Role of G{alpha}12 and G{alpha}13 as Novel Switches for the Activity of Nrf2, a Key Antioxidative Transcription Factor

G{alpha}12 and G{alpha}13 function as molecular regulators responding to extracellular stimuli. NF-E2-related factor 2 (Nrf2) is involved in a protective adaptive response to oxidative stress. This study investigated the regulation of Nrf2 by G{alpha}12 and G{alpha}13. A deficiency of G{alpha}12, but not of G{alpha}13, enhanced Nrf2 activity and target gene transactivation in embryo fibroblasts. In mice, G{alpha}12 knockout activated Nrf2 and thereby facilitated heme catabolism to bilirubin and its glucuronosyl conjugations. An oligonucleotide microarray demonstrated the transactivation of Nrf2 target genes by G{alpha}12 gene knockout. G{alpha}12 deficiency reduced Jun N-terminal protein kinase (JNK)-dependent Nrf2 ubiquitination required for proteasomal degradation, and so did G{alpha}13 deficiency. The absence of G{alpha}12, but not of G{alpha}13, increased protein kinase C {delta} (PKC {delta}) activation and the PKC {delta}-mediated serine phosphorylation of Nrf2. G{alpha}13 gene knockout or knockdown abrogated the Nrf2 phosphorylation induced by G{alpha}12 deficiency, suggesting that relief from G{alpha}12 repression leads to the G{alpha}13-mediated activation of Nrf2. Constitutive activation of G{alpha}13 promoted Nrf2 activity and target gene induction via Rho-mediated PKC {delta} activation, corroborating positive regulation by G{alpha}13. In summary, G{alpha}12 and G{alpha}13 transmit a JNK-dependent signal for Nrf2 ubiquitination, whereas G{alpha}13 regulates Rho-PKC {delta}-mediated Nrf2 phosphorylation, which is negatively balanced by G{alpha}12

FLUIDIZATION TECHNOLOGY FOR STABLE STARTUP OF COMMERCIAL FCC UNIT

Conditions for maintaining good fluidization in the start-up of FCC have been determined. Catalyst defluidization and consequent catalyst losses from reactor cyclone are mainly affected by catalyst properties and stripper operating condition based on previous commercial startup experiences. Effect of fine catalyst contents on bed fluidity was determined. Bed fluidity in stripper was analyzed with slip velocity. Finally new startup guide was proposed and it was successfully applied to commercial FCC process of SK energy, Korea

A 32kb 10T subthreshold SRAM array with bit-interleaving and differential read scheme in 90nm CMOS

We demonstrate a 10T subthreshold SRAM with an efficient bit-interleaving structure for soft-error tolerance and a differential read scheme for improved stability. The 32kb (256128) SRAM array is fabricated in 90nm CMOS and operates at 31.25kHz at 0.18V With more aggressive wordline boosting, the V DD can be reduced to 0.16V At the minimum VDD condition, the operating frequency is 500Hz and the power consumption is 0.123W

Genome-Based Construction of the Metabolic Pathways of Orientia tsutsugamushi and Comparative Analysis within the Rickettsiales Order

Orientia tsutsugamushi, the causative agent of scrub typhus, is an obligate intracellular bacterium that belongs to the order of Rickettsiales. Recently, we have reported that O. tsutsugamushi has a unique genomic structure, consisting of highly repetitive sequences, and suggested that it may provide valuable insight into the evolution of intracellular bacteria. Here, we have used genomic information to construct the major metabolic pathways of O. tsutsugamushi and performed a comparative analysis of the metabolic genes and pathways of O. tsutsugamushi with other members of the Rickettsiales order. While O. tsutsugamushi has the largest genome among the members of this order, mainly due to the presence of repeated sequences, its metabolic pathways have been highly streamlined. Overall, the metabolic pathways of O. tsutsugamushi were similar to Rickettsia but there were notable differences in several pathways including carbohydrate metabolism, the TCA cycle, and the synthesis of cell wall components as well as in the transport systems. Our results will provide a useful guide to the postgenomic analysis of O. tsutsugamushi and lead to a better understanding of the virulence and physiology of this intracellular pathogen

High grade anorectal stricture complicating Crohn's disease: endoscopic treatment using insulated-tip knife

