DISC1–ATF4 transcriptional repression complex: dual regulation of the cAMP-PDE4 cascade by DISC1

Soda, T,Frank, C,Ishizuka, K,Baccarella, A,Park, Y-U,Flood, Z,Park, S K,Sawa, A,Tsai, L-H Nature Publishing Group 2013 Molecular psychiatry Vol.18 No.8

<P>Disrupted-In-Schizophrenia 1 (<I>DISC1</I>), a risk factor for major mental illnesses, has been studied extensively in the context of neurodevelopment. However, the role of DISC1 in neuronal signaling, particularly in conjunction with intracellular cascades that occur in response to dopamine, a neurotransmitter implicated in numerous psychiatric disorders, remains elusive. Previous data suggest that DISC1 interacts with numerous proteins that impact neuronal function, including activating transcription factor 4 (ATF4). In this study, we identify a novel DISC1 and ATF4 binding region in the genomic locus of <I>phosphodiesterase 4D</I> (<I>PDE4D</I>), a gene implicated in psychiatric disorders. We found that the loss of function of either DISC1 or ATF4 increases <I>PDE4D9</I> transcription, and that the association of DISC1 with the <I>PDE4D9</I> locus requires ATF4. We also show that <I>PDE4D9</I> is increased by D1-type dopamine receptor dopaminergic stimulation. We demonstrate that the mechanism for this increase is due to DISC1 dissociation from the <I>PDE4D</I> locus in mouse brain. We further characterize the interaction of DISC1 with ATF4 to show that it is regulated via protein kinase A-mediated phosphorylation of DISC1 serine-58. Our results suggest that the release of DISC1-mediated transcriptional repression of <I>PDE4D9</I> acts as feedback inhibition to regulate dopaminergic signaling. Furthermore, as DISC1 loss-of-function leads to a specific increase in <I>PDE4D9</I>, <I>PDE4D9</I> itself may represent an attractive target for therapeutic approaches in psychiatric disorders.</P>

Identification of a Dual Inhibitor of Janus Kinase 2 (JAK2) and p70 Ribosomal S6 Kinase1 (S6K1) Pathways

Byun, Sanguine,Lim, Semi,Mun, Ji Young,Kim, Ki Hyun,Ramadhar, Timothy R.,Farrand, Lee,Shin, Seung Ho,Thimmegowda, N. R.,Lee, Hyong Joo,Frank, David A.,Clardy, Jon,Lee, Sam W.,Lee, Ki Won American Society for Biochemistry and Molecular Bi 2015 The Journal of biological chemistry Vol.290 No.39

<P>Bioactive phytochemicals can suppress the growth of malignant cells, and investigation of the mechanisms responsible can assist in the identification of novel therapeutic strategies for cancer therapy. Ginger has been reported to exhibit potent anti-cancer effects, although previous reports have often focused on a narrow range of specific compounds. Through a direct comparison of various ginger compounds, we determined that gingerenone A selectively kills cancer cells while exhibiting minimal toxicity toward normal cells. Kinase array screening revealed JAK2 and S6K1 as the molecular targets primarily responsible for gingerenone A-induced cancer cell death. The effect of gingerenone A was strongly associated with relative phosphorylation levels of JAK2 and S6K1, and administration of gingerenone A significantly suppressed tumor growth <I>in vivo</I>. More importantly, the combined inhibition of JAK2 and S6K1 by commercial inhibitors selectively induced apoptosis in cancer cells, whereas treatment with either agent alone did not. These findings provide rationale for dual targeting of JAK2 and S6K1 in cancer for a combinatorial therapeutic approach.</P>

Nitrous Oxide Reduction Kinetics Distinguish Bacteria Harboring Clade I NosZ from Those Harboring Clade II NosZ

Yoon, Sukhwan,Nissen, Silke,Park, Doyoung,Sanford, Robert A.,Loffler, Frank E. American Society for Microbiology 2016 Applied and environmental microbiology Vol.82 No.13

