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The mTOR signaling pathway integrates signaling inputs from nutrients, including glucose and amino acids, which are precisely regulated by transporters depending on nutrient levels. The L-type amino acid transporter 1 (LAT1) affects the activity of mTORC1 through upstream regulators that sense intracellular amino acid levels. While mTORC1 activation by LAT1 has been thoroughly investigated in cultured cells, the effects of LAT1 expression on the activity of mTORC2 has scarcely been studied. Here, we provide evidence that LAT1 recruits and activates mTORC2 on the lysosome for PMA-induced cell migration. LAT1 is translocated to the lysosomes in cells treated with PMA in a dose- and time-dependent manner. Lysosomal LAT1 interacted with mTORC2 through a direct interaction with Rictor, leading to the lysosomal localization of mTORC2. Furthermore, the depletion of LAT1 reduced PMA-induced cell migration in a wound-healing assay. Consistent with these results, the LAT1 N3KR mutant, which is defective in PMA-induced endocytosis and lysosomal localization, did not induce mTORC2 recruitment to the lysosome, with the activation of mTORC2 determined via Akt phosphorylation or the LAT1-mediated promotion of cell migration. Taken together, lysosomal LAT1 recruits and activates the mTORC2 complex and downstream Akt for PMA-mediated cell migration. These results provide insights into the development of therapeutic drugs targeting the LAT1 amino acid transporter to block metastasis, as well as disease progression in various types of cancer. [ABSTRACT FROM AUTHOR]

Golf was developed in Korea between the late nineteenth century and the early 20th century. This was a dark period for the country, during which its name was changed from the Joseon Dynasty to the Korean Empire, and the nation subsequently entered the Japanese colonial era after losing its national sovereignty. The game of golf, which was first introduced by the foreign maritime customs staff at the end of the Joseon Dynasty, spread across upper class society during the Japanese colonial era, as golf courses were being built in major cities and vacation spots around the country. The construction of the courses was undertaken by foreign missionaries, Japanese, and Koreans. The introduction and development of golf in Korea was initially led by the Japanese, as well as by foreign commissioners and missionaries; thereafter, Koreans began to participate in golf. However, golf courses completely disappeared from the Korean Peninsula over the course of the Pacific War and the Korean War after the liberation of Korea from Japan. Korean golfers who survived the Japanese colonial era began to rebuild the golf courses, thereby creating the cornerstone of what has today become a global golf powerhouse. [ABSTRACT FROM AUTHOR]

Abstract: The objective of this study was to investigate the antimicrobial effects of cultured sugar/vinegar (CSV) blend and nisin to control the risk of Listeria monocytogenes in ready to cook (RTC) ravioli. Ravioli dough was prepared with 0.1, 0.3, 0.5, 1% CSV blend and 0.1, 0.2, and 0.3% nisin. Inoculated spinach or artichoke raviolis with 2.0 ± 0.5 log cfu/g of L. monocytogenes were packed aerobically or using modified atmosphere packaging (MAP), and then stored at 4, 10, 17, and 24 °C for 60 days. Growth kinetic parameters of the observed data fit well to the Baranyi equation. Ravioli with spinach filling materials yielded a higher risk than that with artichoke. L. monocytogenes was able to survive in ravioli with artichoke, but did not grow. The addition of 1% CSV blend or 0.3% nisin in spinach ravioli with the combination of MAP effectively controlled the growth of L. monocytogenes at the temperature below 10 °C. The organoleptic quality of spinach ravioli was not also affected by the application of 1% CSV blend. Therefore, the CSV blend can be recommended to improve the microbial safety and quality of natural RTC ravioli at retail market. Practical applications: The risk of ravioli was affected by the filling materials of ravioli at retail market. Addition of 1% cultured sugar/vinegar blend in dough substantially contributes to the extension of shelf‐life of MAP spinach raviolis. classification and regression tree analysis results indicate that refrigeration temperature is the main control factor to affect lag time and growth rate, while packaging method is critical for maximum population density. [ABSTRACT FROM AUTHOR]

