Effect of complement C1-esterase inhibitor on brain edema and inflammation after mild traumatic brain injury in an animal model

Eric Weiss,Teena Dhir,Abigail Collett,Michal Reola,Mark Kaplan,Corrado Minimo,Laurel Omert,Pak Leung 대한응급의학회 2020 Clinical and Experimental Emergency Medicine Vol.7 No.2

Objective Traumatic brain injury (TBI) is characterized by damage to the blood-brain barrier, inflammation, and edema formation. In this pilot study, we aimed to investigate the effects of a complement inhibitor, C1-esterase inhibitor (C1 INH), on brain edema and inflammation in a rat model of mild TBI. Methods Thirty-six male Sprague Dawley rats were randomly assigned to control, TBI, or TBI plus C1 INH groups. TBI and TBI plus C1 INH rats received an injection of saline or 25 IU/kg C1 INH, respectively, with TBI using a weight drop model. Control rats received saline only. Rats were subsequently euthanized and their brain tissue harvested for analysis. The primary outcome was the extent of edema as assessed by the brain’s water content. Secondary outcomes included enzyme-linked immunosorbent assays to determine levels of pro-inflammatory mediators. Results Tumor necrosis factor-α levels were significantly greater in TBI rats than control rats, indicating that inflammation was generated by the weight drop impact. Brain water content following TBI was significantly different between TBI rats treated with C1-INH (78.7%±0.12), untreated TBI rats (79.3%±0.12), and control rats (78.6%±0.15, P=0.001). There was a significant decrease in C3a and interleukin 2 levels among C1 INH–treated rats compared with untreated TBI rats, but no change in levels of tumor necrosis factor-α and S100β. Conclusion C1-INH inhibited the complement pathway, suggesting that C1-INH may have a therapeutic benefit in TBI. Further studies are needed to investigate the effect of C1-INH on clinical outcomes.

Loss-of-function mutations in sodium channel Na_v1.7 cause anosmia

Weiss, Jan,Pyrski, Martina,Jacobi, Eric,Bufe, Bernd,Willnecker, Vivienne,Schick, Bernhard,Zizzari, Philippe,Gossage, Samuel J.,Greer, Charles A.,Leinders-Zufall, Trese,Woods, C. Geoffrey,Wood, John N. Nature Publishing Group, a division of Macmillan P 2011 Nature Vol.472 No.7342

Loss of function of the gene SCN9A, encoding the voltage-gated sodium channel Na<SUB>v</SUB>1.7, causes a congenital inability to experience pain in humans. Here we show that Na<SUB>v</SUB>1.7 is not only necessary for pain sensation but is also an essential requirement for odour perception in both mice and humans. We examined human patients with loss-of-function mutations in SCN9A and show that they are unable to sense odours. To establish the essential role of Na<SUB>v</SUB>1.7 in odour perception, we generated conditional null mice in which Na<SUB>v</SUB>1.7 was removed from all olfactory sensory neurons. In the absence of Na<SUB>v</SUB>1.7, these neurons still produce odour-evoked action potentials but fail to initiate synaptic signalling from their axon terminals at the first synapse in the olfactory system. The mutant mice no longer display vital, odour-guided behaviours such as innate odour recognition and avoidance, short-term odour learning, and maternal pup retrieval. Our study creates a mouse model of congenital general anosmia and provides new strategies to explore the genetic basis of the human sense of smell.

Surface measurements of the 5 June 2013 damaging thunderstorm wind event near Pep, Texas

Gunter, W. Scott,Schroeder, John L.,Weiss, Christopher C.,Bruning, Eric C. Techno-Press 2017 Wind and Structures, An International Journal (WAS Vol.24 No.2

High-resolution wind measurements at 2.25 m in height were used to investigate the mean and turbulence properties of an extreme thunderstorm wind event in West Texas. These data were combined with single Doppler scans from the Texas Tech University Ka-band mobile Doppler radars systems (TTUKa) to provide meteorological context over the surface measurement stations for portions of the outflow. Several features characteristic of a severe wind event were noted in the radar data, including a bowing portion of the thunderstorm complex and a small circulation on the leading edge. These features were reflected in the surface wind time histories and provided natural separation between various regions of the outflow. These features also contributed to the peak 1-s gust at all measurement stations. The turbulence characteristics of each outflow region were also investigated and compared. Reduced values of running turbulence intensity and elevated values of longitudinal integral scales were noted during the period of peak wind speed. Larger scales of turbulence within the outflow were also suggested via spectral analysis.

