Naphthalimide Trifluoroacetyl Acetonate: A Hydrazine-Selective Chemodosimetric Sensor

The trifluoroacetyl acetonate naphthalimide derivative 1 has been synthesized in good yield. In acetonitrile solution, compound 1 reacts selectively with hydrazine (NH2NH2) to give a five-membered ring. This leads to OFF-ON fluorescence with a maximum intensity at 501 nm as well as easily discernible color changes. Based on a readily discernible and reproducible 3.9% change in overall fluorescence intensity, the limit of detection for 1 is 3.2 ppb (0.1 mu M), which is below the accepted limit for hydrazine set by the U.S. Environmental Protection Agency (EPA). Compound 1 is selective for hydrazine over other amines, including NH4OH, NH2OH, ethylenediamine, methylamine, n-butylamine, piperazine, dimethylamine, triethylamine, pyridine, and is not perturbed by environmentally abundant metal ions. When supported on glass-backed silica gel TLC plates, compound 1 acts as a fluorimetric and colorimetric probe for hydrazine vapor at a partial pressure of 9.0 mm Hg, with selectivity over other potentially interfering volatile analytes, including ammonia, methylamine, n-butylamine, formaldehyde, acetaldehyde, H2O2, HCl, and CO2 being observed. Probe 1 can also be used for the detection of hydrazine in HeLa cells and does so without appreciable interference from other biologically abundant amines and metal ions.U.S. National Science Foundation CHE-1057904Robert A. Welch Foundation F-1018CRI project grant from National Research Foundation of Korea (NRF)Korea government (MSIP) 2009-0081566Chemistr

Why your neighbor matters: Positions in preferential trade agreement networks and export growth in global value chains

In rapidly expanding global and regional preferential trade agreements (PTA) networks, policy‐makers are keen to situate their countries in a better position, believing that a better position in PTA networks will help their economies trade more and grow faster. In this paper, we provide a theory that explains how changes in countries’ PTA network positions affect their trade performance. We argue that a dense and deep “neighbor network” provides a country with a wide access to global value chains, better protection to investment, and strong credibility to their policy commitments. To measure trade performance, we compute value‐added exports at the country, year, and industry level across 43 countries, 56 industries, and 15 years (2000–14). The estimation of network position effects is done by panel fixed‐effects methods and the sample‐splitting and cross‐fitting double machine‐learning method. The findings show that as a country’s neighbors have deeper and wider PTA networks, the country’s value‐added exports grow faster. Also, the industry‐level analysis shows that sectors heavily engaging in the fragmentation of production stages exhibit faster growth with the improvement of neighbor networks.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163429/2/ecpo12152.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163429/1/ecpo12152_am.pd

Designing Urban Media Storytelling through Greimas ’ Narrative Model

This article attempts to establish an urban media storytelling model based on Greimas’ narrative model. Greimas ’ narrative model is distinguished into Narrative Schema model and Actantial model. Of course, other contents that reproduced through urban media can also establish storytelling strategies using these. Moreover, it can also be utilized in establishing a storytelling that applies to the entire space called “city. ” To be more specific, it is a process that receives information and entertainment based on the city, explores the city and ultimately recognizes the city image. This writing suggest such storytelling design linked with a narrative schema and actantial model

Increasing myosin light chain 3f (MLC3f) protects against a decline in contractile velocity

