Preclinical Assessment of the Analgesic Pharmacology of NKTR-181 in Rodents

Cellular and Molecular Neurobiology - Pharmacological evaluation of the mu-opioid receptor (MOR) agonist properties of NKTR-181 in rodent models. Graded noxious stimulus intensities were used in...     

Valproate-Induced Epigenetic Upregulation of Hypothalamic Fto Expression Potentially Linked with Weight Gain

Cellular and Molecular Neurobiology - Valproate (VPA), a widely-used antiepileptic drug, is a selective inhibitor of histone deacetylase (HDAC) that play important roles in epigenetic regulation....     

Cultivation and biomass production of the diatom Thalassiosira weissflogii as a live feed for white-leg shrimp in hatcheries and commercial farms in Vietnam

This study investigated the biomass production process from the laboratory to the pilot scale in order to use the nutrient-rich biomass of the diatom Thalassiosira weissflogii as live feed for white-leg shrimp (Litopenaeus vannamei) at larval stages (zoeal, mysis, and postlarval) and in commercial production in hatcheries in Vietnam. Our results showed that T. weissflogii was successfully cultured in 1–2 L Erlenmeyer flasks, 0.2–3.5 m³ composite tanks, and 6.5 m³ tubular photobioreactors, with the highest cell density of 1.6 × 10⁶ cells mL^?1 reached after 6 days of culture. Under optimal culture conditions, the protein, lipid, and carbohydrate contents in this algal biomass were 13.2%, 20.0%, and 10.0% of dry cell weight, respectively. The fatty acid composition contains high amount of palmitic acid (C16:0, 43.11% of total fatty acid), and polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA, C20:5ω-3), approximated 16.5% of total fatty acid. In a 50 L larval rearing tank, at the optimal stocking density of 125 nauplii L^?1, the survival percentage (75.55%), the total body length (from 5.376 ± 0.007 to 10.860 ± 0.030 mm), and weight (at from PL₁ to PL₁₂ stages) (from 0.145 ± 0.002 to 1.158 ± 0.005 g) of the white-leg shrimp larvae reached the highest values but the metamorphosis time (234 h) was shortest compared with the other stocking densities. Further, adding living T. weissflogii biomass to the diet of white-leg shrimp larvae at the nauplii 6 stage led to an increase in the body length, weight, and survival percentage of white-leg shrimp larvae of 21.17%, 35.7%, and 33% higher compared with those of larvae fed the control diet (without the addition of T. weissflogii), respectively. At the same time, the metamorphosis time of larvae (from Z₁ to PL₁) decreased by 4 h compared to the control group. In intensive ponds (area of 6400 m² pond^?1), using seed stocks at the postlarvae 12 stage that had been fed T. weissflogii, the final weight, yield, and survival percentage of the shrimp were increased by 7.3%, 14.2%, and 16.3%, respectively, compared with those of the control group. There were no statistically significant differences in the protein and carbohydrate contents in the shrimp flesh among the experimental and control group (p > 0.05). The lipid, omega-3, omega-6, and omega-9 fatty acid contents of shrimp flesh in experiment formula (per 100 g shrimp) were 1.21 g, 72.9 mg, 114 mg, and 86.1 mg, 11%, 29%, 21.6%, and 17.7% higher than that those in control, respectively. The obtained results show the great potential of using T. weissflogii as live feed on white-leg shrimp farms in Vietnam.

     

Faecalicatena faecalis sp. nov., a moderately alkaliphilic bacterial strain isolated from swine faeces

An obligately anaerobic, Gram-stain-positive, non-motile, non-spore-forming and rod-shaped strain AGMB00832^T was isolated from swine faeces. Phylogenetic analysis based on the 16S rRNA gene, together with the housekeeping genes, gyrB and rpoD, revealed that strain AGMB00832^T belonged to the genus Faecalicatena and was most closely related to Faecalicatena orotica KCTC 15331^T. In biochemical analysis, strain AGMB00832^T was shown to be negative for catalase, oxidase and urease. Furthermore, the isolate was positive for β-glucosidase, β-glucuronidase, glutamic acid decarboxylase, proline arylamidase, acid phosphatase and naphthol-AS-BI-phosphohydrolase. The major cellular fatty acids (>?10%) of the isolate were C_14:0, C_16:0 and C_18:1ω11t DMA. Based on the whole genome sequence analysis, the DNA G?+?C content of strain AGMB00832^T was 44.2 mol%, and the genome size and numbers of rRNA and tRNA genes were 5,175,159 bp, 11 and 53, respectively. The average nucleotide identity and digital DNA–DNA hybridization values between strain AGMB00832^T and related strains were ≤?77.4 and 22.5%, respectively. Furthermore, the genome analysis revealed the presence of genes for alkaline shock protein 23 and cation/proton antiporters, which may facilitate growth of strain AGMB00832^T in alkaline culture condition. On the basis of polyphasic taxonomic approach, strain AGMB00832^T represents a novel species within the genus Faecalicatena, for which the name Faecalicatena faecalis sp. nov. is proposed. The type strain is AGMB00832^T (=?KCTC 15946^T?=?NBRC 114613^T).