<P>Bacteria capable of reduction of nitrous oxide (N2O) to N-2 separate into clade I and clade II organisms on the basis of nos operon structures and nosZ sequence features. To explore the possible ecological consequences of distinct nos clusters, the growth of bacterial isolates with either clade I (Pseudomonas stutzeri strain DCP-Ps1, Shewanella loihica strain PV-4) or clade II (Dechloromonas aromatica strain RCB, Anaeromyxobacter dehalogenans strain 2CP-C) nosZ with N2O was examined. Growth curves did not reveal trends distinguishing the clade I and clade II organisms tested; however, the growth yields of clade II organisms exceeded those of clade I organisms by 1.5- to 1.8-fold. Further, whole-cell half-saturation constants (K(s)s) for N2O distinguished clade I from clade II organisms. The apparent Ks values of 0.324 +/- 0.078 mu M for D. aromatica and 1.34 +/- 0.35 mu M for A. dehalogenans were significantly lower than the values measured for P. stutzeri (35.5 +/- 9.3 mu M) and S. loihica (7.07 +/- 1.13 mu M). Genome sequencing demonstrated that Dechloromonas denitrificans possessed a clade II nosZ gene, and a measured Ks of 1.01 +/- 0.18 mu M for N2O was consistent with the values determined for the other clade II organisms tested. These observations provide a plausible mechanistic basis for why the relative activity of bacteria with clade I nos operons compared to that of bacteria with clade II nos operons may control N2O emissions and determine a soil's N2O sink capacity.</P>

Design and experimental testing of a tactile sensor for self-compensation of contact error in soft tissue stiffness measurement

Frank Efe Erukainure,Victor Parque,Mohsen A. Hassan,Ahmed M. R. Fath El-Bab 대한기계학회 2022 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.36 No.10

The measurement of viscoelastic properties of soft tissues has become a research interest with applications in the stiffness estimation of soft tissues, sorting and quality control of postharvest fruit, and fruit ripeness estimation. This paper presents a tactile sensor configuration to estimate the stiffness properties of soft tissues, using fruit as case study. Previous stiffness-measuring tactile sensor models suffer from unstable and infinite sensor outputs due to irregularities and inclination angles of soft tissue surfaces. The proposed configuration introduces two low stiffness springs at the extreme ends of the sensor with one high stiffness spring in-between. This study also presents a closed form mathematical model that considers the maximum inclination angle of the tissue’s (fruit) surface, and a finite element analysis to verify the mathematical model, which yielded stable sensor outputs. A prototype of the proposed configuration was fabricated and tested on kiwifruit samples. The experimental tests revealed that the sensor’s output remained stable, finite, and independent on both the inclination angle of the fruit surface and applied displacement of the sensor. The sensor distinguished between kiwifruit at various stiffness and ripeness levels with an output error ranging between 0.18 % and 3.50 %, and a maximum accuracy of 99.81 %, which is reasonable and competitive compared to previous design concepts.

FUEL ECONOMY COMPARISON OF CONVENTIONAL DRIVE TRAINS SERIES AND PARALLEL HYBRID ELECTRIC STEP VANS

한성빈,장용훈,정연종,이의용,서범주,A. FRANK 한국자동차공학회 2009 International journal of automotive technology Vol.10 No.2

A hybrid electric vehicle (HEV) is a vehicle that combines a conventional propulsion system with an on-board rechargeable energy storage system to achieve better fuel economy than a conventional vehicle HEVs do not have limited ranges like battery electric vehicles, which use batteries charged by an external source. The different propulsion power systems may have common subsystems or components. The objective of this study is to compare the fuel economies of a conventional step van, a series hybrid electric step van (HESV), and a parallel HESV by calculating the fuel consumption using the ADVISOR software by NREL. We also showed the results of the vehicles in different driving cycles including the Central Business District bus cycles, the New York City Cycle, and the US EPA City and Highway cycles.

