49 CFR 178.70 - Approval of UN pressure receptacles.

Code of Federal Regulations, 2012 CFR

2012-10-01

... designee. (b) IIA pre-audit. The manufacturer must submit an application for initial design type approval... of the manufacturer and the IIA certifying the design type, the test results, chemical analyses, lot... initial design type approval. If the pre-audit is found satisfactory by the IIA, the manufacturer will...

49 CFR 178.70 - Approval of UN pressure receptacles.

Code of Federal Regulations, 2011 CFR

2011-10-01

... designee. (b) IIA pre-audit. The manufacturer must submit an application for initial design type approval... of the manufacturer and the IIA certifying the design type, the test results, chemical analyses, lot... initial design type approval. If the pre-audit is found satisfactory by the IIA, the manufacturer will...

49 CFR 178.70 - Approval of UN pressure receptacles.

Code of Federal Regulations, 2014 CFR

2014-10-01

... designee. (b) IIA pre-audit. The manufacturer must submit an application for initial design type approval... of the manufacturer and the IIA certifying the design type, the test results, chemical analyses, lot... initial design type approval. If the pre-audit is found satisfactory by the IIA, the manufacturer will...

49 CFR 178.70 - Approval of UN pressure receptacles.

Code of Federal Regulations, 2013 CFR

2013-10-01

... designee. (b) IIA pre-audit. The manufacturer must submit an application for initial design type approval... of the manufacturer and the IIA certifying the design type, the test results, chemical analyses, lot... initial design type approval. If the pre-audit is found satisfactory by the IIA, the manufacturer will...

Clavicle hook plate fixation for distal-third clavicle fracture (Neer type II): comparison of clinical and radiologic outcomes between Neer types IIA and IIB.

PubMed

Lee, Wonyong; Choi, Chong-Hyuk; Choi, Yun-Rak; Lim, Kyung-Han; Chun, Yong-Min

2017-07-01

The purpose of this study was to investigate clinical and radiologic outcomes of clavicle hook plate fixation for distal-third clavicle fracture (Neer type II) and to compare the clinical and radiologic outcomes and complications between Neer type IIA and type IIB. We retrospectively reviewed 35 patients who underwent open reduction and internal fixation with AO hook locking compression plate (LCP) for distal clavicle fracture, including 13 patients with Neer type IIA and 22 patients with type IIB. Visual analog scale pain score, shoulder scores (subjective shoulder value, University of California-Los Angeles shoulder score, American Shoulder and Elbow Surgeons score), and active range of motion were evaluated to determine clinical outcome. Coracoclavicular distance was measured, and that of the injured side at last follow-up was compared with that of the uninjured side to evaluate radiologic outcomes. AO hook LCP fixation for distal-third clavicle fracture (Neer type II) produced satisfactory radiologic outcomes, including high union rates (100%) and coracoclavicular distance maintenance, as well as satisfactory clinical outcomes, including visual analog scale score for pain, shoulder scores (subjective shoulder value, University of California-Los Angeles shoulder score, American Shoulder and Elbow Surgeons score), and active range of motion. There were no significant differences between Neer type IIA and type IIB. With regard to complications, 22.9% of patients experienced shoulder stiffness and 17.1% had subacromial erosion; however, there were no significant differences between the 2 groups. The AO hook LCP is a suitable choice for Neer type IIA and type IIB distal-third clavicle fracture fixation. Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Nonmuscle myosin heavy chain IIA is a critical factor contributing to the efficiency of early infection of severe fever with thrombocytopenia syndrome virus.

PubMed

Sun, Yinyan; Qi, Yonghe; Liu, Chenxuan; Gao, Wenqing; Chen, Pan; Fu, Liran; Peng, Bo; Wang, Haimin; Jing, Zhiyi; Zhong, Guocai; Li, Wenhui

2014-01-01

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a novel phlebovirus in the Bunyaviridae family. Most patients infected by SFTSV present with fever and thrombocytopenia, and up to 30% die due to multiple-organ dysfunction. The mechanisms by which SFTSV enters multiple cell types are unknown. SFTSV contains two species of envelope glycoproteins, Gn (44.2 kDa) and Gc (56 kDa), both of which are encoded by the M segment and are cleaved from a precursor polypeptide (about 116 kDa) in the endoplasmic reticulum (ER). Gn fused with an immunoglobulin Fc tag at its C terminus (Gn-Fc) bound to multiple cells susceptible to the infection of SFTSV and blocked viral infection of human umbilical vein endothelial cells (HUVECs). Immunoprecipitation assays following mass spectrometry analysis showed that Gn binds to nonmuscle myosin heavy chain IIA (NMMHC-IIA), a cellular protein with surface expression in multiple cell types. Small interfering RNA (siRNA) knockdown of NMMHC-IIA, but not the closely related NMMHC-IIB or NMMHC-IIC, reduced SFTSV infection, and NMMHC-IIA specific antibody blocked infection by SFTSV but not other control viruses. Overexpression of NMMHC-IIA in HeLa cells, which show limited susceptivity to SFTSV, markedly enhanced SFTSV infection of the cells. These results show that NMMHC-IIA is critical for the cellular entry of SFTSV. As NMMHC-IIA is essential for the normal functions of platelets and human vascular endothelial cells, it is conceivable that NMMHC-IIA directly contributes to the pathogenesis of SFTSV and may be a useful target for antiviral interventions against the viral infection.

Does the Modified Gartland Classification Clarify Decision Making?

PubMed

Leung, Sophia; Paryavi, Ebrahim; Herman, Martin J; Sponseller, Paul D; Abzug, Joshua M

2018-01-01

The modified Gartland classification system for pediatric supracondylar fractures is often utilized as a communication tool to aid in determining whether or not a fracture warrants operative intervention. This study sought to determine the interobserver and intraobserver reliability of the Gartland classification system, as well as to determine whether there was agreement that a fracture warranted operative intervention regardless of the classification system. A total of 200 anteroposterior and lateral radiographs of pediatric supracondylar humerus fractures were retrospectively reviewed by 3 fellowship-trained pediatric orthopaedic surgeons and 2 orthopaedic residents and then classified as type I, IIa, IIb, or III. The surgeons then recorded whether they would treat the fracture nonoperatively or operatively. The κ coefficients were calculated to determine interobserver and intraobserver reliability. Overall, the Wilkins-modified Gartland classification has low-moderate interobserver reliability (κ=0.475) and high intraobserver reliability (κ=0.777). A low interobserver reliability was found when differentiating between type IIa and IIb (κ=0.240) among attendings. There was moderate-high interobserver reliability for the decision to operate (κ=0.691) and high intraobserver reliability (κ=0.760). Decreased interobserver reliability was present for decision to operate among residents. For fractures classified as type I, the decision to operate was made 3% of the time and 27% for type IIa. The decision was made to operate 99% of the time for type IIb and 100% for type III. There is almost full agreement for the nonoperative treatment of Type I fractures and operative treatment for type III fractures. There is agreement that type IIb fractures should be treated operatively and that the majority of type IIa fractures should be treated nonoperatively. However, the interobserver reliability for differentiating between type IIa and IIb fractures is low. Our results validate the Gartland classfication system as a method to help direct treatment of pediatric supracondylar humerus fractures, although the modification of the system, IIa versus IIb, seems to have limited reliability and utility. Terminology based on decision to treat may lead to a more clinically useful classification system in the evaluation and treatment of pediatric supracondylar humerus fractures. Level III-diagnostic studies.

Renaturation and one step purification of the chicken GIIA secreted phospholipase A2 from inclusion bodies.

PubMed

Karray, Aida; Amara, Sawsan; Carrière, Frédéric; Gargouri, Youssef; Bezzine, Sofiane

2014-06-01

The cDNA coding for a mature protein of 123 amino acids, containing all of the structural features of catalytically active group IIA sPLA2, has been amplified from chicken intestine. The gene has been cloned into the bacterial expression vector pET-21a(+), which allows protein over-expression as inclusion bodies and enables about 3mg/l of pure refolded fully active enzyme to be obtained. Recombinant expression of chicken intestinal sPLA2-IIA (ChPLA2-IIA) in Escherichia coli shows that the enzyme is Ca(2+) dependent, maximally active at pH 8-9, and hydrolyses phosphatidylglycerol versus phosphatidylcholine with a 10-fold preference. Indeed, we report in this work, a comparative kinetic study between the wild type and the recombinant ChPLA2-IIA, on zwitterionic head group phospholipids (DDPC) and negatively charged phospholipids (POPG) using the monomolecular film technique. The ability to express reasonably large amounts of the sPLA2 Group IIA, compared to that obtained with the classical purification will provide a basis for future site directed mutagenesis studies of this important enzyme. Copyright © 2014 Elsevier B.V. All rights reserved.

Analysis of the type II-A CRISPR-Cas system of Streptococcus agalactiae reveals distinctive features according to genetic lineages

PubMed Central

Lier, Clément; Baticle, Elodie; Horvath, Philippe; Haguenoer, Eve; Valentin, Anne-Sophie; Glaser, Philippe; Mereghetti, Laurent; Lanotte, Philippe

2015-01-01

CRISPR-Cas systems (clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins) are found in 90% of archaea and about 40% of bacteria. In this original system, CRISPR arrays comprise short, almost unique sequences called spacers that are interspersed with conserved palindromic repeats. These systems play a role in adaptive immunity and participate to fight non-self DNA such as integrative and conjugative elements, plasmids, and phages. In Streptococcus agalactiae, a bacterium implicated in colonization and infections in humans since the 1960s, two CRISPR-Cas systems have been described. A type II-A system, characterized by proteins Cas9, Cas1, Cas2, and Csn2, is ubiquitous, and a type I–C system, with the Cas8c signature protein, is present in about 20% of the isolates. Unlike type I–C, which appears to be non-functional, type II-A appears fully functional. Here we studied type II-A CRISPR-cas loci from 126 human isolates of S. agalactiae belonging to different clonal complexes that represent the diversity of the species and that have been implicated in colonization or infection. The CRISPR-cas locus was analyzed both at spacer and repeat levels. Major distinctive features were identified according to the phylogenetic lineages previously defined by multilocus sequence typing, especially for the sequence type (ST) 17, which is considered hypervirulent. Among other idiosyncrasies, ST-17 shows a significantly lower number of spacers in comparison with other lineages. This characteristic could reflect the peculiar virulence or colonization specificities of this lineage. PMID:26124774

Remarks on non-BPS string amplitudes and their all order α' contact interactions in IIB, IIA

DOE PAGES

Hatefi, Ehsan

2017-03-06

Here, we explore the entire form of S-Matrix elements of a potential C n–1 Ramond-Ramond (RR) form field, a tachyon and two transverse scalar fields on both world volume and transverse directions of type IIB and IIA superstring theories. Apart from V C–2V Φ0V Φ0V T0 the other scattering amplitude, namely V C–1V Φ–1V Φ0V T0 is also revealed. We then start to compare all singularity structures of symmetric and asymmetric analysis, generating all infinite singularity structures as well as all order α' contact interactions on the whole directions. This leads to deriving various new contact terms and several newmore » restricted Bianchi identities in both type IIB and IIA. It is also shown that just some of the new couplings of type IIB (IIA) string theory can be re-verified in an Effective Field Theory (EFT) by pull-back of branes. To construct the rest of S-matrix elements one needs to first derive restricted world volume (or bulk) Bianchi identities and then discover new EFT couplings in both type IIB and IIA. Finally the presence of commutator of scalar fields inside the exponential of Wess-Zumino action for non-BPS branes has been confirmed as well.« less

A fluid inclusion study of blueschist-facies lithologies from the Indus suture zone, Ladakh (India): Implications for the exhumation of the subduction related Sapi-Shergol ophiolitic mélange

NASA Astrophysics Data System (ADS)

Sachan, Himanshu Kumar; Kharya, Aditya; Singh, P. Chandra; Rolfo, Franco; Groppo, Chiara; Tiwari, Sameer K.

2017-09-01

The best occurrence of blueschist-facies lithologies in Himalaya is that of the Shergol Ophiolitic Mélange along the Indus suture zone in Ladakh region of north-western India. These lithologies are characterized by well preserved lawsonite-glaucophane-garnet-quartz assemblages. This paper presents for the first time the results of a detailed fluid inclusion study on these lithologies, in order to understand the fluid P-T evolution and its tectonic implications. The blueschist rocks from Shergol Ophiolitic Mélange record metamorphic peak conditions at ∼19 kbar, 470 °C. Several types of fluid inclusions are trapped in quartz and garnet, most of them being two-phase at room temperature. Three types of fluid inclusions have been recognised, basing on microtextures and fluid composition: Type-I are primary two-phase carbonic-aqueous fluid inclusions (VCO2 - LH2O); Type-II are two-phase (LH2O - VH2O) aqueous fluid inclusions, either primary (Type-IIa) or secondary (Type-IIb); Type-III are re-equilibrated fluid inclusions. In the Type-I primary carbonic-aqueous inclusions, H2O is strongly predominant with respect to CO2; the homogenization temperature of CO2 range from -7 to -2 °C. The clathrate melting temperature in such inclusions varies in between +7.1 and +8.6 °C. Type-II two-phase aqueous fluid inclusions show a wide range of salinity, from 7.8-14 wt.% NaCleq (Type-IIa) to 1.65-6.37 wt.% NaCleq (Type-IIb) with accuracy ±0.4 wt.% NaCleq. Type-I and Type-IIa primary fluid inclusions are hosted in peak minerals (garnet and quartz included in garnet), therefore they were likely entrapped at, or near to, peak P-T conditions. The dominantly aqueous fluid of both Type-I and Type-IIa inclusions was most likely produced through metamorphic devolatilization reactions occurring in the subducting slab. Despite their primary nature, the isochores of Type-I and Type-IIa inclusions do not intersect the peak metamorphic conditions of the blueschist mineral assemblage, suggesting that these inclusions stretched or re-equilibrated during nearly isothermal decompression from 19 kbar to 3 kbar or less, at T = 290 °C. This conclusion is further supported by their large variability in shapes and sizes which range from irregular inclusions ('C'/arc shaped, hook shape and satellite type). This decompression stage was followed by nearly isobaric cooling, testified by the occurrence of dendritic networks of decrepitated and 'imploded' fluid inclusions.

D2-brane as the wormhole and the number of the universes

NASA Astrophysics Data System (ADS)

Gusin, Paweł

2016-02-01

We construct wormhole-like solutions in type IIA string theory. These solutions represent wormholes in four dimensions and are given by the D2-branes within appropriated backgrounds fields. We present the conditions on these fields which lead to the four-dimensional wormholes. In the special case, we show how the particular solution in type IIA theory leads to the dynamic wormhole. We also speculate about the number of universes and the cosmological constant.

Functional properties of slow and fast gastrocnemius muscle fibers after a 17-day spaceflight

NASA Technical Reports Server (NTRS)

Widrick, J. J.; Romatowski, J. G.; Norenberg, K. M.; Knuth, S. T.; Bain, J. L.; Riley, D. A.; Trappe, S. W.; Trappe, T. A.; Costill, D. L.; Fitts, R. H.

2001-01-01

The purpose of this investigation was to study the effects of a 17-day spaceflight on the contractile properties of individual fast- and slow-twitch fibers isolated from biopsies of the fast-twitch gastrocnemius muscle of four male astronauts. Single chemically skinned fibers were studied during maximal Ca2+-activated contractions with fiber myosin heavy chain (MHC) isoform expression subsequently determined by SDS gel electrophoresis. Spaceflight had no significant effect on the mean diameter or specific force of single fibers expressing type I, IIa, or IIa/IIx MHC, although a small reduction in average absolute force (P(o)) was observed for the type I fibers (0.68 +/- 0.02 vs. 0.64 +/- 0.02 mN, P < 0.05). Subject-by-flight interactions indicated significant intersubject variation in response to the flight, as postflight fiber diameter and P(o) where significantly reduced for the type I and IIa fibers obtained from one astronaut and for the type IIa fibers from another astronaut. Average unloaded shortening velocity [V(o), in fiber lengths (FL)/s] was greater after the flight for both type I (0.60 +/- 0.03 vs. 0.76 +/- 0.02 FL/s) and IIa fibers (2.33 +/- 0.25 vs. 3.10 +/- 0.16 FL/s). Postflight peak power of the type I and IIa fibers was significantly reduced only for the astronaut experiencing the greatest fiber atrophy and loss of P(o). These results demonstrate that 1) slow and fast gastrocnemius fibers show little atrophy and loss of P(o) but increased V(o) after a typical 17-day spaceflight, 2) there is, however, considerable intersubject variation in these responses, possibly due to intersubject differences in in-flight physical activity, and 3) in these four astronauts, fiber atrophy and reductions in P(o) were less for slow and fast fibers obtained from the phasic fast-twitch gastrocnemius muscle compared with slow and fast fibers obtained from the slow antigravity soleus [J. J. Widrick, S. K. Knuth, K. M. Norenberg, J. G. Romatowski, J. L. W. Bain, D. A. Riley, M. Karhanek, S. W. Trappe, T. A. Trappe, D. L. Costill, and R. H. Fitts. J Physiol (Lond) 516: 915-930, 1999].

Inhibition Mechanism of an Anti-CRISPR Suppressor AcrIIA4 Targeting SpyCas9.

PubMed

Yang, Hui; Patel, Dinshaw J

2017-07-06

Prokaryotic CRISPR-Cas adaptive immune systems utilize sequence-specific RNA-guided endonucleases to defend against infection by viruses, bacteriophages, and mobile elements, while these foreign genetic elements evolve diverse anti-CRISPR proteins to overcome the CRISPR-Cas-mediated defense of the host. Recently, AcrIIA2 and AcrIIA4, encoded by Listeria monocytogene prophages, were shown to block the endonuclease activity of type II-A Streptococcus pyogene Cas9 (SpyCas9). We now report the crystal structure of AcrIIA4 in complex with single-guide RNA-bound SpyCas9, thereby establishing that AcrIIA4 preferentially targets critical residues essential for PAM duplex recognition, as well as blocks target DNA access to key catalytic residues lining the RuvC pocket. These structural insights, validated by biochemical assays on key mutants, demonstrate that AcrIIA4 competitively occupies both PAM-interacting and non-target DNA strand cleavage catalytic pockets. Our studies provide insights into anti-CRISPR-mediated suppression mechanisms for inactivating SpyCas9, thereby broadening the applicability of CRISPR-Cas regulatory tools for genome editing. Published by Elsevier Inc.

The immunoglobulin-like domains 1 and 2 of the protein tyrosine phosphatase LAR adopt an unusual horseshoe-like conformation

PubMed Central

Biersmith, Bridget H.; Hammel, Michal; Geisbrecht, Erika R.; Bouyain, Samuel

2011-01-01

Neurogenesis depends on exquisitely regulated interactions between macromolecules on the cell surface and in the extracellular matrix. In particular, interactions between proteoglycans and members of the type IIa subgroup of receptor protein tyrosine phosphatases underlie critical developmental processes such as the formation of synapses at the neuromuscular junction and the migration of axons to their appropriate targets. We report here the crystal structures of the first and second immunoglobulin-like domains of the Drosophila type IIa receptor Dlar and its mouse homologue LAR. These two domains adopt an unusual antiparallel arrangement that has not been previously observed in tandem repeats of immunoglobulin-like domains and that is presumably conserved in all type IIa receptor protein tyrosine phosphatases. PMID:21402080

Fiber type-specific muscle glycogen sparing due to carbohydrate intake before and during exercise.

PubMed

De Bock, K; Derave, W; Ramaekers, M; Richter, E A; Hespel, P

2007-01-01

The effect of carbohydrate intake before and during exercise on muscle glycogen content was investigated. According to a randomized crossover study design, eight young healthy volunteers (n = 8) participated in two experimental sessions with an interval of 3 wk. In each session subjects performed 2 h of constant-load bicycle exercise ( approximately 75% maximal oxygen uptake). On one occasion (CHO), they received carbohydrates before ( approximately 150 g) and during (1 g.kg body weight(-1).h(-1)) exercise. On the other occasion they exercised after an overnight fast (F). Fiber type-specific relative glycogen content was determined by periodic acid Schiff staining combined with immunofluorescence in needle biopsies from the vastus lateralis muscle before and immediately after exercise. Preexercise glycogen content was higher in type IIa fibers [9.1 +/- 1 x 10(-2) optical density (OD)/microm(2)] than in type I fibers (8.0 +/- 1 x 10(-2) OD/microm(2); P < 0.0001). Type IIa fiber glycogen content decreased during F from 9.6 +/- 1 x 10(-2) OD/microm(2) to 4.5 +/- 1 x 10(-2) OD/microm(2) (P = 0.001), but it did not significantly change during CHO (P = 0.29). Conversely, in type I fibers during CHO and F the exercise bout decreased glycogen content to the same degree. We conclude that the combination of carbohydrate intake both before and during moderate- to high-intensity endurance exercise results in glycogen sparing in type IIa muscle fibers.

Muscle glycogen depletion patterns during draught work in Standardbred horses.

PubMed

Gottlieb, M

1989-03-01

Muscle fibre recruitment was investigated during draught loaded exercise by studying glycogen depletion patterns from histochemical stains of muscle biopsies from the gluteus and semitendinosus muscles. Three Standardbred trotters performed several intervals of draught loaded exercise on a treadmill with 34 kp at a trot (7 m/sec) and with 34 and 80 kp, respectively at a walk (2m/sec). Exercise was continued until the horses were unwilling to continue. Glycogen depletion was seen in all three fibre types when trotting with 34 kp for 5 or 10 mins. When an equal weight resistance was pulled at a walk, glycogen depletion was first seen in type I fibres only, then followed by a small percentage of type IIA fibres after at least 1 h. When 80 kp was pulled at a walk both type I and IIA fibres showed glycogen depletion, and after at least 30 mins exercise a small percentage of type IIB fibres was also depleted. These results indicate that the muscle fibres are depleted, in order, from type I through IIA to IIB as the intensity or duration of draught work increases.

Inhibition of NHEJ repair by type II-A CRISPR-Cas systems in bacteria.

PubMed

Bernheim, Aude; Calvo-Villamañán, Alicia; Basier, Clovis; Cui, Lun; Rocha, Eduardo P C; Touchon, Marie; Bikard, David

2017-12-12

Type II CRISPR-Cas systems introduce double-strand breaks into DNA of invading genetic material and use DNA fragments to acquire novel spacers during adaptation. These breaks can be the substrate of several DNA repair pathways, paving the way for interactions. We report that non-homologous end-joining (NHEJ) and type II-A CRISPR-Cas systems only co-occur once among 5563 fully sequenced prokaryotic genomes. We investigated experimentally the possible molecular interactions using the NHEJ pathway from Bacillus subtilis and the type II-A CRISPR-Cas systems from Streptococcus thermophilus and Streptococcus pyogenes. Our results suggest that the NHEJ system has no effect on CRISPR immunity. On the other hand, we provide evidence for the inhibition of NHEJ repair by the Csn2 protein. Our findings give insights on the complex interactions between CRISPR-Cas systems and repair mechanisms in bacteria, contributing to explain the scattered distribution of CRISPR-Cas systems in bacterial genome.

The secretory phospholipase A2 group IIA: a missing link between inflammation, activated renin-angiotensin system, and atherogenesis?

PubMed

Divchev, Dimitar; Schieffer, Bernhard

2008-01-01

Inflammation, lipid peroxidation and chronic activation of the renin-angiotensin system (RAS) are hallmarks of the development of atherosclerosis. Recent studies have suggested the involvement of the pro-inflammatory secretory phospholipase A(2) (sPLA(2))-IIA in atherogenesis. This enzyme is produced by different cell types through stimulation by pro-inflammatory cytokines. It is detectable in the intima and in media smooth muscle cells, not only in atherosclerotic lesions but also in the very early stages of atherogenesis. sPLA(2)-IIA can hydrolyse the phospholipid monolayers of low density lipoproteins (LDL). Such modified LDL show increased affinity to proteoglycans. The modified particles have a greater tendency to aggregate and an enhanced ability to insert cholesterol into cells. This modification may promote macrophage LDL uptake leading to the formation of foam cells. Furthermore, sPLA(2)-IIA is not only a mediator for localized inflammation but may be also used as an independent predictor of adverse outcomes in patients with stable coronary artery disease or acute coronary syndromes. An interaction between activated RAS and phospholipases has been indicated by observations showing that inhibitors of sPLA(2) decrease angiotensin (Ang) II-induced macrophage lipid peroxidation. Meanwhile, various interactions between Ang II and oxLDL have been demonstrated suggesting a central role of sPLA(2)-IIA in these processes and offering a possible target for treatment. The role of sPLA(2)-IIA in the perpetuation of atherosclerosis appears to be the missing link between inflammation, activated RAS and lipid peroxidation.

Quantifying the Cerebral Hemodynamics of Dural Arteriovenous Fistula in Transverse Sigmoid Sinus Complicated by Sinus Stenosis: A Retrospective Cohort Study.

PubMed

Guo, W-Y; Lee, C-C J; Lin, C-J; Yang, H-C; Wu, H-M; Wu, C-C; Chung, W-Y; Liu, K-D

2017-01-01

Sinus stenosis occasionally occurs in dural arteriovenous fistulas. Sinus stenosis impedes venous outflow and aggravates intracranial hypertension by reversing cortical venous drainage. This study aimed to analyze the likelihood of sinus stenosis and its impact on cerebral hemodynamics of various types of dural arteriovenous fistulas. Forty-three cases of dural arteriovenous fistula in the transverse-sigmoid sinus were reviewed and divided into 3 groups: Cognard type I, type IIa, and types with cortical venous drainage. Sinus stenosis and the double peak sign (occurrence of 2 peaks in the time-density curve of the ipsilateral drainage of the internal jugular vein) in dural arteriovenous fistula were evaluated. "TTP" was defined as the time at which a selected angiographic point reached maximum concentration. TTP of the vein of Labbé, TTP of the ipsilateral normal transverse sinus, trans-fistula time, and trans-stenotic time were compared across the 3 groups. Thirty-six percent of type I, 100% of type IIa, and 84% of types with cortical venous drainage had sinus stenosis. All sinus stenosis cases demonstrated loss of the double peak sign that occurs in dural arteriovenous fistula. Trans-fistula time (2.09 seconds) and trans-stenotic time (0.67 seconds) in types with cortical venous drainage were the most prolonged, followed by those in type IIa and type I. TTP of the vein of Labbé was significantly shorter in types with cortical venous drainage. Six patients with types with cortical venous drainage underwent venoplasty and stent placement, and 4 were downgraded to type IIa. Sinus stenosis indicated dysfunction of venous drainage and is more often encountered in dural arteriovenous fistula with more aggressive types. Venoplasty ameliorates cortical venous drainage in dural arteriovenous fistulas and serves as a bridge treatment to stereotactic radiosurgery in most cases. © 2017 by American Journal of Neuroradiology.

Class IIa histone deacetylases are hormone-activated regulators of FOXO and mammalian glucose homeostasis.

PubMed

Mihaylova, Maria M; Vasquez, Debbie S; Ravnskjaer, Kim; Denechaud, Pierre-Damien; Yu, Ruth T; Alvarez, Jacqueline G; Downes, Michael; Evans, Ronald M; Montminy, Marc; Shaw, Reuben J

2011-05-13

Class IIa histone deacetylases (HDACs) are signal-dependent modulators of transcription with established roles in muscle differentiation and neuronal survival. We show here that in liver, class IIa HDACs (HDAC4, 5, and 7) are phosphorylated and excluded from the nucleus by AMPK family kinases. In response to the fasting hormone glucagon, class IIa HDACs are rapidly dephosphorylated and translocated to the nucleus where they associate with the promoters of gluconeogenic enzymes such as G6Pase. In turn, HDAC4/5 recruit HDAC3, which results in the acute transcriptional induction of these genes via deacetylation and activation of FOXO family transcription factors. Loss of class IIa HDACs in murine liver results in inhibition of FOXO target genes and lowers blood glucose, resulting in increased glycogen storage. Finally, suppression of class IIa HDACs in mouse models of type 2 diabetes ameliorates hyperglycemia, suggesting that inhibitors of class I/II HDACs may be potential therapeutics for metabolic syndrome. Copyright © 2011 Elsevier Inc. All rights reserved.

Simultaneous induction of apoptosis and necroptosis by Tanshinone IIA in human hepatocellular carcinoma HepG2 cells.

PubMed

Lin, C-Y; Chang, T-W; Hsieh, W-H; Hung, M-C; Lin, I-H; Lai, S-C; Tzeng, Y-J

Tanshinone IIA (Tan IIA), a constituent of the traditional medicinal plant Salvia miltiorrhiza BUNGE, has been reported to possess anticancer activity through induction of apoptosis in many cancer cells. Surprisingly, the present study finds that Tan IIA simultaneously causes apoptosis and necroptosis in human hepatocellular carcinoma HepG2 cells. We further find that apoptosis can be converted to necroptosis by pan-caspase inhibitor Z-VAD-fmk, and the two death modes can be blocked by necroptotic inhibitor necrostatin-1. The underlying mechanisms are revealed by analysis of the signaling molecules using western blotting. In control cells, FLICE inhibitory protein in short form (FLIP S ) is expressed in relatively high levels and binds to caspase 8 in ripoptosome, which supposedly sustains cell survival. However, in Tan IIA-treated cells, FLIP S is down-regulated and may thus cause homodimer formation of cleaved caspase 8, cleavage of receptor-interacting serine/threonine-protein kinases 1, 3 (RIP1, RIP3), and mixed-lineage kinase domain-like (MLKL), in turn leads to cell apoptosis. In parallel, Tan IIA causes necroptosis by forming a suggested necrosomal complex composed of RIP1/RIP3. Regarding the inhibitors, z-VAD-fmk diminishes the cleaved caspase 8, RIP1, RIP3, and MLKL induced by Tan IIA, and reconstructs the ripoptosome complex, which marks cells moving from apoptosis to necroptosis. Nec-1 recovers the Tan IIA down-regulated FLIP S , consequently causes FLIP S to form heterodimer with caspase 8 and thus block apoptosis. Meanwhile, cleaved forms of RIP1 and RIP3 were observed preventing necroptosis. Intriguingly, the cytotoxicity of tumor necrosis factor-related apoptosis-inducing ligand to HepG2 cells is enhanced by Tan IIA in a pilot study, which may be attributed to low FLIP S levels induced by Tan IIA. In short, Tan IIA simultaneously induces both Nec-1 inhibition and FLIP S regulation-mediated apoptosis/necroptosis, which has not been previously documented. Moreover, the involvement of the cleavage type of MLKL in executing necroptosis warrants further investigation.

AMPK Signaling Involvement for the Repression of the IL-1β-Induced Group IIA Secretory Phospholipase A2 Expression in VSMCs

PubMed Central

El Hadri, Khadija; Denoyelle, Chantal; Ravaux, Lucas; Viollet, Benoit; Foretz, Marc; Friguet, Bertrand; Rouis, Mustapha; Raymondjean, Michel

2015-01-01

Secretory Phospholipase A2 of type IIA (sPLA2 IIA) plays a crucial role in the production of lipid mediators by amplifying the neointimal inflammatory context of the vascular smooth muscle cells (VSMCs), especially during atherogenesis. Phenformin, a biguanide family member, by its anti-inflammatory properties presents potential for promoting beneficial effects upon vascular cells, however its impact upon the IL-1β-induced sPLA2 gene expression has not been deeply investigated so far. The present study was designed to determine the relationship between phenformin coupling AMP-activated protein kinase (AMPK) function and the molecular mechanism by which the sPLA2 IIA expression was modulated in VSMCs. Here we find that 5-aminoimidazole-4-carboxamide-1-β-D-ribonucleotide (AICAR) treatment strongly repressed IL-1β-induced sPLA2 expression at least at the transcriptional level. Our study reveals that phenformin elicited a dose-dependent inhibition of the sPLA2 IIA expression and transient overexpression experiments of constitutively active AMPK demonstrate clearly that AMPK signaling is involved in the transcriptional inhibition of sPLA2-IIA gene expression. Furthermore, although the expression of the transcriptional repressor B-cell lymphoma-6 protein (BCL-6) was markedly enhanced by phenformin and AICAR, the repression of sPLA2 gene occurs through a mechanism independent of BCL-6 DNA binding site. In addition we show that activation of AMPK limits IL-1β-induced NF-κB pathway activation. Our results indicate that BCL-6, once activated by AMPK, functions as a competitor of the IL-1β induced NF-κB transcription complex. Our findings provide insights on a new anti-inflammatory pathway linking phenformin, AMPK and molecular control of sPLA2 IIA gene expression in VSMCs. PMID:26162096

AMPK Signaling Involvement for the Repression of the IL-1β-Induced Group IIA Secretory Phospholipase A2 Expression in VSMCs.

PubMed

El Hadri, Khadija; Denoyelle, Chantal; Ravaux, Lucas; Viollet, Benoit; Foretz, Marc; Friguet, Bertrand; Rouis, Mustapha; Raymondjean, Michel

2015-01-01

Secretory Phospholipase A2 of type IIA (sPLA2 IIA) plays a crucial role in the production of lipid mediators by amplifying the neointimal inflammatory context of the vascular smooth muscle cells (VSMCs), especially during atherogenesis. Phenformin, a biguanide family member, by its anti-inflammatory properties presents potential for promoting beneficial effects upon vascular cells, however its impact upon the IL-1β-induced sPLA2 gene expression has not been deeply investigated so far. The present study was designed to determine the relationship between phenformin coupling AMP-activated protein kinase (AMPK) function and the molecular mechanism by which the sPLA2 IIA expression was modulated in VSMCs. Here we find that 5-aminoimidazole-4-carboxamide-1-β-D-ribonucleotide (AICAR) treatment strongly repressed IL-1β-induced sPLA2 expression at least at the transcriptional level. Our study reveals that phenformin elicited a dose-dependent inhibition of the sPLA2 IIA expression and transient overexpression experiments of constitutively active AMPK demonstrate clearly that AMPK signaling is involved in the transcriptional inhibition of sPLA2-IIA gene expression. Furthermore, although the expression of the transcriptional repressor B-cell lymphoma-6 protein (BCL-6) was markedly enhanced by phenformin and AICAR, the repression of sPLA2 gene occurs through a mechanism independent of BCL-6 DNA binding site. In addition we show that activation of AMPK limits IL-1β-induced NF-κB pathway activation. Our results indicate that BCL-6, once activated by AMPK, functions as a competitor of the IL-1β induced NF-κB transcription complex. Our findings provide insights on a new anti-inflammatory pathway linking phenformin, AMPK and molecular control of sPLA2 IIA gene expression in VSMCs.

The Relationship between Muscle Fiber Type-Specific PGC-1α Content and Mitochondrial Content Varies between Rodent Models and Humans

PubMed Central

Gouspillou, Gilles; Sgarioto, Nicolas; Norris, Brandon; Barbat-Artigas, Sébastien; Aubertin-Leheudre, Mylène; Morais, Jose A.; Burelle, Yan; Taivassalo, Tanja; Hepple, Russell T.

2014-01-01

PGC-1α regulates critical processes in muscle physiology, including mitochondrial biogenesis, lipid metabolism and angiogenesis. Furthermore, PGC-1α was suggested as an important regulator of fiber type determination. However, whether a muscle fiber type-specific PGC-1α content exists, whether PGC-1α content relates to basal levels of mitochondrial content, and whether such relationships are preserved between humans and classically used rodent models are all questions that have been either poorly addressed or never investigated. To address these issues, we investigated the fiber type-specific content of PGC-1α and its relationship to basal mitochondrial content in mouse, rat and human muscles using in situ immunolabeling and histochemical methods on muscle serial cross-sections. Whereas type IIa fibers exhibited the highest PGC-1α in all three species, other fiber types displayed a hierarchy of type IIx>I>IIb in mouse, type I = IIx> IIb in rat, and type IIx>I in human. In terms of mitochondrial content, we observed a hierarchy of IIa>IIx>I>IIb in mouse, IIa >I>IIx> IIb in rat, and I>IIa> IIx in human skeletal muscle. We also found in rat skeletal muscle that type I fibers displayed the highest capillarization followed by type IIa >IIx>IIb. Finally, we found in human skeletal muscle that type I fibers display the highest lipid content, followed by type IIa>IIx. Altogether, our results reveal that (i) the fiber type-specific PGC-1α and mitochondrial contents were only matched in mouse, (ii) the patterns of PGC-1α and mitochondrial contents observed in mice and rats do not correspond to that seen in humans in several respects, and (iii) the classical phenotypes thought to be regulated by PGC-1α do not vary exclusively as a function of PGC-1α content in rat and human muscles. PMID:25121500

String Theory Origin of Dyonic N=8 Supergravity and Its Chern-Simons Duals.

PubMed

Guarino, Adolfo; Jafferis, Daniel L; Varela, Oscar

2015-08-28

We clarify the higher-dimensional origin of a class of dyonic gaugings of D=4  N=8 supergravity recently discovered, when the gauge group is chosen to be ISO(7). This dyonically gauged maximal supergravity arises from consistent truncation of massive IIA supergravity on S^6, and its magnetic coupling constant descends directly from the Romans mass. The critical points of the supergravity uplift to new four-dimensional anti-de Sitter space (AdS4) massive type IIA vacua. We identify the corresponding three-dimensional conformal field theory (CFT3) duals as super-Chern-Simons-matter theories with simple gauge group SU(N) and level k given by the Romans mass. In particular, we find a critical point that uplifts to the first explicit N=2 AdS4 massive IIA background. We compute its free energy and that of the candidate dual Chern-Simons theory by localization to a solvable matrix model, and find perfect agreement. This provides the first AdS4/CFT3 precision match in massive type IIA string theory.

Exercise increases the plasma membrane content of the Na+ -K+ pump and its mRNA in rat skeletal muscles.

PubMed

Tsakiridis, T; Wong, P P; Liu, Z; Rodgers, C D; Vranic, M; Klip, A

1996-02-01

Muscle fibers adapt to ionic challenges of exercise by increasing the plasma membrane Na+-K+ pump activity. Chronic exercise training has been shown to increase the total amount of Na+-K+ pumps present in skeletal muscle. However, the mechanism of adaptation of the Na+-K+ pump to an acute bout of exercise has not been determined, and it is not known whether it involves alterations in the content of plasma membrane pump subunits. Here we examine the effect of 1 h of treadmill running (20 m/min, 10% grade) on the subcellular distribution and expression of Na+-K+ pump subunits in rat skeletal muscles. Red type I and IIa (red-I/IIa) and white type IIa and IIb (white-IIa/IIb) hindlimb muscles from resting and exercised female Sprague-Dawley rats were removed for subcellular fractionation. By homogenization and gradient centrifugation, crude membranes and purified plasma membranes were isolated and subjected to gel electrophoresis and immunoblotting by using pump subunit-specific antibodies. Furthermore, mRNA was isolated from specific red type I (red-I) and white type IIb (white-IIb) muscles and subjected to Northern blotting by using subunit-specific probes. In both red-I/IIa and white-IIa/IIb muscles, exercise significantly raised the plasma membrane content of the alpha1-subunit of the pump by 64 +/- 24 and 55 +/- 22%, respectively (P < 0.05), and elevated the alpha2-polypeptide by 43 +/- 22 and 94 +/- 39%, respectively (P < 0.05). No significant effect of exercise could be detected on the amount of these subunits in an internal membrane fraction or in total membranes. In addition, exercise significantly increased the alpha1-subunit mRNA in red-I muscle (by 50 +/- 7%; P < 0.05) and the beta2-subunit mRNA in white-IIb muscles (by 64 +/- 19%; P < 0.01), but the alpha2- and beta1-mRNA levels were unaffected in this time period. We conclude that increased presence of alpha1- and alpha2-polypeptides at the plasma membrane and subsequent elevation of the alpha1- and beta2-subunit mRNAs may be mechanisms by which acute exercise regulates the Na+-K+ pump of skeletal muscle.

Autosomal dominant myopathy: missense mutation (Glu-706 --> Lys) in the myosin heavy chain IIa gene.

PubMed

Martinsson, T; Oldfors, A; Darin, N; Berg, K; Tajsharghi, H; Kyllerman, M; Wahlstrom, J

2000-12-19

We here report on a human myopathy associated with a mutation in a fast myosin heavy chain (MyHC) gene, and also the genetic defect in a hereditary inclusion body myopathy. The disorder has previously been described in a family with an "autosomal dominant myopathy, with joint contractures, ophthalmoplegia, and rimmed vacuoles." Linkage analysis and radiation hybrid mapping showed that the gene locus (Human Genome Map locus name: IBM3) is situated in a 2-Mb region of chromosome 17p13, where also a cluster of MyHC genes is located. These include the genes encoding embryonic, IIa, IIx/d, IIb, perinatal, and extraocular MyHCs. Morphological analysis of muscle biopsies from patients from the family indicated to us that the type 2A fibers frequently were abnormal, whereas other fiber types appeared normal. This observation prompted us to investigate the MyHC-IIa gene, since MyHC-IIa is the major isoform in type 2A fibers. The complete genomic sequence for this gene was deduced by using an "in silico" strategy. The gene, found to consist of 38 exons, was subjected to a complete mutation scan in patients and controls. We identified a missense mutation, Glu-706 --> Lys, which is located in a highly conserved region of the motor domain, the so-called SH1 helix region. By conformational changes this region communicates activity at the nucleotide-binding site to the neck region, resulting in the lever arm swing. The mutation in this region is likely to result in a dysfunctional myosin, compatible with the disorder in the family.

Fiber type dependent upregulation of human skeletal muscle UCP2 and UCP3 mRNA expression by high-fat diet.

PubMed

Schrauwen, P; Hoppeler, H; Billeter, R; Bakker, A H; Pendergast, D R

2001-04-01

To test the hypothesis that consumption of a high-fat diet leads to an increase in UCP mRNA expression in human skeletal muscle. In a group of endurance athletes, with a range in fiber type distribution, we hypothesized that the effect of the high-fat diet on UCP2 and UCP3 mRNA expression is more pronounced in muscle fibers which are known to have a high capacity to shift from carbohydrate to fat oxidation (type IIA fibers). Ten healthy trained athletes (five males, five females) consumed a low-fat diet (17+/-0.9 en% of fat) and high-fat diet (41.4+/-1.4 en% fat) for 4 weeks, separated by a 4 week wash-out period. Muscle biopsies were collected at the end of both dietary periods. Using RT-PCR, levels of UCP2 and UCP3 mRNA expression were measured and the percentage of type I, IIA and IIB fibers were determined using the myofibrillar ATPase method in all subjects. UCP3L mRNA expression tended to be higher on the high-fat diet, an effect which reached significance when only males were considered (P=0.037). Furthermore, diet-induced change in mRNA expression of UCP3T (r: 0.66, P=0.037), UCP3L (r: 0.61, P=0.06) and UCP2 (r: 0.70, P=0.025), but not UCP3S, correlated significantly with percentage dietary fat on the high-fat diet. Plasma FFA levels were not different during the two diets. Finally, the percentage of type IIA fibers was positively correlated with the diet-induced change in mRNA expression for UCP2 (r: 0.7, P=0.03), UCP3L (r: 0.73, P=0.016) and UCP3T (r: 0.68, P=0.03) but not with UCP3S (r: 0.06, NS). UCP2 and UCP3 mRNAs are upregulated by a high-fat diet. This upregulation is more pronounced in humans with high proportions of type IIA fibers, suggesting a role for UCPs in lipid utilization.

Initial Experience with the E-liac® Iliac Branch Device for the Endovascular Aortic Repair of Aorto-iliac Aneurysm.

PubMed

Anton, Susanne; Wiedner, Marcus; Stahlberg, Erik; Jacob, Fabian; Barkhausen, Jörg; Goltz, Jan Peter

2018-05-01

Occlusion of internal iliac arteries during endovascular treatment (EVAR) of abdominal aortic (AAA) and common iliac artery aneurysms might be associated with ischemic pelvic complications. This study evaluates technical and clinical success, safety and mid-term results of a novel iliac branch device (IBD) for revascularization of the internal iliac artery (IIA) during EVAR. Retrospectively, we identified 21 men (mean age 73.3 ± 6.2 years) treated for aorto-iliac aneurysms by use of a novel IBD (E-liac ® , Jotec Hechingen, Germany). We analyzed safety (30-day survival), technical (no type I and III endoleaks, "EL"), clinical (no ischemic complications) success, mid-term patency of this IBD, peri-procedural complications, occurrence of type II ELs, rate of re-interventions and additional treatment of the revascularized IIA for landing zone preparation. Twenty-three IBDs were implanted. Aneurysms of the ipsilateral IIA were present in 6/23 IIAs (26.1%). Super-selective branch embolization was performed in these patients and the landing zone for the iliac sidebranch stent-graft was within the superior gluteal artery. Mean follow-up was 341 days (range 4-1103 days). Technical success and 30-day survival were 100%. Clinical success was 95.2%. Primary patency of the IBDs was 100% at 12 months. Peri-procedural complications occurred in 3/21 patients (14.3%), none of them related to the IBD. AAA-related type II ELs were found in 6 patients (28.6%), IBD-related ELs in 4/23 IBDs (17.4%) (two type Ib, two type II endoleaks). Overall re-intervention rate was 23.8%, IBD-related 8.7%. Utilization of the E-liac ® IBD is safe and effective for the treatment of aorto-iliac aneurysms.

Septin 7 reduces nonmuscle myosin IIA activity in the SNAP23 complex and hinders GLUT4 storage vesicle docking and fusion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wasik, Anita A.; Dumont, Vincent; Tienari, Jukka

Glomerular epithelial cells, podocytes, are insulin responsive and can develop insulin resistance. Here, we demonstrate that the small GTPase septin 7 forms a complex with nonmuscle myosin heavy chain IIA (NMHC-IIA; encoded by MYH9), a component of the nonmuscle myosin IIA (NM-IIA) hexameric complex. We observed that knockdown of NMHC-IIA decreases insulin-stimulated glucose uptake into podocytes. Both septin 7 and NM-IIA associate with SNAP23, a SNARE protein involved in GLUT4 storage vesicle (GSV) docking and fusion with the plasma membrane. We observed that insulin decreases the level of septin 7 and increases the activity of NM-IIA in the SNAP23 complex,more » as visualized by increased phosphorylation of myosin regulatory light chain. Also knockdown of septin 7 increases the activity of NM-IIA in the complex. The activity of NM-IIA is increased in diabetic rat glomeruli and cultured human podocytes exposed to macroalbuminuric sera from patients with type 1 diabetes. Collectively, the data suggest that the activity of NM-IIA in the SNAP23 complex plays a key role in insulin-stimulated glucose uptake into podocytes. Furthermore, we observed that septin 7 reduces the activity of NM-IIA in the SNAP23 complex and thereby hinders GSV docking and fusion with the plasma membrane. - Highlights: • Septin 7, nonmuscle myosin heavy chain IIA (NMHC-IIA) and SNAP23 form a complex. • Knockdown of septin 7 increases NM-IIA activity in the SNAP23 complex. • Insulin decreases septin 7 level and increases NM-IIA activity in the SNAP23 complex. • Septin 7 hinders GSV docking/fusion by reducing NM-IIA activity in the SNAP23 complex.« less

Qubit and fermionic Fock spaces from type II superstring black holes

NASA Astrophysics Data System (ADS)

Belhaj, A.; Bensed, M.; Benslimane, Z.; Sedra, M. B.; Segui, A.

Using Hodge diagram combinatorial data, we study qubit and fermionic Fock spaces from the point of view of type II superstring black holes based on complex compactifications. Concretely, we establish a one-to-one correspondence between qubits, fermionic spaces and extremal black holes in maximally supersymmetric supergravity obtained from type II superstring on complex toroidal and Calabi-Yau compactifications. We interpret the differential forms of the n-dimensional complex toroidal compactification as states of n-qubits encoding information on extremal black hole charges. We show that there are 2n copies of n qubit systems which can be split as 2n = 2n-1 + 2n-1. More precisely, 2n-1 copies are associated with even D-brane charges in type IIA superstring and the other 2n-1 ones correspond to odd D-brane charges in IIB superstring. This correspondence is generalized to a class of Calabi-Yau manifolds. In connection with black hole charges in type IIA superstring, an n-qubit system has been obtained from a canonical line bundle of n factors of one-dimensional projective space ℂℙ1.

Cryptosporidium parvum genotype IIa and Giardia duodenalis assemblage A in Mytilus galloprovincialis on sale at local food markets.

PubMed

Giangaspero, Annunziata; Papini, Roberto; Marangi, Marianna; Koehler, Anson V; Gasser, Robin B

2014-02-03

To date, there has been no study to establish the genotypic or subgenotypic identities of Cryptosporidium and Giardia in edible shellfish. Here, we explored the genetic composition of these protists in Mytilus galloprovincialis (Mediterranean mussel) purchased from three markets in the city of Foggia, Italy, from May to December 2012. Samples from the digestive glands, gills and haemolymph were tested by nested PCR, targeting DNA regions within the 60 kDa glycoprotein (gp60) gene of Cryptosporidium, and the triose-phosphate isomerase (tpi) and β-giardin genes of Giardia. In total, Cryptosporidium and Giardia were detected in 66.7% of mussels (M. galloprovincialis) tested. Cryptosporidium was detected mostly between May and September 2012. Sequencing of amplicons showed that 60% of mussels contained Cryptosporidium parvum genotype IIa (including subgenotypes A15G2R1, IIaA15G2 and IIaA14G3R1), 23.3% Giardia duodenalis assemblage A, and 6.6% had both genetic types. This is the first report of these types in fresh, edible shellfish, particularly the very commonly consumed M. galloprovincialis from highly frequented fish markets. These genetic types of Cryptosporidium and Giardia are known to infect humans and thus likely to represent a significant public health risk. The poor observance of hygiene rules by vendors, coupled to the large numbers of M. galloprovincialis sold and the eating habits of consumers in Italy, call for more effective sanitary measures pertaining to the selling of fresh shellfish in street markets. Copyright © 2013 Elsevier B.V. All rights reserved.

Single muscle fiber adaptations with marathon training.

PubMed

Trappe, Scott; Harber, Matthew; Creer, Andrew; Gallagher, Philip; Slivka, Dustin; Minchev, Kiril; Whitsett, David

2006-09-01

The purpose of this investigation was to characterize the effects of marathon training on single muscle fiber contractile function in a group of recreational runners. Muscle biopsies were obtained from the gastrocnemius muscle of seven individuals (22 +/- 1 yr, 177 +/- 3 cm, and 68 +/- 2 kg) before, after 13 wk of run training, and after 3 wk of taper. Slow-twitch myosin heavy chain [(MHC) I] and fast-twitch (MHC IIa) muscle fibers were analyzed for size, strength (P(o)), speed (V(o)), and power. The run training program led to the successful completion of a marathon (range 3 h 56 min to 5 h 35 min). Oxygen uptake during submaximal running and citrate synthase activity were improved (P < 0.05) with the training program. Muscle fiber size declined (P < 0.05) by approximately 20% in both fiber types after training. P(o) was maintained in both fiber types with training and increased (P < 0.05) by 18% in the MHC IIa fibers after taper. This resulted in >60% increase (P < 0.05) in force per cross-sectional area in both fiber types. Fiber V(o) increased (P < 0.05) by 28% in MHC I fibers with training and was unchanged in MHC IIa fibers. Peak power increased (P < 0.05) in MHC I and IIa fibers after training with a further increase (P < 0.05) in MHC IIa fiber power after taper. These data show that marathon training decreased slow-twitch and fast-twitch muscle fiber size but that it maintained or improved the functional profile of these fibers. A taper period before the marathon further improved the functional profile of the muscle, which was targeted to the fast-twitch muscle fibers.

Black hole entropy in massive Type IIA

NASA Astrophysics Data System (ADS)

Benini, Francesco; Khachatryan, Hrachya; Milan, Paolo

2018-02-01

We study the entropy of static dyonic BPS black holes in AdS4 in 4d N=2 gauged supergravities with vector and hyper multiplets, and how the entropy can be reproduced with a microscopic counting of states in the AdS/CFT dual field theory. We focus on the particular example of BPS black holes in AdS{\\hspace{0pt}}4 × S6 in massive Type IIA, whose dual three-dimensional boundary description is known and simple. To count the states in field theory we employ a supersymmetric topologically twisted index, which can be computed exactly with localization techniques. We find a perfect match at leading order.

Myosin heavy chain profile of equine gluteus medius muscle following prolonged draught-exercise training and detraining.

PubMed

Serrano, A L; Rivero, J L

2000-04-01

Fourteen 4-year old Andalusian mares were used to examine the plasticity of myosin heavy chain (MHC) composition in horse skeletal muscle with heavy draught-exercise training and detraining. Seven horses underwent a training programme based on carriage exercises for 8 months. Afterwards, they were kept in paddocks for 3 months. The remaining seven animals were used as control horses. Three gluteus medius muscle biopsies were removed at depths of 20, 40 and 60 mm from each horse before (month 0), during the training (months 3 and 8) and after detraining (month 11). Myosin heavy chain composition was analysed by electrophoresis and immunohistochemically with anti-MHC monoclonal antibodies. Fibre areas, oxidative capacity and capillaries were studied histochemically. After 8 months of training, MHC-IIX and IIX fibres decreased whereas MHC-I and type I and I + IIA fibres increased. Neither MHC-IIA nor the percentage of IIA fibres changed when the data were considered as a whole, but the proportion of MHC-IIA increased in the superficial region of the muscle after 8 months of training. Mean areas of type II fibres were not affected by training and detraining, but the cross-sectional of type I fibres increased after 3 month of training and not further increases were recorded afterward. The percentage of high-oxidative capacity fibres and the number of capillaries per mm2 increased with training. Most of these muscular adaptations reverted after detraining. These results indicate that long term draught-exercise training induces a reversible transition of MHC composition in equine muscle in the order IIX --> IIA --> I. The physiological implication of these changes is an impact on the velocity of shortening and fatigue resistance of muscle fibres.