Life satisfaction is an essential component of subjective well-being and provides a fundamental resource for optimal everyday functioning. The goal of the present study was to examine how life satisfaction influences self-referential processing of emotionally valenced stimuli. Nineteen individuals with high life satisfaction (HLS) and 21 individuals with low life satisfaction (LLS) were scanned using functional MRI while performing a face-word relevance rating task, which consisted of 3 types of face stimuli (self, public other, and unfamiliar other) and 3 types of word stimuli (positive, negative, and neutral). We found a significant group x word valence interaction effect, most strikingly in the dorsal medial prefrontal cortex. In the positive word condition dorsal medial prefrontal cortex activity was significantly higher in the LLS group, whereas in the negative word condition it was significantly higher in the HLS group. The two groups showed distinct functional connectivity of the dorsal medial prefrontal cortex with emotional processing-related regions. The findings suggest that, in response to emotional stimuli, individuals with HLS may successfully recruit emotion regulation-related regions in contrast to individuals with LLS. The difference in functional connectivity during self-referential processing may lead to an influence of life satisfaction on responses to emotion-eliciting stimuli. [ABSTRACT FROM AUTHOR]

Two types of lithium cobalt oxides (LiCoO 2 ) as cathode materials for lithium ion batteries are synthesized from two cobalt sources of different facial-shapes (octahedral and truncated-octahedral Co 3 O 4 ) and Li 2 CO 3 using solid state synthesis. From X-ray diffraction and scanning electron microscopy measurements, the reaction mechanism of the formation of LiCoO 2 is investigated. It is revealed that LiCoO 2 from octahedral Co 3 O 4 with only {111} surfaces grows in one direction whereas the crystal orientation of LiCoO 2 from truncated-octahedral Co 3 O 4 with {111} and {100} surfaces is not unique and the spinel intermediates of Li x Co 2 O 4 are formed during synthesis. They show largely unequal rate and cycling performances for lithium ion battery, even though their outer appearances are nearly identical. Almost single-crystalline LiCoO 2 from octahedral precursors shows much better electrochemical performances than LiCoO 2 from truncated-octahedral precursors as a lithium ion battery cathode. By studying crystal orientation, it is shown that the poor electrochemical performances of LiCoO 2 from truncated-octahedral Co 3 O 4 are originated by crystal-mismatch between crystallites. [ABSTRACT FROM AUTHOR]

The root bark of Morus has long been appreciated as an antiphlogistic, diuretic and expectorant drug in Chinese herbal medicine, albeit with barely known targets and mechanisms of action. In the 1970s, the development of analytic chemistry allowed for the discovery of morusin as one of 7 different isoprene flavonoid derivatives in the root bark of Morus. However, the remarkable antioxidant capacity of morusin with the unexpected potential for health benefits over the other flavonoid derivatives has recently sparked scientific interest in the biochemical identification of target proteins and signaling pathways and further clinical relevance. In this review, we discuss recent advances in the understanding of the functional roles of morusin in multiple biological processes such as inflammation, apoptosis, metabolism and autophagy. We also highlight recent in vivo and in vitro evidence on the clinical potential of morusin treatment for multiple human pathologies including inflammatory diseases, neurological disorders, diabetes, cancer and the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Interleukin 33 (IL-33) is an IL-1 family cytokine that plays a central role in immune system by regulating and initiating inflammatory responses. The binding of IL-33 to the suppressor of tumorigenicity 2 (ST2) receptor induces mitogen-activated protein kinases (MAPK) and nuclear factor κB (NF-κB) pathways, thereby leading to inflammatory cytokines production in type 2 helper T cells and type 2 innate lymphoid cells. To develop an antibody specific to IL-33 with a defined epitope, we characterized a single-chain antibody variable fragments (scFvs) clone specific to IL-33, C2_2E12, which was selected from a human synthetic library of scFvs using phage display. Affinity (Kd) of C2_2E12 was determined to be 38 nM using enzyme-linked immunosorbent assay. C2_2E12 did not show cross-reactivity toward other interleukin cytokines, including closely related IL-1 family cytokines and unrelated proteins. Mutational scanning analysis revealed that the epitope of IL-33 consisted of residues 149–158 with key residues being L150 and K151 of IL-33. Structural modeling suggested that L150 and K151 residues are important for the interaction of IL-33 with C2_2E12, implicating that C2_2E12 could block the binding of ST2 to IL-33. Pull-down and in-cell assays supported that C2_2E12 can inhibit the IL-33/ST2 signaling axis. These results suggest that the scFv clone characterized here can function as a neutralizing antibody. [ABSTRACT FROM AUTHOR]