A Computer Vision-based Assistive Mobile Application for the Visually Impaired

Arnel A. Secondes,Nikki Anne Dominique D. Otero,Frank I. Elijorde,Yung-Cheol Byun(변영철) 대한전기학회 2016 전기학회논문지 Vol.65 No.12

People with visual disabilities suffer environmentally, socially, and technologically. Navigating through places and recognizing objects are already a big challenge for them who require assistance. This study aimed to develop an android-based assistive application for the visually impaired. Specifically, the study aimed to create a system that could aid visually impaired individuals performs significant tasks through object recognition and identifying locations through GPS and Google Maps. In this study, the researchers used an android phone allowing a visually impaired individual to go from one place to another with the aid of the application. Google Maps is integrated to utilize GPS in identifying locations and giving distance directions and the system has a cloud server used for storing pinned locations. Furthermore, Haar-like features were used in object recognition.

A comparison of healing and complication rates between common flaps utilized in total knee arthroplasty: a review of the literature

( Akhil A. Chandra ),( Filippo Romanelli ),( Alex Tang ),( Luke Menken ),( Maximilian Zhang ),( Adam Feintisch ),( Frank A. Liporace ),( Richard S. Yoon ) 대한슬관절학회 2022 대한슬관절학회지 Vol.34 No.-

Background: Flap reconstruction with perforator, fasciocutaneous, muscular, and/or free microvascular flaps is utilized to cover wound defects and improve vascularization and antibiotic/nutrient delivery. Flap use in revision procedures for total knee arthroplasty has been explored previously; however, current data are limited and studies comparing healing and complication rates between different flap types are lacking. Methods: A literature review was performed using PubMed on 13 January 2022. Studies were included if they reported healing and complication rates for either gastrocnemius, rectus abdominis, latissimus dorsi, fasciocutaneous, chimeric, or gracilis flaps in the setting of revision total knee arthroplasty (TKA). Results: The final cohort included gastrocnemius (n = 421, healing rate 73.8%, complication rate 59.9%), gracilis (n = 9, healing rate 93%, complication rate 55.6%), latissimus dorsi (n = 41, healing rate 67%, complication rate 46.3%), rectus abdominis (n = 3, healing rate 100%, complication rate 0%), fasciocutaneous (n = 78, healing rate 70%, complication rate 19.2%), and chimeric flaps (n = 4, healing rate 100%, complication rate 25%). There was no significant difference when comparing healing rates across flap types (p = 0.39). There was a significant difference when comparing complication rates across flap types (p < 0.0001), with a significant difference being noted between gastrocnemius and fasciocutaneous complication rates (p < 0.0001). All other comparisons between flap types by complication rate were not significantly different. Conclusions: Gastrocnemius flaps are the workhorse flap in the setting of revision TKA, as evidenced by this review. Healing rates did not vary significantly across flap types, which suggests that determining the appropriate flap for coverage of soft-tissue defects in revision TKA should be driven by defect size and location as well as physician experience and patient tolerance.

The Safety and Efficacy of a Dietary Herbal Supplement and Gallic Acid for Weight Loss

Frank L. Greenway,Andrew T. Roberts,Corby K. Martin,Zhijun Liu,Ronald J. Amen,Eugene A. Woltering,Jennifer C. Rood,Mary K. Caruso,Ying Yu,Hui Xie 한국식품영양과학회 2007 Journal of medicinal food Vol.10 No.1

The objective of this study was to test the safety and efficacy of NT, a dietary herbal supplement made fromrhubarb, ginger, astragulus, red sage, and turmeric, combined with gallic acid (GA) to reduce food intake and cause weightloss. A total of 105 healthy subjects, 1860 years old with a body mass index of 2535 kg/m2 and on no chronic medication,were randomized to a 300 mg/1.2 g NT-GA combination, a 600 mg/2.4 g NT-GA combination, or placebo in three divideddoses daily for 24 weeks. Food intake was measured at baseline and 2 weeks, and safety parameters were followed regularly.Pharmacokinetic studies of a 200 mg/800 mg NT-GA combination and 800 g GA alone were performed with and withoutfood. There was no dose-related weight loss or reduction in food intake at the 8-week analysis, and the study was terminatedearly. Pharmacokinetic studies showed plasma levels of GA did not increase above 10 .M and were not dose-related. TheNT-GA at all concentrations was well tolerated, but was ineffective in causing weight loss or in suppressing food intake. Phar-macokinetics suggested that GA plasma levels were limited by oral absorption, and may be the reason for lack of efficacy.