The expression of NFATc1 in adult rat skeletal muscle fibres.

PubMed

Mutungi, Gabriel

2008-03-01

Although numerous studies have recently implicated the calcineurin-nuclear factor of activated T-cells (Cn-NFAT) signalling pathway in the regulation of activity-dependent fibre type switching in adult mammalian skeletal muscles, little is known about the endogenous expression of NFAT proteins in the various fibre types present in these muscles. In this study, the immunolocalization of NFATc1 (also known as NFATc or NFAT2) in the extensor digitorum longus (EDL; a mainly fast-twitch muscle) and the soleus (a predominantly slow-twitch muscle) muscles of adult ( approximately 90-day-old) Wistar rats was investigated. The results show that NFATc1 is expressed only in oxidative fibres (i.e. type I and type IIA fibres) that stain intensely for succinate dehydrogenase activity irrespective of whether they are from the fast- or slow-twitch muscle. Thus, 99 +/- 4% (n = 7 rats) of the muscle fibres in the soleus and 42 +/- 2% (n = 7 rats) of those in the EDL expressed NFATc1. In the soleus muscle fibres, NFATc1 was localized mainly in the fibre nuclei, whereas in the EDL fibres it was localized in both the cytoplasm and the nuclei. However, no difference in its localization was observed between type I and type IIA fibres in both muscles. Western blot experiments showed that the soleus expressed more NFATc1 proteins than the EDL. From these results, we suggest that NFATc1 controls the number and distribution of both type I and type IIA fibres, as well as the oxidative capacity of adult mammalian skeletal muscles.

Myosin heavy chain isoform composition and Ca(2+) transients in fibres from enzymatically dissociated murine soleus and extensor digitorum longus muscles.

PubMed

Calderón, Juan C; Bolaños, Pura; Caputo, Carlo

2010-01-01

Electrically elicited Ca(2+) transients reported with the fast Ca(2+) dye MagFluo-4 AM and myosin heavy chain (MHC) electrophoretic patterns were obtained in intact, enzymatically dissociated fibres from adult mice extensor digitorum longus (EDL) and soleus muscles. Thirty nine fibres (23 from soleus and 16 from EDL) were analysed by both fluorescence microscopy and electrophoresis. These fibres were grouped as follows: group 1 included 13 type I and 4 type IC fibres; group 2 included 2 type IIC, 3 IIA and 1 I/IIA/IIX fibres; group 3 included 4 type IIX and 1 type IIX/IIB fibres; group 4 included 2 type IIB/IIX and 9 type IIB fibres. Ca(2+) transients obtained in groups 1, 2, 3 and 4 had the following kinetic parameters (mean +/- s.e.m.): amplitude (F/F): 0.61 +/- 0.05, 0.53 +/- 0.08, 0.61 +/- 0.06 and 0.61 +/- 0.03; rise time (ms): 1.64 +/- 0.05, 1.35 +/- 0.05, 1.18 +/- 0.06 and 1.14 +/- 0.04; half-amplitude width (ms): 19.12 +/- 1.85, 11.86 +/- 3.03, 4.62 +/- 0.31 and 4.23 +/- 0.37; and time constants of decay (tau(1) and tau(2), ms): 3.33 +/- 0.13 and 52.48 +/- 3.93, 2.69 +/- 0.22 and 41.06 +/- 9.13, 1.74 +/- 0.06 and 12.88 +/- 1.93, and 1.56 +/- 0.11 and 9.45 +/- 1.03, respectively. The statistical differences between the four groups and the analysis of the distribution of the parameters of Ca(2+) release and clearance show that there is a continuum from slow to fast, that parallels the MHC continuum from pure type I to pure IIB. However, type IIA fibres behave more like IIX and IIB fibres regarding Ca(2+) release but closer to type I fibres regarding Ca(2+) clearance. In conclusion, we show for the first time the diversity of Ca(2+) transients for the whole continuum of fibre types and correlate this functional diversity with the structural and biochemical diversity of the skeletal muscle fibres.

Novel single skeletal muscle fiber analysis reveals a fiber type-selective effect of acute exercise on glucose uptake.

PubMed

Cartee, Gregory D; Arias, Edward B; Yu, Carmen S; Pataky, Mark W

2016-11-01

One exercise session can induce subsequently elevated insulin sensitivity that is largely attributable to greater insulin-stimulated glucose uptake by skeletal muscle. Because skeletal muscle is a heterogeneous tissue comprised of diverse fiber types, our primary aim was to determine exercise effects on insulin-independent and insulin-dependent glucose uptake by single fibers of different fiber types. We hypothesized that each fiber type featuring elevated insulin-independent glucose uptake immediately postexercise (IPEX) would be characterized by increased insulin-dependent glucose uptake at 3.5 h postexercise (3.5hPEX). Rat epitrochlearis muscles were isolated and incubated with 2-[ 3 H]deoxyglucose. Muscles from IPEX and sedentary (SED) controls were incubated without insulin. Muscles from 3.5hPEX and SED controls were incubated ± insulin. Glucose uptake (2-[ 3 H]deoxyglucose accumulation) and fiber type (myosin heavy chain isoform expression) were determined for single fibers dissected from the muscles. Major new findings included the following: 1) insulin-independent glucose uptake was increased IPEX in single fibers of each fiber type (types I, IIA, IIB, IIBX, and IIX), 2) glucose uptake values from insulin-stimulated type I and IIA fibers exceeded the values for the other fiber types, 3) insulin-stimulated glucose uptake for type IIX exceeded IIB fibers, and 4) the 3.5hPEX group vs. SED had greater insulin-stimulated glucose uptake in type I, IIA, IIB, and IIBX but not type IIX fibers. Insulin-dependent glucose uptake was increased at 3.5hPEX in each fiber type except for IIX fibers, although insulin-independent glucose uptake was increased IPEX in all fiber types (including type IIX). Single fiber analysis enabled the discovery of this fiber type-related difference for postexercise, insulin-stimulated glucose uptake. Copyright © 2016 the American Physiological Society.

Tanshinone IIA protects PC12 cells from β-amyloid(25-35)-induced apoptosis via PI3K/Akt signaling pathway.

PubMed

Dong, Huimin; Mao, Shanping; Mao, Shanpin; Wei, Jiajun; Liu, Baohui; Zhang, Zhaohui; Zhang, Qian; Yan, Mingmin

2012-06-01

For the aging populations of any nation, Dementia is becoming a primary problem and Alzheimer’s dementia (AD) is the most common type. However, until now, there is no effective treatment for AD. Tanshinone IIA (Tan IIA) has been reported for neuroprotective potential to against amyloid β peptides (Aβ)-induced cytotoxicity in the rat pheochromocytoma cell line PC-12, which is widely used as AD research model, but the mechanism still remains unclear. To investigate the effect of Tan IIA and the possible molecular mechanism in the apoptosis of PC12 cells, we induced apoptosis in PC12 cells with β-amyloid(25-35), and treated cells with Tan IIA. After 24 h treatment, we found that Tan IIA increased the cell viability and reduced the number of apoptotic cells induced by Aβ(25-35). However, neuroprotection of Tan IIA was abolished by PI3K inhibitor LY294002. Meanwhile, Treatment with lithium chloride, a phosphorylation inhibitor of GSK3β, which is a downstream target of PI3K/Akt, can block Aβ(25-35)-induced cell apoptosis in a Tan IIA-like manner. Our findings suggest that Tan IIA is an effective neuroprotective agent and a viable candidate in AD therapy and PI3K/Akt activation and GSK3β phosphorylation are involved in the neuroprotection of Tan IIA.

Regulation of myosin IIA and filamentous actin during insulin-stimulated glucose uptake in 3T3-L1 adipocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stall, Richard; Ramos, Joseph; Kent Fulcher, F.

Insulin stimulated glucose uptake requires the colocalization of myosin IIA (MyoIIA) and the insulin-responsive glucose transporter 4 (GLUT4) at the plasma membrane for proper GLUT4 fusion. MyoIIA facilitates filamentous actin (F-actin) reorganization in various cell types. In adipocytes F-actin reorganization is required for insulin-stimulated glucose uptake. What is not known is whether MyoIIA interacts with F-actin to regulate insulin-induced GLUT4 fusion at the plasma membrane. To elucidate the relationship between MyoIIA and F-actin, we examined the colocalization of MyoIIA and F-actin at the plasma membrane upon insulin stimulation as well as the regulation of this interaction. Our findings demonstrated thatmore » MyoIIA and F-actin colocalized at the site of GLUT4 fusion with the plasma membrane upon insulin stimulation. Furthermore, inhibition of MyoII with blebbistatin impaired F-actin localization at the plasma membrane. Next we examined the regulatory role of calcium in MyoIIA-F-actin colocalization. Reduced calcium or calmodulin levels decreased colocalization of MyoIIA and F-actin at the plasma membrane. While calcium alone can translocate MyoIIA it did not stimulate F-actin accumulation at the plasma membrane. Taken together, we established that while MyoIIA activity is required for F-actin localization at the plasma membrane, it alone is insufficient to localize F-actin to the plasma membrane. - Highlights: • Insulin induces colocalization of MyoIIA and F-actin at the cortex in adipocytes. • MyoIIA is necessary but not sufficient to localize F-actin at the cell cortex. • MyoIIA-F-actin colocalization is regulated by calcium and calmodulin.« less

Changes in skeletal muscle biochemistry and histology relative to fiber type in rats with heart failure.

PubMed

Delp, M D; Duan, C; Mattson, J P; Musch, T I

1997-10-01

One of the primary consequences of left ventricular dysfunction (LVD) after myocardial infarction is a decrement in exercise capacity. Several factors have been hypothesized to account for this decrement, including alterations in skeletal muscle metabolism and aerobic capacity. The purpose of this study was to determine whether LVD-induced alterations in skeletal muscle enzyme activities, fiber composition, and fiber size are 1) generalized in muscles or specific to muscles composed primarily of a given fiber type and 2) related to the severity of the LVD. Female Wistar rats were divided into three groups: sham-operated controls (n = 13) and rats with moderate (n = 10) and severe (n = 7) LVD. LVD was surgically induced by ligating the left main coronary artery and resulted in elevations (P < 0.05) in left ventricular end-diastolic pressure (sham, 5 +/- 1 mmHg; moderate LVD, 11 +/- 1 mmHg; severe LVD, 25 +/- 1 mmHg). Moderate LVD decreased the activities of phosphofructokinase (PFK) and citrate synthase in one muscle composed of type IIB fibers but did not modify fiber composition or size of any muscle studied. However, severe LVD diminished the activity of enzymes involved in terminal and beta-oxidation in muscles composed primarily of type I fibers, type IIA fibers, and type IIB fibers. In addition, severe LVD induced a reduction in the activity of PFK in type IIB muscle, a 10% reduction in the percentage of type IID/X fibers, and a corresponding increase in the portion of type IIB fibers. Atrophy of type I fibers, type IIA fibers, and/or type IIB fibers occurred in soleus and plantaris muscles of rats with severe LVD. These data indicate that rats with severe LVD after myocardial infarction exhibit 1) decrements in mitochondrial enzyme activities independent of muscle fiber composition, 2) a reduction in PFK activity in type IIB muscle, 3) transformation of type IID/X to type IIB fibers, and 4) atrophy of type I, IIA, and IIB fibers.

Changes in skeletal muscle biochemistry and histology relative to fiber type in rats with heart failure

NASA Technical Reports Server (NTRS)

Delp, M. D.; Duan, C.; Mattson, J. P.; Musch, T. I.

1997-01-01

One of the primary consequences of left ventricular dysfunction (LVD) after myocardial infarction is a decrement in exercise capacity. Several factors have been hypothesized to account for this decrement, including alterations in skeletal muscle metabolism and aerobic capacity. The purpose of this study was to determine whether LVD-induced alterations in skeletal muscle enzyme activities, fiber composition, and fiber size are 1) generalized in muscles or specific to muscles composed primarily of a given fiber type and 2) related to the severity of the LVD. Female Wistar rats were divided into three groups: sham-operated controls (n = 13) and rats with moderate (n = 10) and severe (n = 7) LVD. LVD was surgically induced by ligating the left main coronary artery and resulted in elevations (P < 0.05) in left ventricular end-diastolic pressure (sham, 5 +/- 1 mmHg; moderate LVD, 11 +/- 1 mmHg; severe LVD, 25 +/- 1 mmHg). Moderate LVD decreased the activities of phosphofructokinase (PFK) and citrate synthase in one muscle composed of type IIB fibers but did not modify fiber composition or size of any muscle studied. However, severe LVD diminished the activity of enzymes involved in terminal and beta-oxidation in muscles composed primarily of type I fibers, type IIA fibers, and type IIB fibers. In addition, severe LVD induced a reduction in the activity of PFK in type IIB muscle, a 10% reduction in the percentage of type IID/X fibers, and a corresponding increase in the portion of type IIB fibers. Atrophy of type I fibers, type IIA fibers, and/or type IIB fibers occurred in soleus and plantaris muscles of rats with severe LVD. These data indicate that rats with severe LVD after myocardial infarction exhibit 1) decrements in mitochondrial enzyme activities independent of muscle fiber composition, 2) a reduction in PFK activity in type IIB muscle, 3) transformation of type IID/X to type IIB fibers, and 4) atrophy of type I, IIA, and IIB fibers.

Tanshinone IIA ameliorates dextran sulfate sodium-induced inflammatory bowel disease via the pregnane X receptor

PubMed Central

Zhang, Xianxie; Wang, Yuguang; Ma, Zengchun; Liang, Qiande; Tang, Xianglin; Hu, Donghua; Tan, Hongling; Xiao, Chengrong; Gao, Yue

2015-01-01

Tanshinone IIA (Tan IIA) (C19H18O3) is one of the major active lipophilic components in a conventional Chinese medicine called danshen, and it has long been used in the People’s Republic of China and other neighboring countries to treat patients suffering from inflammatory bowel disease (IBD). Previous experiments by many teams determined which mechanism of Tan IIA is relevant to the treatment of IBD associated with inflammation and the pregnane X receptor (PXR). The current study demonstrated that Tan IIA is an efficacious PXR agonist and its ability to induce CYP3A4 mRNA and protein expression was mediated by the transactivation of PXR, a known target of abrogating inflammation in IBD. Clinical symptoms in mice and histological assessment data suggested that administration of Tan IIA in mice demonstrated significant protection and showed that in DSS-induced IBD it acts in a concentration-dependent manner. PXR-silenced mice treated with Tan IIA demonstrated low protection against DSS-induced mouse IBD and exacerbated the severity of IBD compared with wild-type mice; PXR-silenced mice demonstrated the necessity for PXR in Tan IIA-mediated upregulation of xenobiotic metabolism genes. The IBD treatment effects of Tan IIA are partially due to PXR-mediated upregulation of xenobiotic metabolism and downregulation of inflammatory mediators. The novel findings reported here may contribute to the effective utilization of Tan IIA and its derivatives as a PXR ligand in the treatment of human IBD. This suggests that Tan IIA may have considerable clinical utility. PMID:26674743

Tanshinone IIA protects H9c2 cells from oxidative stress-induced cell death via microRNA-133 upregulation and Akt activation.

PubMed

Gu, Yunfei; Liang, Zhuo; Wang, Haijun; Jin, Jun; Zhang, Shouyan; Xue, Shufeng; Chen, Jianfeng; He, Huijuan; Duan, Kadan; Wang, Jing; Chang, Xuewei; Qiu, Chunguang

2016-08-01

The aim of the present study was to investigate the cardioprotective effect of tanshinone IIA and the underlying molecular mechanisms. An in vitro model of oxidative stress injury was established in cardiac H9c2 cells, and the effects of tanshinone IIa were investigated using cell viability, reverse transcription-quantitative polymerase chain reaction and western blotting assays. The results demonstrated that tanshinone IIA protects H9c2 cells from H 2 O 2 -induced cell death in a concentration-dependent manner, via a mechanism involving microRNA-133 (miR-133), and that treatment with TIIA alone exerted no cytotoxic effects on H9c2. In order to further elucidate the mechanisms underlying the actions of TIIA, reverse transcription-quantitative polymease chain reaction and western blot analysis were performed. Reductions in miR-133 expression levels induced by increasing concentrations of H 2 O 2 were reversed by treatment with tanshinone IIA. In addition, the inhibition of miR-133 by transfection with an miR-133 inhibitor abolished the cardioprotective effects of tanshinone IIA against H 2 O 2 -induced cell death. Furthermore, western blot analysis demonstrated that tanshinone IIA activated Akt kinase via the phosphorylation of serine 473. Inhibition of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway by pretreatment with the PI3K specific inhibitors wortmannin and LY294002 also eliminated the cardioprotective effects of tanshinone IIA against H 2 O 2 -induced cell death. Western blot analysis demonstrated that H 2 O 2 -induced reductions in B cell lymphoma 2 (Bcl-2) expression levels were reversed by tanshinone IIA. In addition, the effect of tanshinone IIA on Bcl-2 protein expression level in an oxidative environment was suppressed by a PI3K inhibitor, wortmannin, indicating that tanshinone IIA exerts cardioprotective effects against H 2 O 2 -induced cell death via the activation of the PI3K/Akt signal transduction pathway and the consequent upregulation of Bcl-2. In conclusion, the present study demonstrates that TIIA is able to protcet H9c2 cells from oxidative stress-induced cell death through signalling pathways involving miR-133 and Akt, and that tanshinone IIA is a promising natural cardioprotective agent.

Ifosfamide metabolites CAA, 4-OH-Ifo and Ifo-mustard reduce apical phosphate transport by changing NaPi-IIa in OK cells.

PubMed

Patzer, L; Hernando, N; Ziegler, U; Beck-Schimmer, B; Biber, J; Murer, H

2006-11-01

Renal Fanconi syndrome occurs in about 1-5% of all children treated with Ifosfamide (Ifo) and impairment of renal phosphate reabsorption in about 20-30% of them. Pathophysiological mechanisms of Ifo-induced nephropathy are ill defined. The aim has been to investigate whether Ifo metabolites affect the type IIa sodium-dependent phosphate transporter (NaPi-IIa) in viable opossum kidney cells. Ifo did not influence viability of cells or NaPi-IIa-mediated transport up to 1 mM/24 h. Incubation of confluent cells with chloroacetaldehyde (CAA) and 4-hydroperoxyIfosfamide (4-OH-Ifo) led to cell death by necrosis in a concentration-dependent manner. At low concentrations (50-100 microM/24 h), cell viability was normal but apical phosphate transport, NaPi-IIa protein, and -mRNA expression were significantly reduced. Coincubation with sodium-2-mercaptoethanesulfonate (MESNA) prevented the inhibitory action of CAA but not of 4-OH-Ifo; DiMESNA had no effect. Incubation with Ifosfamide-mustard (Ifo-mustard) did alter cell viability at concentrations above 500 microM/24 h. At lower concentrations (50-100 microM/24 h), it led to significant reduction in phosphate transport, NaPi-IIa protein, and mRNA expression. MESNA did not block these effects. The effect of Ifo-mustard was due to internalization of NaPi-IIa. Cyclophosphamide-mustard (CyP-mustard) did not have any influence on cell survival up to 1000 microM, but the inhibitory effect on phosphate transport and on NaPi-IIa protein was the same as found after Ifo-mustard. In conclusion, CAA, 4-OH-Ifo, and Ifo- and CyP-mustard are able to inhibit sodium-dependent phosphate cotransport in viable opossum kidney cells. The Ifo-mustard effect took place via internalization and reduction of de novo synthesis of NaPi-IIa. Therefore, it is possible that Ifo-mustard plays an important role in pathogenesis of Ifo-induced nephropathy.

Cheiloscopy and dermatoglyphics as genetic markers in the transmission of cleft lip and palate: A case-control study.

PubMed

Saujanya, K; Prasad, M Ghanashyam; Sushma, B; Kumar, J Raghavendra; Reddy, Y S N; Niranjani, K

2016-01-01

Determining the relative risk of cleft lip and palate (CL[P]) on the basis of lip prints and dermatoglyphics as genetic background may be useful for genetic counseling, and the development of future preventive measures. (1) To analyze the various pattern types of lip prints and dermatoglyphics in parents of CL(P) children and to detect if any specific type can be contemplated as a genetic marker in the transmission of CL(P). (2) To compare these patterns with that of parents of unaffected children. 31 parents of children with CL(P) as a study group, and 31 parents of unaffected children as control group were included. Lip prints and finger prints were collected from all subjects and analysis of both patterns was carried out followed by a comparison of the patterns of unaffected parents with the controls statistically. Among the mothers of the study group, type O followed by type IIa lip patterns were found to be significantly higher in upper and lower lips, and in fathers type IIa followed by type O were significantly higher. In the control group, type IIb followed by type III were higher in both fathers and mothers. Dermatoglyphic analysis of palm and finger prints revealed no significant difference in the pattern types and total ridge counts, but the Atd angle asymmetry was found to be significant between study and control group. Types IIa and O lip patterns, asymmetry of Atd angles can be considered as genetic markers for the transmission of CL(P) deformity to offsprings.

Mixed conditional logistic regression for habitat selection studies.

PubMed

Duchesne, Thierry; Fortin, Daniel; Courbin, Nicolas

2010-05-01

1. Resource selection functions (RSFs) are becoming a dominant tool in habitat selection studies. RSF coefficients can be estimated with unconditional (standard) and conditional logistic regressions. While the advantage of mixed-effects models is recognized for standard logistic regression, mixed conditional logistic regression remains largely overlooked in ecological studies. 2. We demonstrate the significance of mixed conditional logistic regression for habitat selection studies. First, we use spatially explicit models to illustrate how mixed-effects RSFs can be useful in the presence of inter-individual heterogeneity in selection and when the assumption of independence from irrelevant alternatives (IIA) is violated. The IIA hypothesis states that the strength of preference for habitat type A over habitat type B does not depend on the other habitat types also available. Secondly, we demonstrate the significance of mixed-effects models to evaluate habitat selection of free-ranging bison Bison bison. 3. When movement rules were homogeneous among individuals and the IIA assumption was respected, fixed-effects RSFs adequately described habitat selection by simulated animals. In situations violating the inter-individual homogeneity and IIA assumptions, however, RSFs were best estimated with mixed-effects regressions, and fixed-effects models could even provide faulty conclusions. 4. Mixed-effects models indicate that bison did not select farmlands, but exhibited strong inter-individual variations in their response to farmlands. Less than half of the bison preferred farmlands over forests. Conversely, the fixed-effect model simply suggested an overall selection for farmlands. 5. Conditional logistic regression is recognized as a powerful approach to evaluate habitat selection when resource availability changes. This regression is increasingly used in ecological studies, but almost exclusively in the context of fixed-effects models. Fitness maximization can imply differences in trade-offs among individuals, which can yield inter-individual differences in selection and lead to departure from IIA. These situations are best modelled with mixed-effects models. Mixed-effects conditional logistic regression should become a valuable tool for ecological research.

Plasma secretory phospholipase A2-IIa as a potential biomarker for lung cancer in patients with solitary pulmonary nodules

PubMed Central

2011-01-01

Background Five-year survival for lung cancer has remained at 16% over last several decades largely due to the fact that over 50% of patients are diagnosed with locally-advanced or metastatic disease. Diagnosis at an earlier and potentially curable stage is crucial. Solitary pulmonary nodules (SPNs) are common, but the difficulty lies in the determination of which SPN is malignant. Currently, there is no convenient and reliable biomarker effective for early diagnosis. Secretory phospholipase A2-IIa (sPLA2-IIa) is secreted into the circulation by cancer cells and may allow for an early detection of lung cancer. Methods Plasma samples from healthy donors, patients with only benign SPN, and patients with lung cancer were analyzed. Expression of sPLA2-IIa protein in lung cancer tissues was also determined. Results We found that the levels of plasma sPLA2-IIa were significantly elevated in lung cancer patients. The receiver operating characteristic curve analysis, comparing lung cancer patients to patients with benign nodules, revealed an optimum cutoff value for plasma sPLA2-IIa of 2.4 ng/ml to predict an early stage cancer with 48% sensitivity and 86% specificity and up to 67% sensitivity for T2 stage lung cancer. Combined sPLA2-IIa, CEA, and Cyfra21.1 tests increased the sensitivity for lung cancer prediction. High level of plasma sPLA2-IIa was associated with a decreased overall cancer survival. sPLA2-IIa was overexpressed in almost all non-small cell lung cancer and in the majority of small cell lung cancer by immunohistochemistry analysis. Conclusion Our finding strongly suggests that plasma sPLA2-IIa is a potential lung biomarker to distinguish benign nodules from lung cancer and to aid lung cancer diagnosis in patients with SPNs. PMID:22151235

Point of care testing of phospholipase A2 group IIA for serological diagnosis of rheumatoid arthritis

NASA Astrophysics Data System (ADS)

Liu, Nathan J.; Chapman, Robert; Lin, Yiyang; Mmesi, Jonas; Bentham, Andrew; Tyreman, Matthew; Abraham, Sonya; Stevens, Molly M.

2016-02-01

Secretory phospholipase A2 group IIA (sPLA2-IIA) was examined as a point of care marker for determining disease activity in rheumatoid (RA) and psoriatic (PsA) arthritis. Serum concentration and activity of sPLA2-IIA were measured using in-house antibodies and a novel point of care lateral flow device assay in patients diagnosed with varying severities of RA (n = 30) and PsA (n = 25) and found to correlate strongly with C-reactive protein (CRP). Levels of all markers were elevated in patients with active RA over those with inactive RA as well as both active and inactive PsA, indicating that sPLA2-IIA can be used as an analogue to CRP for RA diagnosis at point of care.Secretory phospholipase A2 group IIA (sPLA2-IIA) was examined as a point of care marker for determining disease activity in rheumatoid (RA) and psoriatic (PsA) arthritis. Serum concentration and activity of sPLA2-IIA were measured using in-house antibodies and a novel point of care lateral flow device assay in patients diagnosed with varying severities of RA (n = 30) and PsA (n = 25) and found to correlate strongly with C-reactive protein (CRP). Levels of all markers were elevated in patients with active RA over those with inactive RA as well as both active and inactive PsA, indicating that sPLA2-IIA can be used as an analogue to CRP for RA diagnosis at point of care. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr08423g

Recessive myosin myopathy with external ophthalmoplegia associated with MYH2 mutations.

PubMed

Tajsharghi, Homa; Hammans, Simon; Lindberg, Christopher; Lossos, Alexander; Clarke, Nigel F; Mazanti, Ingrid; Waddell, Leigh B; Fellig, Yakov; Foulds, Nicola; Katifi, Haider; Webster, Richard; Raheem, Olayinka; Udd, Bjarne; Argov, Zohar; Oldfors, Anders

2014-06-01

Myosin myopathies comprise a group of inherited diseases caused by mutations in myosin heavy chain (MyHC) genes. Homozygous or compound heterozygous truncating MYH2 mutations have been demonstrated to cause recessive myopathy with ophthalmoplegia, mild-to-moderate muscle weakness and complete lack of type 2A muscle fibers. In this study, we describe for the first time the clinical and morphological characteristics of recessive myosin IIa myopathy associated with MYH2 missense mutations. Seven patients of five different families with a myopathy characterized by ophthalmoplegia and mild-to-moderate muscle weakness were investigated. Muscle biopsy was performed to study morphological changes and MyHC isoform expression. Five of the patients were homozygous for MYH2 missense mutations, one patient was compound heterozygous for a missense and a nonsense mutation and one patient was homozygous for a frame-shift MYH2 mutation. Muscle biopsy demonstrated small or absent type 2A muscle fibers and reduced or absent expression of the corresponding MyHC IIa transcript and protein. We conclude that mild muscle weakness and ophthalmoplegia in combination with muscle biopsy demonstrating small or absent type 2A muscle fibers are the hallmark of recessive myopathy associated with MYH2 mutations.

Myonuclear domain size and myosin isoform expression in muscle fibres from mammals representing a 100,000-fold difference in body size.

PubMed

Liu, Jing-Xia; Höglund, Anna-Stina; Karlsson, Patrick; Lindblad, Joakim; Qaisar, Rizwan; Aare, Sudhakar; Bengtsson, Ewert; Larsson, Lars

2009-01-01

This comparative study of myonuclear domain (MND) size in mammalian species representing a 100,000-fold difference in body mass, ranging from 25 g to 2500 kg, was undertaken to improve our understanding of myonuclear organization in skeletal muscle fibres. Myonuclear domain size was calculated from three-dimensional reconstructions in a total of 235 single muscle fibre segments at a fixed sarcomere length. Irrespective of species, the largest MND size was observed in muscle fibres expressing fast myosin heavy chain (MyHC) isoforms, but in the two smallest mammalian species studied (mouse and rat), MND size was not larger in the fast-twitch fibres expressing the IIA MyHC isofom than in the slow-twitch type I fibres. In the larger mammals, the type I fibres always had the smallest average MND size, but contrary to mouse and rat muscles, type IIA fibres had lower mitochondrial enzyme activities than type I fibres. Myonuclear domain size was highly dependent on body mass in the two muscle fibre types expressed in all species, i.e. types I and IIA. Myonuclear domain size increased in muscle fibres expressing both the beta/slow (type I; r = 0.84, P < 0.001) and the fast IIA MyHC isoform (r = 0.90; P < 0.001). Thus, MND size scales with body size and is highly dependent on muscle fibre type, independent of species. However, myosin isoform expression is not the sole protein determining MND size, and other protein systems, such as mitochondrial proteins, may be equally or more important determinants of MND size.

Geometric engineering on flops of length two

NASA Astrophysics Data System (ADS)

Collinucci, Andrés; Fazzi, Marco; Valandro, Roberto

2018-04-01

Type IIA on the conifold is a prototype example for engineering QED with one charged hypermultiplet. The geometry admits a flop of length one. In this paper, we study the next generation of geometric engineering on singular geometries, namely flops of length two such as Laufer's example, which we affectionately think of as the conifold 2.0. Type IIA on the latter geometry gives QED with higher-charge states. In type IIB, even a single D3-probe gives rise to a nonabelian quiver gauge theory. We study this class of geometries explicitly by leveraging their quiver description, showing how to parametrize the exceptional curve, how to see the flop transition, and how to find the noncompact divisors intersecting the curve. With a view towards F-theory applications, we show how these divisors contribute to the enhancement of the Mordell-Weil group of the local elliptic fibration defined by Laufer's example.

Influence of Tanshinone IIa on heat shock protein 70, Bcl-2 and Bax expression in rats with spinal ischemia/reperfusion injury.

PubMed

Zhang, Li; Gan, Weidong; An, Guoyao

2012-12-25

Tanshinone IIa is an effective monomer component of Danshen, which is a traditional Chinese medicine for activating blood circulation to dissipate blood stasis. Tanshinone IIa can effectively improve brain tissue ischemia/hypoxia injury. The present study established a rat model of spinal cord ischemia/reperfusion injury and intraperitoneally injected Tanshinone IIa, 0.5 hour prior to model establishment. Results showed that Tanshinone IIa promoted heat shock protein 70 and Bcl-2 protein expression, but inhibited Bax protein expression in the injured spinal cord after ischemia/reperfusion injury. Furthermore, Nissl staining indicated a reduction in nerve cell apoptosis and fewer pathological lesions in the presence of Tanshinone IIa, compared with positive control Danshen injection.

Tanshinone IIA Increases the Bystander Effect of Herpes Simplex Virus Thymidine Kinase/Ganciclovir Gene Therapy via Enhanced Gap Junctional Intercellular Communication

PubMed Central

Liu, Xijuan; Wu, Yingya; Du, Biaoyan; Li, Jiefen; Zhou, Jing; Li, Jingjing; Tan, Yuhui

2013-01-01

The bystander effect is an intriguing phenomenon by which adjacent cells become sensitized to drug treatment during gene therapy with herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV). This effect is reported to be mediated by gap junctional intercellular communication (GJIC), and therefore, we postulated that upregulation of genes that facilitate GJIC may enhance the HSV-tk/GCV bystander effect. Previous findings have shown Tanshinone IIA (Tan IIA), a chemical substance derived from a Chinese medicine herb, promotes the upregulation of the connexins Cx26 and Cx43 in B16 cells. Because gap junctions are formed by connexins, we hypothesized that Tan IIA might increase GJIC. Our results show that Tan IIA increased GJIC in B16 melanoma cells, leading to more efficient GCV-induced bystander killing in cells stably expressing HSV-tk. Additionally, in vivo experiments demonstrated that tumors in mice with 10% HSV-tk positive B16 cells and 90% wild-type B16 cells became smaller following treatment with the combination of GCV and Tan IIA as compared to GCV or Tan IIA alone. These data demonstrate that Tan IIA can augment the bystander effect of HSV-tk/GCV system through increased gap junction coupling, which adds strength to the promising strategy that develops connexins inducer to potentiate the effects of suicide gene therapy. PMID:23861780

Anterior-only stabilization using cage versus plating with bone autograft for the treatment of type II/IIA Hangman's fracture combined with intervertebral disc injury.

PubMed

Wei, Fuxin; Pan, Ximin; Zhou, Zhiyu; Cui, Shangbin; Zhong, Rui; Wang, Le; Gao, Manman; Chen, Ningning; Liang, Zijian; Zou, Xuenong; Huang, Sheng; Liu, Shaoyu

2015-03-11

Anterior C2/3 discectomy and interbody fusion (ACDF) with plating is increasingly performed as the primary treatment of unstable Hangman's fracture; however, plate-related complications, such as screw back-out, plate fracture and soft-tissue injury, is not uncommon. Polyetheretherketone (PEEK) cage has now been developed to provide initial stability before fusion; however, whether and how ACDF with PEEK cage offer better clinical results compared with ACDF with plating in management of Hangman's fracture remains unknown. This study compares the efficacy of ACDF with plating to that of ACDF with PEEK cage in management of type II/IIA Hangman's fractures (according to Levine and Edwards classification) retrospectively. From February 2006 to March 2012, a total of 21 patients with type II/IIA Hangman's fractures combined with intervertebral disc injury underwent ACDF with PEEK cage, and 28 patients underwent ACDF with plating. Perioperative parameters were compared. The average follow-up period was 50.3 months (range 27-76 months). The clinical outcome (visual analog scale (VAS), American Spinal Injury Association (ASIA) scale, and clinical post-traumatic neck score (PTNC)) and radiological outcome (translation of C2, local kyphotic angle (LKA), and fusion status of C2/3) was compared retrospectively. The operative time and blood loss were significantly less in the ACDF with cage group compared with that in the ACDF with plating group (P < 0.05). All patients showed neurological recovery and achieved solid fusion. There were no significant differences in the clinical and radiological outcomes at final follow-up between groups, except in the LKA and the correction loss rate of LKA which were higher in the ACDF with plating group (P < 0.05). Donor-site pain occurred in two patients (10.1%) within 6 months after operation in the ACDF with plating group and none in the ACDF with cage group. All patients recovered without any adverse effects. ACDF with PEEK cage is effective and reliable in management of type II/IIA Hangman's fractures and is more cost-effective due to shorter operative time and less blood loss requirements.

Tanshinone IIA inhibits AGEs-induced proliferation and migration of cultured vascular smooth muscle cells by suppressing ERK1/2 MAPK signaling.

PubMed

Lu, Ming; Luo, Ying; Hu, Pengfei; Dou, Liping; Huang, Shuwei

2018-01-01

Vascular smooth muscle cells (VSMCs) play a key role in the pathogenesis of diabetic vascular disease. Our current study sought to explore the effects of tanshinone IIA on the proliferation and migration of VSMCs induced by advanced glycation end products (AGEs). In this study, we examined the effects of tanshinone IIA by cell proliferation assay and cell migration assay. And we explored the underlying mechanism by Western blotting. AGEs significantly induced the proliferation and migration of VSMCs, but treatment with tanshinone IIA attenuated these effects. AGEs could increase the activity of the ERK1/2 and p38 pathways but not the JNK pathway. Treatment with tanshinone IIA inhibited the AGEs-induced activation of the ERK1/2 pathway but not the p38 pathway. Tanshinone IIA inhibits AGEs-induced proliferation and migration of VSMCs by suppressing the ERK1/2 MAPK signaling pathway.

Effect of acute and chronic eccentric exercise on FOXO1 mRNA expression as fiber type transition factor in rat skeletal muscles.

PubMed

Azad, Milad; Khaledi, Neda; Hedayati, Mehdi

2016-06-15

Skeletal muscle is a highly elastic tissue which can respond to various functional demands by altering fiber-type composition. Exercise affects muscle fiber phenotype. One of the transcription factors that induce fiber-type transition is forkhead box O1 (FOXO1). Since eccentric contraction considered an essential part of exercise, so we are interested to see the effects of eccentric exercise (acute/chronic) on FOXO1 as an important factor of fiber-type transition in rat skeletal muscles. Twenty-four Sprague-Dawley rats (190-235g) were divided to 3 groups of 8 rats: 1) chronic eccentric exercise (CEE), 2) acute eccentric exercise (AEE), and 3) control (C). The exercise groups underwent downhill running protocol. CEE was running on treadmill in 3 days of week for 9 weeks, that slope and duration gradually managed from -4° to -16° and 15 to 90 min, respectively. AEE group was running with 16 m/min on -16° slope for 3 consecutive days that included 18 sets of 5 min with rest interval of 2 min in between. Soleus and super vastus lateralis (SVL) muscles mRNA were analyzed by real-time RT-PCR. SVL FOXO1 mRNA levels increased by 3.92-fold in the AEE and decreased 0.56-fold in the CEE group and were not significant in soleus muscle. In soleus muscle, myosin heavy chain (MHC) IIa, IIx, and IIb decreased in the AEE group and MHC IIa and IIx decreased in the CEE group. In SVL muscle, MHC I, IIa, and IIx increased in the AEE group and MHC IIa and IIX increased in the CEE group. In summary, both acute and chronic eccentric exercise could lead to change in FOXO1 mRNA only in fast SVL muscle of rat and so could induce fiber-type transition in both muscles regardless of changes in expression of FOXO1. So, oxidative stress can play important role in change of FOXO1. Copyright © 2016 Elsevier B.V. All rights reserved.

How do type II topoisomerases use ATP hydrolysis to simplify DNA topology beyond equilibrium? Investigating the relaxation reaction of non-supercoiling type II topoisomerases

PubMed Central

Stuchinskaya, Tanya; Mitchenall, Lesley A.; Schoeffler, Allyn J.; Corbett, Kevin D.; Berger, James M.; Bates, Andrew D.; Maxwell, Anthony

2015-01-01

DNA topoisomerases control the topology of DNA (e.g. the level of supercoiling) in all cells. Type IIA topoisomerases are ATP-dependent enzymes that have been shown to simplify the topology of their DNA substrates to a level beyond that expected at equilibrium (i.e. more relaxed than the product of relaxation by ATP-independent enzymes, such as type I topoisomerases, or a lower than equilibrium level of catenation). The mechanism of this effect is currently unknown, although several models have been suggested. We have analysed the DNA relaxation reactions of type II topoisomerases to further explore this phenomenon. We find that all type IIA topoisomerases tested exhibit the effect to a similar degree and that it is not dependent on the C-terminal domains of the enzymes. As recently reported, the type IIB topoisomerase, topo VI (which is only distantly related to the type IIA enzymes), does not exhibit topology simplification. We find that topology simplification is not significantly dependent on circle size in the range ~2–9 kbp, and is not altered by reducing the free energy available from ATP hydrolysis by varying the ATP:ADP ratio. A direct test of one model (DNA tracking, i.e. sliding of a protein clamp along DNA to trap supercoils) suggests that this is unlikely to be the explanation for the effect. We conclude that geometric selection of DNA segments by the enzymes is likely to be a primary source of the effect but that it is possible that other factors contribute. We also speculate whether topology simplification might simply be an evolutionary relic, with no adaptive significance. PMID:19094994

How do type II topoisomerases use ATP hydrolysis to simplify DNA topology beyond equilibrium? Investigating the relaxation reaction of nonsupercoiling type II topoisomerases.

PubMed

Stuchinskaya, Tanya; Mitchenall, Lesley A; Schoeffler, Allyn J; Corbett, Kevin D; Berger, James M; Bates, Andrew D; Maxwell, Anthony

2009-02-06

DNA topoisomerases control the topology of DNA (e.g., the level of supercoiling) in all cells. Type IIA topoisomerases are ATP-dependent enzymes that have been shown to simplify the topology of their DNA substrates to a level beyond that expected at equilibrium (i.e., more relaxed than the product of relaxation by ATP-independent enzymes, such as type I topoisomerases, or a lower-than-equilibrium level of catenation). The mechanism of this effect is currently unknown, although several models have been suggested. We have analyzed the DNA relaxation reactions of type II topoisomerases to further explore this phenomenon. We find that all type IIA topoisomerases tested exhibit the effect to a similar degree and that it is not dependent on the supercoil-sensing C-terminal domains of the enzymes. As recently reported, the type IIB topoisomerase, topoisomerase VI (which is only distantly related to type IIA enzymes), does not exhibit topology simplification. We find that topology simplification is not significantly dependent on circle size in the range approximately 2-9 kbp and is not altered by reducing the free energy available from ATP hydrolysis by varying the ADP:ATP ratio. A direct test of one model (DNA tracking; i.e., sliding of a protein clamp along DNA to trap supercoils) suggests that this is unlikely to be the explanation for the effect. We conclude that geometric selection of DNA segments by the enzymes is likely to be a primary source of the effect, but that it is possible that other kinetic factors contribute. We also speculate whether topology simplification might simply be an evolutionary relic, with no adaptive significance.

Influence of Tanshinone IIa on heat shock protein 70, Bcl-2 and Bax expression in rats with spinal ischemia/reperfusion injury☆

PubMed Central

Zhang, Li; Gan, Weidong; An, Guoyao

2012-01-01

Tanshinone IIa is an effective monomer component of Danshen, which is a traditional Chinese medicine for activating blood circulation to dissipate blood stasis. Tanshinone IIa can effectively improve brain tissue ischemia/hypoxia injury. The present study established a rat model of spinal cord ischemia/reperfusion injury and intraperitoneally injected Tanshinone IIa, 0.5 hour prior to model establishment. Results showed that Tanshinone IIa promoted heat shock protein 70 and Bcl-2 protein expression, but inhibited Bax protein expression in the injured spinal cord after ischemia/reperfusion injury. Furthermore, Nissl staining indicated a reduction in nerve cell apoptosis and fewer pathological lesions in the presence of Tanshinone IIa, compared with positive control Danshen injection. PMID:25317140

MYBPH inhibits NM IIA assembly via direct interaction with NMHC IIA and reduces cell motility

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hosono, Yasuyuki; Usukura, Jiro; Yamaguchi, Tomoya

2012-11-09

Highlights: Black-Right-Pointing-Pointer MYBPH inhibits NMHC IIA assembly and cell motility. Black-Right-Pointing-Pointer MYBPH interacts to assembly-competent NM IIA. Black-Right-Pointing-Pointer MYBPH inhibits RLC and NMHC IIA, independent components of NM IIA. -- Abstract: Actomyosin filament assembly is a critical step in tumor cell migration. We previously found that myosin binding protein H (MYBPH) is directly transactivated by the TTF-1 lineage-survival oncogene in lung adenocarcinomas and inhibits phosphorylation of the myosin regulatory light chain (RLC) of non-muscle myosin IIA (NM IIA) via direct interaction with Rho kinase 1 (ROCK1). Here, we report that MYBPH also directly interacts with an additional molecule, non-muscle myosinmore » heavy chain IIA (NMHC IIA), which was found to occur between MYBPH and the rod portion of NMHC IIA. MYBPH inhibited NMHC IIA assembly and reduced cell motility. Conversely, siMYBPH-induced increased motility was partially, yet significantly, suppressed by blebbistatin, a non-muscle myosin II inhibitor, while more profound effects were attained by combined treatment with siROCK1 and blebbistatin. Electron microscopy observations showed well-ordered paracrystals of NMHC IIA reflecting an assembled state, which were significantly less frequently observed in the presence of MYBPH. Furthermore, an in vitro sedimentation assay showed that a greater amount of NMHC IIA was in an unassembled state in the presence of MYBPH. Interestingly, treatment with a ROCK inhibitor that impairs transition of NM IIA from an assembly-incompetent to assembly-competent state reduced the interaction between MYBPH and NMHC IIA, suggesting that MYBPH has higher affinity to assembly-competent NM IIA. These results suggest that MYBPH inhibits RLC and NMHC IIA, independent components of NM IIA, and negatively regulates actomyosin organization at 2 distinct steps, resulting in firm inhibition of NM IIA assembly.« less

Expressivity of hearing loss in cases with Usher syndrome type IIA.

PubMed

Sadeghi, André M; Cohn, Edward S; Kimberling, William J; Halvarsson, Glenn; Möller, Claes

2013-12-01

The purpose of this study was to compare the genotype/phenotype relationship between siblings with identical USH2A pathologic mutations and the consequent audiologic phenotypes, in particular degree of hearing loss (HL). Decade audiograms were also compared among two groups of affected subjects with different mutations of USH2A. DNA samples from patients with Usher syndrome type II were analysed. The audiological features of patients and affected siblings with USH2A mutations were also examined to identify genotype-phenotype correlations. Genetic and audiometric examinations were performed in 18 subjects from nine families with Usher syndrome type IIA. Three different USH2A mutations were identified in the affected subjects. Both similarities and differences of the auditory phenotype were seen in families with several affected siblings. A variable degree of hearing loss, ranging from mild to profound, was observed among affected subjects. No significant differences in hearing thresholds were found the group of affected subjects with different pathological mutations. Our results indicate that mutations in the USH2A gene and the resulting phenotype are probably modulated by other variables, such as modifying genes, epigenetics or environmental factors which may be of importance for better understanding the etiology of Usher syndrome.

Molecular determinants of force production in human skeletal muscle fibers: effects of myosin isoform expression and cross-sectional area.

PubMed

Miller, Mark S; Bedrin, Nicholas G; Ades, Philip A; Palmer, Bradley M; Toth, Michael J

2015-03-15

Skeletal muscle contractile performance is governed by the properties of its constituent fibers, which are, in turn, determined by the molecular interactions of the myofilament proteins. To define the molecular determinants of contractile function in humans, we measured myofilament mechanics during maximal Ca(2+)-activated and passive isometric conditions in single muscle fibers with homogenous (I and IIA) and mixed (I/IIA and IIA/X) myosin heavy chain (MHC) isoforms from healthy, young adult male (n = 5) and female (n = 7) volunteers. Fibers containing only MHC II isoforms (IIA and IIA/X) produced higher maximal Ca(2+)-activated forces over the range of cross-sectional areas (CSAs) examined than MHC I fibers, resulting in higher (24-42%) specific forces. The number and/or stiffness of the strongly bound myosin-actin cross bridges increased in the higher force-producing MHC II isoforms and, in all isoforms, better predicted force than CSA. In men and women, cross-bridge kinetics, in terms of myosin attachment time and rate of myosin force production, were independent of CSA, although women had faster (7-15%) kinetics. The relative proportion of cross bridges and/or their stiffness was reduced as fiber size increased, causing a decline in specific force. Results from our examination of molecular mechanisms across the range of physiological CSAs explain the variation in specific force among the different fiber types in human skeletal muscle, which may have relevance to understanding how various physiological and pathophysiological conditions modulate single-fiber and whole muscle contractility. Copyright © 2015 the American Physiological Society.

Molecular determinants of force production in human skeletal muscle fibers: effects of myosin isoform expression and cross-sectional area

PubMed Central

Bedrin, Nicholas G.; Ades, Philip A.; Palmer, Bradley M.; Toth, Michael J.

2015-01-01

Skeletal muscle contractile performance is governed by the properties of its constituent fibers, which are, in turn, determined by the molecular interactions of the myofilament proteins. To define the molecular determinants of contractile function in humans, we measured myofilament mechanics during maximal Ca2+-activated and passive isometric conditions in single muscle fibers with homogenous (I and IIA) and mixed (I/IIA and IIA/X) myosin heavy chain (MHC) isoforms from healthy, young adult male (n = 5) and female (n = 7) volunteers. Fibers containing only MHC II isoforms (IIA and IIA/X) produced higher maximal Ca2+-activated forces over the range of cross-sectional areas (CSAs) examined than MHC I fibers, resulting in higher (24–42%) specific forces. The number and/or stiffness of the strongly bound myosin-actin cross bridges increased in the higher force-producing MHC II isoforms and, in all isoforms, better predicted force than CSA. In men and women, cross-bridge kinetics, in terms of myosin attachment time and rate of myosin force production, were independent of CSA, although women had faster (7–15%) kinetics. The relative proportion of cross bridges and/or their stiffness was reduced as fiber size increased, causing a decline in specific force. Results from our examination of molecular mechanisms across the range of physiological CSAs explain the variation in specific force among the different fiber types in human skeletal muscle, which may have relevance to understanding how various physiological and pathophysiological conditions modulate single-fiber and whole muscle contractility. PMID:25567808

Dimethyl ester of bilirubin exhibits anti-inflammatory activity through inhibition of secretory phospholipase A2, lipoxygenase and cyclooxygenase.

PubMed

Joshi, Vikram; Umashankara, M; Ramakrishnan, Chandrasekaran; Nanjaraj Urs, Ankanahalli N; Suvilesh, Kanve Nagaraj; Velmurugan, Devadasan; Rangappa, Kanchugarakoppal S; Vishwanath, Bannikuppe Sannanaik

2016-05-15

Overproduction of arachidonic acid (AA) mediated by secretory phospholipase A2 group IIA (sPLA2IIA) is a hallmark of many inflammatory disorders. AA is subsequently converted into pro-inflammatory eicosanoids through 5-lipoxygenase (5-LOX) and cyclooxygenase-1/2 (COX-1/2) activities. Hence, inhibition of sPLA2IIA, 5-LOX and COX-1/2 activities is critical in regulating inflammation. We have previously reported unconjugated bilirubin (UCB), an endogenous antioxidant, as sPLA2IIA inhibitor. However, lipophilic UCB gets conjugated in liver with glucuronic acid into hydrophilic conjugated bilirubin (CB). Since hydrophobicity is pre-requisite for sPLA2IIA inhibition, conjugation reduces the efficacy of UCB. In this regard, UCB was chemically modified and derivatives were evaluated for sPLA2IIA, 5-LOX and COX-1/2 inhibition. Among the derivatives, BD1 (dimethyl ester of bilirubin) exhibited ∼ 3 fold greater inhibitory potency towards sPLA2IIA compared to UCB. Both UCB and BD1 inhibited human 5-LOX and COX-2 activities; however only BD1 inhibited AA induced platelet aggregation. Molecular docking studies demonstrated BD1 as better inhibitor of aforesaid enzymes than UCB and other endogenous antioxidants. These data suggest that BD1 exhibits strong anti-inflammatory activity through inhibition of AA cascade enzymes which is of great therapeutic importance. Copyright © 2016 Elsevier Inc. All rights reserved.

Estrogen directly and specifically downregulates NaPi-IIa through the activation of both estrogen receptor isoforms (ERα and ERβ) in rat kidney proximal tubule.

PubMed

Burris, Dara; Webster, Rose; Sheriff, Sulaiman; Faroqui, Rashma; Levi, Moshe; Hawse, John R; Amlal, Hassane

2015-03-15

We have previously demonstrated that estrogen (E2) downregulates phosphate transporter NaPi-IIa and causes phosphaturia and hypophosphatemia in ovariectomized rats. In the present study, we examined whether E2 directly targets NaPi-IIa in the proximal tubule (PT) and studied the respective roles of estrogen receptor isoforms (ERα and ERβ) in the downregulation of NaPi-IIa using both in vivo and an in vitro expression systems. We found that estrogen specifically downregulates NaPi-IIa but not NaPi-IIc or Pit2 in the kidney cortex. Proximal tubules incubated in a "shake" suspension with E2 for 24 h exhibited a dose-dependent decrease in NaPi-IIa protein abundance. Results from OVX rats treated with specific agonists for either ERα [4,4',4″;-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol, PPT] or ERβ [4,4',4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol, DPN] or both (PPT + DPN), indicated that only the latter caused a sharp downregulation of NaPi-IIa, along with significant phosphaturia and hypophosphatemia. Lastly, heterologous expression studies demonstrated that estrogen downregulated NaPi-IIa only in U20S cells expressing both ERα and ERβ, but not in cells expressing either receptor alone. In conclusion, these studies demonstrate that rat PT cells express both ERα and ERβ and that E2 induces phosphaturia by directly and specifically targeting NaPi-IIa in the PT cells. This effect is mediated via a mechanism involving coactivation of both ERα and ERβ, which likely form a functional heterodimer complex in the rat kidney proximal tubule. Copyright © 2015 the American Physiological Society.