Disuse induces adaptations in skeletal muscle, which lead to muscle deterioration. Hindlimb-unloading (HU) is a well-established model to investigate cellular mechanisms responsible for disuse-induced skeletal muscle dysfunction. In myosin heavy chain (MHC) type IIB fibers HU induces a reduction in contraction speed (Vo) and a reduction in the relative myosin light chain 3f (MLC3f) protein content compared with myosin light chain 1f (MLC1f) protein. This study tested the hypothesis that increasing the relative MLC3f protein content via rAd-MLC3f vector delivery would attenuate the HU-induced decline in Vo in single MHC type IIB fibers. Fischer-344 rats were randomly assigned to one of three groups: control, HU for 7 days, and HU for 7 days plus rAd-MLC3f. The semimembranosus muscles were injected with rAd-MLC3f (3.75 x 1011-5 x 1011 ifu/ml) at four days after the initiation of HU. In single MHC type IIB fibers the relative MLC3f content decreased by 25% (12.00±0.60% to 9.06±0.66%) and Vo was reduced by 29% (3.22±0.14fl/s vs. 2.27±0.08fl/s) with HU compared to the control group. The rAd-MLC3f injection resulted in an increase in the relative MLC3f content (12.26±1.19%) and a concomitant increase in Vo (2.90±0.15fl/s) of MHC type IIB fibers. A positive relationship was observed between the percent of MLC3f content and Vo. Maximal isometric force and specific tension were reduced with HU by 49% (741.45±44.24μN to 379.09±23.77μN) and 33% (97.58±4.25kN/m2 to 65.05±2.71kN/m2), respectively compared to the control group. The rAd-MLC3f injection did not change the HU-induced decline in force or specific tension. Collectively, these results indicate that rAd-MLC3f injection rescues hindlimb unloading-induced decline in Vo in MHC type IIB single muscle fibers.Published versio

Back Extensor Strengthening Exercise and Backpack Wearing Treatment for Camptocormia in Parkinson's Disease: A Retrospective Pilot Study

Objective To investigate the effect of a conservative treatment regime in Parkinson's disease patients with camptocormia. Methods Nine patients with Parkinson's disease were included in a retrospective pilot study of the value of back extensor strengthening exercise. Six inpatients received a 30-minute treatment, twice daily for 5 weeks, being treated on average for 34 days; while three outpatients visited the clinic and were educated for home exercise and backpack wearing treatment. Outpatients should be scheduled to visit the outpatient department to check physical status every 2–4 weeks for an average of 3 months. Results All patients except one showed statistically significant improvements in activities of daily living (ADL) and motor symptoms, as measured by flexion angle at standing posture, Unified Parkinson's Disease Rating Scale (UPDRS) II and III, and modified Hoehn-Yahr staging. Conclusion Conservative treatment is effective in postural correction of camptocormia in Parkinson's disease, as well as improvement in ADL and motor symptoms

Effect of Catalase/Superoxide Dismutase Mimetic EUK-134 on Damage, Inflammation, and Force Generation of the Diaphragm Muscle in mdx Mice

Duchenne muscular dystrophy (DMD) is the most devastating form of muscular dystrophy caused by a mutation in the dystrophin gene. Defects in the dystrophin gene in DMD, are homologous to that found in mdx mice, and result in profound muscle damage, inflammation and weakness in diaphragm and limb muscles. Dystrophin, a scaffolding protein located in the sarcolemmal cytoskeleton, helps cells to maintain their structural integrity and associates with critical cell signaling molecules that regulate cell growth and repair (e.g., nNOS). While the contributing mechanisms leading to DMD-induced degenerative muscle function and damage are multi-factorial, elevated oxidative stress has been proposed as a central mechanism. In contrast, antioxidants can attenuate muscle damage as well as improve contractile function in dystrophin-deficient muscles. However, it is unknown if oxidative stress is a causal factor in dystrophin-deficient diaphragm muscle pathology and specifically targeted antioxidant (e.g., EUK-134) treated early in the course of the disease (3-4 weeks) can modulate oxidative stress, functional damage and weakness in mdx diaphragm. Therefore, the purpose of this study was to determine the effects of catalase/superoxide dismutase mimetic EUK-134 on damage, inflammation, and contractile function of the diaphragm muscle in mdx mice. We hypothesized that (a) EUK-134 would attenuate muscle damage and oxidative stress in mdx diaphragm, (b) EUK-134 would reduce inflammatory cells and an important transcription factor including nuclear factor-kappaB (NF-kB) in mdx diaphragm and (c) EUK-134 would restore proteins that attach to dystrophin such as nNOS and cytoskeletal proteins back to sarcolemmal region and improve muscle contractility in mdx diaphragm. C57BL/10ScSn wild type and mdx mice were given EUK-134 (30mg/kg, i.p., injection) beginning at 20 days of age for 8 days. The mice were euthanized and the diaphragm muscle was harvested at 4 weeks of age, the time of peak inflammation, and analyzed to measure myofiber inflammation, NF-kB activation, cytoskeletal proteins and oxidative stress markers using Western immunoblotting, ELISA, immunofluoresence, and immunohistochemistry. We found that EUK-134 ameliorated muscle damage and oxidative stress in mdx diaphragm. EUK-134 protected against inflammation by decreasing NF-kB activation in the nucleosome fraction of mdx diaphragm. Further, EUK-134 partially rescued nNOS and k-1 syntrophin back to sarcolemmal membranes and recovered force generation even in acute application in vitro in mdx diaphragm. These results are the first to demonstrate a causal relationship between oxidative stress and pathology caused by dystrophin-deficient diaphragm muscle. Moreover, the data indicate that EUK-134 has a protective effect against muscle damage, inflammation, and contractility in mdx diaphragm. We believe that the results from our investigation will provide clinical significance, as we expect to elucidate mechanisms by which oxidative stress contribute to tissue damage and weakness in dystrophic diaphragm

