proliferation in adult hippocampus. R788 cost As previously shown, it also decreased the long-term survival of newly-generated neurons. We also used data from previously reported RNA and miRNA sequencing analyses to identify differentially expressed genes in brain of calpain-1 knock-out mice related to cell division, cell migration, cell proliferation and cell survival. A number of differentially expressed genes were identified, which could play a significant role in the changes in neurogenesis in calpain-1 knock out mice. The results provide new information regarding the role of calpain-1 in neurogenesis and have implications for better understanding the pathologies associated with calpain-1 mutations in humans.Objective To investigate changes in the urine metabolome of very low birth weight preterm newborns with necrotizing enterocolitis (NEC) and feed intolerance, we conducted a longitudinal study over the first 2 months of life. The metabolome of NEC newborns was compared with two control groups that did not develop NEC the first one included preterm babies with feed intolerance, while the second one preterm babies with good feed tolerance. Methods Newborns developing NEC within the 3 weeks of life were identified as early onset NEC, while the remaining as late onset NEC. Case-control matching was done according to the gestational age (±1 week), birth weight (± 200 g), and postnatal age. A total of 96 urine samples were collected and analyzed. In newborns with NEC, samples were collected before, during and after the diagnosis over the first 2 months of life, while in controls samples were collected as close as possible to the postnatal age of newborns with NEC. Proton nuclear magnetic resonance (1H NMR) spectroscopy was used for metabolomic analysis. Data were analyzed by univariate and multivariate statistical analysis. Results In all the preterm newborns, urine levels of betaine, glycine, succinate, and citrate positively correlated with postnatal age. Suberate and lactate correlated with postnatal age in preterms with NEC and in controls with food intolerance, while N,N-dimethylglycine (N,N-DMG) correlated only in controls with good digestive tolerance. Preterm controls with feed intolerance showed a progressive significant decrease of N-methylnicotinamide and carnitine. Lactate, betaine, myo-inositol, urea, creatinine, and N,N-dimethylglycine discriminated late-onset NEC from controls with good feed tolerance. Conclusion Our findings are discussed in terms of contributions from nutritional and clinical managements of patients and gut microbiota.The oil sands region in northeastern Alberta, Canada contain approximately 165 billion barrels of oil making it the third largest oil reserves in the world. However, processing of extracted bitumen generates vast amounts of toxic byproduct known as oil sands process waters. Naphthenic acids and associated sodium naphthenate salts are considered the primary toxic component of oil sands process waters. Although a significant body of work has been conducted on naphthenic acid toxicity at levels comparable to what is observed in current oil sands process waters, it is also important to understand any impacts of exposure to sublethal concentrations. We conducted a microcosm study using the mayfly Hexagenia spp. to identify sublethal impacts of naphthenic acid exposure on the survival, growth, and metabolome across a concentration gradient (0-100 μg L-1) of sodium naphthenate. Nuclear magnetic resonance-based metabolomic analyses were completed on both the polar and lipophilic extracted fractions of whole organism sms. Results of this research will assist in the determination of appropriate discharge thresholds should oil sands process waters be considered for environmental release.TSPO-associated protein 1 (TSPOAP1) is a cytoplasmic protein and is closely associated with its mitochondrial transmembrane protein partner translocator protein (TSPO). To decipher the canonical signalling pathways of TSPOAP1, its role in human diseases and disorders, and relationship with TSPO; expression analyses of TSPOAP1- and TSPO-associated human genes were performed by Qiagen Ingenuity Pathway Analysis (IPA). In the expression analysis, necroptosis and sirtuin signalling pathways, mitochondrial dysfunction, and inflammasome were the top canonical pathways for both TSPOAP1 and TSPO, confirming the close relationship between these two proteins. A distribution analysis of common proteins in all the canonical pathways predicted for TSPOAP1 revealed that tumor necrosis factor receptor 1 (TNFR1), vascular cell adhesion molecule 1 (VCAM1), cyclic AMP response element-binding protein 1 (CREB1), T-cell receptor (TCR), nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3 (NLRP3), DNA-dependent protein kinase (DNA-PK or PRKDC), and mitochondrial permeability transition pore (mPTP) were the major interaction partners of TSPOAP1, highlighting the role of TSPOAP1 in inflammation, particularly neuroinflammation. An analysis of the overlap between TSPO and TSPOAP1 Homo sapiens genes and top-ranked canonical pathways indicated that TSPO and TSPOAP1 interact via voltage-dependent anion-selective channels (VDAC1/2/3). A heat map analysis indicated that TSPOAP1 has critical roles in inflammatory, neuroinflammatory, psychiatric, and metabolic diseases and disorders, and cancer. Taken together, this information improves our understanding of the mechanism of action and biological functions of TSPOAP1 as well as its relationship with TSPO; furthermore, these results could provide new directions for in-depth functional studies of TSPOAP1 aimed at unmasking its detailed functions.