Estrogen directly and specifically downregulates NaPi-IIa through the activation of both estrogen receptor isoforms (ERα and ERβ) in rat kidney proximal tubule

PubMed Central

Burris, Dara; Webster, Rose; Sheriff, Sulaiman; Faroqui, Rashma; Levi, Moshe; Hawse, John R.

2015-01-01

We have previously demonstrated that estrogen (E2) downregulates phosphate transporter NaPi-IIa and causes phosphaturia and hypophosphatemia in ovariectomized rats. In the present study, we examined whether E2 directly targets NaPi-IIa in the proximal tubule (PT) and studied the respective roles of estrogen receptor isoforms (ERα and ERβ) in the downregulation of NaPi-IIa using both in vivo and an in vitro expression systems. We found that estrogen specifically downregulates NaPi-IIa but not NaPi-IIc or Pit2 in the kidney cortex. Proximal tubules incubated in a “shake” suspension with E2 for 24 h exhibited a dose-dependent decrease in NaPi-IIa protein abundance. Results from OVX rats treated with specific agonists for either ERα [4,4′,4″;-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol, PPT] or ERβ [4,4′,4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol, DPN] or both (PPT + DPN), indicated that only the latter caused a sharp downregulation of NaPi-IIa, along with significant phosphaturia and hypophosphatemia. Lastly, heterologous expression studies demonstrated that estrogen downregulated NaPi-IIa only in U20S cells expressing both ERα and ERβ, but not in cells expressing either receptor alone. In conclusion, these studies demonstrate that rat PT cells express both ERα and ERβ and that E2 induces phosphaturia by directly and specifically targeting NaPi-IIa in the PT cells. This effect is mediated via a mechanism involving coactivation of both ERα and ERβ, which likely form a functional heterodimer complex in the rat kidney proximal tubule. PMID:25608964

The antitumor effect of tanshinone IIA on anti-proliferation and decreasing VEGF/VEGFR2 expression on the human non-small cell lung cancer A549 cell line.

PubMed

Xie, Jun; Liu, Jiahui; Liu, Heng; Liang, Shihui; Lin, Meigui; Gu, Yueyu; Liu, Taoli; Wang, Dongmei; Ge, Hui; Mo, Sui-Lin

2015-11-01

The effects of tanshinone IIA on the proliferation of the human non-small cell lung cancer cell line A549 and its possible mechanism on the VEGF/VEGFR signal pathway were investigated. The exploration of the interaction between tanshinone IIA and its target proteins provides a feasible platform for studying the anticancer mechanism of active components of herbs. The CCK-8 assay was used to evaluate the proliferative activity of A549 cells treated with tanshinone IIA (2.5-80 μmol/L) for 24, 48 and 72 h, respectively. Flow cytometry was used for the detection of cell apoptosis and cell cycle perturbation. VEGF and VEGFR2 expression were studied by Western blotting. The binding mode of tanshinone IIA within the crystal structure of the VEGFR2 protein was evaluated with molecular docking analysis by use of the CDOCKER algorithm in Discovery Studio 2.1. The CCK-8 results showed that tanshinone IIA can significantly inhibit A549 cell proliferation in a dose- and time-dependent manner. Flow cytometry results showed that the apoptosis rate of tested group was higher than the vehicle control, and tanshinone IIA-treated cells accumulated at the S phase, which was higher than the vehicle control. Furthermore, the expression of VEGF and VEGFR2 was decreased in Western blot. Finally, molecular docking analysis revealed that tanshinone IIA could be stably docked into the kinase domain of VEGFR2 protein with its unique modes to form H-bonds with Cys917 and π-π stacking interactions with Val848. In conclusion, tanshinone IIA may suppress A549 proliferation, induce apoptosis and cell cycle arrest at the S phase. This drug may suppress angiogenesis by targeting the protein kinase domains of VEGF/VEGFR2.

The antitumor effect of tanshinone IIA on anti-proliferation and decreasing VEGF/VEGFR2 expression on the human non-small cell lung cancer A549 cell line

PubMed Central

Xie, Jun; Liu, Jiahui; Liu, Heng; Liang, Shihui; Lin, Meigui; Gu, Yueyu; Liu, Taoli; Wang, Dongmei; Ge, Hui; Mo, Sui-lin

2015-01-01

The effects of tanshinone IIA on the proliferation of the human non-small cell lung cancer cell line A549 and its possible mechanism on the VEGF/VEGFR signal pathway were investigated. The exploration of the interaction between tanshinone IIA and its target proteins provides a feasible platform for studying the anticancer mechanism of active components of herbs. The CCK-8 assay was used to evaluate the proliferative activity of A549 cells treated with tanshinone IIA (2.5−80 μmol/L) for 24, 48 and 72 h, respectively. Flow cytometry was used for the detection of cell apoptosis and cell cycle perturbation. VEGF and VEGFR2 expression were studied by Western blotting. The binding mode of tanshinone IIA within the crystal structure of the VEGFR2 protein was evaluated with molecular docking analysis by use of the CDOCKER algorithm in Discovery Studio 2.1. The CCK-8 results showed that tanshinone IIA can significantly inhibit A549 cell proliferation in a dose- and time-dependent manner. Flow cytometry results showed that the apoptosis rate of tested group was higher than the vehicle control, and tanshinone IIA-treated cells accumulated at the S phase, which was higher than the vehicle control. Furthermore, the expression of VEGF and VEGFR2 was decreased in Western blot. Finally, molecular docking analysis revealed that tanshinone IIA could be stably docked into the kinase domain of VEGFR2 protein with its unique modes to form H-bonds with Cys917 and π–π stacking interactions with Val848. In conclusion, tanshinone IIA may suppress A549 proliferation, induce apoptosis and cell cycle arrest at the S phase. This drug may suppress angiogenesis by targeting the protein kinase domains of VEGF/VEGFR2. PMID:26713270

Risk reductions for cardiovascular disease with pravastatin treatment by dyslipidemia phenotype: a post hoc analysis of the MEGA Study.

PubMed

Nishiwaki, Masato; Ikewaki, Katsunori; Ayaori, Makoto; Mizuno, Kyoichi; Ohashi, Yasuo; Ohsuzu, Fumitaka; Ishikawa, Toshitsugu; Nakamura, Haruo

2013-03-01

The beneficial effect of statins for cardiovascular disease (CVD) prevention has been well established. However, the effectiveness among different phenotypes of dyslipidemia has not been confirmed. We evaluated the effect of pravastatin on the incidence of CVD in relation to the phenotype of dyslipidemia. The MEGA Study evaluated the effect of low-dose pravastatin on primary prevention of CVD in 7832 Japanese patients, who were randomized to diet alone or diet plus pravastatin and followed for more than 5 years. These patients were classified into phenotype IIa (n=5589) and IIb (n=2041) based on the electrophoretic pattern for this post hoc analysis. In the diet group there was no significant difference in the incidence of coronary heart disease (CHD), stroke, CVD, and total mortality between the two phenotypes. Phenotype IIb patients, compared to phenotype IIa, had lower levels of high-density lipoprotein cholesterol (HDL-C) and a significantly higher incidence of CVD in relation to a low HDL-C level (<47.5mg/dL; p=0.02). Furthermore, pravastatin decreased the relative risk for each major endpoint in both type IIa and type IIb dyslipidemia. Significant risk reductions were observed for CHD by 38% (p=0.04) and CVD by 31% (p=0.02) in type IIa dyslipidemia but not in phenotype IIb. Pravastatin therapy provided significant risk reductions for CHD and CVD in patients with phenotype IIa dyslipidemia, but not in those with phenotype IIb dyslipidemia. Copyright © 2012 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Usefulness of a simple sleep-deprived EEG protocol for epilepsy diagnosis in de novo subjects.

PubMed

Giorgi, Filippo S; Perini, Daria; Maestri, Michelangelo; Guida, Melania; Pizzanelli, Chiara; Caserta, Anna; Iudice, Alfonso; Bonanni, Enrica

2013-11-01

In case series concerning the role of EEG after sleep deprivation (SD-EEG) in epilepsy, patients' features and protocols vary dramatically from one report to another. In this study, we assessed the usefulness of a simple SD-EEG method in well characterized patients. Among the 963 adult subjects submitted to SD-EEG at our Center, in the period 2003-2010, we retrospectively selected for analysis only those: (1) evaluated for suspected epileptic seizures; (2) with a normal/non-specific baseline EEG; (3) still drug-free at the time of SD-EEG; (4) with an MRI analysis; (5) with at least 1 year follow-up. SD-EEG consisted in SD from 2:00 AM and laboratory EEG from 8:00 AM to 10:30 AM. We analyzed epileptic interictal abnormalities (IIAs) and their correlations with patients' features. Epilepsy was confirmed in 131 patients. SD-EEG showed IIAs in 41.2% of all patients with epilepsy, and a 91.1% specificity for epilepsy diagnosis; IIAs types observed during SD-EEG are different in generalized versus focal epilepsies; for focal epilepsies, the IIAs yield in SD-EEG is higher than in second routine EEG. This simple SD-EEG protocol is very useful in de novo patients with suspected seizures. This study sheds new light on the role of SD-EEG in specific epilepsy populations. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Anti-inflammatory effects of tanshinone IIA on atherosclerostic vessels of ovariectomized ApoE mice are mediated by estrogen receptor activation and through the ERK signaling pathway.

PubMed

Liu, Xin; Guo, Chun-Yu; Ma, Xiao-Juan; Wu, Cai-Feng; Zhang, Ying; Sun, Ming-Yue; Pan, Yu-Ting; Yin, Hui-Jun

2015-01-01

Estrogen plays a protective role in atherosclerosis. Our preliminary work demonstrated that the active conformation of Tanshinone IIA(TanIIA) is similar to the 17β-estradiol and it can bind to the estrogen receptor. Here, we hypothesized that Tanshinone IIA might have anti-inflammatory and anti-oxidative effects in atherosclerosis, mediated through estrogen receptor activation. Subjects for this study were 120 apoE(-/-) female mice and 20 C57/BL female mice. The apoE(-/-) mice were ovariectomized (OVX) and the C57/BL mice were sham ovariectomized. The sham OVX mice were maintained on a normal diet (NOR) group. The OVX apoE(-/-) mice were fed a high fat diet and randomly divided into 6 groups: Model (MOD) group which was fed a high fat diet only, E2 group were given estrogen (E2) 0.13 mg/kg/d; E2+ICI group were given E2:0.13 mg/kg/d and ICI182780:65 mg/kg/m; TLD group (TanIIA low dose) were given TanIIA: 30 mg/kg/d; THD group (TanIIA high dose) were given TanIIA:60 mg/kg/d; and TLD+ICI group were given TanIIA 30 mg/kg/d and ICI182780 65 mg/kg/m. After three months of treatment, the aorta and the blood of the mice from each group was collected. The aorta were used for testing the lipid deposition by using hematoxylin and eosin(HE) and oil red O staining and for testing the expression of p-ERK1/2 by Western blot. The blood was used for testing the serum cholesterol, superoxide dismutase (SOD), methane dicarboxylic aldehyde (MDA), nuclear factor kappa (NF-κB), soluble intercellular cell adhesion molecule-1 (sICAM-1), activating protein-1 (AP-1), E-selectin and 17β-estradiol in serum. Tanshinone IIA significantly reduced the lipid deposition in aorta, decreased the levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), very low density lipoprotein (VLDL), MDA, NF-κB, sICAM-1, AP-1, and E-selectin in serum but increased the levels of high density lipoprotein (HDL) and SOD in serum. Tanshinone IIA also suppressed the expression of p-ERK1/2. Tanshinone IIA had no effect of level of serum 17β-estradiol levels. All of the effects of Tanshinone IIA were similar to estrogen and were inhibited by the estrogen receptor antagonist ICI182780. Tanshinone IIA may play an anti-inflammatory and anti-oxidative stress role in OVX atherosclerotic apoE(-/-) mice by activating the estrogen receptor through the ERK signaling pathway. Therefore, Tanshinone IIA, as a phytoestrogen, could be used for estrogen replacement therapy for cardiovascular disease of postmenopausal women. © 2015 S. Karger AG, Basel.

Common errors in textbook descriptions of muscle fiber size in nontrained humans.

PubMed

Chalmers, Gordon R; Row, Brandi S

2011-09-01

Exercise science and human anatomy and physiology textbooks commonly report that type IIB muscle fibers have the largest cross-sectional area of the three fiber types. These descriptions of muscle fiber sizes do not match with the research literature examining muscle fibers in young adult nontrained humans. For men, most commonly type IIA fibers were significantly larger than other fiber types (six out of 10 cases across six different muscles). For women, either type I, or both I and IIA muscle fibers were usually significantly the largest (five out of six cases across four different muscles). In none of these reports were type IIB fibers significantly larger than both other fiber types. In 27 studies that did not include statistical comparisons of mean fiber sizes across fiber types, in no cases were type IIB or fast glycolytic fibers larger than both type I and IIA, or slow oxidative and fast oxidative glycolytic fibers. The likely reason for mistakes in textbook descriptions of human muscle fiber sizes is that animal data were presented without being labeled as such, and without any warning that there are interspecies differences in muscle fiber properties. Correct knowledge of muscle fiber sizes may facilitate interpreting training and aging adaptations.

Tanshinone IIA inhibits AGEs-induced proliferation and migration of cultured vascular smooth muscle cells by suppressing ERK1/2 MAPK signaling

PubMed Central

Lu, Ming; Luo, Ying; Hu, Pengfei; Dou, Liping; Huang, Shuwei

2018-01-01

Objective(s): Vascular smooth muscle cells (VSMCs) play a key role in the pathogenesis of diabetic vascular disease. Our current study sought to explore the effects of tanshinone IIA on the proliferation and migration of VSMCs induced by advanced glycation end products (AGEs). Materials and Methods: In this study, we examined the effects of tanshinone IIA by cell proliferation assay and cell migration assay. And we explored the underlying mechanism by Western blotting. Results: AGEs significantly induced the proliferation and migration of VSMCs, but treatment with tanshinone IIA attenuated these effects. AGEs could increase the activity of the ERK1/2 and p38 pathways but not the JNK pathway. Treatment with tanshinone IIA inhibited the AGEs-induced activation of the ERK1/2 pathway but not the p38 pathway. Conclusion: Tanshinone IIA inhibits AGEs-induced proliferation and migration of VSMCs by suppressing the ERK1/2 MAPK signaling pathway. PMID:29372041

Use of electromyography to detect muscle exhaustion in finishing barrows fed ractopamine HCl.

PubMed

Noel, J A; Broxterman, R M; McCoy, G M; Craig, J C; Phelps, K J; Burnett, D D; Vaughn, M A; Barstow, T J; O'Quinn, T G; Woodworth, J C; DeRouchey, J M; Rozell, T G; Gonzalez, J M

2016-06-01

The objectives of this study were to determine the effects of dietary ractopamine HCl (RAC) on muscle fiber characteristics and electromyography (EMG) measures of finishing barrow exhaustion when barrows were subjected to increased levels of activity. Barrows ( = 34; 92 ± 2 kg initial BW) were assigned to 1 of 2 treatments: a conventional swine finishing diet containing 0 mg/kg ractopamine HCl (CON) or a diet formulated to meet the requirements of finishing barrows fed 10 mg/kg RAC (RAC+). After 32 d on feed, barrows were individually moved around a track at 0.79 m/s until subjectively exhausted. Wireless EMG sensors were affixed to the deltoideus (DT), triceps brachii lateral head (TLH), tensor fasciae latae (TFL), and semitendinosus (ST) muscles to measure median power frequency (MdPF) and root mean square (RMS) as indicators of action potential conduction velocity and muscle fiber recruitment, respectively. After harvest, samples of each muscle were collected for fiber type, succinate dehydrogenase (SDH), and capillary density analysis. Speed was not different ( = 0.82) between treatments, but RAC+ barrows reached subjective exhaustion earlier and covered less distance than CON barrows ( < 0.01). There were no treatment × muscle interactions or treatment effects for end-point MdPF values ( > 0.29). There was a treatment × muscle interaction ( = 0.04) for end-point RMS values. The RAC diet did not change end-point RMS values in the DT or TLH ( > 0.37); however, the diet tended to decrease and increase end-point RMS in the ST and TFL, respectively ( < 0.07). There were no treatment × muscle interactions for fiber type, SDH, or capillary density measures ( > 0.10). Muscles of RAC+ barrows tended to have less type I fibers and more capillaries per fiber ( < 0.07). Type I and IIA fibers of RAC+ barrows were larger ( < 0.07). Compared with all other muscles, the ST had more ( < 0.01) type IIB fibers and larger type I, IIA, and IIX fibers ( < 0.01). Type I, IIA, and IIX fibers of the ST also contained less SDH compared with the other muscles ( < 0.01). Barrows fed a RAC diet had increased time to subjective exhaustion due to loss of active muscle fibers in the ST, possibly due to fibers being larger and less oxidative in metabolism. Size increases in type I and IIA fibers with no change in oxidative capacity could also contribute to early exhaustion of RAC+ barrows. Overall, EMG technology can measure real-time muscle fiber loss to help explain subjective exhaustion in barrows.

Differences in sodium voltage-gated channel properties according to myosin heavy chain isoform expression in single muscle fibres.

PubMed

Rannou, F; Droguet, M; Giroux-Metges, M A; Pennec, Y; Gioux, M; Pennec, J P

2009-11-01

The myosin heavy chain (MHC) isoform determines the characteristics and shortening velocity of muscle fibres. The functional properties of the muscle fibre are also conditioned by its membrane excitability through the electrophysiological properties of sodium voltage-gated channels. Macropatch-clamp is used to study sodium channels in fibres from peroneus longus (PL) and soleus (Sol) muscles (Wistar rats, n = 8). After patch-clamp recordings, single fibres are identified by SDS-PAGE electrophoresis according to their myosin heavy chain isoform (slow type I and the three fast types IIa, IIx, IIb). Characteristics of sodium currents are compared (Student's t test) between fibres exhibiting only one MHC isoform. Four MHC isoforms are identified in PL and only type I in Sol single fibres. In PL, maximal sodium current (I(max)), maximal sodium conductance (g(Na,max)) and time constants of activation and inactivation ((m) and (h)) increase according to the scheme I-->IIa-->IIx-->IIb (P < 0.05). (m) values related to sodium channel type and/or function, are similar in Sol I and PL IIb fibres (P = 0.97) despite different contractile properties. The voltage dependence of activation (V(a,1/2)) shows a shift towards positive potentials from Sol type I to IIa, IIx and finally IIb fibres from PL (P < 0.05). These data are consistent with the earlier recruitment of slow fibres in a fast-mixed muscle like PL, while slow fibres of postural muscle such as soleus could be recruited in the same ways as IIb fibres in a fast muscle.

Conserved DNA motifs in the type II-A CRISPR leader region.

PubMed

Van Orden, Mason J; Klein, Peter; Babu, Kesavan; Najar, Fares Z; Rajan, Rakhi

2017-01-01

The Clustered Regularly Interspaced Short Palindromic Repeats associated (CRISPR-Cas) systems consist of RNA-protein complexes that provide bacteria and archaea with sequence-specific immunity against bacteriophages, plasmids, and other mobile genetic elements. Bacteria and archaea become immune to phage or plasmid infections by inserting short pieces of the intruder DNA (spacer) site-specifically into the leader-repeat junction in a process called adaptation. Previous studies have shown that parts of the leader region, especially the 3' end of the leader, are indispensable for adaptation. However, a comprehensive analysis of leader ends remains absent. Here, we have analyzed the leader, repeat, and Cas proteins from 167 type II-A CRISPR loci. Our results indicate two distinct conserved DNA motifs at the 3' leader end: ATTTGAG (noted previously in the CRISPR1 locus of Streptococcus thermophilus DGCC7710) and a newly defined CTRCGAG, associated with the CRISPR3 locus of S. thermophilus DGCC7710. A third group with a very short CG DNA conservation at the 3' leader end is observed mostly in lactobacilli. Analysis of the repeats and Cas proteins revealed clustering of these CRISPR components that mirrors the leader motif clustering, in agreement with the coevolution of CRISPR-Cas components. Based on our analysis of the type II-A CRISPR loci, we implicate leader end sequences that could confer site-specificity for the adaptation-machinery in the different subsets of type II-A CRISPR loci.

Conserved DNA motifs in the type II-A CRISPR leader region

PubMed Central

Babu, Kesavan; Najar, Fares Z.

2017-01-01

The Clustered Regularly Interspaced Short Palindromic Repeats associated (CRISPR-Cas) systems consist of RNA-protein complexes that provide bacteria and archaea with sequence-specific immunity against bacteriophages, plasmids, and other mobile genetic elements. Bacteria and archaea become immune to phage or plasmid infections by inserting short pieces of the intruder DNA (spacer) site-specifically into the leader-repeat junction in a process called adaptation. Previous studies have shown that parts of the leader region, especially the 3′ end of the leader, are indispensable for adaptation. However, a comprehensive analysis of leader ends remains absent. Here, we have analyzed the leader, repeat, and Cas proteins from 167 type II-A CRISPR loci. Our results indicate two distinct conserved DNA motifs at the 3′ leader end: ATTTGAG (noted previously in the CRISPR1 locus of Streptococcus thermophilus DGCC7710) and a newly defined CTRCGAG, associated with the CRISPR3 locus of S. thermophilus DGCC7710. A third group with a very short CG DNA conservation at the 3′ leader end is observed mostly in lactobacilli. Analysis of the repeats and Cas proteins revealed clustering of these CRISPR components that mirrors the leader motif clustering, in agreement with the coevolution of CRISPR-Cas components. Based on our analysis of the type II-A CRISPR loci, we implicate leader end sequences that could confer site-specificity for the adaptation-machinery in the different subsets of type II-A CRISPR loci. PMID:28392985

Muscle hypertrophy and fast fiber type conversions in heavy resistance-trained women.

PubMed

Staron, R S; Malicky, E S; Leonardi, M J; Falkel, J E; Hagerman, F C; Dudley, G A

1990-01-01

Twenty-four women completed a 20-week heavy-resistance weight training program for the lower extremity. Workouts were twice a week and consisted of warm-up exercises followed by three sets each of full squats, vertical leg presses, leg extensions, and leg curls. All exercises were performed to failure using 6-8 RM (repetition maximum). Weight training caused a significant increase in maximal isotonic strength (1 RM) for each exercise. After training, there was a decrease in body fat percentage (p less than 0.05), and an increase in lean body mass (p less than 0.05) with no overall change in thigh girth. Biopsies were obtained before and after training from the superficial portion of the vastus lateralis muscle. Sections were prepared for histological and histochemical examination. Six fiber types (I, IC, IIC, IIA, IIAB, and IIB) were distinguished following routine myofibrillar adenosine triphosphatase histochemistry. Areas were determined for fiber types I, IIA, and IIAB + IIB. The heavy-resistance training resulted in significant hypertrophy of all three groups: I (15%), IIA (45%), and IIAB + IIB (57%). These data are similar to those in men and suggest considerable hypertrophy of all major fiber types is also possible in women if exercise intensity and duration are sufficient. In addition, the training resulted in a significant decrease in the percentage of IIB with a concomitant increase in IIA fibers, suggesting that strength training may lead to fiber conversions.

Effects of a traditional Chinese medicine formula and its extraction on muscle fiber characteristics in finishing pigs, porcine cell proliferation and isoforms of myosin heavy chain gene expression in myocytes

PubMed Central

Yu, Qin Ping; Feng, Ding Yuan; He, Xiao Jun; Wu, Fan; Xia, Min Hao; Dong, Tao; Liu, Yi Hua; Tan, Hui Ze; Zou, Shi Geng; Zheng, Tao; Ou, Xian Hua; Zuo, Jian Jun

2017-01-01

Objective This study evaluated the effects of a traditional Chinese medicine formula (TCMF) on muscle fiber characteristics in finishing pigs and the effects of the formula’s extract (distilled water, ethyl acetate and petroleum ether extraction) on porcine cell proliferation and isoforms of myosin heavy chain (MyHC) gene expression in myocytes. Methods In a completely randomized design, ninety pigs were assigned to three diets with five replications per treatment and six pigs per pen. The diets included the basal diet (control group), TCMF1 (basal diet+2.5 g/kg TCMF) and TCMF2 (basal diet+5 g/kg TCMF). The psoas major muscle was obtained from pigs at the end of the experiment. Muscle fiber characteristics in the psoas major muscle were analyzed using myosin ATPase staining. Cell proliferation was measured using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) dye and cytometry. Isoforms of MyHC gene expression were detected by real-time quantitative polymerase chain reaction. Results The final body weight and carcass weight of finishing pigs were increased by TCMF1 (p<0.05), while the psoas major muscle cross-sectional area was increased by TCMF (p<0.05). The cross-sectional area and diameter of psoas major muscle fiber I, IIA, and IIB were increased by TCMF2 (p<0.05). The cross-sectional area and fiber diameter of psoas major muscle fiber IIA and IIB were increased by diet supplementation with TCMF1 (p<0.05). Psoas major muscle fiber IIA and IIB fiber density from the pigs fed the TCMF1 diet and the type IIB fiber density from the pigs fed the TCMF2 diet were lower compared to pigs fed the control diet (p<0.05). Pigs fed TCMF2 had a higher composition of type I fiber and a lower percentage of type IIB fiber in the psoas major muscle (p<0.05). The expression levels of MyHC I, MyHC IIa, and MyHC IIx mRNA increased and the amount of MyHC IIb mRNA decreased in the psoas major muscle from TCMF2, whereas MyHC I and MyHC IIx mRNA increased in the psoas major muscle from TCMF1 (p<0.05). Peroxisome proliferator-activated receptor γ coactivator-1α and CaN mRNA expression in the psoas major muscle were up-regulated by TCMF (p<0.05). Porcine skeletal muscle satellite cell proliferation was promoted by 4 μg/mL and 20 μg/mL TCMF water extraction (p<0.05). Both 1 μg/mL and 5 μg/mL of TCMF water extraction increased MyHC IIa, MyHC IIb, and MyHC IIx mRNA expression in porcine myocytes (p<0.05), while MyHC I mRNA expression in porcine myocytes was decreased by 5 μg/mL TCMF water extraction (p<0.05). Porcine myocyte MyHC I and MyHC IIx mRNA expression were increased, and MyHC IIa and MyHC IIb mRNA expression were down-regulated by 5 μg/mL TCMF ethyl acetate extraction (p<0.05). MyHC I and MyHC IIa mRNA expression in porcine myocytes were increased, and the MyHC IIb mRNA expression was decreased by 1 μg/mL TCMF ethyl acetate extraction (p<0.05). Four isoforms of MyHC mRNA expression in porcine myocytes were reduced by 5 μg/mL TCMF petroleum ether extraction (p<0.05). MyHC IIa mRNA expression in porcine myocytes increased and MyHC IIb mRNA expression decreased by 1 μg/mL in a TCMF petroleum ether extraction (p<0.05). Conclusion These results indicated that TCMF amplified the psoas major muscle cross-sectional area through changing muscle fiber characteristics in finishing pigs. This effect was confirmed as TCMF extraction promoted porcine cell proliferation and affected isoforms of MyHC gene expression in myocytes. PMID:28728382

Effects of starch synthase IIa gene dosage on grain, protein and starch in endosperm of wheat.

PubMed

Konik-Rose, Christine; Thistleton, Jenny; Chanvrier, Helene; Tan, Ihwa; Halley, Peter; Gidley, Michael; Kosar-Hashemi, Behjat; Wang, Hong; Larroque, Oscar; Ikea, Joseph; McMaugh, Steve; Regina, Ahmed; Rahman, Sadequr; Morell, Matthew; Li, Zhongyi

2007-11-01

Starch synthases (SS) are responsible for elongating the alpha-1,4 glucan chains of starch. A doubled haploid population was generated by crossing a line of wheat, which lacks functional ssIIa genes on each genome (abd), and an Australian wheat cultivar, Sunco, with wild type ssIIa alleles on each genome (ABD). Evidence has been presented previously indicating that the SGP-1 (starch granule protein-1) proteins present in the starch granule in wheat are products of the ssIIa genes. Analysis of 100 progeny lines demonstrated co-segregation of the ssIIa alleles from the three genomes with the SGP-1 proteins, providing further evidence that the SGP-1 proteins are the products of the ssIIa genes. From the progeny lines, 40 doubled haploid lines representing the eight possible genotypes for SSIIa (ABD, aBD, AbD, ABd, abD, aBd, Abd, abd) were characterized for their grain weight, protein content, total starch content and starch properties. For some properties (chain length distribution, pasting properties, swelling power, and gelatinization properties), a progressive change was observed across the four classes of genotypes (wild type, single nulls, double nulls and triple nulls). However, for other grain properties (seed weight and protein content) and starch properties (total starch content, granule morphology and crystallinity, granule size distribution, amylose content, amylose-lipid dissociation properties), a statistically significant change only occurred for the triple nulls, indicating that all three genes had to be missing or inactive for a change to occur. These results illustrate the importance of SSIIa in controlling grain and starch properties and the importance of amylopectin fine structure in controlling starch granule properties in wheat.

Eccentric contraction-induced injury to type I, IIa, and IIa/IIx muscle fibers of elderly adults

USDA-ARS?s Scientific Manuscript database

Muscles of old laboratory rodents experience exaggerated force losses after eccentric contractile activity. We extended this line of inquiry to humans and investigated the influence of fiber myosin heavy chain (MHC) isoform content on the injury process. Skinned muscle fiber segments, prepared from ...

Patency of the Internal Iliac Artery after Placement of Common and External Iliac Artery Stents.

PubMed

Vinogradova, Margie; Lee, Hye Joon; Armstrong, Ehrin J; Laird, John; Humphries, Misty D

2017-01-01

Treatment of severe aortoiliac occlusive disease (AIOD) frequently requires long-segment stenting of the common and external iliac arteries (CIA and EIA, respectively). This study aims to analyze the patency of the internal iliac artery (IIA) after placement of a CIA and EIA stents across the orifice. A retrospective analysis of all patients who underwent de novo ipsilateral stent placement in the CIA and EIA between 2006 and 2013 was performed. Kaplan-Meier analysis was used to analyze patency of the IIA, and Cox proportional hazard models were used to identify characteristics associated with occlusion. We identified 77 patients and 93 limbs where ipsilateral CIA and EIA stents were placed. Preintervention angiographic review found 52 cases of a patent ipsilateral IIA where stents were placed across the origin of the IIA in 31 cases and staggered across the orifice in 20 limbs. Kaplan-Meier analysis demonstrated a 37% patency in limbs where the stent covered the IIA orifice compared to 78% patency in uncovered arteries (P = 0.04). New-onset buttock claudication developed in 4 patients, 2 with patent IIAs and 2 with occluded. New-onset impotence also developed in 3 patients with occluded IIA and 5 patients with patent IIAs. Placement of stents across the origin of the IIA may not result in immediate occlusion, but long-term patency of covered IIAs is decreased compared to uncovered IIAs. This study is limited by a small sample size, but when treating AIOD, coverage of the internal iliac origin should be avoided to maintain patency of the pelvic circulation. Copyright © 2016 Elsevier Inc. All rights reserved.

INVESTIGATION OF BONE MINERALIZATION IN PATIENTS WITH CORONARY HEART DISEASE COMPLICATED BY CHRONIC HEART FAILURE, STAGE II-A.

PubMed

Krynytska, I; Marushchak, M; Zaets, T; Savchenko, I; Habor, H

2017-06-01

The majority of the studies have shown that individuals with cardiovascular diseases have a higher risk of experiencing bone loss and thus greater predisposition to risk of fracture. On the other hand there is growing evidence that individuals with low bone mass have higher mortality for cardiovascular events compared to patients with cardiovascular disease with normal bone mass. This research aims to investigate bone mineralization in patients with coronary heart disease complicated by stage II-A chronic heart failure. The study involved 33 men with coronary heart disease complicated by Stage II-A chronic heart failure. Bone mineral density was measured using dual energy x-ray densitometry of lumbar region of spine. Structural and functional changes of bone tissue of the lumbar spine have been found in 49,2% patients with coronary heart disease complicated by Stage II-A chronic heart failure, in particular, I stage of osteopenia - in 44,6%, II stage of osteopenia - in 27,7%, III stage of osteopenia - in 10,8% and osteoporosis - in 16,9%. It was established the same type of downward trend for BMD decreasing in L1 of patients with different stages of osteopenia, but in case of osteoporosis mineralization decreased equally in all vertebrae.

Chloroquine Analog Interaction with C2- and Iota-Toxin in Vitro and in Living Cells.

PubMed

Kronhardt, Angelika; Beitzinger, Christoph; Barth, Holger; Benz, Roland

2016-08-10

C2-toxin from Clostridium botulinum and Iota-toxin from Clostridium perfringens belong both to the binary A-B-type of toxins consisting of two separately secreted components, an enzymatic subunit A and a binding component B that facilitates the entry of the corresponding enzymatic subunit into the target cells. The enzymatic subunits are in both cases actin ADP-ribosyltransferases that modify R177 of globular actin finally leading to cell death. Following their binding to host cells' receptors and internalization, the two binding components form heptameric channels in endosomal membranes which mediate the translocation of the enzymatic components Iota a and C2I from endosomes into the cytosol of the target cells. The binding components form ion-permeable channels in artificial and biological membranes. Chloroquine and related 4-aminoquinolines were able to block channel formation in vitro and intoxication of living cells. In this study, we extended our previous work to the use of different chloroquine analogs and demonstrate that positively charged aminoquinolinium salts are able to block channels formed in lipid bilayer membranes by the binding components of C2- and Iota-toxin. Similarly, these molecules protect cultured mammalian cells from intoxication with C2- and Iota-toxin. The aminoquinolinium salts did presumably not interfere with actin ADP-ribosylation or receptor binding but blocked the pores formed by C2IIa and Iota b in living cells and in vitro. The blocking efficiency of pores formed by Iota b and C2IIa by the chloroquine analogs showed interesting differences indicating structural variations between the types of protein-conducting nanochannels formed by Iota b and C2IIa.

Chloroquine Analog Interaction with C2- and Iota-Toxin in Vitro and in Living Cells

PubMed Central

Kronhardt, Angelika; Beitzinger, Christoph; Barth, Holger; Benz, Roland

2016-01-01

C2-toxin from Clostridium botulinum and Iota-toxin from Clostridium perfringens belong both to the binary A-B-type of toxins consisting of two separately secreted components, an enzymatic subunit A and a binding component B that facilitates the entry of the corresponding enzymatic subunit into the target cells. The enzymatic subunits are in both cases actin ADP-ribosyltransferases that modify R177 of globular actin finally leading to cell death. Following their binding to host cells’ receptors and internalization, the two binding components form heptameric channels in endosomal membranes which mediate the translocation of the enzymatic components Iota a and C2I from endosomes into the cytosol of the target cells. The binding components form ion-permeable channels in artificial and biological membranes. Chloroquine and related 4-aminoquinolines were able to block channel formation in vitro and intoxication of living cells. In this study, we extended our previous work to the use of different chloroquine analogs and demonstrate that positively charged aminoquinolinium salts are able to block channels formed in lipid bilayer membranes by the binding components of C2- and Iota-toxin. Similarly, these molecules protect cultured mammalian cells from intoxication with C2- and Iota-toxin. The aminoquinolinium salts did presumably not interfere with actin ADP-ribosylation or receptor binding but blocked the pores formed by C2IIa and Iota b in living cells and in vitro. The blocking efficiency of pores formed by Iota b and C2IIa by the chloroquine analogs showed interesting differences indicating structural variations between the types of protein-conducting nanochannels formed by Iota b and C2IIa. PMID:27517960

Balloon-Occluded Carbon Dioxide Gas Angiography for Internal Iliac Arteriography and Intervention.

PubMed

Kishino, Mitsuhiro; Nakaminato, Shuichiro; Kitazume, Yoshio; Miyasaka, Naoyuki; Kudo, Toshifumi; Saida, Yukihisa; Tateishi, Ukihide

2018-07-01

The usefulness of carbon dioxide (CO 2 ) gas digital subtraction angiography (DSA) has been reported for patients with renal insufficiency and allergy to iodinated contrast agents. However, CO 2 gas cannot replace the iodinated contrast agent in all cases owing to some disadvantages. We describe balloon-occluded CO 2 DSA (B-CO 2 DSA) as an improved CO 2 DSA procedure for interventions in the internal iliac artery (IIA) region and compare the quality of images obtained using conventional CO 2 DSA and B-CO 2 DSA. B-CO 2 DSA-guided embolization was performed for one case of genital bleeding with an acute anaphylactic reaction to the iodinated contrast agent and for three cases of type II endoleaks after endovascular abdominal aortic aneurysm repair with renal dysfunction. A 9-mm occlusion balloon catheter was placed just after the orifice of the IIA. Then, 10-15 ml of CO 2 gas was injected manually via the catheter with and without balloon occlusion. The quality of sequential digital subtraction angiograms was analyzed based on a scoring criterion. In all four cases, image quality was improved with B-CO 2 DSA; the poor quality of images without balloon occlusion was because of reflux of the CO 2 gas. B-CO 2 DSA improves the image quality of CO 2 DSA in the IIA region and is useful for vascular intervention. Level IV.

Cryptosporidium species and subtype analysis in diarrhoeic pre-weaned lambs and goat kids from north-western Spain.

PubMed

Díaz, Pablo; Quílez, Joaquín; Prieto, Alberto; Navarro, Esther; Pérez-Creo, Ana; Fernández, Gonzalo; Panadero, Rosario; López, Ceferino; Díez-Baños, Pablo; Morrondo, Patrocinio

2015-11-01

Faecal specimens from diarrhoeic pre-weaned lambs (n = 171) and goat kids (n = 118) were collected in 37 sheep and 23 goat flocks, respectively, from NW Spain and microscopically examined for the presence of Cryptosporidium oocysts. Positive specimens were selected for molecular characterization. Presence of Cryptosporidium oocysts were significantly higher in specimens from goat kids (62.7%) than from lambs (31.6%). PCR products of the SSU rRNA locus were obtained for 108 isolates, and three Cryptosporidium species were identified. Cryptosporidium parvum was the most common species identified from both lambs (74.4%) and goat kids (93.8%). The remaining PCR products from lambs (25.6%) and goat kids (7.7%) were identified as Cryptosporidium Ubiquitum and Cryptosporidium xiaoi, respectively. Five C. parvum subtypes were identified; IIaA13G1R1, IIaA14G2R1, IIaA15G2R1 and IIaA16G3R1 were found in both host species, and IIdA17G1 was only detected in goat kids. Subtype IIaA15G2R1 was the most common and widely distributed. The present study provides the first description of subtypes IIaA13G1R1 in both small ruminant species, IIaA14G2R1 in sheep and IIaA16G3R1 in goats. Our results also reveal that diarrhoeic pre-weaned lambs and goat kids must be considered important reservoirs of Cryptosporidium species with zoonotic potential, such as C. parvum and C. ubiquitum.

Genetic uniqueness of Cryptosporidium parvum from dairy calves in Colombia.

PubMed

Avendaño, Catalina; Ramo, Ana; Vergara-Castiblanco, Claudia; Sánchez-Acedo, Caridad; Quílez, Joaquín

2018-05-01

Fecal specimens from 432 pre-weaned calves younger than 35 days were collected over a 2-year period (2010-2012) from 74 dairy cattle farms in the central area of Colombia. These samples were microscopically examined for the presence of Cryptosporidium oocysts, and positive specimens were selected for molecular examination. Microscopy revealed that 115 calves (26.6%) from 44 farms (59.5%) tested positive. Oocyst shedding was recorded in calves aged 3-day-old onwards, although the infection rate peaked at 8-14 days (40.7%). Infection rates were higher in diarrheic (52.2%) than in non-diarrheic calves (19.9%) (p < 0.0001, χ 2 ), and infected calves had up to seven times more probability of having diarrhea than non-infected calves. Cryptosporidium species and subtypes were successfully identified in 73 samples from 32 farms. Restriction and sequence analyses of the SSU rRNA gene revealed C. parvum in all but two isolates identified as Cryptosporidium bovis. Sequence analyses of the 60-KDa glycoprotein (gp60) gene revealed eight subtypes within the IIa family. An unusual subtype (IIaA18G5R1) was the most prevalent and widely distributed (more than 66% specimens and 68% farms) while the subtype most frequently reported in cattle worldwide (IIaA15G2R1) was found in less than 13% of specimens and 16% farms. The remaining subtypes (IIaA16G2R1, IIaA17G4R1, IIaA20G5R1, IIaA19G6R1, IIaA20G6R1, and IIaA20G7R1) were restricted to 1-3 farms. This is the first large-sample size study of Cryptosporidium species and subtypes in Colombia and demonstrates the genetic uniqueness of this protozoan in cattle farms in this geographical area.

Reactive codoping of GaAlInP compound semiconductors

DOEpatents

Hanna, Mark Cooper [Boulder, CO; Reedy, Robert [Golden, CO

2008-02-12

A GaAlInP compound semiconductor and a method of producing a GaAlInP compound semiconductor are provided. The apparatus and method comprises a GaAs crystal substrate in a metal organic vapor deposition reactor. Al, Ga, In vapors are prepared by thermally decomposing organometallic compounds. P vapors are prepared by thermally decomposing phospine gas, group II vapors are prepared by thermally decomposing an organometallic group IIA or IIB compound. Group VIB vapors are prepared by thermally decomposing a gaseous compound of group VIB. The Al, Ga, In, P, group II, and group VIB vapors grow a GaAlInP crystal doped with group IIA or IIB and group VIB elements on the substrate wherein the group IIA or IIB and a group VIB vapors produced a codoped GaAlInP compound semiconductor with a group IIA or IIB element serving as a p-type dopant having low group II atomic diffusion.

Tory II-A: a nuclear ramjet test reactor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hadley, J.W.

Declassified 28 Nov 1973. The first test reactor in the Pluto program, leading to development of a nuclear ramjet engine, is called Tory II-A. While it is not an actual prototype engine, this reactor embodies a core design which is considered feasible for an engine, and operation of the reactor will provide a test of that core type as well as more generalized values in reactor design and testing. The design of Tory II-A and construction of the reactor and of its test facility are described. Operation of the Tory II-A core at a total power of 160 megawatts, withmore » 800 pounds of air per second passing through the core and emerging at a temperature of 2000 deg F, is the central objective of the test program. All other reactor and facility components exist to support operation of the core, and preliminary steps in the test program itself will be directed primarily toward ensuring attalnment of full-power operation and collection of meaningful data on core behavior during that operation. The core, 3 feet in diameter and 41/2 feet long, will be composed of bundled ceramic tubes whose central holes will provide continuous air passages from end to end of the reactor. These tubes are to be composed of a homogeneous mixture of UO/sub 2/ fuel and BeO moderator, compacted and sintered to achieve high strength and density. (30 references) (auth)« less

Prevalence and Molecular Characterization of Cryptosporidium in Goats across Four Provincial Level Areas in China

PubMed Central

Mi, Rongsheng; Wang, Xiaojuan; Huang, Yan; Zhou, Peng; Liu, Yuxuan; Chen, Yongjun; Chen, Jun; Zhu, Wei; Chen, Zhaoguo

2014-01-01

This study assessed the prevalence, species and subtypes of Cryptosporidium in goats from Guangdong Province, Hubei Province, Shandong Province, and Shanghai City of China. Six hundred and four fecal samples were collected from twelve goat farms, and the overall infection rate was 11.4% (69/604). Goats infected with Cryptosporidium were found in eleven farms across four provincial areas, and the infection rate ranged from 2.9% (1/35) to 25.0% (9/36). Three Cryptosporidium species were identified. Cryptosporidium xiaoi (45/69, 65.2%) was the dominant species, followed by C. parvum (14/69, 20.3%) and C. ubiquitum (10/69, 14.5%). The infection rate of Cryptosporidium spp. was varied with host age and goat kids were more susceptible to be infected than adult goats. Subtyping C. parvum and C. ubiquitum positive samples revealed C. parvum subtype IIdA19G1 and C. ubiquitum subtype XIIa were the most common subtypes. Other C. parvum subtypes were detected as well, such as IIaA14G2R1, IIaA15G1R1, IIaA15G2R1 and IIaA17G2R1. All of these subtypes have also been detected in humans, suggesting goats may be a potential source of zoonotic cryptosporidiosis. This was the first report of C. parvum subtypes IIaA14G2R1, IIaA15G1R1 and IIaA17G2R1 infecting in goats and the first molecular identification of C. parvum and its subtypes in Chinese goats. PMID:25343501

Effects of salvianolic acid B and tanshinone IIA on the pharmacokinetics of losartan in rats by regulating the activities and expression of CYP3A4 and CYP2C9.

PubMed

Wang, Rong; Zhang, Hai; Wang, Yujie; Yu, Xiaoyan; Yuan, Yongfang

2016-03-02

Losartan (LST) is a common chemical drug used to treat high blood pressure and reduce the risk of stroke in certain people with heart disease. Danshen, prepared from the dried root and rhizome of Salvia miltiorrhiza Bunge, has been widely used for prevention and treatment of various cardiovascular and cerebrovascular diseases. There are more than 35 formulations containing Danshen indexed in the 2010 Chinese Pharmacopoeia, which are often combined with LST to treat cardiovascular and cerebrovascular diseases in the clinic. The effects of the two major components of Danshen, salvianolic acid B (SA-B) and tanshinone IIA (Tan IIA), on the pharmacokinetics of losartan and its metabolite, EXP3174, in rats were investigated by liquid chromatography coupled with mass spectrometry (LC-MS). Male Sprague-Dawley rats were randomly assigned to 3 groups: LST, LST+SA-B and LST+Tan IIA, and the main pharmacokinetic parameters were estimated after oral administration of LST, LST+SA-B and LST+Tan IIA. It was found that there are significant differences in the pharmacokinetic parameters among the three groups: Cmax, t1/2, AUC, AUMC in the LST+SA-B group was smaller than those in group LST, while larger in group LST+Tan IIA. Further, the effects of SA-B and Tan IIA on the metabolism of losartan was also investigated using rat liver microsomes in vitro. The results indicated that SA-B can induce the metabolism of LST, while Tan IIA can inhibit the metabolism of LST in rat liver microsomes in vitro by regulating activities of CYP450 enzymes. In addition, the effect of SA-B and Tan IIA on CYP3A4 and CYP2C9 expression was studied in Chang liver cells by western-blotting and Real-time PCR. It was concluded that the two components of Danshen, SA-B and Tan IIA have different influences on the metabolism of LST: SA-B can obviously speed up the metabolism of LST by inducing CYP3A4/CYP2C9 activities and expression, however, Tan IIA can slow down the metabolism of LST by inhibiting CYP3A4/CYP2C9 activities. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effect of azithromycin on the LPS-induced production and secretion of phospholipase A2 in lung cells.

PubMed

Kitsiouli, Eirini; Antoniou, Georgia; Gotzou, Helen; Karagiannopoulos, Michalis; Basagiannis, Dimitris; Christoforidis, Savvas; Nakos, George; Lekka, Marilena E

2015-07-01

Azithromycin is a member of macrolides, utilized in the treatment of infections. Independently, these antibiotics also possess anti-inflammatory and immunomodulatory properties. Phospholipase A2 isotypes, which are implicated in the pathophysiology of inflammatory lung disorders, are produced by alveolar macrophages and other lung cells during inflammatory response and can promote lung injury by destructing lung surfactant. The aim of the study was to investigate whether in lung cells azithromycin can inhibit secretory and cytosolic phospholipases A2, (sPLA2) and (cPLA2), respectively, which are induced by an inflammatory trigger. In this respect, we studied the lipopolysaccharide (LPS)-mediated production or secretion of sPLA2 and cPLA2 from A549 cells, a cancer bronchial epithelial cell line, and alveolar macrophages, isolated from bronchoalveolar lavage fluid of ARDS and control patients without cardiopulmonary disease or sepsis. Pre-treatment of cells with azithromycin caused a dose-dependent decrease in the LPS-induced sPLA2-IIA levels in A549 cells. This inhibition was rather due to reduced PLA2G2A mRNA expression and secretion of sPLA2-IIA protein levels, as observed by western blotting and indirect immunofluorescence by confocal microscopy, respectively, than to the inhibition of the enzymic activity per se. On the contrary, azithromycin had no effect on the LPS-induced production or secretion of sPLA2-IIA from alveolar macrophages. The levels of LPS-induced c-PLA2 were not significantly affected by azithromycin in either cell type. We conclude that azithromycin exerts anti-inflammatory properties on lung epithelial cells through the inhibition of both the expression and secretion of LPS-induced sPLA2-IIA, while it does not affect alveolar macrophages. Copyright © 2015 Elsevier B.V. All rights reserved.

Limiting prothrombin activation to meizothrombin is compatible with survival but significantly alters hemostasis in mice

PubMed Central

Shaw, Maureen A.; Kombrinck, Keith W.; McElhinney, Kathryn E.; Sweet, David R.; Flick, Matthew J.; Palumbo, Joseph S.; Cheng, Mei; Esmon, Naomi L.; Esmon, Charles T.; Brill, Alexander; Wagner, Denisa D.; Degen, Jay L.

2016-01-01

Thrombin-mediated proteolysis is central to hemostatic function but also plays a prominent role in multiple disease processes. The proteolytic conversion of fII to α-thrombin (fIIa) by the prothrombinase complex occurs through 2 parallel pathways: (1) the inactive intermediate, prethrombin; or (2) the proteolytically active intermediate, meizothrombin (fIIaMZ). FIIaMZ has distinct catalytic properties relative to fIIa, including diminished fibrinogen cleavage and increased protein C activation. Thus, fII activation may differentially influence hemostasis and disease depending on the pathway of activation. To determine the in vivo physiologic and pathologic consequences of restricting thrombin generation to fIIaMZ, mutations were introduced into the endogenous fII gene, resulting in expression of prothrombin carrying 3 amino acid substitutions (R157A, R268A, and K281A) to limit activation events to yield only fIIaMZ. Homozygous fIIMZ mice are viable, express fII levels comparable with fIIWT mice, and have reproductive success. Although in vitro studies revealed delayed generation of fIIaMZ enzyme activity, platelet aggregation by fIIMZ is similar to fIIWT. Consistent with prior analyses of human fIIaMZ, significant prolongation of clotting times was observed for fIIMZ plasma. Adult fIIMZ animals displayed significantly compromised hemostasis in tail bleeding assays, but did not demonstrate overt bleeding. More notably, fIIMZ mice had 2 significant phenotypic advantages over fIIWT animals: protection from occlusive thrombosis after arterial injury and markedly diminished metastatic potential in a setting of experimental tumor metastasis to the lung. Thus, these novel animals will provide a valuable tool to assess the role of both fIIa and fIIaMZ in vivo. PMID:27252233

Rearrangement of competing U2 RNA helices within the spliceosome promotes multiple steps in splicing

PubMed Central

Perriman, Rhonda J.; Ares, Manuel

2007-01-01

Nuclear pre-messenger RNA (pre-mRNA) splicing requires multiple spliceosomal small nuclear RNA (snRNA) and pre-mRNA rearrangements. Here we reveal a new snRNA conformational switch in which successive roles for two competing U2 helices, stem IIa and stem IIc, promote distinct splicing steps. When stem IIa is stabilized by loss of stem IIc, rapid ATP-independent and Cus2p-insensitive prespliceosome formation occurs. In contrast, hyperstabilized stem IIc improves the first splicing step on aberrant branchpoint pre-mRNAs and rescues temperature-sensitive U6–U57C, a U6 mutation that also suppresses first-step splicing defects of branchpoint mutations. A second, later role for stem IIa is revealed by its suppression of a cold-sensitive allele of the second-step splicing factor PRP16. Our data expose a spliceosomal progression cycle of U2 stem IIa formation, disruption by stem IIc, and then reformation of stem IIa before the second catalytic step. We propose that the competing stem IIa and stem IIc helices are key spliceosomal RNA elements that optimize juxtaposition of the proper reactive sites during splicing. PMID:17403781

Hydrolysis of Phosphatidylcholine-Isoprostanes (PtdCho-IP) by Peripheral Human Group IIA, V and X Secretory Phospholipases A2 (sPLA2).

PubMed

Kuksis, Arnis; Pruzanski, Waldemar

2017-06-01

Biologically active F- and E/D-type-prostane ring isomers (F 2 -IP and E 2 /D 2 -IP, respectively) are produced in situ by non-enzymatic peroxidation of arachidonic acid esterified to GroPCho (PtdCho-IP) and are universally distributed in tissue lipoproteins and cell membranes. Previous work has shown that platelet-activating factor acetylhydrolases (PAF-AH) are the main endogenous PLA 2 involved in degradation of PtdCho-IP. The present study shows that the PtdCho-IP are also subject to hydrolysis by group IIA, V and X secretory PLA 2 , which also have a wide peripheral tissue distribution. For this demonstration, we compared the LC/MS profiles of PtdCho-IP of auto-oxidized plasma lipoproteins after incubation for 1-4 h (37 °C) in the absence or presence of recombinant human sPLA 2 (1-2.5 µg/ml). In the absence of exogenously added sPLA 2 the total PtdCho-IP level after 4 h incubation reached 15.9, 21.6 and 8.7 nmol/mg protein of LDL, HDL and HDL 3 , respectively. In the presence of group V or group X sPLA 2 (2.5 µg/ml), the PtdCho-IP was completely hydrolyzed in 1 h, while in the presence of group IIA sPLA 2 (2.5 µg/ml) the hydrolysis was less than 25% in 4 h, although it was complete after 8-24 h incubation. This report provides the first demonstration that PtdCho-IP are readily hydrolyzed by group IIA, V and X sPLA 2 . A co-location of sPLA 2 and the substrates in various tissues has been recorded. Thus, the initiation of interaction and production of isoprostanes in situ are highly probable.