Structural, electro-magnetic, and optical properties of Ba(Fe,Ni)₂As₂ single-crystal thin film

Yoon, Sejun,Seo, Yu-Seong,Lee, Seokbae,Weiss, Jeremy D,Jiang, Jianyi,Oh, MyeongJun,Lee, Jongmin,Seo, Sehun,Jo, Youn Jung,Hellstrom, Eric E,Hwang, Jungseek,Lee, Sanghan IOP 2017 Superconductor science & technology Vol.30 No.3

<P>We investigated the superconducting transition temperature (<I>T</I> <SUB>c</SUB>), critical current density (<I>J</I> <SUB>c</SUB>) and optical properties of optimally doped Ba(Fe<SUB>0.95</SUB>Ni<SUB>0.05</SUB>)<SUB>2</SUB>As<SUB>2</SUB> (Ni-Ba122) single-crystalline epitaxial thin films grown by pulsed laser deposition for the first time. The <I>T</I> <SUB>c</SUB> at zero resistivity was about 20.5 K and the <I>J</I> <SUB>c</SUB> at self-field and 4.2 K was 2.8 MA cm<SUP>−2</SUP> calculated by the Bean model. The superconducting properties such as <I>T</I> <SUB>c</SUB> and <I>J</I> <SUB>c</SUB> of thin films are comparable to those of bulk single-crystal samples. The superfluid plasma frequency (<I>λ</I> <SUB>p,S</SUB>) of Ni-Ba122 thin film is ∼7033 cm<SUP>−1</SUP> obtained by optical spectroscopic technique. Based on this plasma frequency, we obtained the London penetration depth (<I>λ</I> <SUB>L</SUB>), ∼226 nm at 8 K, which is comparable to those of optimally Co- and K-doped BaFe<SUB>2</SUB>As<SUB>2</SUB> single crystals.</P>

High critical current density over 1 MA cm⁻² at 13 T in BaZrO₃ incorporated Ba(Fe,Co)₂As₂ thin film

Lee, Jongmin,Jiang, Jianyi,Kametani, Fumitake,Oh, Myeong Jun,Weiss, Jeremy D,Collantes, Yesusa,Seo, Sehun,Yoon, Sejun,Tarantini, Chiara,Jo, Youn Jung,Hellstrom, Eric E,Lee, Sanghan IOP 2017 Superconductor science & technology Vol.30 No.8

<P>Achieving high critical current density (<I>J</I> <SUB>c</SUB>) under a high magnetic field in Fe based superconductors is indispensable for practical applications. Here we report that high critical current density over 1 MA cm<SUP>−2</SUP> in high field (13 T) can be achieved in BaZrO<SUB>3</SUB> (BZO) incorporated Ba(Fe,Co)<SUB>2</SUB>As<SUB>2</SUB> (Co-Ba122) thin film grown on CaF<SUB>2</SUB> substrate using pulsed laser deposition. The magnetization <I>J</I> <SUB>c</SUB> of Co-Ba122 thin film incorporated with 2 mol.% BZO reaches 1.3 MA cm<SUP>−2</SUP> (<I>H</I>ǁ<I>c</I>, 13 T and 4.2 K), 14 times higher than that of pure Co-Ba122 thin film. Transmission electron microscopy observation revealed that BZO forms nanorods of ∼4 nm in average diameter with mean separation of 10–11 nm which corresponds to a matching field of about 17–20 T. Incorporating BZO in Co-Ba122 thin films led to a strong vortex pinning effect and a significant enhancement of <I>J</I> <SUB>c</SUB> because a high density of BZO nanorods could form in the superconducting matrix without significant degradation of <I>T</I> <SUB>c</SUB>, and the diameter of BZO nanorods is approximately twice the coherence length of Co-Ba122 (<I>ξ</I> <SUB>ab</SUB>(0) ∼ 2.5 nm) which is the optimal size as pinning centers.</P>

Surface measurements of the 5 June 2013 damaging thunderstorm wind event near Pep, Texas

W. Scott Gunter,John L. Schroeder,Christopher C. Weiss,Eric C. Bruning 한국풍공학회 2017 Wind and Structures, An International Journal (WAS Vol.24 No.2