Stress granules are membraneless organelles composed of numerous components including ribonucleoproteins. The stress granules are characterized by a dynamic complex assembly in response to various environmental stressors, which has been implicated in the coordinated regulation of diverse biological pathways, to exert a protective role against stress-induced cell death. Here, we show that stress granule formation is induced by morusin, a novel phytochemical displaying antitumor capacity through barely known mechanisms. Morusin-mediated induction of stress granules requires activation of protein kinase R (PKR) and subsequent eIF2α phosphorylation. Notably, genetic inactivation of stress granule formation mediated by G3BP1 knockout sensitized cancer cells to morusin treatment. This protective function against morusin-mediated cell death can be attributed at least in part to the sequestration of receptors for activated C kinase-1 (RACK1) within the stress granules, which reduces caspase-3 activation. Collectively, our study provides biochemical evidence for the role of stress granules in suppressing the antitumor capacity of morusin, proposing that morusin treatment, together with pharmacological inhibition of stress granules, could be an efficient strategy for targeting cancer. [ABSTRACT FROM AUTHOR]

Dihydrofolate reductase (DHFR) from bacteriophage T4 is a homodimer consisting of 193-residue subunits. It has been crystallized in the presence of the cofactor (NADPH) and an inhibitor (aminopterin) at 296 K using sodium chloride as precipitant. The crystals are tetragonal, belonging to the space group P4122 (or P4322), with unit-cell parameters a = b = 61.14, c = 123.23 Å under cryogenic conditions. The asymmetric unit contains a single subunit, with a corresponding Vm of 2.65 Å3 Da-1 and a solvent content of 53.6%. Native data have been collected from a crystal to 1.9 Å resolution using synchrotron X-rays. [ABSTRACT FROM AUTHOR]

In the title compound, [Pt(C3H2O4)(C7H16N2O2)], the Pt atom is coordinated to two O and two N atoms in a square-planar arrangement. The two independent mol­ecules, which have very similar structures, are approximately related by pseudo-twofold screw-axis symmetry. The six-membered chelate ring in the leaving ligand assumes a conformation intermediate between the half-chair and boat forms. The seven-membered ring in the carrier ligand assumes a twist-chair conformation and the oxolane ring assumes an envelope conformation. The crystal packing consists of extensive hydrogen-bonding networks which form two-dimensional molecular layers, and there are weak van der Waals interactions between these layers. [ABSTRACT FROM AUTHOR]

Covalent conjugations of the SUMO-1 moiety on a target protein play important roles in the regulation of cellular protein function. SUMO-conjugation of PML is a regulatory step for PML nuclear body (PML-NB) formation, and HIPK2 is SUMO-conjugated and recruited into the PML-NBs. Although HIPK2 mutations (R861W and N951I) were found in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients, little is known about the underlying mechanisms by which HIPK2 mutations are associated with the pathogenesis of leukemia. Here we show that HIPK2 mutants found in AML and MDS patients are defective in SUMO-interacting motif (SIM) function. Due to defective SIM function, the HIPK2 mutants were not modified with SUMO-1, and not recruited to the PML-NBs. However, the HIPK2 mutants can normally bind to and phosphorylate AML1b. Therefore, the HIPK2 mutants can sequestrate the AML1 complex out of the PML-NBs, resulting in the disruption of AML1-mediated activation of target genes for myeloid differentiation. In addition, the differentiation of K562 blast cells was impaired by the expression of the HIPK2 SIM-defective mutants. These results suggest that HIPK2 targeting into the PML-NBs via the SIMs is crucial for HIPK2-mediated induction of myeloid differentiation, and is associated with AML pathogenesis., Competing Interests: None.