Thin filament diversity and physiological properties of fast and slow fiber types in astronaut leg muscles

NASA Technical Reports Server (NTRS)

Riley, Danny A.; Bain, James L W.; Thompson, Joyce L.; Fitts, Robert H.; Widrick, Jeffrey J.; Trappe, Scott W.; Trappe, Todd A.; Costill, David L.

2002-01-01

Slow type I fibers in soleus and fast white (IIa/IIx, IIx), fast red (IIa), and slow red (I) fibers in gastrocnemius were examined electron microscopically and physiologically from pre- and postflight biopsies of four astronauts from the 17-day, Life and Microgravity Sciences Spacelab Shuttle Transport System-78 mission. At 2.5-microm sarcomere length, thick filament density is approximately 1,012 filaments/microm(2) in all fiber types and unchanged by spaceflight. In preflight aldehyde-fixed biopsies, gastrocnemius fibers possess higher percentages (approximately 23%) of short thin filaments than soleus (9%). In type I fibers, spaceflight increases short, thin filament content from 9 to 24% in soleus and from 26 to 31% in gastrocnemius. Thick and thin filament spacing is wider at short sarcomere lengths. The Z-band lattice is also expanded, except for soleus type I fibers with presumably stiffer Z bands. Thin filament packing density correlates directly with specific tension for gastrocnemius fibers but not soleus. Thin filament density is inversely related to shortening velocity in all fibers. Thin filament structural variation contributes to the functional diversity of normal and spaceflight-unloaded muscles.

General N=1 supersymmetric flux vacua of massive type IIA string theory.

PubMed

Behrndt, Klaus; Cvetic, Mirjam

2005-07-08

We derive conditions for the existence of four-dimensional N=1 supersymmetric flux vacua of massive type IIA string theory with general supergravity fluxes turned on. For an SU(3) singlet Killing spinor, we show that such flux vacua exist when the internal geometry is nearly Kähler. The geometry is not warped, all the allowed fluxes are proportional to the mass parameter, and the dilaton is fixed by a ratio of (quantized) fluxes. The four-dimensional cosmological constant, while negative, becomes small in the vacuum with the weak string coupling.

Comparative Adjuvant Effects of Type II Heat-Labile Enterotoxins in Combination with Two Different Candidate Ricin Toxin Vaccine Antigens.

PubMed

Vance, David J; Greene, Christopher J; Rong, Yinghui; Mandell, Lorrie M; Connell, Terry D; Mantis, Nicholas J

2015-12-01

Type II heat-labile enterotoxins (HLTs) constitute a promising set of adjuvants that have been shown to enhance humoral and cellular immune responses when coadministered with an array of different proteins, including several pathogen-associated antigens. However, the adjuvant activities of the four best-studied HLTs, LT-IIa, LT-IIb, LT-IIb(T13I), and LT-IIc, have never been compared side by side. We therefore conducted immunization studies in which LT-IIa, LT-IIb, LT-IIb(T13I), and LT-IIc were coadministered by the intradermal route to mice with two clinically relevant protein subunit vaccine antigens derived from the enzymatic A subunit (RTA) of ricin toxin, RiVax and RVEc. The HLTs were tested with low and high doses of antigen and were assessed for their abilities to stimulate antigen-specific serum IgG titers, ricin toxin-neutralizing activity (TNA), and protective immunity. We found that all four HLTs tested were effective adjuvants when coadministered with RiVax or RVEc. LT-IIa was of particular interest because as little as 0.03 μg when coadministered with RiVax or RVEc proved effective at augmenting ricin toxin-specific serum antibody titers with nominal evidence of local inflammation. Collectively, these results justify the need for further studies into the mechanism(s) underlying LT-IIa adjuvant activity, with the long-term goal of evaluating LT-IIa's activity in humans. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Modulation of Muscle Fiber Compositions in Response to Hypoxia via Pyruvate Dehydrogenase Kinase-1

PubMed Central

Nguyen, Daniel D.; Kim, Gyuyoup; Pae, Eung-Kwon

2016-01-01

Muscle fiber-type changes in hypoxic conditions in accordance with pyruvate dehydrogenase kinase (Pdk)-1 and hypoxia inducible factor (Hif)-1α were investigated in rats. Hif-1α and its down-stream molecule Pdk-1 are well known for readily response to hypoxia. We questioned their roles in relation to changes in myosin heavy chain (MyHC) composition in skeletal muscles. We hypothesize that the level of Pdk-1 with respect to the level of Hif-1α determines MyHC composition of the muscle in rats in hypoxia. Young male rats were housed in a chamber maintained at 11.5% (for sustained hypoxia) or fluctuating between 11.5 and 20.8% (for intermittent hypoxia or IH) oxygen levels. Then, muscle tissues from the geniohyoid (GH), soleus, and anterior tibialis (TA) were obtained at the end of hypoxic conditionings. After both hypoxic conditionings, protein levels of Pdk-1 and Hif-1 increased in GH muscles. GH muscles in acute sustained hypoxia favor an anaerobic glycolytic pathway, resulting in an increase in glycolytic MyHC IIb protein-rich fibers while maintain original fatigue-resistant MyHC IIa protein in the fibers; thus, the numbers of IIa- and IIb MyHC co-expressing fibers increased. Exogenous Pdk-1 over-expression using plasmid vectors elevated not only the glycolytic MyHC IIb, but also IIx as well as IIa expressions in C2C12 myotubes in ambient air significantly. The increase of dual expression of IIa- and IIb MyHC proteins in fibers harvested from the geniohyoid muscle has a potential to improve endurance as shown in our fatigability tests. By increasing the Pdk-1/Hif-1 ratio, a mixed-type muscle could alter endurance within the innate characteristics of the muscle toward more fatigue resistant. We conclude that an increased Pdk-1 level in skeletal muscle helps maintain MyHC compositions to be a fatigue resistant mixed-type muscle. PMID:28018235

Surgical internal iliac artery preservation associated with endovascular repair of infrarenal aortoiliac aneurysms to avoid buttock claudication and distal type I endoleaks.

PubMed

Gaudric, Julien; Tresson, Philippe; Derycke, Lucie; Tezenas Du Montcel, Sophie; Couture, Thibault; Davaine, Jean-Michel; Kashi, Mahine; Lawton, James; Chiche, Laurent; Koskas, Fabien

2018-06-21

The objective of this study was to assess outcomes of a hybrid technique for treatment of abdominal aortic aneurysm (AAA) associated with iliac aneurysm without distal neck by combining an AAA endovascular repair approach with open surgery for preservation of the internal iliac artery (IIA). The files of 51 patients operated on between 1998 and 2017 in a single vascular surgery department were retrospectively analyzed. Inclusion criteria were patients with AAA associated with uni-iliac or bi-iliac aneurysm without suitable distal sealing zone. Surgery consisted of deployment of an aortouni-iliac stent graft combined with an extra-anatomic crossover prosthetic bypass. With use of a limited retroperitoneal approach, the contralateral proximal common iliac aneurysm was surgically excluded and the IIA revascularized by direct ilioiliac anastomosis or terminal common iliac suture, preserving the iliac bifurcation. The patients' mean age was 74 years (58-88 years), and 92% were men. The mean follow-up was 5.8 years (0.1-18 years). Twenty-nine patients (57%) had one or more high-risk criteria for open surgery. Nineteen patients (37.3%) had aortouni-iliac aneurysms, 19 (37.3%) aortobi-iliac aneurysms, 5 (10%) isolated iliac aneurysms, and 8 (15.7%) bi-iliac aneurysms without aortic location. Four patients (7.8%) also had IIA aneurysms. Surgery was successful in all cases. Two patients (4%) died during the 30 days after surgery. One surgically preserved IIA occluded within the first month, resulting in buttock claudication. The 5-year IIA primary patency rate was 96%. Type I proximal endoleaks occurred in two patients, requiring additional surgery 3 years and 13 years after the initial surgery, respectively. This hybrid technique, consisting of AAA endovascular exclusion combined with open IIA revascularization, is safe and effective for preservation of pelvic vascularization. It is associated with long-term patency and low morbidity rates. We have been using this technique since before the advent of branched dedicated devices, allowing preservation of the IIA with good results. This technique should continue to be proposed, especially in patients not eligible for endovascular iliac branch repair because of anatomic contraindications, to avoid pelvic ischemia if the IIA has to be sacrificed. Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

The calibration of photographic and spectroscopic films: 1: A microscopic analysis of IIaO films. 2: The effects of agitation and soaking on IIaO films. 3: The effects of electric field on IIaO films. 4: The effects of X-ray radiation on IIaO films

NASA Technical Reports Server (NTRS)

Hammond, E. C., Jr.; Peters, K.; Boone, K.

1978-01-01

The grain structure of the emulsion using both reflected and transmission light was examined along with the effects of soaking. The effect of a static charge by a Tesla-coil, and the effects of airport equipment, and dental X-rays on the film were also analyzed.

Muscular effects of vitamin D in young athletes and non-athletes and in the elderly.

PubMed

Koundourakis, Nikolaos E; Avgoustinaki, Pavlina D; Malliaraki, Niki; Margioris, Andrew N

2016-10-01

Muscles are major targets of vitamin D. Exposure of skeletal muscles to vitamin D induces the expression of multiple myogenic transcription factors enhancing muscle cell proliferation and differentiation. At the same time vitamin D suppresses the expression of myostatin, a negative regulator of muscle mass. Moreover, vitamin D increases the number of type II or fast twitch muscle cells and in particular that of type IIA cells, while its deficiency causes type IIA cell atrophy. Furthermore, vitamin D supplementation in young males with low vitamin D levels increases the percentage of type IIA fibers in muscles, causing an increase in muscular high power output. Vitamin D levels are strongly associated with exercise performance in athletes and physically active individuals. In the elderly and in adults below the age of 65, several studies have established a close association between vitamin D levels and neuromuscular coordination. The aim of this review is to appraise our current understanding of the significance of vitamin D on muscular performance in both older and frail individuals as well as in younger adults, athletes or non-athletes with regard to both ordinary everyday musculoskeletal tasks and peak athletic performance.

Fat content in individual muscle fibers of lean and obese subjects.

PubMed

Malenfant, P; Joanisse, D R; Thériault, R; Goodpaster, B H; Kelley, D E; Simoneau, J A

2001-09-01

To examine skeletal muscle intracellular triglyceride concentration in different fiber types in relation to obesity. Skeletal muscle fiber type distribution and intracellular lipid content were measured in vastus lateralis samples obtained by needle biopsy from lean and obese individuals. Seven lean controls (body mass index (BMI) 23.0+/-3.3 kg/m(2); mean+/-s.d.) and 14 obese (BMI 33.7+/-2.7 kg/m(2)) individuals; both groups included comparable proportions of men and women. Samples were histochemically stained for the identification of muscle fiber types (myosin ATPase) and intracellular lipid aggregates (oil red O dye). The number and size of fat aggregates as well as their concentration within type I, IIA and IIB muscle fiber types were measured. The cellular distribution of the lipid aggregates was also examined. The size of fat aggregates was not affected by obesity but the number of lipid droplets within muscle fibers was twice as abundant in obese compared to lean individuals. This was seen in type I (298+/-135 vs 129+/-75; obese vs lean, P<0.05), IIA (132+/-67 vs 79+/-29; P<0.05), and IIB (103+/-63 vs 51+/-13; P<0.05) muscle fibers. A more central distribution of lipid droplets was observed in muscle fibers of obese compared to lean subjects (27.2+/-5.7 vs 19.7+/-6.4%; P<0.05). The higher number of lipid aggregates and the disposition to a greater central distribution in all fiber types in obesity indicate important changes in lipid metabolism and/or storage that are fiber type-independent.

AdS6 solutions of type II supergravity

NASA Astrophysics Data System (ADS)

Apruzzi, Fabio; Fazzi, Marco; Passias, Achilleas; Rosa, Dario; Tomasiello, Alessandro

2014-11-01

Very few AdS6 × M 4 supersymmetric solutions are known: one in massive IIA, and two IIB solutions dual to it. The IIA solution is known to be unique; in this paper, we use the pure spinor approach to give a classification for IIB supergravity. We reduce the problem to two PDEs on a two-dimensional space Σ. M 4 is then a fibration of S 2 over Σ; the metric and fluxes are completely determined in terms of the solution to the PDEs. The results seem likely to accommodate near-horizon limits of ( p, q)-fivebrane webs studied in the literature as a source of CFT5's. We also show that there are no AdS6 solutions in eleven-dimensional supergravity.

Isometric contractions of motor units and immunohistochemistry of mouse soleus muscle.

PubMed Central

Lewis, D M; Parry, D J; Rowlerson, A

1982-01-01

1. Isometric contractions of motor units, isolated functionally by ventral root splitting in vivo, were recorded from mouse soleus muscle. 2. Motor unit tensions varied over a narrow symmetrical range and averaged 4.7% of whole muscle tension, corresponding to twenty-one motor units per muscle. 3. There was considerable variation between muscles in isometric twitch times-to-peak and even greater variation for the motor units. The distribution of motor unit times-to-peak was apparently unimodal and could be fitted by a single normal population. A slightly better fit was, however, obtained with two normal populations, as suggested by the histochemistry. 4. Twitch time-to-peak decreased in proportion to axonal conduction velocity in individual animals. The whole population of motor units could be fitted by a linear relation between time-to-peak and the reciprocal of conduction time in the motor axon. Motor unit tension was also linearly related to the reciprocal of conduction time. 5. Histochemistry showed clear division between Type I and Type IIa fibres. Type I fibres reacted strongly with antibody against slow myosin of cat soleus muscle; Type IIa gave a reaction no stronger than the background. The division was as clear as in the cat or rat. Images Fig. 2 Plate 1 PMID:7050345

Is vitamin D hypothesis for schizophrenia valid? Independent segregation of psychosis in a family with vitamin-D-dependent rickets type IIA.

PubMed

Ozer, Suzan; Uluşahin, Aylin; Ulusoy, Semra; Okur, Hamza; Coşkun, Turgay; Tuncali, Timur; Göğüş, Ahmet; Akarsu, A Nurten

2004-03-01

The vitamin D hypothesis of schizophrenia is a recent concept bringing together old observations on environmental risk factors and new findings on the neurodevelopmental effects of vitamin D. Candidate genes related to the vitamin D endocrine system have not yet been fully explored for this purpose. The coexistence of vitamin-D-dependent-rickets type II with alopecia (VDDR IIA) and different forms of psychosis in the same inbred family has provided us with an opportunity to investigate the presumed relationship between vitamin D deficiency and psychosis. Psychiatric examination and molecular genetic studies were performed in this family overloaded with psychotic disorders and VDDR IIA. Forty members were evaluated in order to describe their phenotypic features. The family was tested for a linkage to the chromosome 12q12-q14 region where the vitamin D receptor (VDR) gene is located. Psychosis was the common phenotype in the 18 psychiatrically affected members. Pedigree analysis did not show a cosegregation of psychosis and rickets. Lod scores were not significant to prove a linkage between psychosis and VDR locus. The authors concluded that (1) the neurodevelopmental consequences of vitamin D deficiency do not play a causative role in psychotic disorders, (2) these two syndromes are inherited independently, and (3) vitamin D deficiency does not act as a risk factor in subjects susceptible to psychosis.

Epidemiology and Genetic Characterization of Hepatitis A Virus Genotype IIA▿

PubMed Central

Desbois, Delphine; Couturier, Elisabeth; Mackiewicz, Vincent; Graube, Arielle; Letort, Marie-José; Dussaix, Elisabeth; Roque-Afonso, Anne-Marie

2010-01-01

Three hepatitis A virus (HAV) genotypes, I, II, and III, divided into subtypes A and B, infect humans. Genotype I is the most frequently reported, while genotype II is hardly ever isolated, and its genetic diversity is unknown. From 2002 to 2007, a French epidemiological survey of HAV identified 6 IIA isolates, mostly from patients who did not travel abroad. The possible African origin of IIA strains was investigated by screening the 2008 mandatory notification records of HAV infection: 171 HAV strains from travelers to West Africa and Morocco were identified. Genotyping was performed by sequencing of the VP1/2A junction in 68 available sera. Entire P1 and 5′ untranslated regions of IIA strains were compared to reference sequences of other genotypes. The screening retrieved 5 imported IIA isolates. An additional autochthonous case and 2 more African cases were identified in 2008 and 2009, respectively. A total of 14 IIA isolates (8 African and 6 autochthonous) were analyzed. IIA sequences presented lower nucleotide and amino acid variability than other genotypes. The highest variability was observed in the N-terminal region of VP1, while for other genotypes the highest variability was observed at the VP1/2A junction. Phylogenetic analysis identified 2 clusters, one gathering all African and two autochthonous cases and a second including only autochthonous isolates. In conclusion, most IIA strains isolated in France are imported by travelers returning from West Africa. However, the unexplained contamination mode of autochthonous cases suggests another, still to be discovered geographical origin or a French reservoir to be explored. PMID:20592136

Four-qubit systems and dyonic black Hole-Black branes in superstring theory

NASA Astrophysics Data System (ADS)

Belhaj, A.; Bensed, M.; Benslimane, Z.; Sedra, M. B.; Segui, A.

Using dyonic solutions in the type IIA superstring theory on Calabi-Yau (CY) manifolds, we reconsider the study of black objects and quantum information theory using string/string duality in six dimensions. Concretely, we relate four-qubits with a stringy quaternionic moduli space of type IIA compactification associated with a dyonic black solution formed by black holes (BHs) and black 2-branes (B2B) carrying eight electric charges and eight magnetic charges. This connection is made by associating the cohomology classes of the heterotic superstring on T4 to four-qubit states. These states are interpreted in terms of such dyonic charges resulting from the quaternionic symmetric space SO(4,4) SO(4)×SO(4) corresponding to a N = 4 sigma model superpotential in two dimensions. The superpotential is considered as a functional depending on four quaternionic fields mapped to a class of Clifford algebras denoted as Cl0,4. A link between such an algebra and the cohomology classes of T4 in heterotic superstring theory is also given.

Magnetic Resonance Imaging Susceptibility-Weighted Imaging Lesion and Contrast Enhancement May Represent Infectious Intracranial Aneurysm in Infective Endocarditis.

PubMed

Cho, Sung-Min; Rice, Cory; Marquardt, Robert J; Zhang, Lucy Q; Khoury, Jean; Thatikunta, Prateek; Buletko, Andrew B; Hardman, Julian; Uchino, Ken; Wisco, Dolora

2017-01-01

Infectious intracranial aneurysm (IIA) can complicate infective endocarditis (IE). We aimed to describe the magnetic resonance imaging (MRI) characteristics of IIA. We reviewed IIAs among 116 consecutive patients with active IE by conducting a neurological evaluation at a single tertiary referral center from January 2015 to July 2016. MRIs and digital cerebral angiograms (DSA) were reviewed to identify MRI characteristics of IIAs. MRI susceptibility weighted imaging (SWI) was performed to collect data on cerebral microbleeds (CMBs) and sulcal SWI lesions. Out of 116 persons, 74 (63.8%) underwent DSA. IIAs were identified in 13 (17.6% of DSA, 11.2% of entire cohort) and 10 patients with aneurysms underwent MRI with SWI sequence. Nine (90%) out of 10 persons with IIAs had CMB >5 mm or sulcal lesions in SWI (9 in sulci, 6 in parenchyma, and 5 in both). Five out of 8 persons who underwent MRI brain with contrast had enhancement within the SWI lesions. In a multivariate logistic regression analysis, both sulcal SWI lesions (p < 0.001, OR 69, 95% CI 7.8-610) and contrast enhancement (p = 0.007, OR 16.5, 95% CI 2.3-121) were found to be significant predictors of the presence of IIAs. In the individuals with IE who underwent DSA and MRI, we found that neuroimaging characteristics, such as sulcal SWI lesion with or without contrast enhancement, are associated with the presence of IIA. © 2017 S. Karger AG, Basel.

Carbohydrate feeding and glycogen synthesis during exercise in man.

PubMed

Kuipers, H; Keizer, H A; Brouns, F; Saris, W H

1987-12-01

In 7 male cyclists glycogen synthesis during exercise and rest was studied. Each subject did two exercise trials (A and B), in random order. In both trials, after determining the maximal workload (Wmax), intermittent exercise was given to exhaustion. After the exhaustive exercise and taking a muscle biopsy the subjects either exercised at 40% Wmax for 3 h (trial A) or rested for 3 h (trial B), during which they consumed approximately 2 l of a 25% malto-dextrine drink in both trials. After 3 h rest (trial A) or 3 h of mild exercise (trial B) a second muscle biopsy was taken for total glycogen and histochemistry (ATPase and PAS). Blood glucose and insulin levels were elevated during the first 2 h of exercise (p less than 0.05). Glycogen depletion was most pronounced in type I and to a less extent in type IIA fibers. In trial A muscle glycogen increased from 136 +/- 66 to 199 +/- 71 mmol/kg DW, and in trial B from 145 +/- 56 to 257 +/- 79 mmol/kg DW. During exercise glycogen repletion was restricted to type IIA and IIB fibers, whereas during rest glycogen synthesis occurred both in type I and type II fibers. The present study demonstrates that oral carbohydrate administered during exercise may not only provide substrate for energy metabolism, but can also be utilized for glycogen synthesis in the non-active muscle fibers.

A combination of two truncating mutations in USH2A causes more severe and progressive hearing impairment in Usher syndrome type IIa.

PubMed

Hartel, Bas P; Löfgren, Maria; Huygen, Patrick L M; Guchelaar, Iris; Lo-A-Njoe Kort, Nicole; Sadeghi, Andre M; van Wijk, Erwin; Tranebjærg, Lisbeth; Kremer, Hannie; Kimberling, William J; Cremers, Cor W R J; Möller, Claes; Pennings, Ronald J E

2016-09-01

Usher syndrome is an inherited disorder that is characterized by hearing impairment (HI), retinitis pigmentosa, and in some cases vestibular dysfunction. Usher syndrome type IIa is caused by mutations in USH2A. HI in these patients is highly heterogeneous and the present study evaluates the effects of different types of USH2A mutations on the audiometric phenotype. Data from two large centres of expertise on Usher Syndrome in the Netherlands and Sweden were combined in order to create a large combined sample of patients to identify possible genotype-phenotype correlations. A retrospective study on HI in 110 patients (65 Dutch and 45 Swedish) genetically diagnosed with Usher syndrome type IIa. We used methods especially designed for characterizing and testing differences in audiological phenotype between patient subgroups. These methods included Age Related Typical Audiograms (ARTA) and a method to evaluate the difference in the degree of HI developed throughout life between subgroups. Cross-sectional linear regression analysis of last-visit audiograms for the best hearing ear demonstrated a gradual decline of hearing over decades. The congenital level of HI was in the range of 16-33 dB at 0.25-0.5 kHz, and in the range of 51-60 dB at 1-8 kHz. The annual threshold deterioration was in the range of 0.4-0.5 dB/year at 0.25-2 kHz and in the range of 0.7-0.8 dB/year at 4-8 kHz. Patients with two truncating mutations, including homozygotes for the common c.2299delG mutation, developed significantly more severe HI throughout life than patients with one truncating mutation combined with one nontruncating mutation, and patients with two nontruncating mutations. The results have direct implications for patient counselling in terms of prognosis of hearing and may serve as baseline measures for future (genetic) therapeutic interventions. Copyright © 2016 Elsevier B.V. All rights reserved.

Myosin IIA participates in docking of Glut4 storage vesicles with the plasma membrane in 3T3-L1 adipocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chung, Le Thi Kim, E-mail: ngocanh@nutr.med.tokushima-u.ac.jp; Hosaka, Toshio; Harada, Nagakatsu

2010-01-01

In adipocytes and myocytes, insulin stimulation translocates glucose transporter 4 (Glut4) storage vesicles (GSVs) from their intracellular storage sites to the plasma membrane (PM) where they dock with the PM. Then, Glut4 is inserted into the PM and initiates glucose uptake into these cells. Previous studies using chemical inhibitors demonstrated that myosin II participates in fusion of GSVs and the PM and increase in the intrinsic activity of Glut4. In this study, the effect of myosin IIA on GSV trafficking was examined by knocking down myosin IIA expression. Myosin IIA knockdown decreased both glucose uptake and exposures of myc-tagged Glut4more » to the cell surface in insulin-stimulated cells, but did not affect insulin signal transduction. Interestingly, myosin IIA knockdown failed to decrease insulin-dependent trafficking of Glut4 to the PM. Moreover, in myosin IIA knockdown cells, insulin-stimulated binding of GSV SNARE protein, vesicle-associated membrane protein 2 (VAMP2) to PM SNARE protein, syntaxin 4 was inhibited. These data suggest that myosin IIA plays a role in insulin-stimulated docking of GSVs to the PM in 3T3-L1 adipocytes through SNARE complex formation.« less

Myosin IIA-related Actomyosin Contractility Mediates Oxidative Stress-induced Neuronal Apoptosis

PubMed Central

Wang, Yan; Xu, Yingqiong; Liu, Qian; Zhang, Yuanyuan; Gao, Zhen; Yin, Mingzhu; Jiang, Nan; Cao, Guosheng; Yu, Boyang; Cao, Zhengyu; Kou, Junping

2017-01-01

Oxidative stress-induced neuronal apoptosis plays an important role in the progression of central nervous system (CNS) diseases. In our study, when neuronal cells were exposed to hydrogen peroxide (H2O2), an exogenous oxidant, cell apoptosis was observed with typical morphological changes including membrane blebbing, neurite retraction and cell contraction. The actomyosin system is considered to be responsible for the morphological changes, but how exactly it regulates oxidative stress-induced neuronal apoptosis and the distinctive functions of different myosin II isoforms remain unclear. We demonstrate that myosin IIA was required for neuronal contraction, while myosin IIB was required for neuronal outgrowth in normal conditions. During H2O2-induced neuronal apoptosis, myosin IIA, rather than IIB, interacted with actin filaments to generate contractile forces that lead to morphological changes. Moreover, myosin IIA knockout using clustered regularly interspaced short palindromic repeats/CRISPR-associated protein-9 nuclease (CRISPR/Cas9) reduced H2O2-induced neuronal apoptosis and the associated morphological changes. We further demonstrate that caspase-3/Rho-associated kinase 1 (ROCK1) dependent phosphorylation of myosin light chain (MLC) was required for the formation of the myosin IIA-actin complex. Meanwhile, either inhibition of myosin II ATPase with blebbistatin or knockdown of myosin IIA with siRNA reversely attenuated caspase-3 activation, suggesting a positive feedback loop during oxidative stress-induced apoptosis. Based on our observation, myosin IIA-actin complex contributes to actomyosin contractility and is associated with the positive feedback loop of caspase-3/ROCK1/MLC pathway. This study unravels the biochemical and mechanistic mechanisms during oxidative stress-induced neuronal apoptosis and may be applicable for the development of therapies for CNS diseases. PMID:28352215

Inhibition of class IIa histone deacetylase activity by gallic acid, sulforaphane, TMP269, and panobinostat.

PubMed

Choi, Sin Young; Kee, Hae Jin; Jin, Li; Ryu, Yuhee; Sun, Simei; Kim, Gwi Ran; Jeong, Myung Ho

2018-05-01

Histone deacetylase (HDAC) inhibitors are gaining increasing attention as potential therapeutics for cardiovascular diseases as well as cancer. We recently reported that the class II HDAC inhibitor, MC1568, and the phytochemical, gallic acid, lowered high blood pressure in mouse models of hypertension. We hypothesized that class II HDACs may be involved in the regulation of hypertension. The aim of this study was to determine and compare the effects of well-known HDAC inhibitors (TMP269, panobinostat, and MC1568), phytochemicals (gallic acid, sulforaphane, and piceatannol), and anti-hypertensive drugs (losartan, carvedilol, and furosemide) on activities of class IIa HDACs (HDAC4, 5, 7, and 9). The selective class IIa HDAC inhibitor, TMP269, and the pan-HDAC inhibitor, panobinostat, but not MC1568, clearly inhibited class IIa HDAC activities. Among the three phytochemicals, gallic acid showed remarkable inhibition, whereas sulforaphane presented mild inhibition of class IIa HDACs. Piceatannol inhibited only HDAC7 activity. As expected, the anti-hypertensive drugs losartan, carvedilol, and furosemide did not affect the activity of any class IIa HDAC. In addition, we evaluated the inhibitory effect of several compounds on the activity of class l HDACs (HDAC1, 2, 3, and 8) and class IIb HDAC (HDAC6). MC1568 did not affect the activities of HDAC1, HDAC2, and HDAC3, but it reduced the activity of HDAC8 at concentrations of 1 and 10 μM. Gallic acid weakly inhibited HDAC1 and HDAC6 activities, but strongly inhibited HDAC8 activity with effectiveness comparable to that of trichostatin A. Inhibition of HDAC2 activity by sulforaphane was stronger than that by piceatnnaol. These results indicated that gallic acid is a powerful dietary inhibitor of HDAC8 and class IIa/b HDAC activities. Sulforaphane may also be used as a dietary inhibitor of HDAC2 and class IIa HDAC. Our findings suggest that the class II HDAC inhibitor, MC1568, does not inhibit class IIa HDAC, but inhibits HDAC8. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

The influence of muscle fiber type composition on the patterns of responses for electromyographic and mechanomyographic amplitude and mean power frequency during a fatiguing submaximal isometric muscle action.

PubMed

Beck, T W; Housh, T J; Fry, A C; Cramer, J T; Weir, J P; Schilling, B K; Falvo, M J; Moore, C A

2007-07-01

The purpose of this investigation was to examine the influence of muscle fiber type composition on the patterns of responses for electromyographic (EMG) and mechanomyographic (MMG) amplitude and mean power frequency (MPF) during a fatiguing submaximal isometric muscle action. Five resistance-trained (mean +/- SD age = 23.2 +/- 3.7 yrs) and five aerobically-trained (mean +/- SD age = 32.6 +/- 5.2 yrs) men volunteered to perform a fatiguing, 30-sec submaximal isometric muscle action of the leg extensors at 50% of the maximum voluntary contraction (MVC). Muscle biopsies from the vastus lateralis revealed that the myosin heavy chain (MHC) composition for the resistance-trained subjects was 59.0 +/- 4.2% Type IIa, 0.1 +/- 0.1% Type IIx, and 40.9 +/- 4.3% Type I. The aerobically-trained subjects had 27.4 +/- 7.8% Type IIa, 0.0 +/- 0.0% Type IIx, and 72.6 +/- 7.8% Type I MHC. The patterns of responses and mean values for absolute and normalized EMG amplitude and MPF during the fatiguing muscle action were similar for the resistance-trained and aerobically-trained subjects. The resistance-trained subjects demonstrated relatively stable levels for absolute and normalized MMG amplitude and MPF across time, but the aerobically-trained subjects showed increases in MMG amplitude and decreases in MMG MPE The absolute MMG amplitude and MPF values for the resistance-trained subjects were also greater than those for the aerobi-cally-trained subjects. These findings suggested that unlike surface EMG, MMG may be a useful noninvasive technique for examining fatigue-related differences in muscle fiber type composition.

Neoadjuvant Systemic Therapy Use for Younger Patients with Breast Cancer Treated in Different Types of Cancer Centers Across the United States.

PubMed

Mohiuddin, Jahan J; Deal, Allison M; Carey, Lisa A; Lund, Jennifer L; Baker, Brock R; Zagar, Timothy M; Jones, Ellen L; Marks, Lawrence B; Chen, Ronald C

2016-11-01

Multiple clinical trials have shown that neoadjuvant systemic therapy has a benefit in women who are borderline lumpectomy candidates and in those with locally advanced breast cancers by reducing the mastectomy rate and making inoperable tumors operable. The study aim was to examine the patterns of neoadjuvant chemotherapy and endocrine therapy use among younger women in the United States treated at different types of cancer centers. Data from the National Cancer Data Base for 118,086 women younger than 65 years with clinical stage IIA (T2N0 only) to IIIC breast cancer. Following the National Comprehensive Cancer Network guideline categorization, patients were grouped into those who were borderline lumpectomy candidates (clinical stage IIA [T2N0 only], IIB, or IIIA [T3N1 only]) or those with locally advanced disease (clinical stage IIIA [T0-3N2 only], IIIB, or IIIC). The main outcome was the proportion of women who received neoadjuvant systemic therapy. Use of neoadjuvant chemotherapy ranged from 17% (stage IIA) to 79% (stage IIIB). Across almost all stage and receptor subtypes, the use was lower in community vs academic centers. On multivariable analysis, use of neoadjuvant chemotherapy was decreased in community vs academic centers (borderline lumpectomy candidates: adjusted risk ratio = 0.73; 95% CI, 0.69-0.77; locally advanced disease: adjusted risk ratio = 0.78; 95% CI, 0.74-0.83). Use of guideline-concordant neoadjuvant chemotherapy is significantly higher among women treated at academic vs community centers in young and healthy women who do not commonly have contraindications to this treatment. Our study identified a potential disparity in cancer care by type of center where patients receive treatment. Copyright © 2016 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Quarterly Performance/Technical Report of the National Marrow Donor Program

DTIC Science & Technology

2010-03-31

Implemented the Business to Business ( B2B ) Gateway and Business Services to support : • Incoming HLA typing results incorporating HLA Nomenclature changes...maintenance was performed. IIA.3.2 Task 2: Critical Facility and Staff Related Functions Period 6 Activity: • Business Continuity Planning: o Continued...department development of appropriate detailed tasks to be tested at a remote (non-NMDP controlled) location for the 2010 Business Continuity

A pilot study to determine whether differences exist in histochemical properties between the trapezius and extensor carpi radialis brevis muscles in women with work-related myalgia.

PubMed

Green, Howard J; Ranney, Don; Burnett, Margaret; Galvin, Patti; Kyle, Natasha; Iqbal, Sobia; Lounsbury, David; Ouyang, Jing; Smith, Ian C; Stewart, Riley; Tick, Heather; Tupling, A Russell

2014-04-01

To investigate fibre-type abnormalities in women with work-related myalgia (WRM), tissue samples were extracted from their trapezius (TRAP) and the extensor carpi radialis brevis (ECRB) muscles and compared with healthy controls (CON). For the ECRB samples (CON, n = 6; WRM, n = 11), no differences (P > 0.05) were found between groups for any of the properties examined, namely fibre-type (I, IIA, IIX, IIAX) distribution, cross-sectional fibre area, capillary counts (CC), capillary to fibre area ratio, and succinic dehydrogenase activity. For the TRAP samples (CON, n = 6; WRM, n = 8), the only difference (P < 0.05) observed between groups was for CC (CON > WRM), which was not statistically significant (P > 0.05) when age was used a covariant. A comparison of the properties of these 2 muscles in the CON group indicated a higher (P < 0.05) and lower (P < 0.05) percentage of type I and type IIA fibres, respectively, in the TRAP as well as higher (P < 0.05) CC, which was not specific to fibre type. These preliminary results suggest that the properties employed to characterize fibre types do not differentiate CON from WRM for either the TRAP or ECRB. As a consequence, the role of inherent fibre-type differences between these muscles in the pathogenesis of WRM remains uncertain.

The Dual Regulatory Role of Amino Acids Leu480 and Gln481 of Prothrombin*

PubMed Central

Wiencek, Joesph R.; Hirbawi, Jamila; Yee, Vivien C.; Kalafatis, Michael

2016-01-01

Prothrombin (FII) is activated to α-thrombin (IIa) by prothrombinase. Prothrombinase is composed of a catalytic subunit, factor Xa (fXa), and a regulatory subunit, factor Va (fVa), assembled on a membrane surface in the presence of divalent metal ions. We constructed, expressed, and purified several mutated recombinant FII (rFII) molecules within the previously determined fVa-dependent binding site for fXa (amino acid region 473–487 of FII). rFII molecules bearing overlapping deletions within this significant region first established the minimal stretch of amino acids required for the fVa-dependent recognition exosite for fXa in prothrombinase within the amino acid sequence Ser478–Val479–Leu480–Gln481–Val482. Single, double, and triple point mutations within this stretch of rFII allowed for the identification of Leu480 and Gln481 as the two essential amino acids responsible for the enhanced activation of FII by prothrombinase. Unanticipated results demonstrated that although recombinant wild type α-thrombin and rIIaS478A were able to induce clotting and activate factor V and factor VIII with rates similar to the plasma-derived molecule, rIIaSLQ→AAA with mutations S478A/L480A/Q481A was deficient in clotting activity and unable to efficiently activate the pro-cofactors. This molecule was also impaired in protein C activation. Similar results were obtained with rIIaΔSLQ (where rIIaΔSLQ is recombinant human α-thrombin with amino acids Ser478/Leu480/Gln481 deleted). These data provide new evidence demonstrating that amino acid sequence Leu480–Gln481: 1) is crucial for proper recognition of the fVa-dependent site(s) for fXa within prothrombinase on FII, required for efficient initial cleavage of FII at Arg320; and 2) is compulsory for appropriate tethering of fV, fVIII, and protein C required for their timely activation by IIa. PMID:26601957

Platelet-rich plasma-induced feedback inhibition of activin A/follistatin signaling: A mechanism for tumor-low risk skin rejuvenation in irradiated rats.

PubMed

Omar, Nesreen Nabil; Rashed, Rasha R; El-Hazek, Rania M; El-Sabbagh, Walaa A; Rashed, Engy R; El-Ghazaly, Mona A

2018-03-01

Platelet-rich plasma (PRP) is a source of natural growth factors and is emerging as a treatment modality to mitigate radiotherapy- induced adverse effects. Activin A (ACTA) is a member of the transforming growth factor-β (TGF-β) superfamily, which has been shown to modulate the inflammatory response and macrophages polarization between different phenotypes. The aim of this study is to determine the value of PRP in preventing radiation-induced malignancies in light of the cross-talk between PRP and activin A type II receptors (ActR-IIA)/follistatin (FST) signaling pathways where the inflammatory responses at 2 different time points were evaluated. Male albino rats were exposed to radiation and given PRP over the course of 6 days. Rats were sacrificed on day 7 or day 28 post radiation. Quantitative real-time reverse transcriptase polymerase chain reaction (QRT-PCR) and western-blot showed that after 7 days of administrating of PRP, ActR-IIA/FST signaling was markedly induced and was associated with the expressions of inflammatory, natural killer and M1 macrophages markers, TNF-α, IL-1β, IFN-γ and IL-12. By contrast, on day 28 of PRP administration, ActR-IIA/FST signaling and the expressions of proinflammatory cytokines were downregulated in parallel with inducing M2 macrophages phenotype as indicated by arginase-1, IL-10 and dectin-1. The suppression of inflammation and induction of M2 macrophages phenotype in response to PRP administration were found significantly linked to ActR-IIA/FST signaling downregulation. Furthermore, the specific M2 macrophage subtype was found to express dectin-1 receptors which have high affinity for tumor cells thereby is expected to reduce the potential for developing tumors after radiotherapy. Copyright © 2018 Elsevier B.V. All rights reserved.

Evidence for a non-canonical role of HDAC5 in regulation of the cardiac Ncx1 and Bnp genes.

PubMed

Harris, Lillianne G; Wang, Sabina H; Mani, Santhosh K; Kasiganesan, Harinath; Chou, C James; Menick, Donald R

2016-05-05

Class IIa histone deacetylases (HDACs) are very important for tissue specific gene regulation in development and pathology. Because class IIa HDAC catalytic activity is low, their exact molecular roles have not been fully elucidated. Studies have suggested that class IIa HDACs may serve as a scaffold to recruit the catalytically active class I HDAC complexes to their substrate. Here we directly address whether the class IIa HDAC, HDAC5 may function as a scaffold to recruit co-repressor complexes to promoters. We examined two well-characterized cardiac promoters, the sodium calcium exchanger (Ncx1) and the brain natriuretic peptide (Bnp) whose hypertrophic upregulation is mediated by both class I and IIa HDACs. Selective inhibition of class IIa HDACs did not prevent adrenergic stimulated Ncx1 upregulation, however HDAC5 knockout prevented pressure overload induced Ncx1 upregulation. Using the HDAC5((-/-)) mouse we show that HDAC5 is required for the interaction of the HDAC1/2/Sin3a co-repressor complexes with the Nkx2.5 and YY1 transcription factors and critical for recruitment of the HDAC1/Sin3a co-repressor complex to either the Ncx1 or Bnp promoter. Our novel findings support a non-canonical role of class IIa HDACs in the scaffolding of transcriptional regulatory complexes, which may be relevant for therapeutic intervention for pathologies. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Immunolabelling, histochemistry and in situ hybridisation in human skeletal muscle fibres to detect myosin heavy chain expression at the protein and mRNA level

PubMed Central

SERRANO, A. L.; PÉREZ, MARGARITA; LUCÍA, A.; CHICHARRO, J. L.; QUIROZ-ROTHE, E.; RIVERO, J. L. L.

2001-01-01

The distribution of muscle fibres classified on the basis of their content of different myosin heavy chain (MHC) isoforms was analysed in vastus lateralis muscle biopsies of 15 young men (with an average age of 22 y) by correlating immunohistochemistry with specific anti-MHC monoclonal antibodies, myofibrillar ATPase (mATPase) histochemistry and in situ hybridisation with probes specific for MHC β-slow, MHC-IIA and MHC-IIX. The characterisation of a large number of individual fibres was compared and correlated on a fibre-to-fibre basis. The panel of monoclonal antibodies used in the study allowed classification of human skeletal muscle fibres into 5 categories according to the MHC isoform they express at the protein level, types I, I+IIA, IIA, IIAX and IIX. Hybrid fibres coexpressing two isoforms represented a considerable proportion of the fibre composition (about 14%) and were clearly underestimated by mATPase histochemistry. For a very high percentage of fibres there was a precise correspondence between the MHC protein isoforms and mRNA transcripts. The integrated methods used demonstrate a high degree of precision of the immunohistochemical procedure used for the identification and quantification of human skeletal muscle fibre types. The monoclonal antibody S5-8H2 is particularly useful for identifying hybrid IIAX fibres. This protocol offers new prospects for muscle fibre classification in human experimental studies. PMID:11554510

Altered fibre types in gastrocnemius muscle of high wheel-running selected mice with mini-muscle phenotypes.

PubMed

Guderley, Helga; Joanisse, Denis R; Mokas, Sophie; Bilodeau, Geneviève M; Garland, Theodore

2008-03-01

Selective breeding of mice for high voluntary wheel running has favoured characteristics that facilitate sustained, aerobically supported activity, including a "mini-muscle" phenotype with markedly reduced hind limb muscle mass, increased mass-specific activities of oxidative enzymes, decreased % myosin heavy chain IIb, and, in the medial gastrocnemius, reduced twitch speed, reduced mass-specific isotonic power, and increased fatigue resistance. To evaluate whether selection has altered fibre type expression in mice with either "mini" or normal muscle phenotypes, we examined fibre types of red and white gastrocnemius. In both the medial and lateral gastrocnemius, the mini-phenotype increased activities of oxidative enzymes and decreased activities of glycolytic enzymes. In red muscle samples, the mini-phenotype markedly changed fibre types, with the % type I and type IIA fibres and the surface area of type IIA fibres increasing; in addition, mice from selected lines in general had an increased % type IIA fibres and larger type I fibres as compared with mice from control lines. White muscle samples from mini-mice showed dramatic structural alterations, with an atypical distribution of extremely small, unidentifiable fibres surrounded by larger, more oxidative fibres than normally present in white muscle. The increased proportion of oxidative fibres and these atypical small fibres together may explain the reduced mass and increased mitochondrial enzyme activities in mini-muscles. These and previous results demonstrate that extension of selective breeding beyond the time when the response of the selected trait (i.e. distance run) has levelled off can still modify the mechanistic underpinnings of this behaviour.

Relationships among muscle fiber type composition, fiber diameter and MRF gene expression in different skeletal muscles of naturally grazing Wuzhumuqin sheep during postnatal development.

PubMed

Siqin, Qimuge; Nishiumi, Tadayuki; Yamada, Takahisa; Wang, Shuiqing; Liu, Wenjun; Wu, Rihan; Borjigin, Gerelt

2017-12-01

The aim of this study was to determine the relationships among muscle fiber-type composition, fiber diameter, and myogenic regulatory factor (MRF) gene expression in different skeletal muscles during development in naturally grazing Wuzhumuqin sheep. Three major muscles (i.e. the Longissimus dorsi (LD), Biceps femoris (BF) and Triceps brachii (TB)) were obtained from 20 Wuzhumuqin sheep and 20 castrated rams at each of the following ages: 1, 3, 6, 9, 12 and 18 months. Muscle fiber-type composition and fiber diameter were measured using histochemistry and morphological analysis, and MRF gene expression levels were determined using real-time PCR. In the LD muscle, changes in the proportion of each of different types of fiber (I, IIA and IIB) were relatively small. In the BF muscle, a higher proportion of type I and a 6.19-fold lower proportion of type IIA fibers were observed (P < 0.05). In addition, the compositions of type I and IIA fibers continuously changed in the TB muscle (P < 0.05). Moreover, muscle diameter gradually increased throughout development (P < 0.05). Almost no significant difference was found in MRF gene expression patterns, which appeared to be relatively stable. These results suggest that changes in fiber-type composition and increases in fiber size may be mutually interacting processes during muscle development. © 2017 The Authors Animal Science Journal published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Animal Science.

Solution structure of the phosphoryl transfer complex between the cytoplasmic A domain of the mannitol transporter IIMannitol and HPr of the Escherichia coli phosphotransferase system.

PubMed

Cornilescu, Gabriel; Lee, Byeong Ryong; Cornilescu, Claudia C; Wang, Guangshun; Peterkofsky, Alan; Clore, G Marius

2002-11-01

The solution structure of the complex between the cytoplasmic A domain (IIA(Mtl)) of the mannitol transporter II(Mannitol) and the histidine-containing phosphocarrier protein (HPr) of the Escherichia coli phosphotransferase system has been solved by NMR, including the use of conjoined rigid body/torsion angle dynamics, and residual dipolar couplings, coupled with cross-validation, to permit accurate orientation of the two proteins. A convex surface on HPr, formed by helices 1 and 2, interacts with a complementary concave depression on the surface of IIA(Mtl) formed by helix 3, portions of helices 2 and 4, and beta-strands 2 and 3. The majority of intermolecular contacts are hydrophobic, with a small number of electrostatic interactions at the periphery of the interface. The active site histidines, His-15 of HPr and His-65 of IIA(Mtl), are in close spatial proximity, and a pentacoordinate phosphoryl transition state can be readily accommodated with no change in protein-protein orientation and only minimal perturbations of the backbone immediately adjacent to the histidines. Comparison with two previously solved structures of complexes of HPr with partner proteins of the phosphotransferase system, the N-terminal domain of enzyme I (EIN) and enzyme IIA(Glucose) (IIA(Glc)), reveals a number of common features despite the fact that EIN, IIA(Glc), and IIA(Mtl) bear no structural resemblance to one another. Thus, entirely different underlying structural elements can form binding surfaces for HPr that are similar in terms of both shape and residue composition. These structural comparisons illustrate the roles of surface and residue complementarity, redundancy, incremental build-up of specificity and conformational side chain plasticity in the formation of transient specific protein-protein complexes in signal transduction pathways.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kitchin, Kirk T.; Wallace, Kathleen

A large amount of evidence suggests that arsenicals act via oxidative stress in causing cancer in humans and experimental animals. It is possible that arsenicals could bind in situ close to nuclear DNA followed by Haber-Weiss type oxidative DNA damage. Therefore, we tested this hypothesis by using radioactive {sup 73}As labeled arsenite and vacuum filtration methodology to determine the binding affinity and capacity of {sup 73}As arsenite to calf thymus DNA and Type 2A unfractionated histones, histone H3, H4 and horse spleen ferritin. Arsenicals are known to release redox active Fe from ferritin. At concentrations up to about 1 mM,more » neither DNA nor any of the three proteins studied, Type II-A histones, histone H3, H4 or ferritin, bound radioactive arsenite in a specific manner. Therefore, it appears highly unlikely that initial in situ binding of trivalent arsenicals, followed by in situ oxidative DNA damage, can account for arsenic's carcinogenicity. This experimental evidence (lack of arsenite binding to DNA, histone Type II-A and histone H3, H4) does not rule out other possible oxidative stress modes of action for arsenic such as (a) diffusion of longer lived oxidative stress molecules, such as H{sub 2}O{sub 2} into the nucleus and ensuing oxidative damage, (b) redox chemistry by unbound arsenicals in the nucleus, or (c) arsenical-induced perturbations in Fe, Cu or other metals which are already known to oxidize DNA in vitro and in vivo.« less

Molecular Characterization of Methicillin-Resistant Staphylococcus aureus from Outpatients in Northern Japan: Increasing Tendency of ST5/ST764 MRSA-IIa with Arginine Catabolic Mobile Element.

PubMed

Aung, Meiji Soe; Kawaguchiya, Mitsuyo; Urushibara, Noriko; Sumi, Ayako; Ito, Masahiko; Kudo, Kenji; Morimoto, Shigeo; Hosoya, Shino; Kobayashi, Nobumichi

2017-07-01

Arginine catabolic mobile element (ACME) is a genomic island of staphylococcus and is considered to confer enhanced ability to survive and growth on host bacterial cells. ACME has been typically identified in Panton-Valentine Leukocidin (PVL)-positive ST8 methicillin-resistant Staphylococcus aureus (MRSA) with SCCmec type IVa (USA300 clone), and it is also found in other lineages at low frequency. Prevalence and molecular characteristics of PVL + and/or ACME + MRSA were investigated for 624 clinical isolates collected from outpatients in northern Japan from 2013 to 2014. Both PVL genes and ACME type I were detected in nine isolates (1.4%), which were ST8-MRSA-SCCmec IVa/spa type t008/agr-I; whereas solely PVL genes were positive in two isolates, ST30-MRSA-SCCmec IV and ST59-MRSA-SCCmec V. ACME type II' (previously referred to as ACME ΔII) was detected in 36 isolates (5.8%) with SCCmec II and V (32 and 4 isolates, respectively), exhibiting an increased rate within SCCmec II-MRSA (7.1%) compared with our previous studies (0.86-4.5%, 2008-2011). ACME II'-positive MRSA strains were classified into ST5-SCCmec IIa/V or ST764-SCCmec IIa belonging to five different spa types, with t002 being dominant. They harbored mostly enterotoxin gene clusters (seg-sei-sem-sen-seo-seu) and some more enterotoxin genes (seb1, seb2, sec3, sel, sep), showing resistance to more antimicrobials than ST8-MRSA-SCCmec IVa. ACME-SCCmec composite island (CI) of the 36 ACME II'-positive MRSA was classified into five types (ii)-(vi), among which type (ii) (orfX-ΨSCC ΔJ1 SCCmec I -ACME II'-SCCmec II) was dominant and subdivided into the A3 variant and the less common A2 variant. CI types (v) and (vi) were considered novel genetic organizations having speG (acetyltransferase genes for polyamines) in inserted SCC4610/SCC266-like genetic elements. The present study revealed increased prevalence and genetic diversity of the ST5/ST764-MRSA-SCCmec II with ACME II' in northern Japan.

Cochlear Implantation in Patients With Usher Syndrome Type IIa Increases Performance and Quality of Life.

PubMed

Hartel, Bas P; van Nierop, Josephine W I; Huinck, Wendy J; Rotteveel, Liselotte J C; Mylanus, Emmanuel A M; Snik, Ad F; Kunst, Henricus P M; Pennings, Ronald J E

2017-07-01

Usher syndrome type IIa (USH2a) is characterized by congenital moderate to severe hearing impairment and retinitis pigmentosa. Hearing rehabilitation starts in early childhood with the application of hearing aids. In some patients with USH2a, severe progression of hearing impairment leads to insufficient speech intelligibility with hearing aids and issues with adequate communication and safety. Cochlear implantation (CI) is the next step in rehabilitation of such patients. This study evaluates the performance and benefit of CI in patients with USH2a. Retrospective case-control study to evaluate the performance and benefit of CI in 16 postlingually deaf adults (eight patients with USH2a and eight matched controls). Performance and benefit were evaluated by a speech intelligibility test and three quality-of-life questionnaires. Patients with USH2a with a mean age of 59 years at implantation exhibited good performance after CI. The phoneme scores improved significantly from 41 to 87% in patients with USH2a (p = 0.02) and from 30 to 86% in the control group (p = 0.001). The results of the questionnaire survey demonstrated a clear benefit from CI. There were no differences in performance or benefit between patients with USH2a and control patients before and after CI. CI increases speech intelligibility and improves quality of life in patients with USH2a.