Endoscopic treatments have emerged as an alternative to surgery, in the treatment of benign colorectal stricture. Unlike endoscopic balloon dilatation, there is limited data on endoscopic electrocautery incision therapy for benign colorectal stricture, especially with regards to safety and long-term patency. We present a case of a 29-year-old female with Crohn's disease who had difficulty in defecation and passing thin stools. A pelvic magnetic resonance imaging scan, gastrograffin enema, and sigmoidoscopy showed a high-grade anorectal stricture. An endoscopic insulated-tip knife incision was successfully performed to resolve the problem. From our experience, we suggest that endoscopic insulated-tip knife treatment may be a feasible and effective modality for patients with short-segment, very rigid, fibrotic anorectal stricture

Combined effects of aerobic exercise and 40-Hz light flicker exposure on early cognitive impairments in Alzheimer’s disease of 3×Tg mice

Alzheimer’s disease (AD) is a progressive degenerative brain disease and the primary cause of dementia. At an early stage, AD is generally characterized by short-term memory impairment, owing to dysfunctions of the cortex and hippocampus. We previously reported that a combination of exercise and 40-Hz light flickering can protect against AD-related neuroinflammation, gamma oscillations, reduction in Aβ, and cognitive decline. Therefore, we sought to extend our previous findings to the 5-mo-old 3×Tg-AD mouse model to examine whether the same favorable effects occur in earlier stages of cognitive dysfunction. We investigated the effects of 12 wk of exercise combined with 40-Hz light flickering on cognitive function by analyzing neuroinflammation, mitochondrial function, and neuroplasticity in the hippocampus in a 3×Tg-AD mouse model. Five-month-old 3×Tg-AD mice performed 12 wk of exercise with 40-Hz light flickering administered independently and in combination. Spatial learning and memory, long-term memory, hippocampal Aβ, tau, neuroinflammation, proinflammatory cytokine expression, mitochondrial function, and neuroplasticity were analyzed. Aβ and tau proteins levels were significantly reduced in the early stage of AD, resulting in protection against cognitive decline by reducing neuroinflammation and proinflammatory cytokines. Furthermore, mitochondrial function improved, apoptosis was reduced, and synapse-related protein expression increased. Overall, exercise with 40-Hz light flickering was significantly more effective than exercise or 40-Hz light flickering alone, and the improvement was comparable to the levels in the nontransgenic aged-match control group. Our results indicate a synergistic effect of exercise and 40-Hz light flickering on pathological improvements in the hippocampus during early AD-associated cognitive impairment

Vesicocutaneous Fistula Presenting Groin Abscess and Chronic Osteomyelitis in Pubic Bone

The authors report a case of bladder fistula associated with a medial thigh cutaneous fistula and chronic osteomyelitis of the pubic bone 11 years after surgery for a pelvic bone fracture and bladder rupture. In the presenting case, despite the clinical suspicion, none of the diagnostic tools demonstrated the bladder fistula preoperatively. This case suggests that bladder repair should be prepared, even if the bladder fistula cannot be confirmed by imaging studies because the amount of urine leakage can be minimal or the fistula can close spontaneously

Specific Radius Change of Quantum Dot inside the Lipid Bilayer by Charge Effect of Lipid Head-Group

We studied the quantum dot-liposome complex (QLC), which is the giant unilamellar vesicle with quantum dots (QDs) incorporated in its lipid bilayer. A spin coating method in conjunction with the electroformation technique yielded vesicles with highly homogeneous unilamellar structure. We observed QD size dependence of the QLC formation: QLCs form with blue, green and yellow-emission QD (core radius ~1.05 nm, 1.25 nm and 1.65 nm) but not with red-emission QD (core radius ~2.5 nm). In order to explain this size dependence, we made a simple model explaining the QD size effect on QLC formation in terms of the molecular packing parameter and the lipid conformational change. This model predicts that QDs below a certain critical size (radius ≈ 1.8 nm) can stably reside in a lipid bilayer of 4 - 5 nm in thickness for Egg-PC lipids. This is consistent with our previous experimental results. In the case of red-emission QD, QD-aggregations are only observed on the fluorescent microscopy instead of QLC. We expected that the reduction of packing parameter (P) would lead to the change of specific QD radius. This prediction could be verified by our experimental observation of the shift of the specific QD size by mixing DOPG