C57BL/6 life span study: age-related declines in muscle power production and contractile velocity

Quantification of key outcome measures in animal models of aging is an important step preceding intervention testing. One such measurement, skeletal muscle power generation (force * velocity), is critical for dynamic movement. Prior research focused on maximum power (P max), which occurs around 30-40 % of maximum load. However, movement occurs over the entire load range. Thus, the primary purpose of this study was to determine the effect of age on power generation during concentric contractions in the extensor digitorum longus (EDL) and soleus muscles over the load range from 10 to 90 % of peak isometric tetanic force (P 0). Adult, old, and elderly male C57BL/6 mice were examined for contractile function (6-7 months old, 100 % survival; ~24 months, 75 %; and ~28 months, 50 % P 0). The shape of the force-velocity curve also changed with age (a/P 0 increased). In addition, there were prolonged contraction times to maximum force and shifts in the distribution of the myosin light and heavy chain isoforms in the EDL. The results demonstrate that age-associated difficulty in movement during challenging tasks is likely due, in addition to overall reduced force output, to an accelerated deterioration of power production and contractile velocity under heavily loaded conditions.R01 AG017768 - NIA NIH HHS; F31 AG044108 - NIA NIH HHS; T32 AG029796 - NIA NIH HHS; R01 EY15313 - NEI NIH HHS; R01 EY015313 - NEI NIH HH

The Effects of a NAD(P)H Oxidase Inhibition on Matrix Metalloproteinases and TIMP-1 in the MDX Diaphragm

Duchenne muscular dystrophy (DMD) is characterized by devastating muscle degeneration that includes oxidative stress, loss of contractile tissue, muscle weakness and increased fibrosis in respiratory muscles (e.g., diaphragm). The mdx mice diaphragm undergoes a progressive degeneration similar to that occurring in patients with DMD. We showed that apocynin, a NAD(P)H oxidase inhibitor, protects against reduction in diaphragm mass, oxidative capacity, and apoptosis. We hypothesized that apocynin (1.5mmol/L per day) would attenuate extramyocyte space and collagen content by ameliorating matrix metalloproteinases (e.g., MMP-2, MMP-9), tissue inhibitors of metalloproteinases (e.g., TIMP-1) and transforming growth factor-β (TGF-β) in the mdx diaphragm. Eight to nine week old mdx mice and age-matched C57BL wild-types were divided into 4 groups: wild-type controls + water (WW, n=7); wild-type controls + apocynin (WA, n=7); mdx mice + water (MW, n=7), and mdx mice + apocynin (MA, n=7). After 8 days of treatment, the diaphragm was extracted. Both MMP-2 (-22.6%) and MMP-9 (-27.8%) were lower in MW than WW. TIMP-1 (+61.3 %) and TGF-beta levels (+39.4%) were higher in MW than WW. MMP-2 (-21.8%) and TIMP-1 (-8.5%) levels were significantly decreased with apocynin in the mdx diaphragm. Our findings indicate cell protection of apocynin against fibrosis in the mdx diaphragm by regulating the protein levels of MMP-2/9 and TIMP-1