Connective Tissue Reflex Massage for Type 2 Diabetic Patients with Peripheral Arterial Disease: Randomized Controlled Trial

PubMed Central

Castro-Sánchez, Adelaida María; Moreno-Lorenzo, Carmen; Matarán-Peñarrocha, Guillermo A.; Feriche-Fernández-Castanys, Belen; Granados-Gámez, Genoveva; Quesada-Rubio, José Manuel

2011-01-01

The objective of this study was to evaluate the efficacy of connective tissue massage to improve blood circulation and intermittent claudication symptoms in type 2 diabetic patients. A randomized, placebo-controlled trial was undertaken. Ninety-eight type 2 diabetes patients with stage I or II-a peripheral arterial disease (PAD) (Leriche-Fontaine classification) were randomly assigned to a massage group or to a placebo group treated using disconnected magnetotherapy equipment. Peripheral arterial circulation was determined by measuring differential segmental arterial pressure, heart rate, skin temperature, oxygen saturation and skin blood flow. Measurements were taken before and at 30 min, 6 months and 1 year after the 15-week treatment. After the 15-week program, the groups differed (P < .05) in differential segmental arterial pressure in right lower limb (lower one-third of thigh, upper and lower one-third of leg) and left lower limb (lower one-third of thigh and upper and lower one-third of leg). A significant difference (P < .05) was also observed in skin blood flow in digits 1 and 4 of right foot and digits 2, 4 and 5 of left foot. ANOVA results were significant (P < .05) for right and left foot oxygen saturation but not for heart rate and temperature. At 6 months and 1 year, the groups differed in differential segmental arterial pressure in upper third of left and right legs. Connective tissue massage improves blood circulation in the lower limbs of type 2 diabetic patients at stage I or II-a and may be useful to slow the progression of PAD. PMID:19933770

Immunological study of an attenuated Salmonella Typhimurium expressing ApxIA, ApxIIA, ApxIIIA and OmpA of Actinobacillus pleuropneumoniae in a mouse model.

PubMed

Hur, Jin; Eo, Seong Kug; Park, Sang-Youel; Choi, Yoonyoung; Lee, John Hwa

2016-01-01

Salmonella Typhimurium strain expressing the Actinobacillus pleuropneumoniae antigens, ApxIA, ApxIIA, ApxIIIA and OmpA, was previously constructed as a vaccine candidate for porcine pleuropneumonia. This strain was a live attenuated (∆lon∆cpxR∆asd)Salmonella as a delivery host and contained a vector containing asd. An immunological study of lymphocyte proliferation, T-lymphocyte subsets and cytokines in the splenocytes of a mouse model was carried out after stimulation with the candidate Salmonella Typhimurium by intranasal inoculation. The splenic lymphocyte proliferation and the levels of IL-4, IL-6 and IL-12 of the inoculated mice were significantly increased, and the T- and B-cell populations were also elevated. Collectively, the candidate may efficiently induce the Th1- and Th2-type immune responses.

Capillarization in skeletal muscle of rats with cardiac hypertrophy.

PubMed

Degens, Hans; Anderson, Rebecca K; Alway, Stephen E

2002-02-01

Exercise intolerance during chronic heart failure (CHF) is localized mainly in skeletal muscle. A decreased capillarization may impair exchange of oxygen between capillaries and muscle tissue and in this way contribute to exercise intolerance. We assessed changes in capillary supply in plantaris and diaphragm muscles of a rat aorta-caval fistula (ACF) preparation, a volume overload model for CHF. An ACF was created under equithesin anesthesia. Plantaris and diaphragm muscles were removed 6 wk postsurgery and examined for myosin heavy chain (MyHC) content and capillary supply. Cardiac hypertrophy was 96% (P < 0.002) after ACF. The Type IIb MyHC content of the plantaris muscles increased (33.9 +/- 3.3 vs 49.8 +/- 3.8%; mean +/- SEM) at the expense of Type IIa MyHC (17.6 +/- 1.8 vs 11.2 +/- 1.7%) in ACF rats (P < 0.05). In the diaphragm, the number of Type I (32.1 +/- 2.3 vs 40.6 +/- 2.7%) and IIb fibers (40.6 +/- 1.9 vs 49.6 +/- 3.6%) increased at the expense of Type IIa fibers (26.8 +/- 2.5 vs 9.4 +/- 0.9%) (P < 0.05). The capillary number per fiber did not change, and this indicated that no capillary loss occurred with ACF. Also, the capillary density was maintained in the diaphragm and plantaris muscles of ACF rats. Furthermore, the coupling between fiber type, size, and metabolic type of surrounding fibers, with the capillary supply to a fiber, was maintained in rats with an ACF. The cardiac hypertrophy induced by volume overload seems adequate to prevent atrophy and changes in the microcirculation of limb and diaphragm muscles.

Inverse relationship between exercise economy and oxidative capacity in muscle.

PubMed

Hunter, Gary R; Bamman, Marcas M; Larson-Meyer, D Enette; Joanisse, Denis R; McCarthy, John P; Blaudeau, Tamilane E; Newcomer, Bradley R

2005-08-01

An inverse relationship has been shown between running and cycling exercise economy and maximum oxygen uptake (VO2max). The purposes were: 1) determine the relationship between walking economy and VO2max; and 2) determine the relationship between muscle metabolic economy and muscle oxidative capacity and fiber type. Subjects were 77 premenopausal normal weight women. Walking economy (1/VO2max) was measured at 3 mph and VO2max during graded treadmill test. Muscle oxidative phosphorylation rate (OxPhos), and muscle metabolic economy (force/ATP) were measured in calf muscle using 31P MRS during isometric plantar flexion at 70 and 100% of maximum force, (HI) and (MI) respectively. Muscle fiber type and citrate synthase activity were determined in the lateral gastrocnemius. Significant inverse relationships (r from -0.28 to -0.74) were observed between oxidative metabolism measures and exercise economy (walking and muscle). Type IIa fiber distribution was inversely related to all measures of exercise economy (r from -0.51 to -0.64) and citrate synthase activity was inversely related to muscle metabolic economy at MI (r = -0.56). In addition, Type IIa fiber distribution and citrate synthase activity were positively related to VO2max and muscle OxPhos at HI and MI (r from 0.49 to 0.70). Type I fiber distribution was not related to any measure of exercise economy or oxidative capacity. Our results support the concept that exercise economy and oxidative capacity are inversely related. We have demonstrated this inverse relationship in women both by indirect calorimetry during walking and in muscle tissue by 31P MRS.

Effects of high-intensity interval cycling performed after resistance training on muscle strength and hypertrophy.

PubMed

Tsitkanou, S; Spengos, K; Stasinaki, A-N; Zaras, N; Bogdanis, G; Papadimas, G; Terzis, G

2017-11-01

Aim of the study was to investigate whether high-intensity interval cycling performed immediately after resistance training would inhibit muscle strength increase and hypertrophy expected from resistance training per se. Twenty-two young men were assigned into either resistance training (RE; N = 11) or resistance training plus high-intensity interval cycling (REC; N = 11). Lower body muscle strength and rate of force development (RFD), quadriceps cross-sectional area (CSA) and vastus lateralis muscle architecture, muscle fiber type composition and capillarization, and estimated aerobic capacity were evaluated before and after 8 weeks of training (2 times per week). Muscle strength and quadriceps CSA were significantly and similarly increased after both interventions. Fiber CSA increased significantly and similarly after both RE (type I: 13.6 ± 3.7%, type IIA: 17.6 ± 4.4%, type IIX: 23.2 ± 5.7%, P < 0.05) and REC (type I: 10.0 ± 2.7%, type IIA: 14.8 ± 4.3% type IIX: 20.8 ± 6.0%, P < 0.05). In contrast, RFD decreased and fascicle angle increased (P < 0.05) only after REC. Capillary density and estimated aerobic capacity increased (P < 0.05) only after REC. These results suggest that high-intensity interval cycling performed after heavy-resistance exercise may not inhibit resistance exercise-induced muscle strength/hypertrophy after 2 months of training, while it prompts aerobic capacity and muscle capillarization. The addition of high-intensity cycling after heavy-resistance exercise may decrease RFD partly due to muscle architectural changes. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

On the worldsheet theory of the type IIA {text{Ad}}{{text{S}}_4} × mathbb{C}{mathbb{P}_3} superstring

NASA Astrophysics Data System (ADS)

Sundin, Per

2010-04-01

We perform a detailed study of the type IIA superstring in {text{Ad}}{{text{S}}_4} × mathbb{C}{mathbb{P}_3} . After introducing suitable bosonic light-cone and fermionic kappa worldsheet gauges we derive the pure boson and fermion SU(2|2)×U(1) covariant light-cone Hamiltonian up to quartic order in fields. As a first application of our derivation we calculate energy shifts for string configurations in a closed fermionic subsector and successfully match these with a set of light-cone Bethe equations. We then turn to investigate the mismatch between the degrees of freedom of scattering states and oscillatory string modes. Since only light string modes appear as fundamental Bethe roots in the scattering theory, the physical role of the remaining 4 F + 4 B massive oscillators is rather unclear. By continuing a line of research initiated by Zarembo, we shed light on this question by calculating quantum corrections for the propagators of the bosonic massive fields. We show that, once loop corrections are incorporated, the massive coordinates dissolve in a continuum state of two light particles.

Modularity, quaternion-Kähler spaces, and mirror symmetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alexandrov, Sergei; Banerjee, Sibasish

2013-10-15

We provide an explicit twistorial construction of quaternion-Kähler manifolds obtained by deformation of c-map spaces and carrying an isometric action of the modular group SL(2,Z). The deformation is not assumed to preserve any continuous isometry and therefore this construction presents a general framework for describing NS5-brane instanton effects in string compactifications with N= 2 supersymmetry. In this context the modular invariant parametrization of twistor lines found in this work yields the complete non-perturbative mirror map between type IIA and type IIB physical fields.

Creatine Supplementation Induces Alteration in Cross-Sectional Area in Skeletal Muscle Fibers of Wistar Rats Under Swimming Training

PubMed Central

Santos, Fernando Farias Dos; Moura, José A. A.; Curi, Rui; Fernandes, Luiz C.

2002-01-01

Creatine has been shown to increase the total muscle mass. In this study, we investigated the effect of oral creatine monohydrate supplementation on cross-sectional area of type I, IIA and IIB fibers of gastrocnemius, extensor digitorum longus - EDL and soleus muscles from male Wistar rats subjected to swimming training for 33 days. Four groups were set up: sedentary with no supplementation (CON), sedentary with creatine supplementation (3.3 mg creatine per g chow) (CR), exercised with no supplementation (EX) and exercised with supplementation (CREX). The rats performed in a special swimming pool and swam five times a week for 1 hour each day, with a extra lead weight corresponding to 15% of their body weight. At the end of 33 days, skeletal muscles of the animals were dissected and the samples got immediately frozen using liquid nitrogen. Muscle samples were allocated to slices of 10 μm by a cryostat at -20°C, which was followed by histochemical analysis in order to identify fiber types of the muscles, and morphometrical analysis to calculate the muscle fiber areas. All groups gained body weight at the end of 33 days but there was no statistical difference among them. The EX and CREX rats had a larger food intake than the sedentary groups (CON and CR), and the CREX group had a larger food intake than CR rats. The cross-sectional area of type I and IIA fibers of the soleus muscle, type IIA and IIB fibers of EDL muscle and type IIA and IIB fibers of the white portion of gastrocnemius muscle were greater in the EX and CREX groups in comparison to sedentary rats. In addition, these fibers were greater in the CREX rats than in the EX group. There was no change in the cross sectional area of type I fibers in EDL muscle among all groups studied. Our results suggest that creatine supplementation enhances the exercise related muscle fiber hypertrophy in rodents. PMID:24701129

Neonatal myosin in bovine and pig tensor tympani muscle fibres.

PubMed Central

Scapolo, P A; Rowlerson, A; Mascarello, F; Veggetti, A

1991-01-01

In previous studies of middle ear muscles, the classification of fibre types by histochemical methods was particularly difficult in the bovine and porcine tensor tympani muscle, suggesting the presence of immature fibres. We therefore reexamined the tensor tympani from pigs and cattle of various ages immunohistochemically, using a panel of antimyosin antibodies, including one (anti-NE) specific for neonatal and embryonic myosins. Fibres positive to anti-NE were found in tensor tympani in both species in all ages examined; only a few of these fibres reacted exclusively with this antibody; some also contained slow myosin and the majority also contained adult fast (type IIA) myosin. Furthermore, although the remaining fibres included some of the classical types I and IIA, the majority of them showed a mismatch between their histochemical and immunohistochemical profiles. The morphological appearance of the muscle, the widespread presence of neonatal myosin (often together with another myosin in the same fibre) and the persistence of this composition from birth to adulthood, could be explained by an incomplete development of the muscle fibres, resulting in a 'muscle' much better suited to the role of a ligament. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:1810932

Tanshinone IIA exerts neuroprotective effects on hippocampus-dependent cognitive impairments in diabetic rats by attenuating ER stress-induced apoptosis.

PubMed

Chen, Jian; Bi, Yanli; Chen, Lei; Zhang, Qi; Xu, Linhao

2018-08-01

This study aimed to investigate the mechanism by which tanshinone IIA (Tan IIA) suppresses neuronal apoptosis in the hippocampus of diabetic rats. Sprague-Dawley (SD) rats were randomly divided into the following four groups: a control group, a diabetes group and diabetes groups treated with different doses (2 or 4 mg/kg/day) of Tan IIA. Streptozotocin (STZ) was injected into the rats to induce diabetes. Two days after STZ treatment, Tan IIA was intraperitoneally administered to rats in the Tan IIA groups, whereas an equal volume of saline was administered to rats in the control and diabetes groups. After 6 weeks, a one-trial object recognition task and the Morris water maze were applied. The diabetes group displayed notably decreased learning and memory abilities compared with the control group (P < 0.05). Tan IIA rescued hippocampus-dependent memory. Superoxide dismutase (SOD) activity was reduced, and reactive oxygen species (ROS) production, malondialdehyde (MDA) content, and 78-kDa glucose-regulated protein (Grp78), growth arrest and DNA damage-inducible gene 153 (CHOP/GAD153) and cleaved caspase-3 levels were increased in the hippocampus of diabetic rats compared with that of control rats, changes that were accompanied by an increase in neuronal apoptosis in diabetic rats compared with control rats (P < 0.01). However, Tan IIA reduced the MDA content and GRP78 and CHOP expression by inducing SOD activity. Tan IIA attenuated neuronal apoptosis and improved learning and memory by suppressing endoplasmic reticulum (ER) stress activation. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Fricke S-duality in CHL models

DOE PAGES

Persson, Daniel; Volpato, Roberto

2015-12-23

In this study, we consider four dimensional CHL models with sixteen spacetime supersymmetries obtained from orbifolds of type IIA superstring on K3×T 2 by a Z N symmetry acting (possibly) non-geometrically on K3. We show that most of these models (in particular, for geometric symmetries) are self-dual under a weak-strong duality acting on the heterotic axio-dilaton modulus S by a “Fricke involution” S → -1/NS. This is a novel symmetry of CHL models that lies outside of the standard SL(2,Z)-symmetry of the parent theory, heterotic strings on T 6. For self-dual models this implies that the lattice of purely electricmore » charges is N-modular, i.e. isometric to its dual up to a rescaling of its quadratic form by N. We verify this prediction by determining the lattices of electric and magnetic charges in all relevant examples. We also calculate certain BPS-saturated couplings and verify that they are invariant under the Fricke S-duality. For CHL models that are not self-dual, the strong coupling limit is dual to type IIA compactified on T 6/Z N, for some Z N-symmetry preserving half of the spacetime supersymmetries.« less

Genetic and antigenic characteristics of ApxIIA and ApxIIIA from Actinobacillus pleuropneumoniae serovars 2, 3, 4, 6, 8 and 15.

PubMed

To, Ho; Nagai, Shinya; Iwata, Akira; Koyama, Tomohiro; Oshima, Atsushi; Tsutsumi, Nobuyuki

2016-07-01

Apx toxins produced by Actinobacillus pleuropneumoniae are essential components of new generation vaccines. In this study, apxIIA and apxIIIA genes of serovars 2, 3, 4, 6, 8 and 15 were cloned and sequenced. Amino acid sequences of ApxIIA proteins of serovars 2, 3, 4, 6, 8 and 15 were almost identical to those of serovars 1, 5, 7, 9 and 11-13. Immunoblot analysis showed that rApxIIA from serovars 2 and 15 reacts strongly with sera from animals infected with various serovars. Sequence analysis revealed that ApxIIIA proteins has two variants, one in strains of serovar 2 and the other in strains of serovars 3, 4, 6, 8 and 15. A mouse cross-protection study showed that mice actively immunized with rApxIIIA/2 or rApxIIIA/15 are protected against challenge with A. pleuropneumoniae strains of serovars 3, 4, 6, 8, 15, and 2 expressing ApxIII/15 and ApxIII/2, respectively. Similarly, mice passively immunized with rabbit anti-rApxIIIA/2 or anti-rApxIIIA/15 sera were found to be protected against challenge with strains of serovars 2 and 15. Our study revealed antigenic and sequence similarities within ApxIIA and ApxIIIA proteins, which may help in the development of effective vaccines against disease caused by A. pleuropneumoniae. © 2016 The Societies and John Wiley & Sons Australia, Ltd.

Inorganic Nitrate Mimics Exercise-Stimulated Muscular Fiber-Type Switching and Myokine and γ-Aminobutyric Acid Release.

PubMed

Roberts, Lee D; Ashmore, Tom; McNally, Ben D; Murfitt, Steven A; Fernandez, Bernadette O; Feelisch, Martin; Lindsay, Ross; Siervo, Mario; Williams, Elizabeth A; Murray, Andrew J; Griffin, Julian L

2017-03-01

Exercise is an effective intervention for the prevention and treatment of type 2 diabetes. Skeletal muscle combines multiple signals that contribute to the beneficial effects of exercise on cardiometabolic health. Inorganic nitrate increases exercise efficiency, tolerance, and performance. The transcriptional regulator peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) coordinates the exercise-stimulated skeletal muscle fiber-type switch from glycolytic fast-twitch (type IIb) to oxidative slow-twitch (type I) and intermediate (type IIa) fibers, an effect reversed in insulin resistance and diabetes. We found that nitrate induces PGC1α expression and a switch toward type I and IIa fibers in rat muscle and myotubes in vitro. Nitrate induces the release of exercise/PGC1α-dependent myokine FNDC5/irisin and β-aminoisobutyric acid from myotubes and muscle in rats and humans. Both exercise and nitrate stimulated PGC1α-mediated γ-aminobutyric acid (GABA) secretion from muscle. Circulating GABA concentrations were increased in exercising mice and nitrate-treated rats and humans; thus, GABA may function as an exercise/PGC1α-mediated myokine-like small molecule. Moreover, nitrate increased circulating growth hormone levels in humans and rodents. Nitrate induces physiological responses that mimic exercise training and may underlie the beneficial effects of this metabolite on exercise and cardiometabolic health. © 2017 by the American Diabetes Association.

Influence of chronic food deprivation on structure-function relationship of juvenile rat fast muscles.

PubMed

Ruiz-Rosado, Azucena; Cabrera-Fuentes, Héctor A; González-Calixto, Cecilia; González-López, Lorena; Cázares-Raga, Febe E; Segura-Alegría, Bertha; Lochnit, Günter; de la Cruz Hernández-Hernández, Fidel; Preissner, Klaus T; Jiménez-Estrada, Ismael

2013-12-01

In the present study, we analyze the influence of chronic undernutrition on protein expression, muscle fiber type composition, and fatigue resistance of the fast extensor digitorum longus (EDL) muscle of male juvenile rats (45 ± 3 days of life; n = 25 and 31 rats for control and undernourished groups, respectively). Using 2D gel electrophoresis and mass spectrometry, we identified in undernourished muscles 12 proteins up-regulated (8 proteins of the electron transport chain and the glycolytic pathway, 2 cross-bridge proteins, chaperone and signaling proteins that are related to the stress response). In contrast, one down-regulated protein related to the fast muscle contractile system and two other proteins with no changes in expression were used as charge controls. By means of COX and alkaline ATPase histochemical techniques and low-frequency fatigue protocols we determined that undernourished muscles showed a larger proportion (15% increase) of Type IIa/IId fibers (oxidative-glycolytic) at the expense of Type IIb (glycolytic) fibers (15.5% decrease) and increased fatigue resistance (55.3%). In addition, all fiber types showed a significant reduction in their cross-sectional area (slow: 64.4%; intermediate: 63.9% and fast: 61.2%). These results indicate that undernourished EDL muscles exhibit an increased expression of energy metabolic and myofibrillar proteins which are associated with the predominance of oxidative and Type IIa/IId fibers and to a higher resistance to fatigue. We propose that such alterations may act as protective and/or adaptive mechanisms that counterbalance the effect of chronic undernourishment.

Promiscuous Actions of Small Molecule Inhibitors of the Protein Kinase D-Class IIa HDAC Axis in Striated Muscle

PubMed Central

Lemon, Douglas D.; Harrison, Brooke C.; Horn, Todd R.; Stratton, Matthew S.; Ferguson, Bradley S.; Wempe, Michael F.; McKinsey, Timothy A.

2015-01-01

PKD-mediated phosphorylation of class IIa HDACs frees the MEF2 transcription factor to activate genes that govern muscle differentiation and growth. Studies of the regulation and function of this signaling axis have involved MC1568 and Gö-6976, which are small molecule inhibitors of class IIa HDAC and PKD catalytic activity, respectively. We describe unanticipated effects of these compounds. MC1568 failed to inhibit class IIa HDAC catalytic activity in vitro, and exerted divergent effects on skeletal muscle differentiation compared to a bona fide inhibitor of these HDACs. In cardiomyocytes, Gö-6976 triggered calcium signaling and activated stress-inducible kinases. Based on these findings, caution is warranted when employing MC1568 and Gö-6976 as pharmacological tool compounds to assess functions of class IIa HDACs and PKD. PMID:25816750

Inhibition of Group IIA Secretory Phospholipase A2 and its Inflammatory Reactions in Mice by Ethanolic Extract of Andrographis paniculata, a Well-known Medicinal Food

PubMed Central

Kishore, V.; Yarla, N. S.; Zameer, F.; Nagendra Prasad, M. N.; Santosh, M. S.; More, S. S.; Rao, D. G.; Dhananjaya, Bhadrapura Lakkappa

2016-01-01

Andrographis paniculata Nees is an important medicinal plant found in the tropical regions of the world, which has been traditionally used in Indian and Chinese medicinal systems. It is also used as medicinal food. A. paniculata is found to exhibit anti-inflammatory activities; however, its inhibitory potential on inflammatory Group IIA phospholipases A2 (PLA2) and its associated inflammatory reactions are not clearly understood. The aim of the present study is to evaluate the inhibitory/neutralizing potential of ethanolic extract of A. paniculata on the isolated inflammatory PLA2 (VRV-PL-VIIIa) from Daboii rusellii pulchella (belonging to Group IIA inflammatory secretory PLA2 [sPLA2]) and its associated edema-induced activities in Swiss albino mice. A. paniculata extract dose dependently inhibited the Group IIA sPLA2 enzymatic activity with an IC50 value of 10.3 ± 0.5 μg/ml. Further, the extract dose dependently inhibited the edema formation, when co-injected with enzyme indicating that a strong correlation exists between lipolytic and pro-inflammatory activities of the enzyme. In conclusion, results of this study shows that the ethanolic extract of A. paniculata effectively inhibits Group IIA sPLA2 and its associated inflammatory activities, which substantiate its anti-inflammatory properties. The results of the present study warranted further studies to develop bioactive compound (s) in ethanolic extract of A. paniculata as potent therapeutic agent (s) for inflammatory diseases. SUMMARY This study emphasis the anti-inflammatory effect of A. paniculata by inhibiting the inflammatory Group IIA sPLA2 and its associated inflammatory activities such as edema. It was found that there is a strong correlation between lipolytic activity and pro-inflammatory activity inhibition. Therefore, the study suggests that the extract processes potent anti-inflammatory agents, which could be developed as a potential therapeutic agent against inflammatory and related diseases. PMID:27365993

Rat limb unloading - Soleus histochemistry, ultrastructure, and electromyography

NASA Technical Reports Server (NTRS)

Riley, D. A.; Slocum, G. R.; Bain, J. L. W.; Sedlak, F. R.; Sowa, T. E.

1990-01-01

The effects of hindlimb unloading on rat-soleus histochemisty, ultrastructure, and electromyogram (EMG) activity were investigated. It was found that, after 14 days of tail suspension, the area of type I and type IIa muscle fibers decreased by 63 and 47 percent, respectively, mainly due to the degradation of subsarcolemmal mitochondria and myofibrils. After 10 days, 3 percent of type IIa fibers exhibited segmental necrosis. After four days, video monitoring revealed abnormal plantar flexion of the hindfeet, which shortened the soleus working range. The EMG activity shifted from tonic to phasic, and aggregate activity decreased drastically after only seven days. The results indictate that the pathological changes in the soleus resulted from unloaded contractions, reduced use, compromised blood flow, and shortened working length.

Association of vitamin D and vitamin D receptor gene polymorphisms with chronic inflammation, insulin resistance and metabolic syndrome components in type 2 diabetic Egyptian patients.

PubMed

Mackawy, Amal M H; Badawi, Mohammed E H

2014-12-01

To date the published data concerning the possible interplay between vitamin D (VitD) and Vit D receptor (VDR) gene polymorphism with the immune/inflammatory mediators in type 2 diabetes mellitus (DM) is insufficient. Some of the immune non-classical actions of vitamin D may point to its role in the pathogenesis of type 2 DM through down-regulation of cytokines (IL-6). Although there is evidence to support a relationship among vitamin D status, chronic inflammation and insulin resistance, the underlying mechanism requires further exploration. We aimed to investigate the role of vitamin D in chronic inflammation and insulin resistance in type 2 DM. Moreover, to examine the association of VDR gene polymorphisms [VDR 2228570 C > T (FokI); VDR 1544410 A > G (BsmI)] with the components of metabolic syndrome (MetSyn) in type 2 diabetic Egyptian patients . A total of 190 subjects were enrolled in this study, 60 controls and 130 type 2 diabetic patients (Group II). Group II was subdivided into 63 patients without MetSyn (subgroup IIa) and 67 patients with MetSyn (subgroup IIb). Genetic analysis for VDR gene polymorphisms was done in all subjects. VitD and IL-6 plasma levels were estimated. The TT genotype for the VDR FokI was significantly more frequent in subgroup IIb than in subgroup IIa and controls (X (2) = 6.83, P = 0.03 and X (2) = 16.592, P = 0.000) respectively. The T allele was more frequent in the MetSyn group as compared to diabetics without MetSyn (p = 0.001), odds ratio (OR) and 95% CI for the T allele of C > T (FokI) = 2.30 (1.37-3.86). We did not detect any significant difference in VDR BsmI genotypes between patients and control groups (P = 0.947). FokI VDR was significantly associated with the lipid profile parameters, VitD and IL-6 plasma levels in subgroup IIa and associated with HOMA-IR, insulin, VitD, IL-6 levels, waist circumference (WC) and body mass index (BMI) in subgroup IIb while BsmI VDR variant was associated only with VitD values in both subgroups. The present study suggests an interaction between VDR polymorphisms and important components of MetSyn, VitD and pro-inflammatory cytokines (IL-6). FokI VDR polymorphisms may be linked to mild inflammation and insulin resistance and might represent a genetic determinant for developing MetSyn in type 2 diabetic Egyptian patients. The challenge is determining the mechanisms of VitD action for recommendation of VitD supplementation that reduces the risks of MetSyn, insulin resistance and progression to type 2 diabetes.

Association of vitamin D and vitamin D receptor gene polymorphisms with chronic inflammation, insulin resistance and metabolic syndrome components in type 2 diabetic Egyptian patients

PubMed Central

Mackawy, Amal M.H.; Badawi, Mohammed E.H.

2014-01-01

Background To date the published data concerning the possible interplay between vitamin D (VitD) and Vit D receptor (VDR) gene polymorphism with the immune/inflammatory mediators in type 2 diabetes mellitus (DM) is insufficient. Some of the immune non-classical actions of vitamin D may point to its role in the pathogenesis of type 2 DM through down-regulation of cytokines (IL-6). Although there is evidence to support a relationship among vitamin D status, chronic inflammation and insulin resistance, the underlying mechanism requires further exploration. We aimed to investigate the role of vitamin D in chronic inflammation and insulin resistance in type 2 DM. Moreover, to examine the association of VDR gene polymorphisms [VDR 2228570 C > T (FokI); VDR 1544410 A > G (BsmI)] with the components of metabolic syndrome (MetSyn) in type 2 diabetic Egyptian patients . Subjects and methods A total of 190 subjects were enrolled in this study, 60 controls and 130 type 2 diabetic patients (Group II). Group II was subdivided into 63 patients without MetSyn (subgroup IIa) and 67 patients with MetSyn (subgroup IIb). Genetic analysis for VDR gene polymorphisms was done in all subjects. VitD and IL-6 plasma levels were estimated. Results The TT genotype for the VDR FokI was significantly more frequent in subgroup IIb than in subgroup IIa and controls (X2 = 6.83, P = 0.03 and X2 = 16.592, P = 0.000) respectively. The T allele was more frequent in the MetSyn group as compared to diabetics without MetSyn (p = 0.001), odds ratio (OR) and 95% CI for the T allele of C > T (FokI) = 2.30 (1.37–3.86). We did not detect any significant difference in VDR BsmI genotypes between patients and control groups (P = 0.947). FokI VDR was significantly associated with the lipid profile parameters, VitD and IL-6 plasma levels in subgroup IIa and associated with HOMA-IR, insulin, VitD, IL-6 levels, waist circumference (WC) and body mass index (BMI) in subgroup IIb while BsmI VDR variant was associated only with VitD values in both subgroups. Conclusion The present study suggests an interaction between VDR polymorphisms and important components of MetSyn, VitD and pro-inflammatory cytokines (IL-6). FokI VDR polymorphisms may be linked to mild inflammation and insulin resistance and might represent a genetic determinant for developing MetSyn in type 2 diabetic Egyptian patients. The challenge is determining the mechanisms of VitD action for recommendation of VitD supplementation that reduces the risks of MetSyn, insulin resistance and progression to type 2 diabetes. PMID:25606437

Activity-induced regulation of myosin isoform distribution - Comparison of two contractile activity programs

NASA Technical Reports Server (NTRS)

Diffee, Gary M.; Caiozzo, Vince J.; Mccue, Samuel A.; Herrick, Robert E.; Baldwin, Kenneth M.

1993-01-01

This study examined the role of specific types of contractile activity in regulating myosin heavy chain (MHC) isoform expression in rodent soleus. A combination of hindlimb suspension (SN) and two programmed contractile training activity paradigms, either isometric contractile activity (ST-IM) or high-load slowly shortening isovelocity activity, were utilized. Both training paradigms increased muscle mass compared with SN alone. However, only ST-IM resulted in a partial prevention of the suspension-induced decrease in type I MHC. With the use of a fluorescently labeled antibody to type IIa MHC, the distribution of MHCs among fibers was examined immunohistochemically. In SN, the percentage of cells staining positive for type IIa MHC was increased but the staining intensity of the positively staining cells was unchanged compared with control cells. In the ST-IM soleus, the percentage of positively staining fibers was unchanged but the intensity of the positively staining cells was decreased compared with SN values. These results suggest that 1) isometric contractile activity is more effective than isovelocity activity in preventing suspension-induced shifts in soleus MHC distribution and 2) changes associated with both suspension and training occur in only a small number of fibers, with the majority of fibers apparently unresponsive to these interventions.

Dual Pathology in Rasmussen's Encephalitis: A Report of Coexistent Focal Cortical Dysplasia and Review of the Literature.

PubMed

Prayson, Richard A

2012-01-01

Rasmussen's encephalitis is a well-established, albeit rare cause of medically intractable epilepsy. In a small number of Rasmussen's cases, a second pathology is identified, which independently can cause medically intractable seizures (dual pathology). This paper documents a case of a 13-year-old male who presented with medically intractable epilepsy. The patient underwent a series of surgical resections, early on resulting in a diagnosis of focal cortical dysplasia and later yielding a diagnosis of coexistent Rasmussen's encephalitis, marked by chronic inflammation, microglial nodules, and focal cortical atrophy, combined with focal cortical dysplasia (Palmini et al. type IIA, ILAE type IIA). The literature on dual pathology in the setting of Rasmussen's encephalitis is reviewed.

Dual Pathology in Rasmussen's Encephalitis: A Report of Coexistent Focal Cortical Dysplasia and Review of the Literature

PubMed Central

Prayson, Richard A.

2012-01-01

Rasmussen's encephalitis is a well-established, albeit rare cause of medically intractable epilepsy. In a small number of Rasmussen's cases, a second pathology is identified, which independently can cause medically intractable seizures (dual pathology). This paper documents a case of a 13-year-old male who presented with medically intractable epilepsy. The patient underwent a series of surgical resections, early on resulting in a diagnosis of focal cortical dysplasia and later yielding a diagnosis of coexistent Rasmussen's encephalitis, marked by chronic inflammation, microglial nodules, and focal cortical atrophy, combined with focal cortical dysplasia (Palmini et al. type IIA, ILAE type IIA). The literature on dual pathology in the setting of Rasmussen's encephalitis is reviewed. PMID:23056977

Muscle mechanics: adaptations with exercise-training.

PubMed

Fitts, R H; Widrick, J J

1996-01-01

Based on the MHC isoform pattern, adult mammalian limb skeletal muscles contain two and, in some species, three types of fast fibers (Type IIa, IIx, and IIb), and one slow fiber (Type I). Slow muscles, such as the soleus, contain primarily the slow Type I fiber, whereas fast-twitch muscles are composed primarily of a mixture of the fast myosin isozymes. Force generation involves cross-bridge interaction and transition from a weakly bound, low-force state (AM-ADP-P(i)) to the strongly bound, high-force state (AM-ADP). This transition is thought to be rate limiting in terms of dP/dt, and the high-force state is the dominant cross-bridge form during a peak isometric contraction. Intact fast and slow skeletal muscles generate approximately the same amount of peak force (Po) of between 200 and 250 kN.m-2. However, the rate of transition from the low- to high-force state shows Ca2+ sensitivity and is 7-fold higher in fast-twitch, as compared to slow-twitch, skeletal muscle fibers. Fiber Vo or the maximal cross-bridge cycle rate is highly correlated with and thought to be dependent on the specific activity of the myosin or myofibrillar ATPase. The hierarchy for Vo is the Type IIb > IIx > IIa > I. This functional difference for the fast fiber types explains the higher Vo observed in the predominantly Type IIb SVL vs. the mixed fast Type IIa and IIb EDL muscle. A plot of Vo vs. species size demonstrates that an inverse relationship exists between Vo and body mass. From the standpoint of work capacity, the important property is power output. An analysis of individual muscles indicates that peak power is obtained at loads considerably below 50% of Po. Individuals with a high percentage of fast-twitch fibers generate a greater torque and higher power at a given velocity than those with predominantly slow-twitch fibers. In humans, mean peak power occurred in a ratio of 10:5:1 for the Type IIb, IIa, and I fibers. The in vivo measurement of the torque-velocity relationship and Vmax in human muscle is difficult because of limitations inherent in the equipment used and the inability to study the large limb muscles independently. Nevertheless, the in vivo torque-velocity relationships are similar to those measured in vitro in animals. This observation suggests that little central nervous system inhibition exists and that healthy subjects are able to achieve maximal activation of their muscles. Although peak isometric tension is not dependent on fiber type distribution, a positive correlation exists between the percentage of fast fibers and peak torque output at moderate-to-high angular isokinetic velocities. Consequently, peak power output is substantially greater in subjects possessing a predominance of fast fibers. The mechanical properties of slow and fast muscles do adapt to programs of regular exercise. Endurance exercise training has been shown to increase the Vo of the slow soleus by 20%. This increase could have been caused by either a small increase in all, or most, of the fibers, or to a conversion of a few fibers from slow to fast. Recently, the increase was shown to be caused by the former, as the individual slow Type I fibers of the soleus showed a 20% increase in Vo, but there was little or no change in the percentage of fast fibers. The increased Vo was correlated with, and likely caused by, an increased fiber ATPase. We hypothesize that the increased ATPase and cross-bridge cycling speed might be attributable to an increased expression of fast MLCs in the slow Type I fibers (Fig. 14.10). This hypothesis is based on the fact that light chains have been shown to be involved in the power stroke, and removal of light chains depresses force and velocity. Regular endurance exercise training had no effect on fiber size, but with prolonged durations of daily training it depressed Po and peak power. When the training is maintained over prolonged periods, it may even induce atrophy of the slow Type I and fast Type IIa fibers. (ABSTRACT TRUNCATED)

Computing the scalar field couplings in 6D supergravity

NASA Astrophysics Data System (ADS)

Saidi, El Hassan

2008-11-01

Using non-chiral supersymmetry in 6D space-time, we compute the explicit expression of the metric the scalar manifold SO(1,1)×{SO(4,20)}/{SO(4)×SO(20)} of the ten-dimensional type IIA superstring on generic K3. We consider as well the scalar field self-couplings in the general case where the non-chiral 6D supergravity multiplet is coupled to generic n vector supermultiplets with moduli space SO(1,1)×{SO(4,n)}/{SO(4)×SO(n)}. We also work out a dictionary giving a correspondence between hyper-Kähler geometry and the Kähler geometry of the Coulomb branch of 10D type IIA on Calabi-Yau threefolds. Others features are also discussed.

Enhanced protein electrophoresis technique for separating human skeletal muscle myosin heavy chain isoforms

NASA Technical Reports Server (NTRS)

Bamman, M. M.; Clarke, M. S.; Talmadge, R. J.; Feeback, D. L.

1999-01-01

Talmadge and Roy (J. Appl. Physiol. 1993, 75, 2337-2340) previously established a sodium dodecyl sulfate - polyacrylamide gel electrophoresis (SDS-PAGE) protocol for separating all four rat skeletal muscle myosin heavy chain (MHC) isoforms (MHC I, IIa, IIx, IIb); however, when applied to human muscle, the type II MHC isoforms (Ila, IIx) are not clearly distinguished. In this brief paper we describe a modification of the SDS-PAGE protocol which yields distinct and consistent separation of all three adult human MHC isoforms (MHC I, IIa, IIx) in a minigel system. MHC specificity of each band was confirmed by Western blot using three monoclonal IgG antibodies (mAbs) immunoreactive against MHCI (mAb MHCs, Novacastra Laboratories), MHCI+IIa (mAb BF-35), and MHCIIa+IIx (mAb SC-71). Results provide a valuable SDS-PAGE minigel technique for separating MHC isoforms in human muscle without the difficult task of casting gradient gels.

Altered inhibition in Tuberous Sclerosis and Type IIb cortical dysplasia

PubMed Central

Talos, Delia M.; Sun, Hongyu; Kosaras, Bela; Joseph, Annelise; Folkerth, Rebecca D.; Poduri, Annapurna; Madsen, Joseph R.; Black, Peter M.; Jensen, Frances E.

2012-01-01

Objective The most common neurological symptom of tuberous sclerosis complex (TSC) and focal cortical dysplasia (FCD) is early-life refractory epilepsy. As previous studies have shown enhanced excitatory glutamatergic neurotransmission in TSC and FCD brains, we hypothesized that neurons associated with these lesions may also express altered GABAA receptor (GABAAR)-mediated inhibition. Methods Expression of the GABAAR subunitsα1 and α4, the Na+-K+-2Cl− (NKCC1), and the K+−Cl− (KCC2) transporters in human TSC and FCD Type II specimens were analyzed by Western blot and double label immunocytochemistry. GABAAR responses in dysplastic neurons from a single case of TSC were measured by perforated-patch recording and compared to normal-appearing cortical neurons from a non-TSC epilepsy case. Results TSC and FCD Type IIb lesions demonstrated decreased expression of the GABAAR α1, increased NKCC1 and decreased KCC2 levels. In contrast, FCD Type IIa lesions showed decreased α4, and increased expression of both NKCC1 and KCC2 transporters. Patch clamp recordings from dysplastic neurons in acute slices from TSC tubers demonstrated excitatory GABAAR responses that were significantly attenuated by the NKCC1 inhibitor bumetanide, in contrast to hyperpolarizing GABAAR-mediated currents in normal neurons from non-TSC cortical slices. Interpretation Expression and function of GABAARs in TSC and FCD IIb suggests the relative benzodiazepine insensitivity and more excitatory action of GABA compared to FCD IIa. These factors may contribute to resistance of seizure activity to anticonvulsants that increase GABAergic function, and may justify add-on trials of the NKCC1 inhibitor bumetanide for the treatment of TSC and FCD Type IIb related epilepsy. PMID:22447678

Rescue therapy with Tanshinone IIA hinders transition of acute kidney injury to chronic kidney disease via targeting GSK3β

PubMed Central

Jiang, Chunming; Zhu, Wei; Yan, Xiang; Shao, Qiuyuan; Xu, Biao; Zhang, Miao; Gong, Rujun

2016-01-01

Acute kidney injury (AKI) remains challenging for clinical practice and poses a risk of developing progressive chronic kidney disease (CKD) with no definitive treatment available yet. Tanshinone IIA, an active ingredient of Chinese herbal Salvia miltiorrhiza, has been widely used in Asia for the remarkable organoprotective activities. Its effect on established AKI, however, remains unknown. In mice with folic acid-induced AKI, delayed treatment with Tanshinone IIA, commenced early or late after injury, diminished renal expression of kidney injury markers, reduced apoptosis and improved kidney dysfunction, concomitant with mitigated histologic signs of AKI to CKD transition, including interstitial fibrosis and tubular atrophy, and with an ameliorated inflammatory infiltration in tubulointerstitium and a favored M2-skewed macrophage polarization. Mechanistically, Tanshinone IIA blunted glycogen synthase kinase (GSK)3β overactivity and hyperactivation of its downstream mitogen-activated protein kinases that are centrally implicated in renal fibrogenesis and inflammation. Inhibition of GSK3β is likely a key mechanism mediating the therapeutic activity of Tanshinone IIA, because sodium nitroprusside, a GSK3β activator, largely offset its renoprotective effect. In confirmatory studies, rescue treatment with Tanshinone IIA likewise ameliorated ischemia/reperfusion-induced kidney destruction in mice. Our data suggest that Tanshinone IIA represents a valuable treatment that improves post-AKI kidney salvage via targeting GSK3β. PMID:27857162

Glycyrrhetinic acid-decorated and reduction-sensitive micelles to enhance the bioavailability and anti-hepatocellular carcinoma efficacy of tanshinone IIA.

PubMed

Chen, Fengqian; Zhang, Jinming; He, Yao; Fang, Xiefan; Wang, Yitao; Chen, Meiwan

2016-01-01

It remains a challenge to increase drug tumor-specific accumulation as well as to achieve intracellular-controlled drug release for hepatocellular carcinoma (HCC) chemotherapy. Herein, we developed a dual-functional biodegradable micellar system constituted by glycyrrhetinic acid coupling poly(ethylene glycol)-disulfide linkage-poly(lactic-co-glycolic acid) (GA-PEG-SS-PLGA) to achieve both hepatoma-targeting and redox-responsive intracellular drug release. Tanshinone IIA (TAN IIA), an effective anti-HCC drug, was encapsulated. Notably, it exhibited rapid aggregation and faster drug release in 10 mM dithiothreitol compared with the redox-insensitive control. Furthermore, GA-decorated micelles revealed HCC-specific cellular uptake in human liver cancer HepG2 cells with an energy-dependent manner, in which micropinocytosis and caveolae-mediated endocytosis were demonstrated as the major cellular pathways. The enhanced cytotoxicity and pro-apoptotic effects against HepG2 cells in vitro were observed, mediated by up-regulation of the intracellular ROS level, the increased cell cycle arrest at S phase, enhanced necrocytosis and up-regulation of caspase 3/7, P38 protein expression. In addition, TAN IIA-loaded micelles had a significantly prolonged circulation time, improved bioavailability, and resulted in an increased accumulation of TAN IIA in the liver. With the synergistic effects of HCC-targeting and controlled drug release, TAN IIA-loaded GA-PEG-SS-PLGA micelles significantly inhibited tumor growth and increased survival time in a mouse HCC-xenograft model. Collectively, the GA-PEG-SS-PLGA micelles with HCC-targeting and redox-sensitive characters would provide a novel strategy to deliver TAN IIA effectively for HCC therapy.

Regulation of pathogenicity in hop stunt viroid-related group II citrus viroids.

PubMed

Reanwarakorn, K; Semancik, J S

1998-12-01

Nucleotide sequences were determined for two hop stunt viroid-related Group II citrus viroids characterized as either a cachexia disease non-pathogenic variant (CVd-IIa) or a pathogenic variant (CVd-IIb). Sequence identity between the two variants of 95.6% indicated a conserved genome with the principal region of nucleotide difference clustered in the variable (V) domain. Full-length viroid RT-PCR cDNA products were cloned into plasmid SP72. Viroid cDNA clones as well as derived RNA transcripts were transmissible to citron (Citrus medica L.) and Luffa aegyptiaca Mill. To determine the locus of cachexia pathogenicity as well as symptom expression in Luffa, chimeric viroid cDNA clones were constructed from segments of either the left terminal, pathogenic and conserved (T1-P-C) domains or the conserved, variable and right terminal (C-V-T2) domains of CVd-IIa or CVd-IIb in reciprocal exchanges. Symptoms induced by the various chimeric constructs on the two bioassay hosts reflected the differential response observed with CVd-IIa and -IIb. Constructs with the C-V-T2 domains region from clone-IIa induced severe symptoms on Luffa typical of CVd-IIa, but were non-symptomatic on mandarin as a bioassay host for the cachexia disease. Constructs with the same region (C-V-T2) from the clone-IIb genome induced only mild symptoms on Luffa, but produced a severe reaction on mandarin, as observed for CVd-IIb. Specific site-directed mutations were introduced into the V domain of the CVd-IIa clone to construct viroid cDNA clones with either partial or complete conversions to the CVd-IIb sequence. With the introduction of six site-specific changes into the V domain of the clone-IIa genome, cachexia pathogenicity was acquired as well as a moderation of severe symptoms on Luffa.

Preferential type II muscle fiber damage from plyometric exercise.

PubMed

Macaluso, Filippo; Isaacs, Ashwin W; Myburgh, Kathryn H

2012-01-01

Plyometric training has been successfully used in different sporting contexts. Studies that investigated the effect of plyometric training on muscle morphology are limited, and results are controversial with regard to which muscle fiber type is mainly affected. To analyze the skeletal muscle structural and ultrastructural change induced by an acute bout of plyometric exercise to determine which type of muscle fibers is predominantly damaged. Descriptive laboratory study. Research laboratory. Eight healthy, untrained individuals (age = 22 ± 1 years, height = 179.2 ± 6.4 cm, weight = 78.9 ± 5.9 kg). Participants completed an acute bout of plyometric exercise (10 sets of 10 squat-jumps with a 1-minute rest between sets). Blood samples were collected 9 days and immediately before and 6 hours and 1, 2, and 3 days after the acute intervention. Muscle samples were collected 9 days before and 3 days after the exercise intervention. Blood samples were analyzed for creatine kinase activity. Muscle biopsies were analyzed for damage using fluorescent and electron transmission microscopy. Creatine kinase activity peaked 1 day after the exercise bout (529.0 ± 317.8 U/L). Immunofluorescence revealed sarcolemmal damage in 155 of 1616 fibers analyzed. Mainly fast-twitch fibers were damaged. Within subgroups, 7.6% of type I fibers, 10.3% of type IIa fibers, and 14.3% of type IIx fibers were damaged as assessed by losses in dystrophin staining. Similar damage was prevalent in IIx and IIa fibers. Electron microscopy revealed clearly distinguishable moderate and severe sarcomere damage, with damage quantifiably predominant in type II muscle fibers of both the glycolytic and oxidative subtypes (86% and 84%, respectively, versus only 27% of slow-twitch fibers). We provide direct evidence that a single bout of plyometric exercise affected mainly type II muscle fibers.

Cellular Uptake of Clostridium botulinum C2 Toxin Requires Acid Sphingomyelinase Activity.

PubMed

Nagahama, Masahiro; Takehara, Masaya; Takagishi, Teruhisa; Seike, Soshi; Miyamoto, Kazuaki; Kobayashi, Keiko

2017-04-01

Clostridium botulinum C2 toxin consists of an enzyme component (C2I) and a binding component (C2II). Activated C2II (C2IIa) binds to a cell receptor, giving rise to lipid raft-dependent oligomerization, and it then assembles with C2I. The whole toxin complex is then endocytosed into the cytosol, resulting in the destruction of the actin cytoskeleton and cell rounding. Here, we showed that C2 toxin requires acid sphingomyelinase (ASMase) activity during internalization. In this study, inhibitors of ASMase and lysosomal exocytosis blocked C2 toxin-induced cell rounding. C2IIa induced Ca 2+ influx from the extracellular medium to cells. C2 toxin-induced cell rounding was enhanced in the presence of Ca 2+ ASMase was released extracellularly when cells were incubated with C2IIa in the presence of Ca 2+ Small interfering RNA (siRNA) knockdown of ASMase reduced C2 toxin-induced cell rounding. ASMase hydrolyzes sphingomyelin to ceramide on the outer leaflet of the membrane at acidic pH. Ceramide was detected in cytoplasmic vesicles containing C2IIa. These results indicated that ASMase activity is necessary for the efficient internalization of C2 toxin into cells. Inhibitors of ASMase may confer protection against infection. Copyright © 2017 American Society for Microbiology.

Performance evaluation type II and type IIA box beam end terminals--volume II : appendices.

DOT National Transportation Integrated Search

2010-01-10

Two types of guide rail end terminals were constructed and evaluated according to the American Association of State Highway : and Transportation Officials (AASHTOs) Manual for Assessing Safety Hardware (MASH). The guide rail end terminals are u...

Chloroquine derivatives block the translocation pores and inhibit cellular entry of Clostridium botulinum C2 toxin and Bacillus anthracis lethal toxin.

PubMed

Kreidler, Anna-Maria; Benz, Roland; Barth, Holger

2017-03-01

The pathogenic bacteria Clostridium botulinum and Bacillus anthracis produce the binary protein toxins C2 and lethal toxin (LT), respectively. These toxins consist of a binding/transport (B 7 ) component that delivers the separate enzyme (A) component into the cytosol of target cells where it modifies its specific substrate and causes cell death. The B 7 components of C2 toxin and LT, C2IIa and PA 63 , respectively, are ring-shaped heptamers that bind to their cellular receptors and form complexes with their A components C2I and lethal factor (LF), respectively. After receptor-mediated endocytosis of the toxin complexes, C2IIa and PA 63 insert into the membranes of acidified endosomes and form trans-membrane pores through which C2I and LF translocate across endosomal membranes into the cytosol. C2IIa and PA 63 also form channels in planar bilayer membranes, and we used this approach earlier to identify chloroquine as a potent blocker of C2IIa and PA 63 pores. Here, a series of chloroquine derivatives was investigated to identify more efficient toxin inhibitors with less toxic side effects. Chloroquine, primaquine, quinacrine, and fluphenazine blocked C2IIa and PA 63 pores in planar lipid bilayers and in membranes of living epithelial cells and macrophages, thereby preventing the pH-dependent membrane transport of the A components into the cytosol and protecting cells from intoxication with C2 toxin and LT. These potent inhibitors of toxin entry underline the central role of the translocation pores for cellular uptake of binary bacterial toxins and as relevant drug targets, and might be lead compounds for novel pharmacological strategies against severe enteric diseases and anthrax.

IIaO ultraviolet and nuclear emulsion films responses to orbital flights on STS-3, STS-7, STS-8, and STS-40

NASA Technical Reports Server (NTRS)

Hammond, E. C., Jr.; Peters, K. A.; Blake, S. M.; Bailey, Y.; Johnson, D.; Robancho, S.; Stober, A.

1992-01-01

Two types of film were flown on STS-40 space shuttle mission in June 1991. The IIaO special purpose ultraviolet film showed continued desensitization because of various thermal and cosmic ray interactions. The films were exposed to the space orbital environment for 9 days. There were several built-in launch pad delays of the shuttle mission. However, there was adequate monitoring of the temperature variations on board the shuttle that allowed for adequate knowledge of the thermal film history. This IIaO film was flown on the ASTRO I mission and is currently slated for use with the ASTRO II mission. A 50 micron thick IIIford Nuclear emulsion film was also placed on a 175 micron polyester base. The exposure to space produced several cosmic ray interactions that were analyzed and measured using Digital Image Processing techniques. This same nuclear emulsion film was flown on STS-8 and produced a similar number of cosmic ray and thermal interactions. From previous experiments of film using various laboratory electromagnetic radiation sources (e.g., alpha, beta, and neutron particles), we have been able to infer the possible oribtal interactions of both IIaO and nuclear emulsion films. The characteristic responses of IIaO on STS-40 compared favorably to the results obtained from previous STS-7 and STS-8 gas can experiments. The results indicate sufficient evidence correlating increased density on the film with possible cosmic ray, thermal and shuttle out gassing interactions.

Tetrapentylammonium block of chloramine-T and veratridine modified rat brain type IIA sodium channels

PubMed Central

Ghatpande, A S; Rao, S; Sikdar, S K

2001-01-01

Tetrapentylammonium (TPeA) block of rat brain type IIA sodium channel α subunit was studied using whole cell patch clamp. Results indicate that TPeA blocks the inactivating brain sodium channel in a potential and use-dependent manner similar to that of the cardiac sodium channel. Removal of inactivation using chloramine-T (CT) unmasks a time-dependent block by TPeA consistent with slow blocking kinetics. On the other hand, no time dependence is observed when inactivation is abolished by modification with veratridine. TPeA does not bind in a potential-dependent fashion to veratridine-modified channels and does not significantly affect gating of veratridine-modified channels suggesting that high affinity binding of TPeA to the brain sodium channel is lost after veratridine modification. PMID:11309247

Phospholipids and their degrading enzyme in the tears of soft contact lens wearers.

