Intrinsic Structural Features of the Human IRE1α Transmembrane Domain Sense Membrane Lipid Saturation

Activation of inositol-requiring enzyme (IRE1α) is an indispensable step in remedying the cellular stress associated with lipid perturbation in the endoplasmic reticulum (ER) membrane. IRE1α is a single-spanning ER transmembrane protein possessing both kinase and endonuclease functions, and its activation can be fully achieved through the dimerization and/or oligomerization process. How IRE1α senses membrane lipid saturation remains largely unresolved. Using both computational and experimental tools, we systematically investigated the dimerization process of the transmembrane domain (TMD) of IRE1α and found that, with help of the serine 450 residue, the conserved tryptophan 457 residue buttresses the core dimerization interface of IRE1α-TMD. BiFC (bimolecular fluorescence complementation) experiments revealed that mutation on these residues abolished the saturated fatty acid-induced dimerization in the ER membrane and subsequently inactivated IRE1α activity in vivo. Therefore, our results suggest that the structural elements of IRE1α-TMD serve as a key sensor that detects membrane aberrancy

An Infantile Case of Sturge-Weber Syndrome in Association with Klippel-Trenaunay-Weber Syndrome and Phakomatosis Pigmentovascularis

Sturge-Weber syndrome can be associated with facial port-wine stains and intracranial calcification, and concurrent Klippel-Trenaunay-Weber syndrome has been reported. Klippel-Trenaunay-Weber syndrome is a rare congenital mesodermal phakomatosis characterized by cutaneous hemangiomas, venous varicosities and soft tissue or bone hypertrophy of the affected extremities. This report is presented a rare case of the Sturge-Weber syndrome in combination with the Klippel-Trennaunay syndrome and phakomatosis pigmentovascularis in a 4-month-old infant. He showed nevus flameus on the right leg and both part of the face and back, leptomeningeal angiomatosis on right hemisphere, hypertrophy of the right leg, hemiconvulsion on the left and also evidences of congenital glaucoma and nevus of Ota. Very rare case combined with these three kinds of phakomatosis has been reported

Impact of immunosuppressant therapy on early recurrence of hepatocellular carcinoma after liver transplantation

Background/AimsThe most commonly used immunosuppressant therapy after liver transplantation (LT) is a combination of tacrolimus and steroid. Basiliximab induction has recently been introduced; however, the most appropriate immunosuppression for hepatocellular carcinoma (HCC) patients after LT is still debated.MethodsNinety-three LT recipients with HCC who took tacrolimus and steroids as major immunosuppressants were included. Induction with basiliximab was implemented in 43 patients (46.2%). Mycophenolate mofetil (MMF) was added to reduce the tacrolimus dosage (n=28, 30.1%). The 1-year tacrolimus exposure level was 7.2 ± 1.3 ng/mL (mean ± SD).ResultsThe 1- and 3-year recurrence rates of HCC were 12.9% and 19.4%, respectively. Tacrolimus exposure, cumulative steroid dosages, and MMF dosages had no impact on HCC recurrence. Induction therapy with basiliximab, high alpha fetoprotein (AFP; >400 ng/mL) and protein induced by vitamin K absence/antagonist-II (PIVKA-II; >100 mAU/mL) levels, and microvascular invasion were significant risk factors for 1-year recurrence (P<0.05). High AFP and PIVKA-II levels, and positive 18fluoro-2-deoxy-d-glucose positron-emission tomography findings were significantly associated with 3-year recurrence (P<0.05).ConclusionsInduction therapy with basiliximab, a strong immunosuppressant, may have a negative impact with respect to early HCC recurrence (i.e., within 1 year) in high-risk patients

A pepper MSRB2 gene confer drought tolerance in rice through the protection of chloroplast-targeted genes