Background/aims: Syndecan-2 (SDC2) methylation was previously reported as a sensitive serologic biomarker for the early detection of colorectal cancer (CRC). The purpose of this study was to investigate whether SDC2 methylation is detectable in precancerous lesions and to determine the feasibility of using SDC2 methylation for the detection of CRC and precancerous lesions in bowel lavage fluid (BLF)., Methods: A total of 190 BLF samples were collected from the rectum at the beginning of colonoscopy from patients with colorectal neoplasm and healthy normal individuals. Fourteen polypectomy specimens were obtained during colonoscopy. A bisulfite pyrosequencing assay and quantitative methylation-specific polymerase chain reaction were conducted to measure SDC2 methylation in tissues and BLF DNA., Results: SDC2 methylation was positive in 100% of villous adenoma (VA) and high-grade dysplasia, and hyperplastic polyp samples; 88.9% of tubular adenoma samples; and 0% of normal mucosa samples. In the BLF DNA test for SDC2 methylation, the sensitivity for detecting CRC and VA was 80.0% and 64.7%, respectively, at a specificity of 88.9%. The BLF of patients with multiple tubular adenomas, single tubular adenoma and hyperplastic polyps showed 62.8%, 26.7% and 28.6% rates of methylation-positive SDC2 , respectively., Conclusions: Our results demonstrated that SDC2 methylation was a frequent event in precancerous lesions and showed high potential in BLF for detecting patients with colorectal neoplasm.

The objective of this study was to investigate the antimicrobial effects of cultured sugar/vinegar (CSV) blend and nisin to control the risk of Listeria monocytogenes in ready to cook (RTC) ravioli. Ravioli dough was prepared with 0.1, 0.3, 0.5, 1% CSV blend and 0.1, 0.2, and 0.3% nisin. Inoculated spinach or artichoke raviolis with 2.0 ± 0.5 log cfu/g of L. monocytogenes were packed aerobically or using modified atmosphere packaging (MAP), and then stored at 4, 10, 17, and 24 °C for 60 days. Growth kinetic parameters of the observed data fit well to the Baranyi equation. Ravioli with spinach filling materials yielded a higher risk than that with artichoke. L. monocytogenes was able to survive in ravioli with artichoke, but did not grow. The addition of 1% CSV blend or 0.3% nisin in spinach ravioli with the combination of MAP effectively controlled the growth of L. monocytogenes at the temperature below 10 °C. The organoleptic quality of spinach ravioli was not also affected by the application of 1% CSV blend. Therefore, the CSV blend can be recommended to improve the microbial safety and quality of natural RTC ravioli at retail market., Practical Applications: The risk of ravioli was affected by the filling materials of ravioli at retail market. Addition of 1% cultured sugar/vinegar blend in dough substantially contributes to the extension of shelf-life of MAP spinach raviolis. classification and regression tree analysis results indicate that refrigeration temperature is the main control factor to affect lag time and growth rate, while packaging method is critical for maximum population density.

Autophagy is a cellular process by which damaged organelles and dysfunctional proteins are degraded. Morusin is an anti-cancer drug isolated from the root bark of Morus alba . Morusin induces apoptosis in human prostate cancer cells by reducing STAT3 activity. In this study, we examined whether morusin induces autophagy and also examined the effects of autophagy on the morusin-induced apoptosis. Morusin induces LC3-II accumulation and ULK1 activation in HeLa cells. In addition, we found that induction of ULK1 Ser317 phosphorylation and reduction of ULK1 Ser757 phosphorylation occurred simultaneously during morusin-induced autophagy. Consistently, morusin induces autophagy by activation of AMPK and inhibition of mTOR activity. Next, we investigated the role of autophagy in morusin-induced apoptosis. Inhibition of autophagy by treating cells with the 3-methyladenine (3-MA) autophagic inhibitor induces high levels of morusin-mediated apoptosis, while treatment of cells with morusin alone induces moderate levels of apoptosis. Cell survival was greatly reduced when cells were treated with morusin and 3-MA. Taken together, morusin induces autophagy, which is an impediment for morusin-induced apoptosis, suggesting combined treatment of morusin with an autophagic inhibitor would increase the efficacy of morusin as an anti-cancer drug.