High-resolution wind measurements at 2.25 m in height were used to investigate the mean and turbulence properties of an extreme thunderstorm wind event in West Texas. These data were combined with single Doppler scans from the Texas Tech University Ka-band mobile Doppler radars systems (TTUKa) to provide meteorological context over the surface measurement stations for portions of the outflow. Several features characteristic of a severe wind event were noted in the radar data, including a bowing portion of the thunderstorm complex and a small circulation on the leading edge. These features were reflected in the surface wind time histories and provided natural separation between various regions of the outflow. These features also contributed to the peak 1-s gust at all measurement stations. The turbulence characteristics of each outflow region were also investigated and compared. Reduced values of running turbulence intensity and elevated values of longitudinal integral scales were noted during the period of peak wind speed. Larger scales of turbulence within the outflow were also suggested via spectral analysis.

Fermented Soy Beverage Q-CAN Plus Consumption Improves Serum Cholesterol and Cytokines

Suyavaran Arumugam,Evangelos Dioletis,Ricardo Paiva,Maxine R. Fields,Theresa R. Weiss,Eric R. Secor,Ather Ali 한국식품영양과학회 2020 Journal of medicinal food Vol.23 No.5

Soy-based beverages are well recognized for their rich nutritional contents and positive health benefits. However, there is little information regarding the composition of various commercially available soy-based beverages and uncertainty among patients regarding the utility of fermented soy products. Current study evaluates the health benefits of QCAN® Plus—an easily available fermented soy drink. This study was performed in lean (n = 10) and obese (n = 10) subjects. The subjects were observed during pre-soy (weeks −2, −1, and 0), on-soy (weeks 1, 2, 3, and 4), and post-soy (weeks 6, 8, 10, and 12) periods. The serum samples during these visits were subjected to lipid profile analysis and multiplex assay for cytokines. The results revealed that total cholesterol and low-density lipoprotein (LDL) cholesterol levels were significantly reduced in both lean and obese individuals during on-soy (P ≤ .05). Furthermore, cytokines such as platelet-derived growth factor (PDGF) AA and AB/BB were significantly lowered on-soy compared with pre-soy (P ≤ .05) in lean subjects and PDGF AA, IL-1RA, and GMCSF were significantly reduced on-soy (P ≤ .05) in obese subjects. In addition, a qualitative and quantitative analysis of the Q-CAN Plus by a third-party laboratory confirmed its chemical and microbial safety. Our preliminary study on Q-CAN Plus ensures its safety for consumption and highlights its hypolipidemic and suppressive effect on certain cytokines. These observations and relevant studies in future might guide clinicians in future to consider Q-CAN Plus as a therapeutic nutritional supplement.

A p53/miRNA-34 axis regulates Snail1-dependent cancer cell epithelial–mesenchymal transition

Kim, Nam Hee,Kim, Hyun Sil,Li, Xiao-Yan,Lee, Inhan,Choi, Hyung-Seok,Kang, Shi Eun,Cha, So Young,Ryu, Joo Kyung,Yoon, Dojun,Fearon, Eric R.,Rowe, R. Grant,Lee, Sanghyuk,Maher, Christopher A.,Weiss, Ste The Rockefeller University Press 2011 The Journal of cell biology Vol.195 No.3

<▼1><P>Expression of the essential EMT inducer Snail1 is inhibited by miR-34 through a p53-dependent regulatory pathway.</P></▼1><▼2><P>Snail1 is a zinc finger transcriptional repressor whose pathological expression has been linked to cancer cell epithelial–mesenchymal transition (EMT) programs and the induction of tissue-invasive activity, but pro-oncogenic events capable of regulating Snail1 activity remain largely uncharacterized. Herein, we demonstrate that p53 loss-of-function or mutation promotes cancer cell EMT by de-repressing Snail1 protein expression and activity. In the absence of wild-type p53 function, Snail1-dependent EMT is activated in colon, breast, and lung carcinoma cells as a consequence of a decrease in miRNA-34 levels, which suppress Snail1 activity by binding to highly conserved 3′ untranslated regions in Snail1 itself as well as those of key Snail1 regulatory molecules, including β-catenin, LEF1, and Axin2. Although p53 activity can impact cell cycle regulation, apoptosis, and DNA repair pathways, the EMT and invasion programs initiated by p53 loss of function or mutation are completely dependent on Snail1 expression. These results identify a new link between p53, miR-34, and Snail1 in the regulation of cancer cell EMT programs.</P></▼2>