     

Anaerocolumna sedimenticola sp. nov., isolated from fresh water sediment

Strain CBA3638^T was isolated from the Geum River sediment, Republic of Korea. The cells of strain CBA3638^T were Gram-stain-positive, strictly anaerobic, rod-shaped, and 0.5–1.0 μm wide, and 4.0–4.5 μm long. Optimal growth occurred at 37 °C, pH 7.0, and 1.0% (w/v) NaCl. Based on the 16S rRNA gene sequence, the phylogenetic analysis showed that strain CBA3638^T belongs to the genus Anaerocolumna in the family Lachnospiraceae, and is most closely related to Anaerocolumna cellulosilytica (94.6–95.0%). The DDH value with A. cellulosilytica SN021^T showed 15.0% relatedness. The genome of strain CBA3638^T consisted of one circular chromosome that is 5,500,435 bp long with a 36.7 mol% G?+?C content. The genome contained seven 16S-5S-23S rRNA operons and one antibiotic resistance-related transporter gene (mefA). Quinones were not detected. The predominant cellular fatty acids were C_16:0 and C_14:0 and the polar lipids were diphosphatidylglycerol, phosphatidylcholine, and uncharacterised polar lipids. Based on the polyphasic taxonomic analysis, we propose strain CBA3638^T as a novel species in the genus Anaerocolumna, with the name Anaerocolumna sedimenticola sp. nov. The type strain is CBA3638^T (=?KACC 21652^T?=?DSM 110663^T).

     

O-GlcNAc modification of nuclear pore complexes accelerates bidirectional transport

Macromolecular transport across the nuclear envelope depends on facilitated diffusion through nuclear pore complexes (NPCs). The interior of NPCs contains a permeability barrier made of phenylalanine-glycine (FG) repeat domains that selectively facilitates the permeation of cargoes bound to nuclear transport receptors (NTRs). FG-repeat domains in NPCs are a major site of O-linked N-acetylglucosamine (O-GlcNAc) modification, but the functional role of this modification in nucleocytoplasmic transport is unclear. We developed high-throughput assays based on optogenetic probes to quantify the kinetics of nuclear import and export in living human cells. We found that increasing O-GlcNAc modification of the NPC accelerated NTR-facilitated transport of proteins in both directions, and decreasing modification slowed transport. Superresolution imaging revealed strong enrichment of O-GlcNAc at the FG-repeat barrier. O-GlcNAc modification also accelerated passive permeation of a small, inert protein through NPCs. We conclude that O-GlcNAc modification accelerates nucleocytoplasmic transport by enhancing the nonspecific permeability of the FG-repeat barrier, perhaps by steric inhibition of interactions between FG repeats.     

ArfGAP1 inhibits mTORC1 lysosomal localization and activation

The mammalian target of rapamycin complex 1 (mTORC1) integrates nutrients, growth factors, stress, and energy status to regulate cell growth and metabolism. Amino acids promote mTORC1 lysosomal localization and subsequent activation. However, the subcellular location or interacting proteins of mTORC1 under amino acid‐deficient conditions is not completely understood. Here, we identify ADP‐ribosylation factor GTPase‐activating protein 1 (ArfGAP1) as a crucial regulator of mTORC1. ArfGAP1 interacts with mTORC1 in the absence of amino acids and inhibits mTORC1 lysosomal localization and activation. Mechanistically, the membrane curvature‐sensing amphipathic lipid packing sensor (ALPS) motifs that bind to vesicle membranes are crucial for ArfGAP1 to interact with and regulate mTORC1 activity. Importantly, ArfGAP1 represses cell growth through mTORC1 and is an independent prognostic factor for the overall survival of pancreatic cancer patients. Our study identifies ArfGAP1 as a critical regulator of mTORC1 that functions by preventing the lysosomal transport and activation of mTORC1, with potential for cancer therapeutics.