Background: The perturbation of the steady state of reactive oxygen species (ROS) due to biotic and abiotic stresses in a plant could lead to protein denaturation through the modification of amino acid residues, including the oxidation of methionine residues. Methionine sulfoxide reductases (MSRs) catalyze the reduction of methionine sulfoxide back to the methionine residue. To assess the role of this enzyme, we generated transgenic rice using a pepper CaMSRB2 gene under the control of the rice Rab21 (responsive to ABA protein 21) promoter with/without a selection marker, the bar gene. Results: A drought resistance test on transgenic plants showed that CaMSRB2 confers drought tolerance to rice, as evidenced by less oxidative stress symptoms and a strengthened PSII quantum yield under stress conditions, and increased survival rate and chlorophyll index after the re-watering. The results from immunoblotting using a methionine sulfoxide antibody and nano-LC-MS/MS spectrometry suggest that porphobilinogen deaminase (PBGD), which is involved in chlorophyll synthesis, is a putative target of CaMSRB2. The oxidized methionine content of PBGD expressed in E. coli increased in the presence of H2O2, and the Met-95 and Met-227 residues of PBGD were reduced by CaMSRB2 in the presence of dithiothreitol (DTT). An expression profiling analysis of the overexpression lines also suggested that photosystems are less severely affected by drought stress. Conclusions: Our results indicate that CaMSRB2 might play an important functional role in chloroplasts for conferring drought stress tolerance in rice.OAIID:oai:osos.snu.ac.kr:snu2014-01/102/0000005113/8SEQ:8PERF_CD:SNU2014-01EVAL_ITEM_CD:102USER_ID:0000005113ADJUST_YN:NEMP_ID:A077085DEPT_CD:517CITE_RATE:3.73FILENAME:msrb-김연기.pdfDEPT_NM:식물생산과학부EMAIL:[email protected]_YN:YCONFIRM:

Combined Hurdle Technologies Using UVC Waterproof LED for Inactivating Foodborne Pathogens on Fresh-Cut Fruits

This study investigated the combined bactericidal efficacy of slightly acidic electrolyzed water (SAEW), fumaric acid (FA), and ultravioletC waterproof light-emitting diodes (UVC W-LED) for the control of Staphylococcus aureus and Listeria monocytogenes in fresh-cut fruits. Cherry tomato, grape, apple, and pineapple were inoculated with S. aureus and L. monocytogenes and then washed with 30 ppm SAEW containing 0.5% FA in a container equipped with two UVC W-LEDs. Behaviors of S. aureus and L. monocytogenes and quality properties of fresh-cut fruits were monitored after storage at 10 °C and 15 °C for 7 days. The most effective reductions of S. aureus (1.65 log CFU/g) and L. monocytogenes (2.63 log CFU/g) were observed in the group with the combined treatment of SAEW + FA and UVC W-LED. At 10 °C and 15 °C, populations of both pathogens in the combined treatment group were lower than those in a control. Combined treatment showed no negative effect on moisture retention in the fruit. Moreover, visual changes were less significant than in the control. These results demonstrate that the combined treatment can improve the microbial safety and the quality of fruits. If it is properly used in the sanitizing step of the fresh produce industry, a positive effect can be expected

Emerging pathogenic role of peripheral blood factors following BBB disruption in neurodegenerative disease

The responses of central nervous system (CNS) cells such as neurons and glia in neurodegenerative diseases (NDs) suggest that regulation of neuronal and glial functions could be a strategy for ND prevention and/or treatment. However, attempts to develop such therapeutics for NDs have been hindered by the challenge of blood-brain barrier (BBB) permeability and continued constitutive neuronal loss. These limitations indicate the need for additional perspectives for the prevention/treatment of NDs. In particular, the disruption of the blood-brain barrier (BBB) that accompanies NDs allows brain infiltration by peripheral factors, which may stimulate innate immune responses involved in the progression of neurodegeneration. The accumulation of blood factors like thrombin, fibrinogen, c-reactive protein (CRP) and complement components in the brain has been observed in NDs and may activate the innate immune system in the CNS. Thus, strengthening the integrity of the BBB may enhance its protective role to attenuate ND progression and functional loss. In this review, we describe the innate immune system in the CNS and the contribution of blood factors to the role of the CNS immune system in neurodegeneration and neuroprotection. © 2021 The Authors1