PubMed

Yamada, Masakazu; Mochizuki, Hiroshi; Kawashima, Motoko; Hata, Seiichiro

2006-12-01

Low tear phospholipids levels are associated with tear film instability in soft contact lens wearers. We assayed levels of phospholipids and their degrading enzyme secretory phospholipase A2 (sPLA2) both in tears and deposited on contact lenses composed of 2 hydrophilic materials after 1 day of routine use. Polymacon (Medalist; FDA group 1, low water/nonionic) and Etafilcon A (One Day Acuvue; group 4, high water/ionic) contact lenses were worn for 12 hours by 16 experienced contact lens wearers. Phospholipids in tear fluids and deposited on contact lenses were estimated by phosphorus determination with ammonium molybdate through enzymatic digestion. Double-antibody sandwich ELISA was used to determine group IIa sPLA2 concentrations, and sPLA2 activity was assayed using 1,2-diheptanoyl thio-phosphatidylcholine as substrate. Phospholipids concentrations in tears with Polymacon and Etafilcon A were 186 +/- 39 and 162 +/- 33 microg/mL, respectively. The latter concentration was significantly lower than that observed in the same subjects when not wearing contact lenses (P = 0.0023). In tears, both group IIa sPLA2 concentrations and enzymatic activity remained unchanged, regardless of lens wearing. However, Etafilcon A (0.57 +/- 0.09 microg/lens) showed more group IIa sPLA2 deposition than Polymacon (0.01 +/- 0.01 microg/lens; P < 0.001). Furthermore, group IIa sPLA2 deposited on Etafilcon A but not on Polymacon lenses retained its enzymatic activity. Significant differences of group IIa sPLA2 deposition were found in the 2 lenses tested. Such deposition might induce phospholipid hydrolysis in tears and thereby promote tear film instability in hydrophilic contact lens wearers.

Tanshinone IIA combined with adriamycin inhibited malignant biological behaviors of NSCLC A549 cell line in a synergistic way.

PubMed

Xie, Jun; Liu, Jia-Hui; Liu, Heng; Liao, Xiao-Zhong; Chen, Yuling; Lin, Mei-Gui; Gu, Yue-Yu; Liu, Tao-Li; Wang, Dong-Mei; Ge, Hui; Mo, Sui-Lin

2016-11-18

The study was designed to develop a platform to verify whether the extract of herbs combined with chemotherapy drugs play a synergistic role in anti-tumor effects, and to provide experimental evidence and theoretical reference for finding new effective sensitizers. Inhibition of tanshinone IIA and adriamycin on the proliferation of A549, PC9 and HLF cells were assessed by CCK8 assays. The combination index (CI) was calculated with the Chou-Talalay method, based on the median-effect principle. Migration and invasion ability of A549 cells were determined by wound healing assay and transwell assay. Flow cytometry was used to detect the cell apoptosis and the distribution of cell cycles. TUNEL staining was used to detect the apoptotic cells. Immunofluorescence staining was used to detect the expression of Cleaved Caspase-3. Western blotting was used to detect the proteins expression of relative apoptotic signal pathways. CDOCKER module in DS 2.5 was used to detect the binding modes of the drugs and the proteins. Both tanshinone IIA and adriamycin could inhibit the growth of A549, PC9, and HLF cells in a dose- and time-dependent manner, while the proliferative inhibition effect of tanshinone IIA on cells was much weaker than that of adriamycin. Different from the cancer cells, HLF cells displayed a stronger sensitivity to adriamycin, and a weaker sensitivity to tanshinone IIA. When tanshinone IIA combined with adriamycin at a ratio of 20:1, they exhibited a synergistic anti-proliferation effect on A549 and PC9 cells, but not in HLF cells. Tanshinone IIA combined with adriamycin could synergistically inhibit migration, induce apoptosis and arrest cell cycle at the S and G2 phases in A549 cells. Both groups of the single drug treatment and the drug combination up-regulated the expressions of Cleaved Caspase-3 and Bax, but down-regulated the expressions of VEGF, VEGFR2, p-PI3K, p-Akt, Bcl-2, and Caspase-3 protein. Compared with the single drug treatment groups, the drug combination groups were more statistically significant. The molecular docking algorithms indicated that tanshinone IIA could be docked into the active sites of all the tested proteins with H-bond and aromatic interactions, compared with that of adriamycin. Tanshinone IIA can be developed as a novel agent in the postoperative adjuvant therapy combined with other anti-tumor agents, and improve the sensibility of chemotherapeutics for non-small cell lung cancer with fewer side effects. In addition, this experiment can not only provide a reference for the development of more effective anti-tumor medicine ingredients, but also build a platform for evaluating the anti-tumor effects of Chinese herbal medicines in combination with chemotherapy drugs.

Irritant-induced asthma.

PubMed

Labrecque, Manon

2012-04-01

To describe the recent insights into the definition, causes, natural outcome, and key elements of irritant-induced asthma (IIA) management. IIA is a subtype of occupational asthma without immunologic sensitization and includes the typical reactive airway dysfunction syndrome (RADS) and a more gradual form called not-so-sudden IIA, when onset of asthma follows repeated low-dose exposure to irritants. The World Trade Center tragedy brought new insight in the understanding of IIA, suggesting that it can exhibit a prolonged interval between exposure and recognition of clinical symptoms and disease. Dimethyl sulfate has been recently reported to cause RADS and repeated diesel exhaust exposure to cause not-so-sudden IIA in patients who worked in a bus garage. Cleaning workers who are exposed to a large variety of irritants and sensitizers are especially at risk of occupational asthma and IIA. IIA includes RADS and not-so-sudden IIA. Outcome of IIA is as poor as occupational asthma with sensitization. Treatment of IIA does not differ from standard asthma treatment, but high-dose vitamin D could be assessed further for possible therapeutic benefit.

FGF-23 transgenic mice demonstrate hypophosphatemic rickets with reduced expression of sodium phosphate cotransporter type IIa.

PubMed

Shimada, Takashi; Urakawa, Itaru; Yamazaki, Yuji; Hasegawa, Hisashi; Hino, Rieko; Yoneya, Takashi; Takeuchi, Yasuhiro; Fujita, Toshiro; Fukumoto, Seiji; Yamashita, Takeyoshi

2004-02-06

Fibroblast growth factor (FGF)-23 was identified as a causative factor of tumor-induced osteomalacia and also as a responsible gene for autosomal dominant hypophosphatemic rickets. To clarify the pathophysiological roles of FGF-23 in these diseases, we generated its transgenic mice. The transgenic mice expressing human FGF-23 reproduced the common clinical features of these diseases such as hypophosphatemia probably due to increased renal phosphate wasting, inappropriately low serum 1,25-dihydroxyvitamin D level, and rachitic bone. The renal phosphate wasting in the transgenic mice was accompanied by the reduced expression of sodium phosphate cotransporter type IIa in renal proximal tubules. These results reinforce the notion that the excessive action of FGF-23 plays a causative role in the development of several hypophosphatemic rickets/osteomalacia.

A densitometric analysis of IIaO film flown aboard the space shuttle transportation system STS #3, 7, and 8

NASA Technical Reports Server (NTRS)

Hammond, Ernest C., Jr.

1989-01-01

Since the United States of America is moving into an age of reusable space vehicles, both electronic and photographic materials will continue to be an integral part of the recording techniques available. Film as a scientifically viable recording technique in astronomy is well documented. There is a real need to expose various types of films to the Shuttle environment. Thus, the main objective was to look at the subtle densitometric changes of canisters of IIaO film that was placed aboard the Space Shuttle 3 (STS-3).

Structure and Activity Analyses of Escherichia coli K-12 NagD Provide Insight into the Evolution of Biochemical Function in the Haloakanoic Acid Dehlogenase Superfamily

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tremblay,L.; Dunaway-Mariano, D.; Allen, K.

2006-01-01

The HAD superfamily is a large superfamily of proteins which share a conserved core domain that provides those active site residues responsible for the chemistry common to all family members. The superfamily is further divided into the four subfamilies I, IIA, IIB, and III, based on the topology and insertion site of a cap domain that provides substrate specificity. This structural and functional division implies that members of a given HAD structural subclass may target substrates that have similar structural characteristics. To understand the structure/function relationships in all of the subfamilies, a type IIA subfamily member, NagD from Escherichia colimore » K-12, was selected (type I, IIB, and III members have been more extensively studied). The structure of the NagD protein was solved to 1.80 Angstroms with R{sub work} = 19.8% and R{sub free} = 21.8%. Substrate screening and kinetic analysis showed NagD to have high specificity for nucleotide monophosphates with kcat/Km = 3.12 x 10{sup 4} and 1.28 x 10{sup 4} {micro}M{sup -1} s{sup -1} for UMP and GMP, respectively. This specificity is consistent with the presence of analogues of NagD that exist as fusion proteins with a nucleotide pyrophosphatase from the Nudix family. Docking of the nucleoside substrate in the active site brings it in contact with conserved residues from the cap domain that can act as a substrate specificity loop (NagD residues 144-149) in the type IIA subfamily. NagD and other subfamily IIA and IIB members show the common trait that substrate specificity and catalytic efficiencies (k{sub cat}/K{sub m}) are low (1 x 10{sup 4} M{sup -1} s{sup -1}) and the boundaries defining physiological substrates are somewhat overlapping. The ability to catabolize other related secondary metabolites indicates that there is regulation at the genetic level.« less

Results of minimal invasive coracoclavicular fixation by double button lift-up system in Neer type II distal clavicle fractures.

PubMed

Dedeoğlu, Süleyman Semih; İmren, Yunus; Çabuk, Haluk; Çakar, Murat; Arslan, Samet Murat; Esenyel, Cem Zeki

2017-01-01

We aimed to evaluate clinical and functional outcomes of indirect fracture reduction performed by coracoclavicular fixation with minimal invasive double button lift-up system in Neer type IIa unstable fractures of distal clavicle. 22 patients with Neer type 2 distal clavicle fracture were enrolled in that prospective study. All patients underwent indirect reduction and osteosynthesis performed by coracoclavicular fixation with minimal invasive double button lift-up system. Postoperative follow-up was carried out clinically and radiologically with plain X-rays and utilization of Constant and American Shoulder and Elbow Surgeons Standardized Shoulder Assessment (ASES) shoulder scores. Mean follow-up time was 15 months. A standard sling was applied for 2 weeks, postoperatively. Rehabilitation program was started on postoperative day 1. Mean age was 39 (range: 21-60), 18 of the patients were male. Right dominant extremity was affected in 14 patients. Mean duration of the surgical intervention was 40 min (range: 30-55 min). Mean union time was found to be 14 weeks (range: 7-21 weeks). Mean postoperative ASES and Constant scores were 79.9 (66.9-88.3) and 82.2 (71-100), respectively. The duration of return to normal daily activities were found to be 4.5 months. Any loss of reduction, AC joint arthrosis, and clavicular shortening were not detected in X-rays. This study has demonstrated that indirect osteosynthesis performed by coracoclavicular fixation with double button lift-up system in the treatment of unstable Neer type IIa fractures of the distal clavicle had successful clinical, radiological, and functional outcomes.

The Type II Heat-Labile Enterotoxins LT-IIa and LT-IIb and Their Respective B Pentamers Differentially Induce and Regulate Cytokine Production in Human Monocytic Cells

PubMed Central

Hajishengallis, George; Nawar, Hesham; Tapping, Richard I.; Russell, Michael W.; Connell, Terry D.

2004-01-01

The type II heat-labile enterotoxins, LT-IIa and LT-IIb, exhibit potent adjuvant properties. However, little is known about their immunomodulatory activities upon interaction with innate immune cells, unlike the widely studied type I enterotoxins that include cholera toxin (CT). We therefore investigated interactions of LT-IIa and LT-IIb with human monocytic THP-1 cells. We found that LT-II enterotoxins were inactive in stimulating cytokine release, whereas CT induced low levels of interleukin-1β (IL-1β) and IL-8. However, all three enterotoxins potently regulated cytokine induction in cells activated by bacterial lipopolysaccharide or fimbriae. Induction of proinflammatory (tumor necrosis factor α [TNF-α]) or chemotactic (IL-8) cytokines was downregulated, whereas induction of cytokines with anti-inflammatory (IL-10) or mucosal adjuvant properties (IL-1β) was upregulated by the enterotoxins. These effects appeared to depend on their A subunits, because isolated B-pentameric subunits lacked regulatory activity. Enterotoxin-mediated inhibition of proinflammatory cytokine induction in activated cells was partially attributable to synergism for endogenous production of IL-10 and to an IL-10-independent inhibition of nuclear factor κB (NF-κB) activation. In sharp contrast to the holotoxins, the B pentamers (LT-IIaB and, to a greater extent, LT-IIbB) stimulated cytokine production, suggesting a link between the absence of the A subunit and increased proinflammatory properties. In this regard, the ability of LT-IIbB to activate NF-κB and induce TNF-α and IL-8 was antagonized by the LT-IIb holotoxin. These findings support distinct immunomodulatory roles for the LT-II holotoxins and their respective B pentamers. Moreover, the anti-inflammatory properties of the holotoxins may serve to suppress innate immunity and promote the survival of the pathogen. PMID:15501764

Performance evaluation of type II and type IIA box beam end terminals--volume I : research results and discussion.

DOT National Transportation Integrated Search

2010-01-20

Two types of guide rail end terminals were constructed and evaluated according to the American Association of State Highway : Transportation Officials (AASHTOs)Manual for Assessing Safety Hardware (MASH). The guide rail end terminals are used w...

Predictors of cardiovascular fitness in sedentary men.

PubMed

Riou, Marie-Eve; Pigeon, Etienne; St-Onge, Josée; Tremblay, Angelo; Marette, André; Weisnagel, S John; Joanisse, Denis R

2009-04-01

The relative contribution of anthropometric and skeletal muscle characteristics to cardiorespiratory fitness was studied in sedentary men. Cardiorespiratory fitness (maximal oxygen consumption) was assessed using an incremental bicycle ergometer protocol in 37 men aged 34-53 years. Vastus lateralis muscle biopsy samples were used to assess fiber type composition (I, IIA, IIX) and areas, capillary density, and activities of glycolytic and oxidative energy metabolic pathway enzymes. Correlations (all p < 0.05) were observed between maximal oxygen consumption (L.min-1) and body mass (r = 0.53), body mass index (r = 0.39), waist circumference (r = 0.34), fat free mass (FFM; r = 0.68), fat mass (r = 0.33), the enzyme activity of cytochrome c oxidase (COX; r = 0.39), muscle type IIA (r = 0.40) and IIX (r = 0.50) fiber area, and the number of capillaries per type IIA (r = 0.39) and IIX (r = 0.37) fiber. When adjusted for FFM in partial correlations, all correlations were lost, with the exception of COX (r = 0.48). Stepwise multiple regression revealed that maximal oxygen consumption was independently predicted by FFM, COX activity, mean capillary number per fiber, waist circumference, and, to a lesser extent, muscle capillary supply. In the absence of regular physical activity, cardiorespiratory fitness is strongly predicted by the potential for aerobic metabolism of skeletal muscle and negatively correlated with abdominal fat deposition.

Effects of Calorie Restriction and Fiber Type on Glucose Uptake and Abundance of Electron Transport Chain and Oxidative Phosphorylation Proteins in Single Fibers from Old Rats.

PubMed

Wang, Haiyan; Arias, Edward B; Yu, Carmen S; Verkerke, Anthony R P; Cartee, Gregory D

2017-11-09

Calorie restriction (CR; reducing calorie intake by ~40% below ad libitum) can increase glucose uptake by insulin-stimulated muscle. Because skeletal muscle is comprised of multiple, heterogeneous fiber types, our primary aim was to determine the effects of CR (initiated at 14 weeks old) and fiber type on insulin-stimulated glucose uptake by single fibers of diverse fiber types in 23-26-month-old rats. Isolated epitrochlearis muscles from AL and CR rats were incubated with [3H]-2-deoxyglucose ± insulin. Glucose uptake and fiber type were determined for single fibers dissected from the muscles. We also determined CR-effects on abundance of several key metabolic proteins in single fibers. CR resulted in: (a) significantly (p < .05 to .001) greater glucose uptake by insulin-stimulated type I, IIA, IIB, IIBX, and IIX fibers; (b) significantly (p < .05 to .001) reduced abundance of several mitochondrial electron transport chain (ETC) and oxidative phosphorylation (OxPhos) proteins in type I, IIA, and IIBX but not IIB and IIX fibers; and (c) unaltered hexokinase II abundance in each fiber type. These results demonstrate that CR can enhance glucose uptake in each fiber type of rat skeletal muscle in the absence of upregulation of the abundance of hexokinase II or key mitochondrial ETC and OxPhos proteins. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Excess TSH causes abnormal skeletal development in young mice with hypothyroidism via suppressive effects on the growth plate.

PubMed

Endo, Toyoshi; Kobayashi, Tetsuro

2013-09-01

Hypothyroidism in the young leads to irreversible growth failure. hyt/hyt Mice have a nonfunctional TSH receptor (TSHR) and are severely hypothyroid, but growth retardation was not observed in adult mice. We found that epiphysial cartilage as well as cultured chondrocytes expressed functional TSHR at levels comparable to that seen in the thyroid, and that addition of TSH to cultured chondrocytes suppressed expression of chondrocyte differentiation marker genes such as Sox-9 and type IIa collagen. Next, we compared the long bone phenotypes of two distinct mouse models of hypothyroidism: thyroidectomized (THYx) mice and hyt/hyt mice. Although both THYx and hyt/hyt mice were severely hypothyroid and had similar serum Ca(2+) and growth hormone levels, the tibia was shorter and the proliferating and hypertrophic zones in the growth plate was significantly narrower in THYx mice than in hyt/hyt mice. Supplementation of hyt/hyt mice thyroid hormone resulted in a wider growth plate compared with that of wild-type mice. Expressions of chondrocyte differentiation marker genes Sox-9 and type IIa collagen in growth plate from THYx mice were 52 and 60% lower than those of hyt/hyt mice, respectively. High serum TSH causes abnormal skeletal development in young mice with hypothyroidism via suppressive effects on the growth plate.

γT -S195A thrombin reduces the anticoagulant effects of dabigatran in vitro and in vivo.

PubMed

Sheffield, W P; Lambourne, M D; Eltringham-Smith, L J; Bhakta, V; Arnold, D M; Crowther, M A

2014-07-01

Dabigatran etexilate (DE) is an oral direct thrombin inhibitor used to prevent strokes in patients with atrial fibrillation. No licensed DE antidote is currently available. We hypothesized that active site-mutated S195A thrombin (S195A-IIa) and/or its trypsinized derivative (γT -S195A-IIa) would sequester dabigatran, the active form of DE, and reduce its anticoagulant effects. To assess active site-mutated S195A or γT -S195A-IIa as dabigatran reversal agents in vitro and in vivo. Diluted thrombin time (dTT) assays were performed using human or murine plasma containing dabigatran, combined with S195A-IIa, γT -S195A-IIa or FPR-chloromethyl ketone-treated thrombin (FPR-IIa). Bleeding times were determined in anesthetized DE-treated mice also receiving γT -S195A-IIa or vehicle 15 min prior to tail transection. The time to occlusion of carotid arteries of DE-treated mice also receiving S195A-IIa, γT -S195A-IIa, prothrombin complex concentrate (PCC) or vehicle, 15 min prior to topical FeCl3 , was determined using Doppler ultrasound. γT-S195A-IIa reduced dTT values of dabigatran-containing human and murine plasma more effectively than S195-IIa; FPR-IIa had no effect. A dose of 13 mg kg(-1) DE abrogated occlusive thrombus formation in the carotid arteries of FeCl3 -treated mice; γT -S195A-IIa (6 mg kg(-1) ) or PCC (14.3 IU kg(-1) ), but not saline vehicle or S195A-IIa (6 mg kg(-1) ), was equally effective in restoring thrombus formation. Bleeding times of mice treated with 60 mg kg(-1) DE and γT -S195A-IIa (6 mg kg(-1) ) or saline vehicle did not differ. Our data suggest that γT -S195A-IIa decreases the anticoagulant effects of dabigatran in vitro and is partially effective at restoring hemostasis-related thrombus formation in DE-treated mice in vivo. © 2014 International Society on Thrombosis and Haemostasis.

Immunohistochemical analysis of MCT1 and CD147 in equine skeletal muscle fibres.

PubMed

Mykkänen, A K; Hyyppä, S; Pösö, A R; Ronéus, N; Essén-Gustavsson, B

2010-12-01

Monocarboxylate transporter 1 (MCT1) and its ancillary protein CD147 facilitate efflux of lactate from the muscle. Expression of MCT1 and CD147 were studied with immunohistochemistry in type I, IIA, IIAB and IIB fibres of equine gluteal muscle. Staining intensity of MCT1 in the cytoplasm as well as in the membranes of fibre types decreased in the order I=IIA>IIAB>IIB and correlated with the oxidative capacity. Capillaries were pronounced in the MCT1 staining. CD147 antibody stained plasma membranes of all fibre types evenly, whereas the staining in the cytoplasm followed that of MCT1. In the middle gluteal muscle the expression of MCT1 follows the oxidative capacity of muscle fibres, but the expression of CD147 in sarcolemma does not vary among fibre types. The use of horse specific MCT1 and CD147 antibodies can in future studies help to evaluate lactate efflux from different muscle fibre types. Copyright © 2010 Elsevier Ltd. All rights reserved.

Hypermultiplet gaugings and supersymmetric solutions from 11D and massive IIA supergravity on H^{(p,q)} spaces

NASA Astrophysics Data System (ADS)

Guarino, Adolfo

2018-03-01

Supersymmetric {AdS}4, {AdS}2 × Σ 2 and asymptotically AdS4 black hole solutions are studied in the context of non-minimal N=2 supergravity models involving three vector multiplets (STU-model) and Abelian gaugings of the universal hypermultiplet moduli space. Such models correspond to consistent subsectors of the {SO}(p,q) and {ISO}(p,q) gauged maximal supergravities that arise from the reduction of 11D and massive IIA supergravity on {H}^{(p,q)} spaces down to four dimensions. A unified description of all the models is provided in terms of a square-root prepotential and the gauging of a duality-hidden symmetry pair of the universal hypermultiplet. Some aspects of M-theory and massive IIA holography are mentioned in passing.

Genotypes and subtypes of Cryptosporidium spp. in diarrheic lambs and goat kids in northern Greece.

PubMed

Papanikolopoulou, Vasiliki; Baroudi, Djamel; Guo, Yaqiong; Wang, Yuanfei; Papadopoulos, Elias; Lafi, Shwakat Q; Abd El-Tawab, Mohamed M; Diakou, Anastasia; Giadinis, Nektarios D; Feng, Yaoyu; Xiao, Lihua

2018-08-01

Inconsistent data exist on the distribution of zoonotic Cryptosporidium species and subtypes in sheep and goats in European countries, and few such data are available from Greece. In this study, 280 fecal specimens were collected from 132 diarrheic lambs and 148 diarrheic goat kids aged 4 to 15 days on 15 farms in northern Greece, and examined for Cryptosporidium spp. using microscopy of Ziehl-Neelsen-stained fecal smears. Cryptosporidium spp. in 80 microscopy-positive fecal specimens (39 from lambs and 41 from goat kids) were genotyped by PCR-RFLP analysis of the small subunit rRNA gene and subtyped by sequence analysis the 60 kDa glycoprotein gene. Among the 33 specimens successfully genotyped, C. parvum was found in 32 and C. xiaoi in one. Seven subtypes belonging to two subtype families (IIa and IId) were identified among the 29 C. parvum specimens successfully subtyped, including IIaA14G2R1 (1/29), IIaA15G2R1 (6/29), IIaA20G1R1 (7/29), IIdA14G2 (1/29), IIdA15G1 (9/29), IIdA16G1 (3/29), and IIdA23G1 (2/29). Lambs were more commonly infected with C. parvum IIa subtypes, whereas goat kids were more with IId subtypes. The results illustrate that C. parvum is prevalent in diarrheic lambs and goat kids in northern Greece and these animals could potentially play a role in epidemiology of human cryptosporidiosis. Copyright © 2018 Elsevier B.V. All rights reserved.

Class IIa Histone Deacetylases Are Conserved Regulators of Circadian Function*

PubMed Central

Fogg, Paul C. M.; O'Neill, John S.; Dobrzycki, Tomasz; Calvert, Shaun; Lord, Emma C.; McIntosh, Rebecca L. L.; Elliott, Christopher J. H.; Sweeney, Sean T.; Hastings, Michael H.; Chawla, Sangeeta

2014-01-01

Class IIa histone deacetylases (HDACs) regulate the activity of many transcription factors to influence liver gluconeogenesis and the development of specialized cells, including muscle, neurons, and lymphocytes. Here, we describe a conserved role for class IIa HDACs in sustaining robust circadian behavioral rhythms in Drosophila and cellular rhythms in mammalian cells. In mouse fibroblasts, overexpression of HDAC5 severely disrupts transcriptional rhythms of core clock genes. HDAC5 overexpression decreases BMAL1 acetylation on Lys-537 and pharmacological inhibition of class IIa HDACs increases BMAL1 acetylation. Furthermore, we observe cyclical nucleocytoplasmic shuttling of HDAC5 in mouse fibroblasts that is characteristically circadian. Mutation of the Drosophila homolog HDAC4 impairs locomotor activity rhythms of flies and decreases period mRNA levels. RNAi-mediated knockdown of HDAC4 in Drosophila clock cells also dampens circadian function. Given that the localization of class IIa HDACs is signal-regulated and influenced by Ca2+ and cAMP signals, our findings offer a mechanism by which extracellular stimuli that generate these signals can feed into the molecular clock machinery. PMID:25271152

Class IIa histone deacetylases are conserved regulators of circadian function.

PubMed

Fogg, Paul C M; O'Neill, John S; Dobrzycki, Tomasz; Calvert, Shaun; Lord, Emma C; McIntosh, Rebecca L L; Elliott, Christopher J H; Sweeney, Sean T; Hastings, Michael H; Chawla, Sangeeta

2014-12-05

Class IIa histone deacetylases (HDACs) regulate the activity of many transcription factors to influence liver gluconeogenesis and the development of specialized cells, including muscle, neurons, and lymphocytes. Here, we describe a conserved role for class IIa HDACs in sustaining robust circadian behavioral rhythms in Drosophila and cellular rhythms in mammalian cells. In mouse fibroblasts, overexpression of HDAC5 severely disrupts transcriptional rhythms of core clock genes. HDAC5 overexpression decreases BMAL1 acetylation on Lys-537 and pharmacological inhibition of class IIa HDACs increases BMAL1 acetylation. Furthermore, we observe cyclical nucleocytoplasmic shuttling of HDAC5 in mouse fibroblasts that is characteristically circadian. Mutation of the Drosophila homolog HDAC4 impairs locomotor activity rhythms of flies and decreases period mRNA levels. RNAi-mediated knockdown of HDAC4 in Drosophila clock cells also dampens circadian function. Given that the localization of class IIa HDACs is signal-regulated and influenced by Ca(2+) and cAMP signals, our findings offer a mechanism by which extracellular stimuli that generate these signals can feed into the molecular clock machinery. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Genital herpes: gynaecological aspects.

PubMed

Money, Deborah; Steben, Marc

2008-04-01

The purpose of this guideline is to provide recommendations to gynaecology health care providers on optimal management of genital herpes. More effective prevention of complications and transmission of genital herpes. Medline was searched for articles published in French and English related to genital herpes and gynaecology. Additional articles were identified through the references of these articles. All study types and recommendation reports were reviewed. 1. Up to 70% of all genital HSV-2 infections are transmitted during asymptomatic shedding; therefore, the use of condoms is recommended to lessen the likelihood of disease transmission. (II-A) 2. A laboratory-based diagnosis of genital herpes is essential for its effective management. (II-A) 3. Suppressive treatment is suggested for patients who have * at least 6 recurrences per year * significant complications, but fewer than 6 recurrences per year * their quality of life significantly affected * social and sexual dysfunction * to lower the risk of transmission to a sexual partner or fetus/neonate. (II-B) 4. The use of the anti-viral valacyclovir, coupled with condoms and safer sex counselling, is recommended for individuals with proven genital herpes. (I-B) 5. Routine or targeted HSV screening is not indicated.

Morphometric investigations on the portal tracts of the liver, the differentiation of variable progression in chronic persistent hepatitis.

PubMed

Volmer, J; Lüders, C J

1981-01-01

Morphometric investigations were carried out on the portal tracts of the liver in different forms of chronic hepatitis. The investigation groups each contained 25 liver biopsies, which were subdivided into cases with normal liver, a subsiding acute virus hepatitis, three different forms of chronic persistent hepatitis (CPH) and chronic aggressive hepatitis type IIa (CAH IIa). Determinations of the volume and surface of the portal tracts and their components enabled three forms of COH (type Ia, Ib, Ic) to be characterised. Preliminary clinical and semiquantitative histological investigations were correlated with a significant difference in the histological characteristics and prognosis. HBsAg-positive and HBsAg-negative cases showed no significant morphologically detectable differences in all grups investigated. Morphometry is suitable for investigation of pathological changes in liver tissue, especially the portal tracts.

Role of the Streptococcus mutans CRISPR-Cas Systems in Immunity and Cell Physiology

PubMed Central

Serbanescu, M. A.; Cordova, M.; Krastel, K.; Flick, R.; Beloglazova, N.; Latos, A.; Yakunin, A. F.; Senadheera, D. B.

2014-01-01

CRISPR-Cas systems provide adaptive microbial immunity against invading viruses and plasmids. The cariogenic bacterium Streptococcus mutans UA159 has two CRISPR-Cas systems: CRISPR1 (type II-A) and CRISPR2 (type I-C) with several spacers from both CRISPR cassettes matching sequences of phage M102 or genomic sequences of other S. mutans. The deletion of the cas genes of CRISPR1 (ΔC1S), CRISPR2 (ΔC2E), or both CRISPR1+2 (ΔC1SC2E) or the removal of spacers 2 and 3 (ΔCR1SP13E) in S. mutans UA159 did not affect phage sensitivity when challenged with virulent phage M102. Using plasmid transformation experiments, we demonstrated that the CRISPR1-Cas system inhibits transformation of S. mutans by the plasmids matching the spacers 2 and 3. Functional analysis of the cas deletion mutants revealed that in addition to a role in plasmid targeting, both CRISPR systems also contribute to the regulation of bacterial physiology in S. mutans. Compared to wild-type cells, the ΔC1S strain displayed diminished growth under cell membrane and oxidative stress, enhanced growth under low pH, and had reduced survival under heat shock and DNA-damaging conditions, whereas the ΔC2E strain exhibited increased sensitivity to heat shock. Transcriptional analysis revealed that the two-component signal transduction system VicR/K differentially modulates expression of cas genes within CRISPR-Cas systems, suggesting that VicR/K might coordinate the expression of two CRISPR-Cas systems. Collectively, we provide in vivo evidence that the type II-A CRISPR-Cas system of S. mutans may be targeted to manipulate its stress response and to influence the host to control the uptake and dissemination of antibiotic resistance genes. PMID:25488301

Lactobacillus buchneri genotyping on the basis of clustered regularly interspaced short palindromic repeat (CRISPR) locus diversity.

PubMed

Briner, Alexandra E; Barrangou, Rodolphe

2014-02-01

Clustered regularly interspaced short palindromic repeats (CRISPR) in combination with associated sequences (cas) constitute the CRISPR-Cas immune system, which uptakes DNA from invasive genetic elements as novel "spacers" that provide a genetic record of immunization events. We investigated the potential of CRISPR-based genotyping of Lactobacillus buchneri, a species relevant for commercial silage, bioethanol, and vegetable fermentations. Upon investigating the occurrence and diversity of CRISPR-Cas systems in Lactobacillus buchneri genomes, we observed a ubiquitous occurrence of CRISPR arrays containing a 36-nucleotide (nt) type II-A CRISPR locus adjacent to four cas genes, including the universal cas1 and cas2 genes and the type II signature gene cas9. Comparative analysis of CRISPR spacer content in 26 L. buchneri pickle fermentation isolates associated with spoilage revealed 10 unique locus genotypes that contained between 9 and 29 variable spacers. We observed a set of conserved spacers at the ancestral end, reflecting a common origin, as well as leader-end polymorphisms, reflecting recent divergence. Some of these spacers showed perfect identity with phage sequences, and many spacers showed homology to Lactobacillus plasmid sequences. Following a comparative analysis of sequences immediately flanking protospacers that matched CRISPR spacers, we identified a novel putative protospacer-adjacent motif (PAM), 5'-AAAA-3'. Overall, these findings suggest that type II-A CRISPR-Cas systems are valuable for genotyping of L. buchneri.

Hearing aid fitting for visual and hearing impaired patients with Usher syndrome type IIa.

PubMed

Hartel, B P; Agterberg, M J H; Snik, A F; Kunst, H P M; van Opstal, A J; Bosman, A J; Pennings, R J E

2017-08-01

Usher syndrome is the leading cause of hereditary deaf-blindness. Most patients with Usher syndrome type IIa start using hearing aids from a young age. A serious complaint refers to interference between sound localisation abilities and adaptive sound processing (compression), as present in today's hearing aids. The aim of this study was to investigate the effect of advanced signal processing on binaural hearing, including sound localisation. In this prospective study, patients were fitted with hearing aids with a nonlinear (compression) and linear amplification programs. Data logging was used to objectively evaluate the use of either program. Performance was evaluated with a speech-in-noise test, a sound localisation test and two questionnaires focussing on self-reported benefit. Data logging confirmed that the reported use of hearing aids was high. The linear program was used significantly more often (average use: 77%) than the nonlinear program (average use: 17%). The results for speech intelligibility in noise and sound localisation did not show a significant difference between type of amplification. However, the self-reported outcomes showed higher scores on 'ease of communication' and overall benefit, and significant lower scores on disability for the new hearing aids when compared to their previous hearing aids with compression amplification. Patients with Usher syndrome type IIa prefer a linear amplification over nonlinear amplification when fitted with novel hearing aids. Apart from a significantly higher logged use, no difference in speech in noise and sound localisation was observed between linear and nonlinear amplification with the currently used tests. Further research is needed to evaluate the reasons behind the preference for the linear settings. © 2016 The Authors. Clinical Otolaryngology Published by John Wiley & Sons Ltd.

Effect of season on contractile and metabolic properties of desert camel muscle (Camelus dromedarius).

PubMed

Abdelhadi, O M A; Babiker, S A; Picard, B; Jurie, C; Jailler, R; Hocquette, J F; Faye, B

2012-01-01

Thirty fattened one humped desert camels were used to examine the effect of season on contractile and metabolic properties of Longissimus thoracis (LT) muscle. Ten camels were slaughtered according to seasons of the year (winter, summer and autumn). Season significantly influenced muscle chemical composition, ultimate pH (pHu) and color. Activities of metabolic enzymes were higher during autumn season compared to summer and winter for phosphofructokinase (+64% compared to both seasons) and for isocitrate dehydrogenase (+35% and +145% in autumn vs. summer and winter, respectively). Quantification of muscle myosin heavy chain isoforms by SDS-PAGE electrophoresis showed only presence of type I and type IIa MyHC in camel muscle and indicated high proportion in winter for type I and in autumn for type IIa with respect to other seasons. Several correlations between different MyHC proportions and enzyme activities were reported. These findings indicated that muscle characteristics in camels are influenced by season. Copyright © 2011 Elsevier Ltd. All rights reserved.

The co-existence of transcriptional activator and transcriptional repressor MEF2 complexes influences tumor aggressiveness

PubMed Central

Di Giorgio, Eros; Franforte, Elisa; Cefalù, Sebastiano; Rossi, Sabrina; Dei Tos, Angelo Paolo; Polano, Maurizio; Maestro, Roberta; Paluvai, Harikrishnareddy

2017-01-01

The contribution of MEF2 TFs to the tumorigenic process is still mysterious. Here we clarify that MEF2 can support both pro-oncogenic or tumor suppressive activities depending on the interaction with co-activators or co-repressors partners. Through these interactions MEF2 supervise histone modifications associated with gene activation/repression, such as H3K4 methylation and H3K27 acetylation. Critical switches for the generation of a MEF2 repressive environment are class IIa HDACs. In leiomyosarcomas (LMS), this two-faced trait of MEF2 is relevant for tumor aggressiveness. Class IIa HDACs are overexpressed in 22% of LMS, where high levels of MEF2, HDAC4 and HDAC9 inversely correlate with overall survival. The knock out of HDAC9 suppresses the transformed phenotype of LMS cells, by restoring the transcriptional proficiency of some MEF2-target loci. HDAC9 coordinates also the demethylation of H3K4me3 at the promoters of MEF2-target genes. Moreover, we show that class IIa HDACs do not bind all the regulative elements bound by MEF2. Hence, in a cell MEF2-target genes actively transcribed and strongly repressed can coexist. However, these repressed MEF2-targets are poised in terms of chromatin signature. Overall our results candidate class IIa HDACs and HDAC9 in particular, as druggable targets for a therapeutic intervention in LMS. PMID:28419090

Performance of the 2015 International Task Force Consensus Statement Risk Stratification Algorithm for Implantable Cardioverter-Defibrillator Placement in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy.

PubMed

Orgeron, Gabriela M; Te Riele, Anneline; Tichnell, Crystal; Wang, Weijia; Murray, Brittney; Bhonsale, Aditya; Judge, Daniel P; Kamel, Ihab R; Zimmerman, Stephan L; Tandri, Harikrishna; Calkins, Hugh; James, Cynthia A

2018-02-01

Ventricular arrhythmias are a feared complication of arrhythmogenic right ventricular dysplasia/cardiomyopathy. In 2015, an International Task Force Consensus Statement proposed a risk stratification algorithm for implantable cardioverter-defibrillator placement in arrhythmogenic right ventricular dysplasia/cardiomyopathy. To evaluate performance of the algorithm, 365 arrhythmogenic right ventricular dysplasia/cardiomyopathy patients were classified as having a Class I, IIa, IIb, or III indication per the algorithm at baseline. Survival free from sustained ventricular arrhythmia (VT/VF) in follow-up was the primary outcome. Incidence of ventricular fibrillation/flutter cycle length <240 ms was also assessed. Two hundred twenty-four (61%) patients had a Class I implantable cardioverter-defibrillator indication; 80 (22%), Class IIa; 54 (15%), Class IIb; and 7 (2%), Class III. During a median 4.2 (interquartile range, 1.7-8.4)-year follow-up, 190 (52%) patients had VT/VF and 60 (16%) had ventricular fibrillation/flutter. Although the algorithm appropriately differentiated risk of VT/VF, incidence of VT/VF was underestimated (observed versus expected: 29.6 [95% confidence interval, 25.2-34.0] versus >10%/year Class I; 15.5 [confidence interval 11.1-21.6] versus 1% to 10%/year Class IIa). In addition, the algorithm did not differentiate survival free from ventricular fibrillation/flutter between Class I and IIa patients ( P =0.97) or for VT/VF in Class I and IIa primary prevention patients ( P =0.22). Adding Holter results (<1000 premature ventricular contractions/24 hours) to International Task Force Consensus classification differentiated risks. While the algorithm differentiates arrhythmic risk well overall, it did not distinguish ventricular fibrillation/flutter risks of patients with Class I and IIa implantable cardioverter-defibrillator indications. Limited differentiation was seen for primary prevention cases. As these are vital uncertainties in clinical decision-making, refinements to the algorithm are suggested prior to implementation. © 2018 American Heart Association, Inc.

Inulin based glutathione-responsive delivery system for colon cancer treatment.

PubMed

Wang, Dongdong; Sun, Feifei; Lu, Chunbo; Chen, Peng; Wang, Zhaojie; Qiu, Yuanhao; Mu, Haibo; Miao, Zehong; Duan, Jinyou

2018-05-01

Colorectal cancer is one of the most common types of tumor in the world. Here we developed a lipoic acid esterified polysaccharide (inulin) delivery system for tanshinone IIA to treat colorectal cancer in vitro. The release of tanshinone IIA in the system was highly responsive to glutathione, which is commonly abundant in cancer cells. In addition, this drug delivery system was proliferative to Bifidobacterium longum, the common inhabitant of human intestine. Thus, this strategy might be useful to improve colon cancer therapy efficacy of anticancer drugs and meanwhile promote the growth of beneficial commensal flora in the gut. Copyright © 2018 Elsevier B.V. All rights reserved.

Relamorelin: A Novel Gastrocolokinetic Synthetic Ghrelin Agonist

PubMed Central

Camilleri, Michael; Acosta, Andres

2015-01-01

Synthetic ghrelin agonists, predominantly small molecules, are being developed as prokinetic agents that may prove useful in the treatment of gastrointestinal motility disorders. Relamorelin (RM-131) is a pentapeptide synthetic ghrelin analog that activates the growth hormone secretagogue (GHS)-1a (also called the ghrelin) receptor with approximately 6-fold greater potency than natural ghrelin. The ability of relamorelin to stimulate growth hormone (GH) release is comparable to that of native ghrelin. Relamorelin has enhanced efficacy and plasma stability compared to native ghrelin. In this review, we discuss the pharmacokinetics, pharmacodynamics and potential indications for relamorelin. Relamorelin is administered subcutaneously, dosed daily or twice daily. Relamorelin is being studied for the treatment of patients with gastrointestinal motility disorders. Phase IIA pharmacodynamic studies have demonstrated acceleration of gastric emptying in patients with type 1 diabetes mellitus (T1DM) and type 2 DM (T2DM) and upper gastrointestinal symptoms. In a phase IIA study in patients with diabetic gastroparesis, relamorelin accelerated gastric emptying and significantly improved vomiting frequency compared to placebo and improved other symptoms of gastroparesis in a pre-specified subgroup of patients with vomiting at baseline. In patients with chronic idiopathic constipation with defined transit profile at baseline, relamorelin relieved constipation and accelerated colonic transit compared to placebo. These characteristics suggest that this new ghrelin analog shows great promise to relieve patients with upper or lower gastrointestinal motility disorders. PMID:25545036

A new animal model for modulating myosin isoform expression by altered mechanical activity

NASA Technical Reports Server (NTRS)

Caiozzo, V. J.; Ma, E.; McCue, S. A.; Smith, E.; Herrick, R. E.; Baldwin, K. M.

1992-01-01

The purpose of this study was to develop a new rodent model that is capable of delineating the importance of mechanical loading on myosin heavy chain (MHC) isoform expression of the plantar and dorsi flexor muscles of the ankle. The essential components of this system include 1) stimulating electrodes that are chronically implanted into a muscle, allowing for the control of the activation pattern of the target muscle(s); 2) a training apparatus that translates the moment of the ankle into a linear force; and 3) a computer-controlled Cambridge 310 ergometer. The isovelocity profile of the ergometer ensured that the medial gastrocnemius (MG) produced forces that were > 90% of maximal isometric force (Po), and the eccentric contractions of the tibialis anterior (TA) were typically 120% of Po. Both the concentric and eccentric training programs produced statistically significant increases in the muscle mass of the MG (approximately 15%) and TA (approximately 7%) as well as a decrease in myofibrillar adenosinetriphosphatase activity. Both the white and red regions of the MG and TA exhibited significant increases in the relative content of the type IIa MHC and concomitant decreases in type IIb MHC expression. Although the red regions of the MG and red TA contained approximately 10% type I MHC, the training programs did not affect this isoform. It appears that when a fast-twitch muscle is stimulated at a high frequency (100 Hz) and required to contract either concentrically or eccentrically under high loading conditions, the expression of the type IIa MHC isoform will be upregulated, whereas that of the type IIb MHC will be concomitantly downregulated.

Cadaveric and radiologic study of the anatomical variations of the prostatic arteries: A review of the literature and a new classification proposal with application to prostatectomy.

PubMed

Moya, Celia; Cuesta, Julián; Friera, Alfonsina; Gil-Vernet Sedó, Jose María; Valderrama-Canales, Francisco J

2017-01-01

Development of prostatic arterial embolization (PAE) to treat benign prostatic hyperplasia (BPH) has raised interest in the variations of the prostatic arteries (PA). The aim of this study is to identify these vascular variations, to compare them with previous data, and to propose a simple classification. Ten adult male pelvis sides from embalmed cadavers were dissected, ages 69 to 92 years, and 10 PA were examined. In a retrospective analysis of 34 DSA pelvic angiographies on 28 patients aged 50 to 90 years, 48 PA were identified. A total of 58 PA were therefore analyzed. Six types are defined. Type I: PA originates from the anterior division (AD) of the internal iliac artery (IIA), 20.7%; Type II: PA emerges from the obturator artery (OA), 5.2%; type III: PA arises from the gluteal-pudendal trunk (GPT), 27.5%; Type IV: PA originates from the internal pudendal artery (IPA), 29.3%; Type V: PA comes from the middle rectal artery (MRA), 15.5%. Other origins, not observed in our sample but described in the literature, were amalgamated under Type VI. The AD/GPT/IPA stem is the main source of the PA. Analysis of the definitions of IIA branches and the associated terminology is necessary for interpreting the results reported by several authors on different samples, but in general the results fit the meta-analysis well. A new, simple, and complete classification for vascular variations of the PA is proposed. Clin. Anat. 30:71-80, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

SCORE: Service Corps of Retired Executives. Counselor's Guidebook. One Part of ACTION.

ERIC Educational Resources Information Center

Small Business Administration, Washington, DC.

This guidebook, designed for the use of SCORE volunteers, is intended to familiarize new counselors with SCORE operations and to provide reference material to assist counselors in handling cases. Chapters are: (1) SCORE Purposes and Objectives; (II-A-1) Approach to Counseling; (II-A-2) Organization of the Business--legal forms, management or…

Preferential Type II Muscle Fiber Damage From Plyometric Exercise

PubMed Central

Macaluso, Filippo; Isaacs, Ashwin W.; Myburgh, Kathryn H.

2012-01-01

Context Plyometric training has been successfully used in different sporting contexts. Studies that investigated the effect of plyometric training on muscle morphology are limited, and results are controversial with regard to which muscle fiber type is mainly affected. Objective To analyze the skeletal muscle structural and ultrastructural change induced by an acute bout of plyometric exercise to determine which type of muscle fibers is predominantly damaged. Design Descriptive laboratory study. Setting Research laboratory. Patients or Other Participants Eight healthy, untrained individuals (age = 22 ± 1 years, height = 179.2 ± 6.4 cm, weight = 78.9 ± 5.9 kg). Intervention(s) Participants completed an acute bout of plyometric exercise (10 sets of 10 squat-jumps with a 1-minute rest between sets). Main Outcome Measure(s) Blood samples were collected 9 days and immediately before and 6 hours and 1, 2, and 3 days after the acute intervention. Muscle samples were collected 9 days before and 3 days after the exercise intervention. Blood samples were analyzed for creatine kinase activity. Muscle biopsies were analyzed for damage using fluorescent and electron transmission microscopy. Results Creatine kinase activity peaked 1 day after the exercise bout (529.0 ± 317.8 U/L). Immunofluorescence revealed sarcolemmal damage in 155 of 1616 fibers analyzed. Mainly fast-twitch fibers were damaged. Within subgroups, 7.6% of type I fibers, 10.3% of type IIa fibers, and 14.3% of type IIx fibers were damaged as assessed by losses in dystrophin staining. Similar damage was prevalent in IIx and IIa fibers. Electron microscopy revealed clearly distinguishable moderate and severe sarcomere damage, with damage quantifiably predominant in type II muscle fibers of both the glycolytic and oxidative subtypes (86% and 84%, respectively, versus only 27% of slow-twitch fibers). Conclusions We provide direct evidence that a single bout of plyometric exercise affected mainly type II muscle fibers. PMID:22889657

Cellular uptake of Clostridium botulinum C2 toxin: membrane translocation of a fusion toxin requires unfolding of its dihydrofolate reductase domain.

PubMed

Haug, Gerd; Wilde, Christian; Leemhuis, Jost; Meyer, Dieter K; Aktories, Klaus; Barth, Holger

2003-12-30

The Clostridium botulinum C2 toxin is the prototype of the family of binary actin-ADP-ribosylating toxins. C2 toxin is composed of two separated nonlinked proteins. The enzyme component C2I ADP-ribosylates actin in the cytosol of target cells. The binding/translocation component C2II mediates cell binding of the enzyme component and its translocation from acidic endosomes into the cytosol. After proteolytic activation, C2II forms heptameric pores in endosomal membranes, and most likely, C2I translocates through these pores into the cytosol. For this step, the cellular heat shock protein Hsp90 is essential. We analyzed the effect of methotrexate on the cellular uptake of a fusion toxin in which the enzyme dihydrofolate reductase (DHFR) was fused to the C-terminus of C2I. Here, we report that unfolding of C2I-DHFR is required for cellular uptake of the toxin via the C2IIa component. The C2I-DHFR fusion toxin catalyzed ADP-ribosylation of actin in vitro and was able to intoxicate cultured cells when applied together with C2IIa. Binding of the folate analogue methotrexate favors a stable three-dimensional structure of the dihydrofolate reductase domain. Pretreatment of C2I-DHFR with methotrexate prevented cleavage of C2I-DHFR by trypsin. In the presence of methotrexate, intoxication of cells with C2I-DHFR/C2II was inhibited. The presence of methotrexate diminished the translocation of the C2I-DHFR fusion toxin from endosomal compartments into the cytosol and the direct C2IIa-mediated translocation of C2I-DHFR across cell membranes. Methotrexate had no influence on the intoxication of cells with C2I/C2IIa and did not alter the C2IIa-mediated binding of C2I-DHFR to cells. The data indicate that methotrexate prevented unfolding of the C2I-DHFR fusion toxin, and thereby the translocation of methotrexate-bound C2I-DHFR from endosomes into the cytosol of target cells is inhibited.

Virulence factors associated with cytotoxic necrotizing factor type two in bovine diarrheic and septicemic strains of Escherichia coli.

PubMed Central

Oswald, E; de Rycke, J; Lintermans, P; van Muylem, K; Mainil, J; Daube, G; Pohl, P

1991-01-01

Forty-three bovine isolates of Escherichia coli producing a second type of cytotoxic necrotizing factor (CNF2) and three K-12 strains carrying different Vir plasmids coding for CNF2 were tested for the presence of several virulence factors. Most of the strains were serum resistant (79%), produced an aerobactin (70%), and adhered to calf villi (53%); some of them produced a colicin (32%) and a hemolysin (9%). These strains were also tested by a colony hybridization assay with gene probes for six toxins (classical heat-stable [STaP and STb] and heat-labile [LT-I and LT-IIa] enterotoxins and Shiga-like toxins [SLT-I and SLT-II]) and five adhesion factors (K99, K88, 987P, F17, and F41). Only two gene probes, LT-IIa (9%) and F17A (53%), hybridized with the CNF2 strains. However, antibodies raised against F17 fimbriae did not agglutinate the strains hybridizing with the F17A probe. In contrast, all except one of these strains adhered to calf villi. Interestingly, these two properties, F17A positivity and adherence to calf villi, were the only ones expressed by the K-12 strains carrying different Vir plasmids. In conclusion, this study confirmed that CNF2-producing strains are unrelated to previously described toxigenic E. coli strains and also demonstrated that in half of the strains the production of CNF2 was associated with an adhesion factor genetically related to, but different from, F17, which is more than likely encoded by Vir plasmids. PMID:1774259

AMPK activation by Tanshinone IIA protects neuronal cells from oxygen-glucose deprivation

PubMed Central

Weng, Yingfeng; Lin, Jixian; Liu, Hui; Wu, Hui; Yan, Zhimin; Zhao, Jing

2018-01-01

The current study tested the potential neuroprotective function of Tanshinone IIA (ThIIA) in neuronal cells with oxygen-glucose deprivation (ODG) and re-oxygenation (OGDR). In SH-SY5Y neuronal cells and primary murine cortical neurons, ThIIA pre-treatment attenuated OGDR-induced viability reduction and apoptosis. Further, OGDR-induced mitochondrial depolarization, reactive oxygen species production, lipid peroxidation and DNA damages in neuronal cells were significantly attenuated by ThIIA. ThIIA activated AMP-activated protein kinase (AMPK) signaling, which was essential for neuroprotection against OGDR. AMPKα1 knockdown or complete knockout in SH-SY5Y cells abolished ThIIA-induced AMPK activation and neuroprotection against OGDR. Further studies found that ThIIA up-regulated microRNA-135b to downregulate the AMPK phosphatase Ppm1e. Notably, knockdown of Ppm1e by targeted shRNA or forced microRNA-135b expression also activated AMPK and protected SH-SY5Y cells from OGDR. Together, AMPK activation by ThIIA protects neuronal cells from OGDR. microRNA-135b-mediated silence of Ppm1e could be the key mechanism of AMPK activation by ThIIA. PMID:29435120

Kidney and Phosphate Metabolism

PubMed Central

2008-01-01

The serum phosphorus level is maintained through a complex interplay between intestinal absorption, exchange intracellular and bone storage pools, and renal tubular reabsorption. The kidney plays a major role in regulation of phosphorus homeostasis by renal tubular reabsorption. Type IIa and type IIc Na+/Pi transporters are important renal Na+-dependent inorganic phosphate (Pi) transporters, which are expressed in the brush border membrane of proximal tubular cells. Both are regulated by dietary Pi intake, vitamin D, fibroblast growth factor 23 (FGF23) and parathyroid hormone. The expression of type IIa Na+/Pi transporter result from hypophosphatemia quickly. However, type IIc appears to act more slowly. Physiological and pathophysiological alteration in renal Pi reabsorption are related to altered brush border membrane expression/content of the type II Na+/Pi cotransporter. Many studies of genetic and acquired renal phosphate wasting disorders have led to the identification of novel genes. Two novel Pi regulating genes, PHEX and FGF23, play a role in the pathophysiology of genetic and acquired renal phosphate wasting disorders and studies are underway to define their mechanism on renal Pi regulation. In recent studies, sodium-hydrogen exchanger regulatory factor 1 (NHERF1) is reported as another new regulator for Pi reabsorption mechanism. PMID:24459526

Effect of chronic ethanol ingestion and exercise training on skeletal muscle in rat.