Photochemical Grafting of Organic Alkenes to Single-Crystal TiO₂ Surfaces: A Mechanistic Study

Franking, Ryan,Kim, Heesuk,Chambers, Scott A.,Mangham, Andrew N.,Hamers, Robert J. American Chemical Society 2012 Langmuir Vol.28 No.33

<P>The UV-induced photochemical grafting of terminal alkenes has emerged as a versatile way to form molecular layers on semiconductor surfaces. Recent studies have shown that grafting reactions can be initiated by photoelectron emission into the reactant liquid as well as by excitation across the semiconductor band gap, but the relative importance of these two processes is expected to depend on the nature of the semiconductors, the reactant alkene and the excitation wavelength. Here we report a study of the wavelength-dependent photochemical grafting of alkenes onto single-crystal TiO<SUB>2</SUB> samples. Trifluoroacetamide-protected 10-aminododec-1-ene (TFAAD), 10-<I>N</I>-BOC-aminodec-1-ene (t-BOC), and 1-dodecene were used as model alkenes. On rutile (110), photons with energy above the band gap but below the expected work function are not effective at inducing grafting, while photons with energy sufficient to induce electronic transitions from the TiO<SUB>2</SUB> Fermi level to electronic acceptor states of the reactant molecules induce grafting. A comparison of rutile (110), rutile (001), anatase (001), and anatase (101) samples shows slightly enhanced grafting for rutile but no difference between crystal faces for a given crystal phase. Hydroxylation of the surface increases the reaction rate by lowering the work function and thereby facilitating photoelectron ejection into the adjacent alkene. These results demonstrate that photoelectron emission is the dominant mechanism responsible for grafting when using short-wavelength (∼254 nm) light and suggest that photoemission events beginning on mid-gap states may play a crucial role.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/langd5/2012/langd5.2012.28.issue-33/la302169k/production/images/medium/la-2012-02169k_0004.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/la302169k'>ACS Electronic Supporting Info</A></P>

The Effectiveness of Protraction Face Mask Therapy : A Meta-analysis

Kim, Jeong-Hwan,Viana, Marlos A.G.,Grabe, Tom M.,Omerza, Frank F.,BeGole, Ellen A. 가톨릭대학교 2000 Bulletin of The Catholic Research Institutes of Me Vol.28 No.-

This study examined effectiveness of maxillary protraction with orthopedic appliances in Class III patients. A meta-analysis of relevant literature was performed to determine whether a consensus exists regarding controversial issues such as the timing of treatment and the use of adjunctive intraoral appliances. An initial search identified 440 articles relating to Class III malocclusion. Among those articles, 11 studies in English and 3 studies in foreign languages met the previously established selection criteria. Data from the selected studies were categorized by age and appliance groups for the meta-analysis. The sample sizes were categorized by age and appliance groups for the meta-analysis. The sample sizes were comparable between the groups. The statistical synthesis of changes before and after treatment in selected cephalometric landmarks showed no distinct difference between the palatal expansion group and nonexpansion group except for 1 variable, upper incisor angulation, which increased to a greater degree in the nonexpansion group. This finding implies that more skeletal effect and less dental change are produced in the expansion appliance group. Examination of the effects of age revealed greater treatment changes in the younger group. Results indicate that protraction face mask therapy is effective in patients who are growing, but to a lesser degree in patients who are older than 10 years of age, and that protraction in combination with an initial period of expansion may provide more significant skeletal effects. Overall mean values and corresponding standard deviations for the studies selected can also be used to estimate mean treatment effects expected from the use of protraction face mask (American Journal of Orthodontics and Orthopedics 114:675085, 1999)