PubMed

Vila, L; Ferrando, A; Voces, J; Cabral de Oliveira, C; Prieto, J G; Alvarez, A I

2001-09-01

The aim of this study was to investigate the interactive effects of exercise training and chronic ethanol consumption on metabolism, capillarity, and myofibrillar composition in rat limb muscles. Male Wistar rats were treated in separate groups as follows: non exercised-control; ethanol (15%) in animals' drinking water for 12 weeks; exercise training in treadmill and ethanol administration plus exercise for 12 weeks. Ethanol administration decreased capillarity and increased piruvate kinase and lactate dehydrogenase activities in white gastrocnemius; in plantaris muscle, ethanol increased citrate synthase activity and decreased cross-sectional area of type I, IIa, and IIb fibres. Exercise increased capillarity in all four limb muscles and decreased type I fibre area in plantaris. The decreased capillarity effect induced by ethanol in some muscles, was ameliorated when alcohol was combined with exercise. While alcoholic myopathy affects predominantly type IIb fibres, ethanol administration and aerobic exercise in some cases can affect type I and type IIa fibre areas. The exercise can decrease some harmful effects produced by ethanol in the muscle, including the decrease in the fibre area and capillary density.

HDL cholesterol transport during inflammation.

PubMed

van der Westhuyzen, Deneys R; de Beer, Frederick C; Webb, Nancy R

2007-04-01

The aim of this article is to review recent advances made towards understanding how inflammation and acute phase proteins, particularly serum amyloid A and group IIa secretory phospholipase A2, may alter reverse cholesterol transport by HDL during inflammation and the acute phase response. Findings suggest that the decreased apoA-I content and markedly increased serum amyloid A content in HDL during the acute phase response result from reciprocal and coordinate transcriptional regulation of these proteins as well as HDL remodeling by group IIa secretory phospholipase A2. Serum amyloid A functions efficiently in a lipid-free or lipid-poor form to promote cholesterol efflux by ATP binding cassette protein ABCA1, evidently by functioning directly as an acceptor for cholesterol efflux as well as by increasing the availability of cellular free cholesterol. Serum amyloid A increases the ability of acute phase HDL to serve as an acceptor for SR-BI-dependent cellular cholesterol efflux. Altered remodeling of HDL by group IIa secretory phospholipase A2 in concert with cholesterol ester transfer protein may contribute to the generation of lipid-poor apoA-I and serum amyloid A acceptors for cholesterol efflux. Current data support a model for the acute phase response in which serum amyloid A and sPLA2-IIa, present at sites of inflammation and tissue damage, play a protective role by enhancing cellular cholesterol efflux, thereby promoting the removal of excess cholesterol from macrophages.

Megakaryocyte and platelet abnormalities in a patient with a W33C mutation in the conserved SH3-like domain of myosin heavy chain IIA.

PubMed

Kahr, Walter H A; Savoia, Anna; Pluthero, Fred G; Li, Ling; Christensen, Hilary; De Rocco, Daniela; Traivaree, Chanchai; Butchart, Sheila E; Curtin, Julie; Stollar, Elliott J; Forman-Kay, Julie D; Blanchette, Victor S

2009-12-01

Heterozygous mutations in MYH9, which encodes non-muscle myosin heavy chain IIA (MHC-IIA), result in autosomal dominant inherited MYH9-related disorders characterised by macro-thrombocytopenia, granulocyte inclusions, variable sensorineural deafness, cataracts and nephritis. MHC-IIA is assembled into a complex consisting of two pairs of light chains and two heavy chains, where the latter contain a neck region, SH3-like, motor and rod domains. We describe a patient with a Trp33Cys missense mutation in the SH3-like domain of MHC-IIA. Abnormal platelet function was observed using platelet aggregometry with the agonists epinephrine and adenosine diphosphate (ADP). Patient granulocytes and megakaryocytes, but not platelets, contained abnormal MHC-IIA inclusions visualised by confocal immunofluorescence or electron microscopy. Megakaryocytes grown in culture were smaller and contained hypolobulated nuclei compared to controls. Bone marrow-derived megakaryocytes revealed a preponderance of immature forms, the presence of structurally diverse inclusion bodies, and frequent emperipolesis as assessed by electron microscopy. Platelets and leukocytes contained indistinguishable amounts of total MHC-IIA determined by immunoblotting. Molecular modelling studies indicated that mutation of Trp33 destabilises the interface between the SH3-like and motor domain of MHC-IIA, which is close to previously described motor domain mutations, implying an important structural and/or functional role for this region in MHC-IIA.

Analysis of transcriptional isoforms of collagen types IX, II, and I in the developing avian cornea by competitive polymerase chain reaction.

PubMed

Fitch, J M; Gordon, M K; Gibney, E P; Linsenmayer, T F

1995-01-01

The genes for the alpha 1(IX), alpha 1(II), and alpha 2(I) collagen chains can give rise to different isoforms of mRNA, generated by alternative promotor usage [for alpha 1(IX) and alpha 2(I)] or alternative splicing [for alpha 1(II)]. In this study, we employed competitive reverse transcriptase PCR to quantitate the amounts of transcriptional isoforms for these genes in the embryonic avian cornea from its inception (about 3 1/2 days of development) to 11 days. In order to compare values at different time points, the results were normalized to those obtained for the "housekeeping" enzyme, glycerol-3-phosphate dehydrogenase (G3PDH). These values were compared to those obtained from other tissues (anterior optic cup and cartilage) that synthesize different combinations of the collagen isoforms. We found that, in the cornea, transcripts from the upstream promotor of alpha 1(IX) collagen (termed "long IX") were predominant at stage 18-20 (about 3 1/2 days), but then fell rapidly, and remained at a low level. By 5 days (just before stromal swelling) the major mRNA isoform of alpha 1(IX) was from the downstream promoter (termed "short IX"). The relative amount of transcript for the short form of type IX collagen rose to a peak at about 6 days of development, and then declined. Throughout this period, the predominant transcriptional isoform of the collagen type II gene was IIA (i.e., containing the alternatively spliced exon 2). This indicates that the molecules of type II collagen that are assembled into heterotypic fibrils with type I collagen possess, at least transiently, an amino-terminal globular domain similar to that found in collagen types I, III, and V. For type I, the "bone/tendon" mRNA isoform of the alpha 2(I) collagen gene was predominant; transcripts from the downstream promotor were at basal levels. In other tissues expressing collagen types IX and II, long IX was expressed predominantly with the IIA form in the anterior optic cup at stage 22/23; in 14 1/2 day cartilage, long IX was expressed predominantly along with the IIB form of alpha 1(II). The downstream transcript of the alpha 2(I) gene (Icart) was found at high levels only in cartilage.

Endovascular Treatment of Dural Arteriovenous Fistulas: Single Center Experience

PubMed Central

Oh, Jae-Sang; Oh, Hyuk-Jin; Shim, Jai-Joon; Bae, Hack-Gun; Lee, Kyeong-Seok

2016-01-01

Objective Treatment of intracranial dural arteriovenous fistulas (dAVFs) remains a challenge. However, after introduction of Onyx, transarterial approach is the preferred treatment option in many centers. We report our experience of dAVFs embolization with special emphasis on transarterial approach. Methods Seventeen embolization procedures were performed in 13 patients with dAVFs between Jan 2009 and Oct 2014. Clinical symptoms, location and type of fistulas, embolization methods, complications, radiological and clinical outcomes were evaluated using charts and PACS images. Results All 13 patients had symptomatic lesions. The locations of fistulas were transverse-sigmoid sinus in 6, middle fossa dura in 4, cavernous sinus in 2, and superior sagittal sinus in 1 patient. Cognard types were as follows : I in 4, IIa in 2, IIa+IIb in 5, and IV in 2. Embolization procedures were performed ≥2 times in 3 patients. Nine patients were treated with transarterial Onyx embolization alone. One of these required direct surgical puncture of middle meningeal artery. Complete obliteration of fistulas was achieved in 11/13 (85%) patients. There were no complications except for 1 case of Onyx migration in cavernous dAVF. Modified Rankin scale score at post-operative 3 months were 0 in 11, and 3 in 2 patients. Conclusion Transarterial Onyx embolization can be a first line therapeutic option in patients with dAVFs. However, transvenous approach should be tried first in cavernous sinus dAVF because of the risk of intracranial migration of liquid embolic materials. Furthermore, combined surgical endovascular approach can be considered as a useful option in inaccessible route. PMID:26885282

Audiological and vestibular features in affected subjects with USH3: a genotype/phenotype correlation.

PubMed

Sadeghi, Mehdi; Cohn, Edward S; Kimberling, William J; Tranebjaerg, Lisbeth; Möller, Claes

2005-05-01

The aims were to compare the genotype/phenotype relationship between USH3 mutations and the consequent hearing and vestibular phenotype; and to compare hearing loss (HL) progression between Usher syndrome types IB, IIA and USH3. Genetic, audiometric and vestibular examinations were performed in 28 subjects with USH3. Five different mutations in USH3 were identified. Severe HL was present from an early age (4 to 6 years) in 35% of subjects with USH3. Progression of HL begins in the first decade, and approximately 50% of subjects with USH3 become profoundly deaf by age 40. Various vestibular abnormalities were found in about half (10/22) of the tested subjects with USH3. Depending on the severity of HL, subjects with USH3 might be misdiagnosed as either Usher type IB or IIA. The results from this study can be used as discriminatory features in differential diagnosis of this syndrome.

40 CFR 796.3500 - Hydrolysis as a function of pH at 25 °C.

Code of Federal Regulations, 2013 CFR

2013-07-01

... biodegradation. ASTM Type IIA water is described in ASTM D 1193-77 (Reapproved 1983), “Standard Specification for... solutions and in carrying out all hydrolysis experiments to eliminate or minimize biodegradation. Glassware...

40 CFR 796.3500 - Hydrolysis as a function of pH at 25 °C.

Code of Federal Regulations, 2012 CFR

2012-07-01

... biodegradation. ASTM Type IIA water is described in ASTM D 1193-77 (Reapproved 1983), “Standard Specification for... carrying out all hydrolysis experiments to eliminate or minimize biodegradation. Glassware can be...

40 CFR 796.3500 - Hydrolysis as a function of pH at 25 °C.

Code of Federal Regulations, 2011 CFR

2011-07-01

... biodegradation. ASTM Type IIA water is described in ASTM D 1193-77 (Reapproved 1983), “Standard Specification for... carrying out all hydrolysis experiments to eliminate or minimize biodegradation. Glassware can be...

Mechanism of inhibition of human secretory phospholipase A2 by flavonoids: rationale for lead design

NASA Astrophysics Data System (ADS)

Lättig, Jens; Böhl, Markus; Fischer, Petra; Tischer, Sandra; Tietböhl, Claudia; Menschikowski, Mario; Gutzeit, Herwig O.; Metz, Peter; Pisabarro, M. Teresa

2007-08-01

The human secretory phospholipase A2 group IIA (PLA2-IIA) is a lipolytic enzyme. Its inhibition leads to a decrease in eicosanoids levels and, thereby, to reduced inflammation. Therefore, PLA2-IIA is of high pharmacological interest in treatment of chronic diseases such as asthma and rheumatoid arthritis. Quercetin and naringenin, amongst other flavonoids, are known for their anti-inflammatory activity by modulation of enzymes of the arachidonic acid cascade. However, the mechanism by which flavonoids inhibit Phospholipase A2 (PLA2) remained unclear so far. Flavonoids are widely produced in plant tissues and, thereby, suitable targets for pharmaceutical extractions and chemical syntheses. Our work focuses on understanding the binding modes of flavonoids to PLA2, their inhibition mechanism and the rationale to modify them to obtain potent and specific inhibitors. Our computational and experimental studies focused on a set of 24 compounds including natural flavonoids and naringenin-based derivatives. Experimental results on PLA2-inhibition showed good inhibitory activity for quercetin, kaempferol, and galangin, but relatively poor for naringenin. Several naringenin derivatives were synthesized and tested for affinity and inhibitory activity improvement. 6-(1,1-dimethylallyl)naringenin revealed comparable PLA2 inhibition to quercetin-like compounds. We characterized the binding mode of these compounds and the determinants for their affinity, selectivity, and inhibitory potency. Based on our results, we suggest C(6) as the most promising position of the flavonoid scaffold to introduce chemical modifications to improve affinity, selectivity, and inhibition of PLA2-IIA by flavonoids.

Characterization of antigenic determinants in ApxIIA exotoxin capable of inducing protective immunity to Actinobacillus pleuropneumoniae challenge.

PubMed

Seo, Ki-Weon; Kim, Dong-Heon; Kim, Ah Hyun; Yoo, Han-Sang; Lee, Kyung-Yeol; Jang, Yong-Suk

2011-01-01

Actinobacillus pleuropneumoniae is the causative agent of porcine pleuropneumonia. Among the virulence factors of the pathogen, ApxIIA, a bacterial exotoxin, is expressed by many serotypes and presents a plausible target for vaccine development. We characterized the region within ApxIIA that induces a protective immune response against bacterial infection using mouse challenge model. Recombinant proteins spanning the length of ApxIIA were produced and antiserum to the full-length ApxIIA was induced in mice. This antiserum recognized fragments #2, #3 and #5 with high binding specificity, but showed poor recognition for fragments #1 and #4. Of the antisera induced in mice by injection of each fragments, only the antiserum to fragment #4 failed to efficiently recognize the full-length antigen, although the individual antisera recognized their cognate antigens with almost equal efficiency. The protective potency of the immunogenic proteins against a challenge injection of bacteria in vivo correlated well with the antibody titer. Fragment #5 induced the highest level of protective activity, comparable to that by the full-length protein. These results support the use of fragment #5 to produce a vaccine against A. pleuropneumoniae challenge, since the small antigen peptide is easier to handle than is the full-length protein and can be expressed efficiently in heterologous expression systems.

How type II CRISPR-Cas establish immunity through Cas1-Cas2-mediated spacer integration.

PubMed

Xiao, Yibei; Ng, Sherwin; Nam, Ki Hyun; Ke, Ailong

2017-10-05

CRISPR (clustered regularly interspaced short palindromic repeats) and the nearby Cas (CRISPR-associated) operon establish an RNA-based adaptive immunity system in prokaryotes. Molecular memory is created when a short foreign DNA-derived prespacer is integrated into the CRISPR array as a new spacer. Whereas the RNA-guided CRISPR interference mechanism varies widely among CRISPR-Cas systems, the spacer integration mechanism is essentially identical. The conserved Cas1 and Cas2 proteins form an integrase complex consisting of two distal Cas1 dimers bridged by a Cas2 dimer. The prespacer is bound by Cas1-Cas2 as a dual-forked DNA, and the terminal 3'-OH of each 3' overhang serves as an attacking nucleophile during integration. The prespacer is preferentially integrated into the leader-proximal region of the CRISPR array, guided by the leader sequence and a pair of inverted repeats inside the CRISPR repeat. Spacer integration in the well-studied Escherichia coli type I-E CRISPR system also relies on the bacterial integration host factor. In type II-A CRISPR, however, Cas1-Cas2 alone integrates spacers efficiently in vitro; other Cas proteins (such as Cas9 and Csn2) have accessory roles in the biogenesis phase of prespacers. Here we present four structural snapshots from the type II-A system of Enterococcus faecalis Cas1 and Cas2 during spacer integration. Enterococcus faecalis Cas1-Cas2 selectively binds to a splayed 30-base-pair prespacer bearing 4-nucleotide 3' overhangs. Three molecular events take place upon encountering a target: first, the Cas1-Cas2-prespacer complex searches for half-sites stochastically, then it preferentially interacts with the leader-side CRISPR repeat, and finally, it catalyses a nucleophilic attack that connects one strand of the leader-proximal repeat to the prespacer 3' overhang. Recognition of the spacer half-site requires DNA bending and leads to full integration. We derive a mechanistic framework to explain the stepwise spacer integration process and the leader-proximal preference.

How Type II CRISPR-Cas establish immunity through Cas1-Cas2 mediated spacer integration

PubMed Central

Xiao, Yibei; Ng, Sherwin; Nam, Ki Hyun; Ke, Ailong

2017-01-01

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) and the nearby cas (CRISPR-associated) operon establish an RNA-based adaptive immunity system in prokaryotes1–5. Molecular memory is created when a short foreign DNA-derived prespacer is integrated into the CRISPR array as a new spacer6–9. Whereas the RNA-guided CRISPR interference mechanism varies widely among CRISPR-Cas systems, the spacer integration mechanism is essentially identical7–9. The conserved Cas1 and Cas2 proteins form an integrase complex consisting two distal Cas1 dimers bridged by a Cas2 dimer in the middle6,10. The prespacer is bound by Cas1-Cas2 as a dual forked DNA, and the terminal 3′-OH of each 3′-overhang serves as an attacking nucleophile during integration11–14. Importantly, the prespacer is preferentially integrated into the leader-proximal region of the CRISPR array1,7,10,15, guided by the leader sequence and a pair of inverted repeats (IRs) inside the CRISPR repeat7,15–20. Spacer integration in the most well-studied Escherichia coli Type I-E CRISPR system further relies on the bacterial Integration Host Factor (IHF)21,22. In Type II-A CRISPR, however, Cas1-Cas2 alone integrates spacer efficiently in vitro18; other Cas proteins (Cas9 and Csn2) play accessory roles in prespacer biogenesis17,23. Focusing on the Enterococcus faecalis Type II-A system24, here we report four structure snapshots of Cas1-Cas2 during spacer integration. EfaCas1-Cas2 selectively binds to a splayed 30-bp prespacer bearing 4-nt 3′-overhangs. Three molecular events take place upon encountering a target: Cas1-Cas2/prespacer first searches for half-sites stochastically, then preferentially interacts with the leader-side CRISPR repeat and catalyzes a nucleophilic attack that connects one strand of the leader-proximal repeat to the prespacer 3′-overhang. Recognition of the spacer half-site requires DNA bending and leads to full integration. We derive a mechanistic framework explaining the stepwise spacer integration process and the leader-proximal preference. PMID:28869593

Functional characteristics of the rat jaw muscles: daily muscle activity and fiber type composition.

PubMed

Kawai, Nobuhiko; Sano, Ryota; Korfage, Joannes A M; Nakamura, Saika; Tanaka, Eiji; van Wessel, Tim; Langenbach, Geerling E J; Tanne, Kazuo

2009-12-01

Skeletal muscles have a heterogeneous fiber type composition, which reflects their functional demand. The daily muscle use and the percentage of slow-type fibers have been shown to be positively correlated in skeletal muscles of larger animals but for smaller animals there is no information. The examination of this relationship in adult rats was the purpose of this study. We hypothesized a positive relationship between the percentage of fatigue-resistant fibers in each muscle and its total duration of use per day. Fourteen Wistar strain male rats (410-450 g) were used. A radio-telemetric device was implanted to record muscle activity continuously from the superficial masseter, deep masseter, anterior belly of digastric and anterior temporalis muscles. The degree of daily muscle use was quantified by the total duration of muscle activity per day (duty time) exceeding specified levels of the peak activity (2, 5, 20 and 50%). The fiber type composition of the muscles was examined by the myosin heavy chain content of the fibers by means of immunohistochemical staining. At lower activity levels (exceeding 2 and 5% of the peak activity), the duty time of the anterior belly of digastric muscle was significantly (P < 0.01) longer than those of the other muscles. The anterior belly of digastric muscle also contained the highest percentage of slow-type fibers (type I fiber and hybrid fiber co-expressing myosin heavy chain I + IIA) (ca. 11%; P < 0.05). By regression analysis for all four muscles, an inter-muscular comparison showed a positive relationship between the duty time (exceeding 50% of the peak activity) and the percentage of type IIX fibers (P < 0.05), which demonstrate intermediate physiological properties relative to type IIA and IIB fibers. For the jaw muscles of adult male rats, the variations of fiber type composition and muscle use suggest that the muscle containing the largest amounts of slow-type fibers (the anterior belly of digastric muscle) is mainly involved in low-amplitude activities and that the amount of type IIX fibers is positively related to the generation of large muscle forces, validating our hypothesis.

Cationic PAMAM dendrimers as pore-blocking binary toxin inhibitors.

PubMed

Förstner, Philip; Bayer, Fabienne; Kalu, Nnanya; Felsen, Susanne; Förtsch, Christina; Aloufi, Abrar; Ng, David Y W; Weil, Tanja; Nestorovich, Ekaterina M; Barth, Holger

2014-07-14

Dendrimers are unique highly branched macromolecules with numerous groundbreaking biomedical applications under development. Here we identified poly(amido amine) (PAMAM) dendrimers as novel blockers for the pore-forming B components of the binary anthrax toxin (PA63) and Clostridium botulinum C2 toxin (C2IIa). These pores are essential for delivery of the enzymatic A components of the internalized toxins from endosomes into the cytosol of target cells. We demonstrate that at low μM concentrations cationic PAMAM dendrimers block PA63 and C2IIa to inhibit channel-mediated transport of the A components, thereby protecting HeLa and Vero cells from intoxication. By channel reconstitution and high-resolution current recording, we show that the PAMAM dendrimers obstruct transmembrane PA63 and C2IIa pores in planar lipid bilayers at nM concentrations. These findings suggest a new potential role for the PAMAM dendrimers as effective polyvalent channel-blocking inhibitors, which can protect human target cells from intoxication with binary toxins from pathogenic bacteria.

Cationic PAMAM Dendrimers as Pore-Blocking Binary Toxin Inhibitors

PubMed Central

2015-01-01

Dendrimers are unique highly branched macromolecules with numerous groundbreaking biomedical applications under development. Here we identified poly(amido amine) (PAMAM) dendrimers as novel blockers for the pore-forming B components of the binary anthrax toxin (PA63) and Clostridium botulinum C2 toxin (C2IIa). These pores are essential for delivery of the enzymatic A components of the internalized toxins from endosomes into the cytosol of target cells. We demonstrate that at low μM concentrations cationic PAMAM dendrimers block PA63 and C2IIa to inhibit channel-mediated transport of the A components, thereby protecting HeLa and Vero cells from intoxication. By channel reconstitution and high-resolution current recording, we show that the PAMAM dendrimers obstruct transmembrane PA63 and C2IIa pores in planar lipid bilayers at nM concentrations. These findings suggest a new potential role for the PAMAM dendrimers as effective polyvalent channel-blocking inhibitors, which can protect human target cells from intoxication with binary toxins from pathogenic bacteria. PMID:24954629

The Finding of a Group IIE Phospholipase A2 Gene in a Specified Segment of Protobothrops flavoviridis Genome and Its Possible Evolutionary Relationship to Group IIA Phospholipase A2 Genes

PubMed Central

Yamaguchi, Kazuaki; Chijiwa, Takahito; Ikeda, Naoki; Shibata, Hiroki; Fukumaki, Yasuyuki; Oda-Ueda, Naoko; Hattori, Shosaku; Ohno, Motonori

2014-01-01

The genes encoding group IIE phospholipase A2, abbreviated as IIE PLA2, and its 5' and 3' flanking regions of Crotalinae snakes such as Protobothrops flavoviridis, P. tokarensis, P. elegans, and Ovophis okinavensis, were found and sequenced. The genes consisted of four exons and three introns and coded for 22 or 24 amino acid residues of the signal peptides and 134 amino acid residues of the mature proteins. These IIE PLA2s show high similarity to those from mammals and Colubridae snakes. The high expression level of IIE PLA2s in Crotalinae venom glands suggests that they should work as venomous proteins. The blast analysis indicated that the gene encoding OTUD3, which is ovarian tumor domain-containing protein 3, is located in the 3' downstream of IIE PLA2 gene. Moreover, a group IIA PLA2 gene was found in the 5' upstream of IIE PLA2 gene linked to the OTUD3 gene (OTUD3) in the P. flavoviridis genome. It became evident that the specified arrangement of IIA PLA2 gene, IIE PLA2 gene, and OTUD3 in this order is common in the genomes of humans to snakes. The present finding that the genes encoding various secretory PLA2s form a cluster in the genomes of humans to birds is closely related to the previous finding that six venom PLA2 isozyme genes are densely clustered in the so-called NIS-1 fragment of the P. flavoviridis genome. It is also suggested that venom IIA PLA2 genes may be evolutionarily derived from the IIE PLA2 gene. PMID:25529307

[Study on solid dispersion of copovidone-based tanshinone II(A)].

PubMed

Jiang, Yan-Rong; Zhang, Zhen-Hai; Xia, Hai-Jiang; Jia, Xiao-Bin

2013-01-01

To apply PVP-S630 in the preparation of tanshinone II(A) (TS II(A)) solid dispersion, in order to improve its dissolution in vitro and reduce the moisture absorption of the solid dispersion. Tanshinone II(A) solid dispersion was prepared by spray drying method. Such analytical methods as SEM, DSC, XRD were used to characterize their phases and detect their dissolution, moisture absorption and stability. In the solid dispersion prepared with tanshinone II(A) and copovidone with proportion of 1:10, tanshinone II(A) was scattered on the surface of the carrier in the amorphous form, with a dissolution in vitro up to 100% at 0.5 h and a lower moisture absorption than PVP-K30 solid dispersion prepared with the same proportion. After a three-month accelerated stability test, it showed no significant change in drug dissolution and content. The solid dispersion prepared with copovidone as the carrier can significantly improve the dissolution of tanshinone II(A), with a relatively low moisture absorption and high stability, thereby having a good prospect of application.

Gamma Knife surgery for clival epidural-osseous dural arteriovenous fistulas.

PubMed

Lee, Cheng-Chia; Chen, Ching-Jen; Chen, Shao-Ching; Yang, Huai-Che; Lin, Chung Jung; Wu, Chih-Chun; Chung, Wen-Yuh; Guo, Wan-Yuo; Hung-Chi Pan, David; Shiau, Cheng-Ying; Wu, Hsiu-Mei

2018-05-01

OBJECTIVE Clival epidural-osseous dural arteriovenous fistula (DAVF) is often associated with a large nidus, multiple arterial feeders, and complex venous drainage. In this study the authors report the outcomes of clival epidural-osseous DAVFs treated using Gamma Knife surgery (GKS). METHODS Thirteen patients with 13 clival epidural-osseous DAVFs were treated with GKS at the authors' institution between 1993 and 2015. Patient age at the time of GKS ranged from 38 to 76 years (median 55 years). Eight DAVFs were classified as Cognard Type I, 4 as Type IIa, and 1 as Type IIa+b. The median treatment volume was 17.6 cm 3 (range 6.2-40.3 cm 3 ). The median prescribed margin dose was 16.5 Gy (range 15-18 Gy). Clinical and radiological follow-ups were performed at 6-month intervals. Patient outcomes after GKS were categorized as 1) complete improvement, 2) partial improvement, 3) stationary, and 4) progression. RESULTS All 13 patients demonstrated symptomatic improvement, and on catheter angiography 12 of the 13 patients had complete obliteration and 1 patient had partial obliteration. The median follow-up period was 26 months (range 14-186 months). The median latency period from GKS to obliteration was 21 months (range 8-186 months). There was no intracranial hemorrhage during the follow-up period, and no deaths occurred. Two adverse events were observed following treatment, and 2 patients required repeat GKS treatment with eventual complete obliteration. CONCLUSIONS Gamma Knife surgery offers a safe and effective primary or adjuvant treatment modality for complex clival epidural-osseous DAVFs. All patients in this case series demonstrated symptomatic improvement, and almost all patients attained complete obliteration.

40 CFR 796.3500 - Hydrolysis as a function of pH at 25 °C.

Code of Federal Regulations, 2014 CFR

2014-07-01

... equivalent grade) shall be used to minimize biodegradation. ASTM Type IIA water is described in ASTM D 1193... experiments to eliminate or minimize biodegradation. Glassware can be sterilized in an autoclave or by any...

Characterization of Phytophthora infestans populations in Colombia: first report of the A2 mating type.

PubMed

Vargas, Angela M; Quesada Ocampo, Lina M; Céspedes, Maria Catalina; Carreño, Natalia; González, Adriana; Rojas, Alejandro; Zuluaga, A Paola; Myers, Kevin; Fry, William E; Jiménez, Pedro; Bernal, Adriana J; Restrepo, Silvia

2009-01-01

Phytophthora infestans, the causal agent of late blight in crops of the Solanaceae family, is one of the most important plant pathogens in Colombia. Not only are Solanum lycopersicum, and S. tuberosum at risk, but also several other solanaceous hosts (Physalis peruviana, S. betaceum, S. phureja, and S. quitoense) that have recently gained importance as new crops in Colombia may be at risk. Because little is known about the population structure of Phytophthora infestans in Colombia, we report here the phenotypic and molecular characterization of 97 isolates collected from these six different solanaceous plants in Colombia. All the isolates were analyzed for mating type, mitochondrial haplotypes, genotype for several microsatellites, and sequence of the internal transcribed spacer (ITS) region. This characterization identified a single individual of A2 mating type (from Physalis peruviana) for the first time in Colombia. All isolates had an ITS sequence that was at least 97% identical to the consensus sequence. Of the 97 isolates, 96 were mitochondrial haplotype IIa, with the single A2 isolate being Ia. All isolates were invariant for the microsatellites. Additionally, isolates collected from S. tuberosum and P. peruviana (64 isolates) were tested for: aggressiveness on both hosts, genotype for the isozymes (glucose-6-phosphate isomerase and peptidase), and restriction fragment length polymorphism fingerprint pattern as detected by RG57. Isolates from S. tuberosum were preferentially pathogenic on S. tuberosum, and isolates from P. peruviana were preferentially pathogenic on P. peruviana. The population from these two hosts was dominated by a single clonal lineage (59 of 64 individuals assayed), previously identified from Ecuador and Peru as EC-1. This lineage was mating type A1, IIa for mitochondrial DNA, invariant for two microsatellites, and invariant for both isozymes. The remaining four A1 isolates were in lineages very closely related to EC-1 (named EC-1.1, CO-1, and CO-2). The remaining lineage (the A2 mating type) had characteristics of the US-8 lineage (previously identified in Mexico, the United States, and Canada). These results have important epidemiological implications for the production of these two crops in Colombia.

Lactobacillus buchneri Genotyping on the Basis of Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) Locus Diversity

PubMed Central

Briner, Alexandra E.

2014-01-01

Clustered regularly interspaced short palindromic repeats (CRISPR) in combination with associated sequences (cas) constitute the CRISPR-Cas immune system, which uptakes DNA from invasive genetic elements as novel “spacers” that provide a genetic record of immunization events. We investigated the potential of CRISPR-based genotyping of Lactobacillus buchneri, a species relevant for commercial silage, bioethanol, and vegetable fermentations. Upon investigating the occurrence and diversity of CRISPR-Cas systems in Lactobacillus buchneri genomes, we observed a ubiquitous occurrence of CRISPR arrays containing a 36-nucleotide (nt) type II-A CRISPR locus adjacent to four cas genes, including the universal cas1 and cas2 genes and the type II signature gene cas9. Comparative analysis of CRISPR spacer content in 26 L. buchneri pickle fermentation isolates associated with spoilage revealed 10 unique locus genotypes that contained between 9 and 29 variable spacers. We observed a set of conserved spacers at the ancestral end, reflecting a common origin, as well as leader-end polymorphisms, reflecting recent divergence. Some of these spacers showed perfect identity with phage sequences, and many spacers showed homology to Lactobacillus plasmid sequences. Following a comparative analysis of sequences immediately flanking protospacers that matched CRISPR spacers, we identified a novel putative protospacer-adjacent motif (PAM), 5′-AAAA-3′. Overall, these findings suggest that type II-A CRISPR-Cas systems are valuable for genotyping of L. buchneri. PMID:24271175

Contour variations of the body and tail of the pancreas: evaluation with MDCT.

PubMed

Omeri, Ahmad Khalid; Matsumoto, Shunro; Kiyonaga, Maki; Takaji, Ryo; Yamada, Yasunari; Kosen, Kazuhisa; Mori, Hiromu; Miyake, Hidetoshi

2017-06-01

To analyze morphology/contour variations of the pancreatic body and tail in subjects free of pancreatic disease. We retrospectively reviewed triple-phase, contrast-enhanced multi-detector row computed tomography (3P-CE-MDCT) examinations of 449 patients who had no clinical or CT evidence of pancreatic diseases. These patients were evaluated for morphologic/contour variations of the pancreatic body and tail, which were classified into two types. In Type I, a portion of normal pancreatic parenchyma protrudes >1 cm in maximum diameter from the body or tail (Ia-anteriorly; Ib-posteriorly). Type II was defined as a morphologic anomaly of the pancreatic tail (IIa-globular; IIb-lobulated; IIc-tapered; IId-bifid). Thirty-eight (8.5%) out of 449 patients had body or tail variations. Of those, 23 patients showed Type I variant: Ia in 21 and Ib in two. Type II variant was identified in 15 patients: IIa in eight, IIb in two, IIc in two and IId in three. Protrusion of the anterior surface of the normal pancreas, especially in the tail, was the most frequently occurring variant. Recognizing the types and subtypes of morphology/contour variations of the pancreatic body and tail could help prevent misinterpretation of normal variants as pancreatic tumors on unenhanced MDCT.

Tanshinone IIA inhibits cervix carcinoma stem cells migration and invasion via inhibiting YAP transcriptional activity.

PubMed

Qin, Jinghao; Shi, Hongbing; Xu, Yanjie; Zhao, Fang; Wang, Qing

2018-06-14

This study aims to explore the effects and related mechanisms of Tanshinone IIA in cervix carcinoma (CC) stemness-like cells migration, invasion, stemness and chemotherapeutical sensitivity. Here, we found that Tanshinone IIA suppressed CC stemness-like cells migration and invasion in a concentration- and time-dependent manner. And consistent results were obtained in CC cells stemness characterized as the decrease of CC stemness markers expression and cells spheroid formation ability. Mechanistically, we found that Tanshinone IIA suppressed RNA binding protein HuR translocation from nuclear to cytoplasm, and thus reduced YAP mRNAs stability and transcriptional activity. Importantly, overexpression YAP-5SA rescued the inhibition of Tanshinone IIA on CC cells stemness. Furthermore, Tanshinone IIA enhanced adriamycin sensitivity in CC stemness-like cells, this effect was attenuated by YAP-5SA overexpression too. Therefore, Tanshinone IIA could suppress CC stemness-like cells migration and invasion by inhibiting YAP transcriptional activity. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

HPHT growth and x-ray characterization of high-quality type IIa diamond.

PubMed

Burns, R C; Chumakov, A I; Connell, S H; Dube, D; Godfried, H P; Hansen, J O; Härtwig, J; Hoszowska, J; Masiello, F; Mkhonza, L; Rebak, M; Rommevaux, A; Setshedi, R; Van Vaerenbergh, P

2009-09-09

The trend in synchrotron radiation (x-rays) is towards higher brilliance. This may lead to a very high power density, of the order of hundreds of watts per square millimetre at the x-ray optical elements. These elements are, typically, windows, polarizers, filters and monochromators. The preferred material for Bragg diffracting optical elements at present is silicon, which can be grown to a very high crystal perfection and workable size as well as rather easily processed to the required surface quality. This allows x-ray optical elements to be built with a sufficient degree of lattice perfection and crystal processing that they may preserve transversal coherence in the x-ray beam. This is important for the new techniques which include phase-sensitive imaging experiments like holo-tomography, x-ray photon correlation spectroscopy, coherent diffraction imaging and nanofocusing. Diamond has a lower absorption coefficient than silicon, a better thermal conductivity and lower thermal expansion coefficient which would make it the preferred material if the crystal perfection (bulk and surface) could be improved. Synthetic HPHT-grown (high pressure, high temperature) type Ib material can readily be produced in the necessary sizes of 4-8 mm square and with a nitrogen content of typically a few hundred parts per million. This material has applications in the less demanding roles such as phase plates: however, in a coherence-preserving beamline, where all elements must be of the same high quality, its quality is far from sufficient. Advances in HPHT synthesis methods have allowed the growth of type IIa diamond crystals of the same size as type Ib, but with substantially lower nitrogen content. Characterization of this high purity type IIa material has been carried out with the result that the crystalline (bulk) perfection of some of the HPHT-grown materials is approaching the quality required for the more demanding applications such as imaging applications and imaging applications with coherence preservation. The targets for further development of the type IIa diamond are size, crystal perfection, as measured by the techniques of white beam and monochromatic x-ray diffraction imaging (historically called x-ray topography), and also surface quality. Diamond plates extracted from the cubic growth sector furthest from the seed of the new low strain material produces no measurable broadening of the x-ray rocking curve width. One measures essentially the crystal reflectivity as defined by the intrinsic reflectivity curve (Darwin curve) width of a perfect crystal. In these cases the more sensitive technique of plane wave topography has been used to establish a local upper limit of the strain at the level of an 'effective misorientation' of 10(-7) rad.

Src-dependent Tyrosine Phosphorylation of Non-muscle Myosin Heavy Chain-IIA Restricts Listeria monocytogenes Cellular Infection*

PubMed Central

Almeida, Maria Teresa; Mesquita, Francisco S.; Cruz, Rui; Osório, Hugo; Custódio, Rafael; Brito, Cláudia; Vingadassalom, Didier; Martins, Mariana; Leong, John M.; Holden, David W.; Cabanes, Didier; Sousa, Sandra

2015-01-01

Bacterial pathogens often interfere with host tyrosine phosphorylation cascades to control host responses and cause infection. Given the role of tyrosine phosphorylation events in different human infections and our previous results showing the activation of the tyrosine kinase Src upon incubation of cells with Listeria monocytogenes, we searched for novel host proteins undergoing tyrosine phosphorylation upon L. monocytogenes infection. We identify the heavy chain of the non-muscle myosin IIA (NMHC-IIA) as being phosphorylated in a specific tyrosine residue in response to L. monocytogenes infection. We characterize this novel post-translational modification event and show that, upon L. monocytogenes infection, Src phosphorylates NMHC-IIA in a previously uncharacterized tyrosine residue (Tyr-158) located in its motor domain near the ATP-binding site. In addition, we found that other intracellular and extracellular bacterial pathogens trigger NMHC-IIA tyrosine phosphorylation. We demonstrate that NMHC-IIA limits intracellular levels of L. monocytogenes, and this is dependent on the phosphorylation of Tyr-158. Our data suggest a novel mechanism of regulation of NMHC-IIA activity relying on the phosphorylation of Tyr-158 by Src. PMID:25635050

Remarkable heterogeneity in myosin heavy-chain composition of the human young masseter compared with young biceps brachii.

PubMed

Osterlund, Catharina; Lindström, Mona; Thornell, Lars-Eric; Eriksson, Per-Olof

2012-10-01

Adult human jaw muscles differ from limb and trunk muscles in enzyme-histochemical fibre type composition. Recently, we showed that the human masseter and biceps differ in fibre type pattern already at childhood. The present study explored the myosin heavy-chain (MyHC) expression in the young masseter and biceps muscles by means of gel electrophoresis (GE) and immuno-histochemical (IHC) techniques. Plasticity in MyHC expression during life was evaluated by comparing the results with the previously reported data for adult muscles. In young masseter, GE identified MyHC-I, MyHC-IIa MyHC-IIx and small proportions of MyHC-fetal and MyHC-α cardiac. Western blots confirmed the presence of MyHC-I, MyHC-IIa and MyHC-IIx. IHC revealed in the masseter six isomyosins, MyHC-I, MyHC-IIa, MyHC-IIx, MyHC-fetal, MyHC α-cardiac and a previously not reported isoform, termed MyHC-IIx'. The majority of the masseter fibres co-expressed two to four isoforms. In the young biceps, both GE and IHC identified MyHC-I, MyHC-IIa and MyHC-IIx. MyHC-I predominated in both muscles. Young masseter showed more slow and less-fast and fetal MyHC than the adult and elderly masseter. These results provide evidence that the young masseter muscle is unique in MyHC composition, expressing MyHC-α cardiac and MyHC-fetal isoforms as well as hitherto unrecognized potential spliced isoforms of MyHC-fetal and MyHC-IIx. Differences in masseter MyHC expression between young adult and elderly suggest a shift from childhood to adulthood towards more fast contractile properties. Differences between masseter and biceps are proposed to reflect diverse evolutionary and developmental origins and confirm that the masseter and biceps present separate allotypes of muscle.

DNA G-segment bending is not the sole determinant of topology simplification by type II DNA topoisomerases.

PubMed

Thomson, Neil H; Santos, Sergio; Mitchenall, Lesley A; Stuchinskaya, Tanya; Taylor, James A; Maxwell, Anthony

2014-08-21

DNA topoisomerases control the topology of DNA. Type II topoisomerases exhibit topology simplification, whereby products of their reactions are simplified beyond that expected based on thermodynamic equilibrium. The molecular basis for this process is unknown, although DNA bending has been implicated. To investigate the role of bending in topology simplification, the DNA bend angles of four enzymes of different types (IIA and IIB) were measured using atomic force microscopy (AFM). The enzymes tested were Escherichia coli topo IV and yeast topo II (type IIA enzymes that exhibit topology simplification), and Methanosarcina mazei topo VI and Sulfolobus shibatae topo VI (type IIB enzymes, which do not). Bend angles were measured using the manual tangent method from topographical AFM images taken with a novel amplitude-modulated imaging mode: small amplitude small set-point (SASS), which optimises resolution for a given AFM tip size and minimises tip convolution with the sample. This gave improved accuracy and reliability and revealed that all 4 topoisomerases bend DNA by a similar amount: ~120° between the DNA entering and exiting the enzyme complex. These data indicate that DNA bending alone is insufficient to explain topology simplification and that the 'exit gate' may be an important determinant of this process.

DNA G-segment bending is not the sole determinant of topology simplification by type II DNA topoisomerases

NASA Astrophysics Data System (ADS)

Thomson, Neil H.; Santos, Sergio; Mitchenall, Lesley A.; Stuchinskaya, Tanya; Taylor, James A.; Maxwell, Anthony

2014-08-01

DNA topoisomerases control the topology of DNA. Type II topoisomerases exhibit topology simplification, whereby products of their reactions are simplified beyond that expected based on thermodynamic equilibrium. The molecular basis for this process is unknown, although DNA bending has been implicated. To investigate the role of bending in topology simplification, the DNA bend angles of four enzymes of different types (IIA and IIB) were measured using atomic force microscopy (AFM). The enzymes tested were Escherichia coli topo IV and yeast topo II (type IIA enzymes that exhibit topology simplification), and Methanosarcina mazei topo VI and Sulfolobus shibatae topo VI (type IIB enzymes, which do not). Bend angles were measured using the manual tangent method from topographical AFM images taken with a novel amplitude-modulated imaging mode: small amplitude small set-point (SASS), which optimises resolution for a given AFM tip size and minimises tip convolution with the sample. This gave improved accuracy and reliability and revealed that all 4 topoisomerases bend DNA by a similar amount: ~120° between the DNA entering and exiting the enzyme complex. These data indicate that DNA bending alone is insufficient to explain topology simplification and that the `exit gate' may be an important determinant of this process.

Soft x-ray measurements using photoconductive type-IIa and single-crystal chemical vapor deposited diamond detectors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moore, A. S.; Bentley, C. D.; Foster, J. M.

2008-10-15

Photoconductive detectors (PCDs) are routinely used alongside vacuum x-ray diodes (XRDs) to provide an alternative x-ray flux measurement at laser facilities such as HELEN at AWE Aldermaston, UK, and Omega at the Laboratory for Laser Energetics. To evaluate diamond PCDs as an alternative to XRD arrays, calibration measurements made at the National Synchrotron Light Source (NSLS) at Brookhaven National Laboratory are used to accurately calculate the x-ray flux from a laser-heated target. This is compared to a flux measurement using the Dante XRD diagnostic. Estimates indicate that the photoinduced conductivity from measurements made at Omega are too large, and calculationsmore » using the radiometric calibrations made at the NSLS agree with this hypothesis. High-purity, single-crystal, chemical vapor deposited (CVD) diamond samples are compared to natural type-IIa PCDs and show promising high resistivity effects, the corollary of which preliminary results show is a slower response time.« less

Generation of transgenic corn-derived Actinobacillus pleuropneumoniae ApxIIA fused with the cholera toxin B subunit as a vaccine candidate

PubMed Central

Shin, Min-Kyoung; Jung, Myung Hwan; Lee, Won-Jung; Choi, Pil Son; Jang, Yong-Suk

2011-01-01

Corn, one of the most important forage crops worldwide, has proven to be a useful expression vehicle due to the availability of established transformation procedures for this well-studied plant. The exotoxin Apx, a major virulence factor, is recognized as a common antigen of Actinobacillus (A.) pleuropneumoniae, the causative agent of porcine pleuropneumonia. In this study, a cholera toxin B (CTB)-ApxIIA#5 fusion protein and full-size ApxIIA expressed in corn seed, as a subunit vaccine candidate, were observed to induce Apx-specific immune responses in mice. These results suggest that transgenic corn-derived ApxIIA and CTB-ApxIIA#5 proteins are potential vaccine candidates against A. pleuropneumoniae infection. PMID:22122907

Voluntary wheel running increases satellite cell abundance and improves recovery from disuse in gastrocnemius muscles from mice.

PubMed

Brooks, Matthew J; Hajira, Ameena; Mohamed, Junaith S; Alway, Stephen E

2018-06-01

Reloading of atrophied muscles after hindlimb suspension unloading (HSU) can induce injury and prolong recovery. Low-impact exercise, such as voluntary wheel running, has been identified as a nondamaging rehabilitation therapy in rodents, but its effects on muscle function, morphology, and satellite cell activity after HSU are unclear. This study tested the hypothesis that low-impact wheel running would increase satellite cell proliferation and improve recovery of muscle structure and function after HSU in mice. Young adult male and female C57BL/6 mice ( n = 6/group) were randomly placed into five groups. These included HSU without recovery (HSU), normal ambulatory recovery for 14 days after HSU (HSU+NoWR), and voluntary wheel running recovery for 14 days after HSU (HSU+WR). Two control groups were used: nonsuspended mouse cage controls (Control) and voluntary wheel running controls (ControlWR). Satellite cell activation was evaluated by providing mice 5-bromo-2'-deoxyuridine (BrdU) in their drinking water. As expected, HSU significantly reduced in vivo maximal force, decreased in vivo fatigability, and decreased type I and IIa myosin heavy chain (MHC) abundance in plantarflexor muscles. HSU+WR mice significantly improved plantarflexor fatigue resistance, increased type I and IIa MHC abundance, increased fiber cross-sectional area, and increased the percentage of type I and IIA muscle fibers in the gastrocnemius muscle. HSU+WR mice also had a significantly greater percentage of BrdU-positive and Pax 7-positive nuclei inside muscle fibers and a greater MyoD-to-Pax 7 protein ratio compared with HSU+NoWR mice. The mechanotransduction protein Yes-associated protein (YAP) was elevated with reloading after HSU, but HSU+WR mice had lower levels of the inactive phosphorylated YAP serine127 , which may have contributed to increased satellite cell activation with reloading after HSU. These results indicate that voluntary wheel running increased YAP signaling and satellite cell activity after HSU and this was associated with improved recovery. NEW & NOTEWORTHY Although satellite cell involvement in muscle remodeling has been challenged, the data in this study suggest that voluntary wheel running increased satellite cell activity and suppressed Yes-associated protein (YAP) protein relative to no wheel running and this was associated with improved muscle recovery of force, fatigue resistance, expression of type I myosin heavy chain, and greater fiber cross-sectional area after disuse.

Ling classification describes endoscopic progressive process of achalasia and successful peroral endoscopy myotomy prevents endoscopic progression of achalasia.

PubMed

Zhang, Wen-Gang; Linghu, En-Qiang; Chai, Ning-Li; Li, Hui-Kai

2017-05-14

To verify the hypothesis that the Ling classification describes the endoscopic progressive process of achalasia and determine the ability of successful peroral endoscopic myotomy (POEM) to prevent endoscopic progression of achalasia. We retrospectively reviewed the endoscopic findings, symptom duration, and manometric data in patients with achalasia. A total of 359 patients (197 women, 162 men) with a mean age of 42.1 years (range, 12-75 years) were evaluated. Symptom duration ranged from 2 to 360 mo, with a median of 36 mo. Patients were classified with Ling type I ( n = 119), IIa ( n = 106), IIb ( n = 60), IIc ( n = 60), or III ( n = 14), according to the Ling classification. Of the 359 patients, 349 underwent POEM, among whom 21 had an endoscopic follow-up for more than 2 years. Pre-treatment and post-treatment Ling classifications of these 21 patients were compared. Symptom duration increased significantly with increasing Ling classification (from I to III) ( P < 0.05), whereas lower esophageal sphincter pressure decreased with increasing Ling type (from I to III) ( P < 0.05). There was no difference in sex ratio or onset age among the Ling types, although the age at time of diagnosis was higher in Ling types IIc and III than in Ling types I, IIa, and IIb. Of the 21 patients, 19 underwent high-resolution manometry both before and after treatment. The mean preoperative and postoperative lower esophageal sphincter pressure were 34.6 mmHg (range, 15.3-59.4 mmHg) and 15.0 mmHg (range, 2.1-21.6 mmHg), respectively, indicating a statistically significant decrease after POEM. All of the 21 patients were treated successfully by POEM (postoperative Eckardt score ≤ 3) and still had the same Ling type during a mean follow-up period of 37.8 mo (range, 24-51 mo). The Ling classification represents the endoscopic progressive process of achalasia and may be able to serve as an endoscopic assessment criterion for achalasia. Successful POEM (Eckardt score ≤ 3) seems to have the ability to prevent endoscopic evolvement of achalasia. However, studies with larger populations are warranted to confirm our findings.

Two hybridization events define the population structure of Trypanosoma cruzi.

PubMed

Westenberger, Scott J; Barnabé, Christian; Campbell, David A; Sturm, Nancy R

2005-10-01

Genetic variation in Trypanosoma cruzi is likely a key determinant in transmission and pathogenesis of Chagas disease. We have examined nine loci as markers for the extant T. cruzi strains. Four distinct alleles were found for each locus, corresponding to the sequence classes present in the homozygous discrete typing units (DTUs) I, IIa, IIb, and IIc. The alleles in DTUs IIa and IIc showed a spectrum of polymorphism ranging from DTU I-like to DTU IIb-like, in addition to DTU-specific sequence variation. DTUs IId and IIe were indistinguishable, showing DTU homozygosity at one locus and heterozygosity with DTU IIb and IIc allelic sequences at eight loci. Recombination between the DTU IIb and IIc alleles is evidenced from mosaic polymorphisms. These data imply that two discrete hybridization events resulted in the formation of the current DTUs. We propose a model in which a fusion between ancestral DTU I and IIb strains gave rise to a heterozygous hybrid that homogenized its genome to become the homozygous progenitor of DTUs IIa and IIc. The second hybridization between DTU IIb and IIc strains that generated DTUs IId and IIe resulted in extensive heterozygosity with subsequent recombination of parental genotypes.

Crystal structure of MboIIA methyltransferase.

PubMed

Osipiuk, Jerzy; Walsh, Martin A; Joachimiak, Andrzej

2003-09-15

DNA methyltransferases (MTases) are sequence-specific enzymes which transfer a methyl group from S-adenosyl-L-methionine (AdoMet) to the amino group of either cytosine or adenine within a recognized DNA sequence. Methylation of a base in a specific DNA sequence protects DNA from nucleolytic cleavage by restriction enzymes recognizing the same DNA sequence. We have determined at 1.74 A resolution the crystal structure of a beta-class DNA MTase MboIIA (M.MboIIA) from the bacterium Moraxella bovis, the smallest DNA MTase determined to date. M.MboIIA methylates the 3' adenine of the pentanucleotide sequence 5'-GAAGA-3'. The protein crystallizes with two molecules in the asymmetric unit which we propose to resemble the dimer when M.MboIIA is not bound to DNA. The overall structure of the enzyme closely resembles that of M.RsrI. However, the cofactor-binding pocket in M.MboIIA forms a closed structure which is in contrast to the open-form structures of other known MTases.

Indirect myosin immunocytochemistry for the identification of fibre types in equine skeletal muscle

NASA Technical Reports Server (NTRS)

Sinha, A. K.; Rose, R. J.; Pozgaj, I.; Hoh, J. F.

1992-01-01

The histochemical ATPase method for muscle fibre typing was first described by Brooke and Kaiser in 1970. However, problems have been found with the subdivision of type II fibres using this technique. To determine whether indirect myosin immunocytochemistry using anti-slow (5-4D), anti-fast (1A10) and anti-fast red (5-2B) monoclonal antibodies with cross reactivity for type I, II and IIa fibres, respectively, in a number of species, could identify three fibre types in equine skeletal muscle, data on fibre type composition and fibre size obtained using the two different techniques were compared. Results indicate that different myosin heavy chains can coexist in single equine muscle fibres. Type I and type II fibres were identified by immunocytochemistry, but subdivision of type II fibres was not possible. Although the percentage of type I and type II fibres was not significantly different for the two techniques, a few fibres reacted with both the 1A10 and 5-4D antibodies.

Native defect properties and p -type doping efficiency in group-IIA doped wurtzite AlN

NASA Astrophysics Data System (ADS)

Zhang, Yong; Liu, Wen; Niu, Hanben

2008-01-01

Using the first-principles full-potential linearized augmented plane-wave (FPLAPW) method based on density functional theory (DFT), we have investigated the native defect properties and p -type doping efficiency in AlN doped with group-IIA elements such as Be, Mg, and Ca. It is shown that nitrogen vacancies (VN) have low formation energies and introduce deep donor levels in wurtzite AlN, while in zinc blende AlN and GaN, these levels are reported to be shallow. The calculated acceptor levels γ(0/-) for substitutional Be (BeAl) , Mg (MgAl) , and Ca (CaAl) are 0.48, 0.58, and 0.95eV , respectively. In p -type AlN, Be interstitials (Bei) , which act as donors, have low formation energies, making them a likely compensating center in the case of acceptor doping. Whereas, when N-rich growth conditions are applied, Bei are energetically not favorable. It is found that p -type doping efficiency of substitutional Be, Mg, and Ca impurities in w-AlN is affected by atomic size and electronegativity of dopants. Among the three dopants, Be may be the best candidate for p -type w-AlN . N-rich growth conditions help us to increase the concentration of BeAl , MgAl , and CaAl .

Breast cancer metastasis to the stomach resembling early gastric cancer.

PubMed

Eo, Wan Kyu

2008-12-01

Breast cancer metastases to the stomach are infrequent, with an estimated incidence rate of approximately 0.3%. Gastric metastases usually are derived from lobular rather than from ductal breast cancer. The most frequent type of a breast cancer metastasis as seen on endoscopy to the stomach is linitis plastica; features of a metastatic lesion that resemble early gastric cancer (EGC) are extremely rare. In this report, we present a case of a breast cancer metastasis to the stomach from an infiltrating ductal carcinoma (IDC) of the breast in a 48-year-old woman. The patient had undergone a left modified radical mastectomy with axillary dissection nine years prior. A gastric endoscopy performed for evaluation of nausea and anorexia showed the presence of a slightly elevated mucosal lesion in the cardia, suggestive of a type IIa EGC. A histological examination revealed nests of a carcinoma in the subepithelial lymphatics, and immunohistochemical staining for estrogen receptor was positive. This is an extremely rare case with features of type IIa EGC, but the lesion was finally identified as a cancer metastasis to the cardia of the stomach from an IDC of the breast.

Tanshinon IIA injection accelerates tissue expansion by reducing the formation of the fibrous capsule.

PubMed

Yu, Qingxiong; Sheng, Lingling; Yang, Mei; Zhu, Ming; Huang, Xiaolu; Li, Qingfeng

2014-01-01

The tissue expansion technique has been applied to obtain new skin tissue to repair large defects in clinical practice. The implantation of tissue expander could initiate a host response to foreign body (FBR), which leads to fibrotic encapsulation around the expander and prolongs the period of tissue expansion. Tanshinon IIA (Tan IIA) has been shown to have anti-inflammation and immunoregulation effect. The rat tissue expansion model was used in this study to observe whether Tan IIA injection systematically could inhibit the FBR to reduce fibrous capsule formation and accelerate the process of tissue expansion. Forty-eight rats were randomly divided into the Tan IIA group and control group with 24 rats in each group. The expansion was conducted twice a week to maintain a capsule pressure of 60 mmHg. The expansion volume and expanded area were measured. The expanded tissue in the two groups was harvested, and histological staining was performed; proinflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) and transforming growth factor-β (TGF-β) were examined. The expansion volume and the expanded area in the Tan IIA group were greater than that of the control group. The thickness of the fibrous capsule in the Tan IIA group was reduced with no influence on the normal skin regeneration. Decreased infiltration of macrophages, lower level of TNF-α, IL-6, IL-1β and TGF-β, less proliferating myofibroblasts and enhanced neovascularization were observed in the Tan IIA group. Our findings indicated that the Tan IIA injection reduced the formation of the fibrous capsule and accelerated the process of tissue expansion by inhibiting the FBR.

Penrose limits and spin chains in the GJV/CS-SYM duality

NASA Astrophysics Data System (ADS)

Araujo, Thiago; Itsios, Georgios; Nastase, Horatiu; Colgáin, Eoin Ó.

2017-12-01

We examine Penrose limits of the duality proposed by Guarino, Jafferis and Varela between a type IIA massive background of the type of a warped, squashed AdS 4 × S 6, and a 2+1 dimensional IR fixed point of N=8 super Yang-Mills deformed by Chern-Simons terms to N=2 supersymmetry. One type of Penrose limit for closed strings corresponds to a large charge closed spin chain, and another, for open strings on giant graviton D-branes, corresponds to an open spin chain on sub-determinant operators. For the first limit, we find that like in the ABJM case, there are functions f a ( λ) that interpolate between the perturbative and nonperturbative (string) regions for the magnon energy. For the second, we are unable to match the gravity result with the expected field theory result, making this model more interesting than ones with more supersymmetry.

High-throughput genotyping assay for the large-scale genetic characterization of Cryptosporidium parasites from human and bovine samples.

PubMed

Abal-Fabeiro, J L; Maside, X; Llovo, J; Bello, X; Torres, M; Treviño, M; Moldes, L; Muñoz, A; Carracedo, A; Bartolomé, C

2014-04-01

The epidemiological study of human cryptosporidiosis requires the characterization of species and subtypes involved in human disease in large sample collections. Molecular genotyping is costly and time-consuming, making the implementation of low-cost, highly efficient technologies increasingly necessary. Here, we designed a protocol based on MALDI-TOF mass spectrometry for the high-throughput genotyping of a panel of 55 single nucleotide variants (SNVs) selected as markers for the identification of common gp60 subtypes of four Cryptosporidium species that infect humans. The method was applied to a panel of 608 human and 63 bovine isolates and the results were compared with control samples typed by Sanger sequencing. The method allowed the identification of species in 610 specimens (90·9%) and gp60 subtype in 605 (90·2%). It displayed excellent performance, with sensitivity and specificity values of 87·3 and 98·0%, respectively. Up to nine genotypes from four different Cryptosporidium species (C. hominis, C. parvum, C. meleagridis and C. felis) were detected in humans; the most common ones were C. hominis subtype Ib, and C. parvum IIa (61·3 and 28·3%, respectively). 96·5% of the bovine samples were typed as IIa. The method performs as well as the widely used Sanger sequencing and is more cost-effective and less time consuming.

Molecular Characterization of Cryptosporidium spp. in Children from Mexico

PubMed Central

Valenzuela, Olivia; González-Díaz, Mariana; Garibay-Escobar, Adriana; Burgara-Estrella, Alexel; Cano, Manuel; Durazo, María; Bernal, Rosa M.; Hernandez, Jesús; Xiao, Lihua

2014-01-01

Cryptosporidiosis is a parasitic disease caused by Cryptosporidium spp. In immunocompetent individuals, it usually causes an acute and self-limited diarrhea; in infants, infection with Cryptosporidium spp. can cause malnutrition and growth retardation, and declined cognitive ability. In this study, we described for the first time the distribution of C. parvum and C. hominis subtypes in 12 children in Mexico by sequence characterization of the 60-kDa glycoprotein (GP60) gene of Cryptosporidium. Altogether, 7 subtypes belonging to 4 subtype families of C. hominis (Ia, Ib, Id and Ie) and 1 subtype family of C. parvum (IIa) were detected, including IaA14R3, IaA15R3, IbA10G2, IdA17, IeA11G3T3, IIaA15G2R1 and IIaA16G1R1. The frequency of the subtype families and subtypes in the samples analyzed in this study differed from what was observed in other countries. PMID:24755606

Molecular characterization of Cryptosporidium spp. in children from Mexico.

PubMed

Valenzuela, Olivia; González-Díaz, Mariana; Garibay-Escobar, Adriana; Burgara-Estrella, Alexel; Cano, Manuel; Durazo, María; Bernal, Rosa M; Hernandez, Jesús; Xiao, Lihua

2014-01-01

Cryptosporidiosis is a parasitic disease caused by Cryptosporidium spp. In immunocompetent individuals, it usually causes an acute and self-limited diarrhea; in infants, infection with Cryptosporidium spp. can cause malnutrition and growth retardation, and declined cognitive ability. In this study, we described for the first time the distribution of C. parvum and C. hominis subtypes in 12 children in Mexico by sequence characterization of the 60-kDa glycoprotein (GP60) gene of Cryptosporidium. Altogether, 7 subtypes belonging to 4 subtype families of C. hominis (Ia, Ib, Id and Ie) and 1 subtype family of C. parvum (IIa) were detected, including IaA14R3, IaA15R3, IbA10G2, IdA17, IeA11G3T3, IIaA15G2R1 and IIaA16G1R1. The frequency of the subtype families and subtypes in the samples analyzed in this study differed from what was observed in other countries.

Morphologic classification of the right auricule on 256-slice computed tomography.

PubMed

Li, Cai-Ying; Gao, Bu-Lang; Pan, Tong; Xiang, Cheng; Liu, Xiao-Wei; Yang, Hai-Qing; Yi, Lan-Ying; Liao, Qi-Bin

2017-06-01

To investigate the shape of right auricule on 256-slice computed tomography (CT). Five hundred people (250 men, age range 16-84 years) who had cardiac multidetector CT angiography were recruited in this study. All patients had normal sinus rhythm with normal blood pressure (<140/90 mmHg for systolic/diastolic pressure). The morphology of the right auricule was studied and compared after reconstruction of the raw images. All patients successfully had cardiac CT angiography (100%), and the right auricule morphology was divided into five types and nine subtypes, including Type I of triangular shape (Ia and Ib), Type II of M shape (IIa and IIb), Type III of L shape (IIIa and IIIb), Type IV of reverse L shape (IVa and IVb), and Type V of balanced shape. The most common type of right auricule is Type IV (28.4%) followed by Type II (24.0%), whereas the least common is Type V (11.0%). Type Ia was present significantly (P < 0.0001) more frequently in females than in males, whereas Type IIa significantly (P = 0.042) more frequently in males than females. No other significant (P > 0.05) sex difference existed in the constitution ratio of the types. The normal angle was greater in Type Ib than in Ia. The greater the normal angle in Type I, the greater the deviation of the right auricule tip towards the left. A good understanding of the right auricule anatomical morphology can better guide atrial pacing, radiofrequency ablation and other surgical procedures while preventing possible intra-procedural complications.

IGF-I treatment improves the functional properties of fast- and slow-twitch skeletal muscles from dystrophic mice.

PubMed

Lynch, G S; Cuffe, S A; Plant, D R; Gregorevic, P

2001-04-01

Although insulin-like growth factor-I (IGF-I) has been proposed for use by patients suffering from muscle wasting conditions, few studies have investigated the functional properties of dystrophic skeletal muscle following IGF-I treatment. 129P1 ReJ-Lama2(dy) (129 ReJ dy/dy) dystrophic mice suffer from a deficiency in the structural protein, laminin, and exhibit severe muscle wasting and weakness. We tested the hypothesis that 4 weeks of IGF-I treatment ( approximately 2 mg/kg body mass, 50 g/h via mini-osmotic pump, subcutaneously) would increase the mass and force producing capacity of skeletal muscles from dystrophic mice. IGF-I treatment increased the mass of the extensor digitorum longus (EDL) and soleus muscles of dystrophic mice by 20 and 29%, respectively, compared with untreated dystrophic mice (administered saline-vehicle only). Absolute maximum force (P(o)) of the EDL and soleus muscle was increased by 40 and 32%, respectively, following IGF-I treatment. Specific P(o) (sP(o)) was increased by 23% in the EDL muscles of treated compared with untreated mice, but in the soleus muscle sP(o) was unchanged. IGF-I treatment increased the proportion of type IIB and type IIA fibres and decreased the proportion of type I fibres in the EDL muscles of dystrophic mice. In the soleus muscles of dystrophic mice, IGF-I treatment increased the proportion of type IIA fibres and decreased the proportion of type I fibres. Average fibre cross-sectional area was increased in the EDL and soleus muscles of treated compared with untreated mice. We conclude that IGF-I treatment ameliorates muscle wasting and improves the functional properties of skeletal muscles of dystrophic mice. The findings have important implications for the role of IGF-I in ameliorating muscle wasting associated with the muscular dystrophies.

30 CFR 57.22307 - Methane monitors (II-A mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Methane monitors (II-A mines). 57.22307 Section... Standards for Methane in Metal and Nonmetal Mines Equipment § 57.22307 Methane monitors (II-A mines). (a) Methane monitors shall be installed on continuous mining machines, longwall mining systems, bench and face...

30 CFR 57.22307 - Methane monitors (II-A mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Methane monitors (II-A mines). 57.22307 Section... Standards for Methane in Metal and Nonmetal Mines Equipment § 57.22307 Methane monitors (II-A mines). (a) Methane monitors shall be installed on continuous mining machines, longwall mining systems, bench and face...

The Compact Mutation of Myostatin Causes a Glycolytic Shift in the Phenotype of Fast Skeletal Muscles

PubMed Central

Baán, Júlia Aliz; Kocsis, Tamás; Keller-Pintér, Anikó; Müller, Géza; Zádor, Ernö; Dux, László

2013-01-01

Myostatin is an important negative regulator of skeletal muscle growth. The hypermuscular Compact (Cmpt) mice carry a 12-bp natural mutation in the myostatin propeptide, with additional modifier genes being responsible for the phenotype. Muscle cellularity of the fast-type tibialis anterior (TA) and extensor digitorum longus (EDL) as well as the mixed-type soleus (SOL) muscles of Cmpt and wild-type mice was examined by immunohistochemical staining of the myosin heavy chain (MHC) proteins. In addition, transcript levels of MHC isoforms were quantified by qPCR. Based on our results, all investigated muscles of Cmpt mice were significantly larger compared with that of wild-type mice, as characterized by fiber hyperplasia of different grades. Fiber hypertrophy was not present in TA; however, EDL muscles showed specific IIB fiber hypertrophy while the (I and IIA) fibers of SOL muscles were generally hypertrophied. Both the fast TA and EDL muscles of Cmpt mice contained significantly more glycolytic IIB fibers accompanied by a decreased number of IIX and IIA fibers; however, this was not the case for SOL muscles. In summary, despite the variances found in muscle cellularity between the different myostatin mutant mice, similar glycolytic shifts were observed in Cmpt fast muscles as in muscles from myostatin knockout mice. PMID:23979839

30 CFR 57.22219 - Seals and stoppings (II-A mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Seals and stoppings (II-A mines). 57.22219... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22219 Seals and stoppings (II-A mines... fire resistance. (b) Seals shall be of substantial construction. Exposed surfaces on the fresh air side...

30 CFR 57.22219 - Seals and stoppings (II-A mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Seals and stoppings (II-A mines). 57.22219... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22219 Seals and stoppings (II-A mines... fire resistance. (b) Seals shall be of substantial construction. Exposed surfaces on the fresh air side...

30 CFR 57.22311 - Electrical cables (II-A mines).

Code of Federal Regulations, 2013 CFR

2013-07-01

... Standards for Methane in Metal and Nonmetal Mines Equipment § 57.22311 Electrical cables (II-A mines). Only jacketed electrical cables accepted or approved by MSHA as flame resistant shall be used to supply power to... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Electrical cables (II-A mines). 57.22311...

30 CFR 57.22311 - Electrical cables (II-A mines).

Code of Federal Regulations, 2012 CFR

2012-07-01

... Standards for Methane in Metal and Nonmetal Mines Equipment § 57.22311 Electrical cables (II-A mines). Only jacketed electrical cables accepted or approved by MSHA as flame resistant shall be used to supply power to... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Electrical cables (II-A mines). 57.22311...

30 CFR 57.22311 - Electrical cables (II-A mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... Standards for Methane in Metal and Nonmetal Mines Equipment § 57.22311 Electrical cables (II-A mines). Only jacketed electrical cables accepted or approved by MSHA as flame resistant shall be used to supply power to... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Electrical cables (II-A mines). 57.22311...

30 CFR 57.22311 - Electrical cables (II-A mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... Standards for Methane in Metal and Nonmetal Mines Equipment § 57.22311 Electrical cables (II-A mines). Only jacketed electrical cables accepted or approved by MSHA as flame resistant shall be used to supply power to... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Electrical cables (II-A mines). 57.22311...

30 CFR 57.22311 - Electrical cables (II-A mines).

Code of Federal Regulations, 2014 CFR

2014-07-01

... Standards for Methane in Metal and Nonmetal Mines Equipment § 57.22311 Electrical cables (II-A mines). Only jacketed electrical cables accepted or approved by MSHA as flame resistant shall be used to supply power to... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Electrical cables (II-A mines). 57.22311...

Crystal structure of MboIIA methyltransferase.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Osipiuk, J.; Walsh, M. A.; Joachimiak, A.

2003-09-15

DNA methyltransferases (MTases) are sequence-specific enzymes which transfer a methyl group from S-adenosyl-L-methionine (AdoMet) to the amino group of either cytosine or adenine within a recognized DNA sequence. Methylation of a base in a specific DNA sequence protects DNA from nucleolytic cleavage by restriction enzymes recognizing the same DNA sequence. We have determined at 1.74 {angstrom} resolution the crystal structure of a {beta}-class DNA MTase MboIIA (M {center_dot} MboIIA) from the bacterium Moraxella bovis, the smallest DNA MTase determined to date. M {center_dot} MboIIA methylates the 3' adenine of the pentanucleotide sequence 5'-GAAGA-3'. The protein crystallizes with two molecules inmore » the asymmetric unit which we propose to resemble the dimer when M {center_dot} MboIIA is not bound to DNA. The overall structure of the enzyme closely resembles that of M {center_dot} RsrI. However, the cofactor-binding pocket in M {center_dot} MboIIA forms a closed structure which is in contrast to the open-form structures of other known MTases.« less

International investment agreements and public health: neutralizing a threat through treaty drafting

PubMed Central

2014-01-01

Abstract The high profile investment claims filed by Philip Morris challenging Uruguayan and Australian measures that restrict advertising and logos on tobacco packaging awakened the public health community to the existence and potential detrimental impact of international investment agreements (IIAs). More recently, Eli Lilly challenged Canada’s invalidation of a pharmaceutical patent under an IIA. All of the cases claim that the intellectual property rights of the investor were infringed. As a result of these cases, many commentators and activists view IIAs as a threat to public health and have lobbied against their inclusion in ongoing trade negotiations. This article does not argue against IIAs. Instead, it seeks to demonstrate how more sophisticated treaty drafting can neutralize the threat to public health. In this regard, the article seeks to engage members of the public health community as campaigners not against IIAs but as advocates of better treaty drafting to ensure that IIAs do not infringe upon the right of a nation to take non-discriminatory measures for the promotion and protection of the health of their populations. PMID:25110377

International investment agreements and public health: neutralizing a threat through treaty drafting.

PubMed

Mercurio, Bryan

2014-07-01

The high profile investment claims filed by Philip Morris challenging Uruguayan and Australian measures that restrict advertising and logos on tobacco packaging awakened the public health community to the existence and potential detrimental impact of international investment agreements (IIAs). More recently, Eli Lilly challenged Canada's invalidation of a pharmaceutical patent under an IIA. All of the cases claim that the intellectual property rights of the investor were infringed. As a result of these cases, many commentators and activists view IIAs as a threat to public health and have lobbied against their inclusion in ongoing trade negotiations. This article does not argue against IIAs. Instead, it seeks to demonstrate how more sophisticated treaty drafting can neutralize the threat to public health. In this regard, the article seeks to engage members of the public health community as campaigners not against IIAs but as advocates of better treaty drafting to ensure that IIAs do not infringe upon the right of a nation to take non-discriminatory measures for the promotion and protection of the health of their populations.

Diversity and regulation of plant Ca2+ pumps: insights from expression in yeast

NASA Technical Reports Server (NTRS)

Sze, H.; Liang, F.; Hwang, I.; Curran, A. C.; Harper, J. F.; Evans, M. L. (Principal Investigator)

2000-01-01

The spatial and temporal regulation of calcium concentration in plant cells depends on the coordinate activities of channels and active transporters located on different organelles and membranes. Several Ca2+ pumps have been identified and characterized by functional expression of plant genes in a yeast mutant (K616). This expression system has opened the way to a genetic and biochemical characterization of the regulatory and catalytic features of diverse Ca2+ pumps. Plant Ca(2+)-ATPases fall into two major types: AtECA1 represents one of four or more members of the type IIA (ER-type) Ca(2+)-ATPases in Arabidopsis, and AtACA2 is one of seven or more members of the type IIB (PM-type) Ca(2+)-ATPases that are regulated by a novel amino terminal domain. Type IIB pumps are widely distributed on membranes, including the PM (plasma membrane), vacuole, and ER (endoplasmic reticulum). The regulatory domain serves multiple functions, including autoinhibition, calmodulin binding, and sites for modification by phosphorylation. This domain, however, is considerably diverse among several type IIB ATPases, suggesting that the pumps are differentially regulated. Understanding of Ca2+ transporters at the molecular level is providing insights into their roles in signaling networks and in regulating fundamental processes of cell biology.

Deforming baryons into confining strings

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hartnoll, Sean A.; Portugues, Ruben

2004-09-15

We find explicit probe D3-brane solutions in the infrared of the Maldacena-Nunez background. The solutions describe deformed baryon vertices: q external quarks are separated in spacetime from the remaining N-q. As the separation is taken to infinity we recover known solutions describing infinite confining strings in N=1 gauge theory. We present results for the mass of finite confining strings as a function of length. We also find probe D2-brane solutions in a confining type IIA geometry, the reduction of a G{sub 2} holonomy M theory background. The relation between these deformed baryons and confining strings is not as straightforward.

An improved immune algorithm for optimizing the pulse width modulation control sequence of inverters

NASA Astrophysics Data System (ADS)

Sheng, L.; Qian, S. Q.; Ye, Y. Q.; Wu, Y. H.

2017-09-01

In this article, an improved immune algorithm (IIA), based on the fundamental principles of the biological immune system, is proposed for optimizing the pulse width modulation (PWM) control sequence of a single-phase full-bridge inverter. The IIA takes advantage of the receptor editing and adaptive mutation mechanisms of the immune system to develop two operations that enhance the population diversity and convergence of the proposed algorithm. To verify the effectiveness and examine the performance of the IIA, 17 cases are considered, including fixed and disturbed resistances. Simulation results show that the IIA is able to obtain an effective PWM control sequence. Furthermore, when compared with existing immune algorithms (IAs), genetic algorithms (GAs), a non-traditional GA, simplified simulated annealing, and a generalized Hopfield neural network method, the IIA can achieve small total harmonic distortion (THD) and large magnitude. Meanwhile, a non-parametric test indicates that the IIA is significantly better than most comparison algorithms. Supplemental data for this article can be accessed at http://dx.doi.org/10.1080/0305215X.2016.1250894.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chang, C.; Coggill, P.; Bateman, A.

Many Gram-positive lactic acid bacteria (LAB) produce anti-bacterial peptides and small proteins called bacteriocins, which enable them to compete against other bacteria in the environment. These peptides fall structurally into three different classes, I, II, III, with class IIa being pediocin-like single entities and class IIb being two-peptide bacteriocins. Self-protective cognate immunity proteins are usually co-transcribed with these toxins. Several examples of cognates for IIa have already been solved structurally. Streptococcus pyogenes, closely related to LAB, is one of the most common human pathogens, so knowledge of how it competes against other LAB species is likely to prove invaluable. Wemore » have solved the crystal structure of the gene-product of locus Spy-2152 from S. pyogenes, (PDB: 2fu2), and found it to comprise an anti-parallel four-helix bundle that is structurally similar to other bacteriocin immunity proteins. Sequence analyses indicate this protein to be a possible immunity protein protective against class IIa or IIb bacteriocins. However, given that S. pyogenes appears to lack any IIa pediocin-like proteins but does possess class IIb bacteriocins, we suggest this protein confers immunity to IIb-like peptides. Combined structural, genomic and proteomic analyses have allowed the identification and in silico characterization of a new putative immunity protein from S. pyogenes, possibly the first structure of an immunity protein protective against potential class IIb two-peptide bacteriocins. We have named the two pairs of putative bacteriocins found in S. pyogenes pyogenecin 1, 2, 3 and 4.« less

Design of an Anticancer Copper(II) Prodrug Based on the Lys199 Residue of the Active Targeting Human Serum Albumin Nanoparticle Carrier.

PubMed

Gou, Yi; Zhang, Yao; Zhang, Zhenlei; Wang, Jun; Zhou, Zuping; Liang, Hong; Yang, Feng

2017-06-05

We not only modified the types and numbers of coordinated ligands in a metal agent to enhance its anticancer activity, but we also designed a metal prodrug based on the N-donor residues of the human serum albumin (HSA) IIA subdomain to improve its delivery efficiency and selectivity in vivo. However, there may be a conflict in simultaneously achieving the two goals because Lys199 and His242 in the IIA subdomain of HSA can replace its two coordinated ligands, which will decrease its anticancer activity relative to the original metal agent. Thus, to improve the delivery efficiency of the metal agent and simultaneously avoid decreasing its anticancer activity in vivo, we decided to develop an anticancer metal prodrug by regulating its pharmacophore ligand so that it would not be displaced by the Lys199 residue of the folic acid (FA)-functionalized HSA nanoparticle (NP) carrier. To this end, we first synthesized two (E)-N'-(5-chloro-2-hydroxybenzylidene)benzohydrazide Schiff base (HL) Cu(II) compounds by designing a second ligand with a different coordinating atom with Cu 2+ /Cu(L)(QL)(Br) [C1, QL = quinolone] and Cu(L)(DMF)(Br) [C2, DMF = N,N-dimethylformamide]. As revealed by the structures of the two HSA complexes, the Cu compounds bind to the hydrophobic cavity in the HSA IIA subdomain. The QL ligand of C1 is replaced by Lys199, which coordinates with Cu 2+ , whereas the DMF ligand of C2 is kept intact and His242 is replaced with Br - of C2 and coordinates with Cu 2+ . The cytotoxicity of the Cu compounds was enhanced by the FA-HSA NPs in the Bel-7402 cells approximately 2-4-fold; however, they raise the cytotoxicity levels in the normal cells in vitro, and the FA-HSA NPs did not. Importantly, the in vivo data showed that FA-HSA-C2 NPs increased selectivity and the capacity to inhibit tumor growth and were less toxic than HSA-C2 NPs and C2. Moreover, C2/HSA-C2 NPs/FA-HSA-C2 NPs induced Bel-7402 cell death by potentially multiple mechanisms.

Bone morphogenetic protein 9 (BMP9) and BMP10 enhance tumor necrosis factor-α-induced monocyte recruitment to the vascular endothelium mainly via activin receptor-like kinase 2.

PubMed

Mitrofan, Claudia-Gabriela; Appleby, Sarah L; Nash, Gerard B; Mallat, Ziad; Chilvers, Edwin R; Upton, Paul D; Morrell, Nicholas W

2017-08-18

Bone morphogenetic proteins 9 and 10 (BMP9/BMP10) are circulating cytokines with important roles in endothelial homeostasis. The aim of this study was to investigate the roles of BMP9 and BMP10 in mediating monocyte-endothelial interactions using an in vitro flow adhesion assay. Herein, we report that whereas BMP9/BMP10 alone had no effect on monocyte recruitment, at higher concentrations both cytokines synergized with tumor necrosis factor-α (TNFα) to increase recruitment to the vascular endothelium. The BMP9/BMP10-mediated increase in monocyte recruitment in the presence of TNFα was associated with up-regulated expression levels of E-selectin, vascular cell adhesion molecule (VCAM-1), and intercellular adhesion molecule 1 (ICAM-1) on endothelial cells. Using siRNAs to type I and II BMP receptors and the signaling intermediaries (Smads), we demonstrated a key role for ALK2 in the BMP9/BMP10-induced surface expression of E-selectin, and both ALK1 and ALK2 in the up-regulation of VCAM-1 and ICAM-1. The type II receptors, BMPR-II and ACTR-IIA were both required for this response, as was Smad1/5. The up-regulation of cell surface adhesion molecules by BMP9/10 in the presence of TNFα was inhibited by LDN193189, which inhibits ALK2 but not ALK1. Furthermore, LDN193189 inhibited monocyte recruitment induced by TNFα and BMP9/10. BMP9/10 increased basal IκBα protein expression, but did not alter p65/RelA levels. Our findings suggest that higher concentrations of BMP9/BMP10 synergize with TNFα to induce the up-regulation of endothelial selectins and adhesion molecules, ultimately resulting in increased monocyte recruitment to the vascular endothelium. This process is mediated mainly via the ALK2 type I receptor, BMPR-II/ACTR-IIA type II receptors, and downstream Smad1/5 signaling. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Evidence for ACTN3 as a Speed Gene in Isolated Human Muscle Fibers.

PubMed

Broos, Siacia; Malisoux, Laurent; Theisen, Daniel; van Thienen, Ruud; Ramaekers, Monique; Jamart, Cécile; Deldicque, Louise; Thomis, Martine A; Francaux, Marc

2016-01-01

To examine the effect of α-actinin-3 deficiency due to homozygosity for the ACTN3 577X-allele on contractile and morphological properties of fast muscle fibers in non-athletic young men. A biopsy was taken from the vastus lateralis of 4 RR and 4 XX individuals to test for differences in morphologic and contractile properties of single muscle fibers. The cross-sectional area of the fiber and muscle fiber composition was determined using standard immunohistochemistry analyses. Skinned single muscle fibers were subjected to active tests to determine peak normalized force (P0), maximal unloading velocity (V0) and peak power. A passive stretch test was performed to calculate Young's Modulus and hysteresis to assess fiber visco-elasticity. No differences were found in muscle fiber composition. The cross-sectional area of type IIa and IIx fibers was larger in RR compared to XX individuals (P<0.001). P0 was similar in both groups over all fiber types. A higher V0 was observed in type IIa fibers of RR genotypes (P<0.001) but not in type I fibers. The visco-elasticity as determined by Young's Modulus and hysteresis was unaffected by fiber type or genotype. The greater V0 and the larger fast fiber CSA in RR compared to XX genotypes likely contribute to enhanced whole muscle performance during high velocity contractions.

Periodic arrays of M2-branes

NASA Astrophysics Data System (ADS)

Jeon, Imtak; Lambert, Neil; Richmond, Paul

2012-11-01

We consider periodic arrays of M2-branes in the ABJM model in the spirit of a circle compactification to D2-branes in type IIA string theory. The result is a curious formulation of three-dimensional maximally supersymmetric Yang-Mills theory in terms of fermions, seven transverse scalars, a non-dynamical gauge field and an additional scalar `dual gluon'. Upon further T-duality on a transverse torus we obtain a non-manifest- Lorentz-invariant description of five-dimensional maximally supersymmetric Yang-Mills. Here the additional scalar field can be thought of as the components of a two-form along the torus. This action can be viewed as an M-theory description of M5-branes on {{{T}}^3}.

Preferential motor unit loss in the SOD1G93A transgenic mouse model of amyotrophic lateral sclerosis

PubMed Central

Hegedus, J; Putman, C T; Tyreman, N; Gordon, T

2008-01-01

The present study investigated motor unit (MU) loss in a murine model of familial amyotrophic lateral sclerosis (ALS). The fast-twitch tibialis anterior (TA) and medial gastrocnemius (MG) muscles of transgenic SOD1G93A and SOD1WT mice were studied during the presymptomatic phase of disease progression at 60 days of age. Whole muscle maximum isometric twitch and tetanic forces were 80% lower (P < 0.01) in the TA muscles of SOD1G93A compared to SOD1WT mice. Enumeration of total MU numbers within TA muscles showed a 60% reduction (P < 0.01) within SOD1G93A mice (38 ± 7) compared with SOD1WT controls (95 ± 12); this was attributed to a lower proportion of the most forceful fast-fatigable (FF) MU in SOD1G93A mice, as seen by a significant (P < 0.01) leftward shift in the cumulative frequency histogram of single MU forces. Similar patterns of MU loss and corresponding decreases in isometric twitch force were observed in the MG. Immunocytochemical analyses of the entire cross-sectional area (CSA) of serial sections of TA muscles stained with anti-neural cell adhesion molecule (NCAM) and various monoclonal antibodies for myosin heavy chain (MHC) isoforms showed respective 65% (P < 0.01) and 28% (P < 0.05) decreases in the number of innervated IIB and IID/X muscle fibres in SOD1G93A, which paralleled the 60% decrease (P < 0.01) in the force generating capacity of individual fibres. The loss of fast MUs was partially compensated by activity-dependent fast-to-slower fibre type transitions, as determined by increases (P < 0.04) in the CSA and proportion of IIA fibres (from 4% to 14%) and IID/X fibres (from 31% to 39%), and decreases (P < 0.001) in the CSA and proportion of type IIB fibres (from 65% to 44%). We conclude that preferential loss of IIB fibres is incomplete at 60 days of age, and is consistent with a selective albeit gradual loss of FF MUs that is not fully compensated by sprouting of the remaining motoneurons that innervate type IIA or IID/X muscle fibres. Our findings indicate that disease progression in fast-twitch muscles of SOD1G93A mice involves parallel processes: (1) gradual selective motor axon die-back of the FF motor units that contain large type IIB muscle fibres, and of fatigue-intermediate motor units that innervate type IID/X muscle fibres, and (2) activity-dependent conversion of motor units to those innervated by smaller motor axons innervating type IIA fatigue-resistant muscle fibres. PMID:18467368

A universal counting of black hole microstates in AdS4

NASA Astrophysics Data System (ADS)

Azzurli, Francesco; Bobev, Nikolay; Crichigno, P. Marcos; Min, Vincent S.; Zaffaroni, Alberto

2018-02-01

Many three-dimensional N=2 SCFTs admit a universal partial topological twist when placed on hyperbolic Riemann surfaces. We exploit this fact to derive a universal formula which relates the planar limit of the topologically twisted index of these SCFTs and their three-sphere partition function. We then utilize this to account for the entropy of a large class of supersymmetric asymptotically AdS4 magnetically charged black holes in M-theory and massive type IIA string theory. In this context we also discuss novel AdS2 solutions of eleven-dimensional supergravity which describe the near horizon region of large new families of supersymmetric black holes arising from M2-branes wrapping Riemann surfaces.

Investigation of the feasibility of elective irradiation to neck level Ib using intensity-modulated radiotherapy for patients with nasopharyngeal carcinoma: a retrospective analysis.

PubMed

Zhang, Fan; Cheng, Yi-Kan; Li, Wen-Fei; Guo, Rui; Chen, Lei; Sun, Ying; Mao, Yan-Ping; Zhou, Guan-Qun; Liu, Xu; Liu, Li-Zhi; Lin, Ai-Hua; Tang, Ling-Long; Ma, Jun

2015-10-15

To assess the feasibility of elective neck irradiation to level Ib in nasopharyngeal carcinoma (NPC) using intensity-modulated radiation therapy (IMRT). We retrospectively analyzed 1438 patients with newly-diagnosed, non-metastatic and biopsy-proven NPC treated with IMRT. Greatest dimension of level IIa LNs (DLN-IIa) ≥ 20 mm and/or level IIa LNs with extracapsular spread (ES), oropharynx involvement and positive bilateral cervical lymph nodes (CLNs) were independently significantly associated with metastasis to level Ib LN at diagnosis. No recurrence at level Ib was observed in the 904 patients without these characteristics (median follow-up, 38.7 months; range, 1.3-57.8 months), these patients were classified as low risk. Level Ib irradiation was not an independent risk factor for locoregional failure-free survival, distant failure-free survival, failure-free survival or overall survival in low risk patients. The frequency of grade ≥ 2 subjective xerostomia at 12 months after radiotherapy was not significantly different between low risk patients who received level Ib-sparing, unilateral level Ib-covering or bilateral level Ib-covering IMRT. Level Ib-sparing IMRT should be safe and feasible for patients without a DLN-IIa ≥ 20 mm and/or level IIa LNs with ES, positive bilateral CLNs or oropharynx involvement at diagnosis. Further investigations based on specific criteria for dose constraints for the submandibular glands are warranted to confirm the benefit of elective level Ib irradiation.

Relationship between uterine biopsy score, endometrial infection and inflammation in the mare.

PubMed

Buczkowska, Justyna; Kozdrowski, Roland; Nowak, Marcin; Sikora, Monika

2016-06-16

Endometrial biopsy score is an accepted marker of uterine health and predicted fertility, and it has been suggested that endometrial alternations are correlated with susceptibility to persistent infectious endometritis. The objective of this study was to investigate associations of endometrial biopsy score with: 1) presence of polymorphonuclear cells (PMNs) in the epithelium and stratum compactum in histopathology; 2) presence of PMNs in cytology and 3) presence of infection in microbiology. The material for examination was collected from 69 mares suspected for subclinical endometritis (bred three or more times unsuccessfully in the same breeding season) and from 15 maiden mares. Samples were collected by endometrial biopsy and cytobrush technique. Endometrial alterations (biopsy score IIA, IIB, III) were found in 64 of 82 mares (78%). There was an increase in PMN occurrence for grades IIA, IIB and III. When comparing grades and PMNs infiltration, we observed statistically significant differences between grades I and IIA (p  = 0.222) and grades I and IIB (p = 0.042) in samples collected by endometrial biopsy. Statistically significant differences were found in microbiological examination (biopsy p = 0.036; cytobrush p = 0.189), cytological examination (biopsy p = 0.040; cytobrush p = 0.079) and PMN infiltration (p    =    0.042) between mares with biopsy scores I and IIB. Furthermore, the highest percentage of infected mares was in grade IIA and IIB, and we found statistically significant differences between grades I and IIA (p = 0.043), and grades I and IIB (p = 0.036) in biopsy samples. We observed a tendency to higher prevalence of endometrial infection in mares with biopsy score IIA, IIB and III than with biopsy score I in samples collected using cytobrush technique. However, there were no statistical significant differences. Degenerative endometrial changes can predispose to uterine infection and inflammation. Our study shows that mares with endometrial score I are less predisposed to infection than mares with category IIA, IIB and III. Endometrial biopsy is a reliable diagnostic tool.

Structural Basis for Catalysis of a Tetrameric Class IIa Fructose 1,6-Bisphosphate Aldolase from Mycobacterium tuberculosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pegan, Scott D.; Ruskseree, Kamolchanok; Franzblau, Scott G.

2009-03-04

Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), currently infects one-third of the world's population in its latent form. The emergence of multidrug-resistant and extensive drug-resistant strains has highlighted the need for new pharmacological targets within M. tuberculosis. The class IIa fructose 1,6-bisphosphate aldolase (FBA) enzyme from M. tuberculosis (MtFBA) has been proposed as one such target since it is upregulated in latent TB. Since the structure of MtFBA has not been determined and there is little information available on its reaction mechanism, we sought to determine the X-ray structure of MtFBA in complex with its substrates. By lowering themore » pH of the enzyme in the crystalline state, we were able to determine a series of high-resolution X-ray structures of MtFBA bound to dihydroxyacetone phosphate, glyceraldehyde 3-phosphate, and fructose 1,6-bisphosphate at 1.5, 2.1, and 1.3 {angstrom}, respectively. Through these structures, it was discovered that MtFBA belongs to a novel tetrameric class of type IIa FBAs. The molecular details at the interface of the tetramer revealed important information for better predictability of the quaternary structures among the FBAs based on their primary sequences. These X-ray structures also provide interesting and new details on the reaction mechanism of class II FBAs. Substrates and products were observed in geometries poised for catalysis; in addition, unexpectedly, the hydroxyl-enolate intermediate of dihydroxyacetone phosphate was also captured and resolved structurally. These concise new details offer a better understanding of the reaction mechanisms for FBAs in general and provide a structural basis for inhibitor design efforts aimed at this class of enzymes.« less

Structural basis for catalysis of a tetrameric, class IIa fructose 1,6-bisphosphate aldolase from M. tuberculosis

PubMed Central

Pegan, Scott D.; Rukseree, Kamolchanok; Franzblau, Scott G.; Mesecar, Andrew D.

2009-01-01

Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), currently infects one third of the world’s population in its latent form. The emergence of multidrug resistant strains, MDR-TB and XDR-TB has highlighted the need for new pharmacological targets within M. tuberculosis. The Class IIa fructose 1,6-bisphosphate aldolase (FBA) enzyme from M. tuberculosis (MtFBA) has been proposed as one such target since its upregulated in latent TB. Since the structure of MtFBA had not been determined and since there was little information available on its reaction mechanism, we sought to determine the X-ray structure of MtFBA in complex with its substrates. By lowering the pH of the enzyme in the crystalline state, we were able to determine a series of high-resolution X-ray structures of MtFBA bound to dihydroxyacetonephosphate (DHAP), glyceraldehyde-3-phosphate (G3P), and fructose 1,6-bisphosphate (FBP) at 1.5 Å, 2.1 Å, and 1.3 Å respectively. Through these structures it was discovered that MtFBA belongs to a novel tetrameric class of the type IIa FBAs. The molecular details at the interface of the tetramer revealed important information for being able to better predict the quaternary structures among the FBAs based on their primary sequences. These X-ray structures also provide interesting and new details on the reaction mechanism of class II FBAs. Not only were the substrates and products observed in geometries poised for catalysis, but unexpectedly the hydroxyl enolate intermediate of DHAP was also captured and resolved structurally. These concise new details provide a better understanding of the reaction mechanisms for FBAs in general and provide a structural basis for inhibitor design efforts aimed at this class of enzymes. PMID:19167403

30 CFR 57.22206 - Main ventilation failure (I-A, II-A, III, and V-A mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Main ventilation failure (I-A, II-A, III, and V-A mines). 57.22206 Section 57.22206 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... Main ventilation failure (I-A, II-A, III, and V-A mines). (a) When there has been a main ventilation...

S-duality in twistor space

NASA Astrophysics Data System (ADS)

Alexandrov, Sergei; Pioline, Boris

2012-08-01

In type IIB string compactifications on a Calabi-Yau threefold, the hypermultiplet moduli space {{M}_H} must carry an isometric action of the modular group SL(2 , {Z} ), inherited from the S-duality symmetry of type IIB string theory in ten dimensions. We investigate how this modular symmetry is realized at the level of the twistor space of {{M}_H} , and construct a general class of SL(2 , {Z} )-invariant quaternion-Kähler metrics with two commuting isometries, parametrized by a suitably covariant family of holomorphic transition functions. This family should include {{M}_H} corrected by D3-D1-D(-1)-instantons (with five-brane corrections ignored) and, after taking a suitable rigid limit, the Coulomb branch of five-dimensional {N} = {2} gauge theories compactified on a torus, including monopole string instantons. These results allow us to considerably simplify the derivation of the mirror map between type IIA and IIB fields in the sector where only D1-D(-1)-instantons are retained.

30 CFR 57.22101 - Smoking (I-A, II-A, III, and V-A mines).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Smoking (I-A, II-A, III, and V-A mines). 57.22101 Section 57.22101 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... Smoking (I-A, II-A, III, and V-A mines). Persons shall not smoke or carry smoking materials, matches, or...

30 CFR 57.22101 - Smoking (I-A, II-A, III, and V-A mines).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Smoking (I-A, II-A, III, and V-A mines). 57.22101 Section 57.22101 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... Smoking (I-A, II-A, III, and V-A mines). Persons shall not smoke or carry smoking materials, matches, or...

30 CFR 57.22101 - Smoking (I-A, II-A, III, and V-A mines).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Smoking (I-A, II-A, III, and V-A mines). 57.22101 Section 57.22101 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... Smoking (I-A, II-A, III, and V-A mines). Persons shall not smoke or carry smoking materials, matches, or...

30 CFR 57.22101 - Smoking (I-A, II-A, III, and V-A mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Smoking (I-A, II-A, III, and V-A mines). 57.22101 Section 57.22101 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... Smoking (I-A, II-A, III, and V-A mines). Persons shall not smoke or carry smoking materials, matches, or...

30 CFR 57.22608 - Secondary blasting (I-A, II-A, and V-A mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Secondary blasting (I-A, II-A, and V-A mines). 57.22608 Section 57.22608 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF... blasting (I-A, II-A, and V-A mines). Prior to secondary blasting, tests for methane shall be made in the...

30 CFR 57.22608 - Secondary blasting (I-A, II-A, and V-A mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Secondary blasting (I-A, II-A, and V-A mines). 57.22608 Section 57.22608 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF... blasting (I-A, II-A, and V-A mines). Prior to secondary blasting, tests for methane shall be made in the...

26 CFR 1.148-1 - Definitions and elections.

Code of Federal Regulations, 2011 CFR

2011-04-01

... working capital expenditures to which the de minimis rule under § 1.148-6(d)(3)(ii)(A) applies, that carry... are in a commingled fund. De minimis amount means— (1) In reference to original issue discount (as... proceeds of an issue. Investment-type property is defined in paragraph (e) of this section. Issue price...

First-principle approach based bandgap engineering for cubic boron nitride doped with group IIA elements

NASA Astrophysics Data System (ADS)

Li, Yubo; Wang, Pengtao; Hua, Fei; Zhan, Shijie; Wang, Xiaozhi; Luo, Jikui; Yang, Hangsheng

2018-03-01

Electronic properties of cubic boron nitride (c-BN) doped with group IIA elements were systematically investigated using the first principle calculation based on density functional theory. The electronic bandgap of c-BN was found to be narrowed when the impurity atom substituted either the B (IIA→B) or the N (IIA→N) atom. For IIA→B, a shallow accept level degenerated into valence band (VB); while for IIA→N, a shallow donor level degenerated conduction band (CB). In the cases of IIBe→N and IIMg→N, deep donor levels were also induced. Moreover, a zigzag bandgap narrowing pattern was found, which is in consistent with the variation pattern of dopants' radius of electron occupied outer s-orbital. From the view of formation energy, the substitution of B atom under N-rich conditions and the substitution of N atom under B-rich conditions were energetically favored. Our simulation results suggested that Mg and Ca are good candidates for p-type dopants, and Ca is the best candidate for n-type dopant.

A rapid UFLC-MS/MS method for simultaneous determination of formononetin, cryptotanshinone, tanshinone IIA and emodin in rat plasma and its application to a pharmacokinetic study of Bu Shen Huo Xue formula.

PubMed

Xu, Yuping; Huang, Kexin; Pan, Yu; Wang, Xianqin; Yan, Pengcheng; Ren, Yiping; Xiang, Zheng

2013-08-01

Bu Shen Huo Xue formula (BSHX) is a traditional Chinese medicine prescription used for clinical treatment of chronic kidney diseases. A rapid and selective Ultra fast liquid chromatography with tandem mass spectrometry (UFLC-MS/MS) method was developed for simultaneous determination of four bioactive components of BSHX including formononetin, cryptotanshinone, tanshinone IIA, and emodin in control and unilateral ureteral obstruction (UUO) model rat plasma for the first time. Atorvastatin was used as the internal standard (IS). Plasma samples were extracted by liquid-liquid extraction with ethyl acetate. The chromatographic separation was carried out on a Shim-pack XR-ODS III column with a gradient mobile phase consisting of acetonitrile and 0.1% formic acid. The detection was performed on a triple-quad tandem mass spectrometer by multiple reaction monitoring (MRM) via electrospray ionization (ESI) source with positive ionization mode for formononetin, cryptotanshinone, tanshinone IIA, and negative mode for emodin. The method was linear for four analytes over the range of investigated concentration with all coefficients of determination (R(2)) greater than 0.9938. The lower limits of quantification (LLOQ) for formononetin, cryptotanshinone, tanshinone IIA, and emodin were defined as 0.3, 0.5, 1.5, and 0.3ng/mL, respectively. The rapid and sensitive method was fully validated and successfully applied to the pharmacokinetic study of formononetin, cryptotanshinone, tanshinone IIA and emodin in rats following oral administration of Bu Shen Huo Xue formula. Copyright © 2013 Elsevier B.V. All rights reserved.

A National-Level Validation of the New American Joint Committee on Cancer 8th Edition Subclassification of Stage IIA and B Anal Squamous Cell Cancer.

PubMed

Goffredo, Paolo; Garancini, Mattia; Robinson, Timothy J; Frakes, Jessica; Hoshi, Hisakazu; Hassan, Imran

2018-06-01

The 8th edition of the American Joint Committee on Cancer (AJCC) updated the staging system of anal squamous cell cancer (ASCC) by subdividing stage II into A (T2N0M0) and B (T3N0M0) based on a secondary analysis of the RTOG 98-11 trial. We aimed to validate this new subclassification utilizing two nationally representative databases. The National Cancer Database (NCDB) [2004-2014] and the Surveillance, Epidemiology, and End Results (SEER) database [1988-2013] were queried to identify patients with stage II ASCC. A total of 6651 and 2579 stage IIA (2-5 cm) and 1777 and 641 stage IIB (> 5 cm) patients were identified in the NCDB and SEER databases, respectively. Compared with stage IIB patients, stage IIA patients within the NCDB were more often females with fewer comorbidities. No significant differences were observed between age, race, receipt of chemotherapy and radiation, and mean radiation dose. Demographic, clinical, and pathologic characteristics were comparable between patients in both datasets. The 5-year OS was 72% and 69% for stage IIA versus 57% and 50% for stage IIB in the NCDB and SEER databases, respectively (p < 0.001). After adjustment for available demographic and clinical confounders, stage IIB was significantly associated with worse survival in both cohorts (hazard ratio 1.58 and 2.01, both p < 0.001). This study validates the new AJCC subclassification of stage II anal cancer into A and B based on size (2-5 cm vs. > 5 cm) in the general ASCC population. AJCC stage IIB patients represent a higher risk category that should be targeted with more aggressive/novel therapies.

The calibration of photographic and spectroscopic films. 1: Film batch variations of reciprocity failure in IIaO film. 2: Thermal and aging effects in relationship to reciprocity failure. 3: Shifting of reciprocity failure points as a function of thermal and aging effects

NASA Technical Reports Server (NTRS)

Peters, K. A.; Atkinson, P. F.; Hammond, E. C., Jr.

1986-01-01

Reciprocity failure was examined for IIaO spectroscopic film. Three separate experiments were performed in order to study film batch variations, thermal and aging effects in relationship to reciprocity failure, and shifting of reciprocity failure points as a function of thermal and aging effects. The failure was examined over ranges of time between 5 and 60 seconds. The variation to illuminance was obtained by using thirty neutral density filters. A standard sensitometer device imprinted the wedge pattern on the film as exposure time was subjected to variation. The results indicate that film batch differences, temperature, and aging play an important role in reciprocity failure of IIaO spectroscopic film. A shifting of the failure points was also observed in various batches of film.

The calibration of photographic and spectroscopic films: Reciprocity failure and thermal responses of IIaO film at liquid nitrogen temperatures

NASA Technical Reports Server (NTRS)

Hammond, E. C., Jr.; Peters, K. A.; Gunther, S. O.; Cunningham, L. M.; Wright, D. D.

1985-01-01

Reciprocity failure was examined for IIaO spectroscopic film. The results indicate reciprocity failure occurs at three distinct minimum points in time; 15 min, 30 min and 90 min. The results are unique because theory suggests only one minimum reciprocity failure point should occur. When incubating 70mm IIaO film for 15 and 30 min at temperatures of 30, 40, 50, and 60 C and then placing in a liquid nitrogen bath at a temperature of -190 C the film demonstrated an increase of the optical density when developed at a warm-up time of 30 min. Longer warm-up periods of 1, 2 and 3 hrs yield a decrease in optical density of the darker wedge patterns; whereas, shorter warm-up times yield an overall increase in the optical densities.

Discovery of tanshinone derivatives with anti-MRSA activity via targeted bio-transformation.

PubMed

He, Wenni; Liu, Miaomiao; Huang, Pei; Abdel-Mageed, Wael M; Han, Jianying; Watrous, Jeramie D; Nguyen, Don D; Wang, Wenzhao; Song, Fuhang; Dai, Huanqin; Zhang, Jingyu; Quinn, Ronald J; Grkovi, Tanja; Luo, Houwei; Zhang, Lixin; Liu, Xueting

2016-09-01

Two potent anti-MRSA tanshinone glycosides ( 1 and 2 ) were discovered by targeted microbial biotransformation, along with rapid identification via MS/MS networking. Serial reactions including dehydrogenation, demethylations, reduction, glycosylation and methylation have been observed after incubation of tanshinone IIA and fungus Mucor rouxianus AS 3.3447. In addition, tanshinosides B ( 2 ) showed potent activities against serial clinical isolates of oxacillin-resistant Staphylococcus aureus with MIC values of 0.78 μg/mL. This is the first study that shows a significant increase in the level and activities of tanshinone glycosides relative to the substrate tanshinone IIA.

Cellular and Morphological Alterations in the Vastus Lateralis Muscle as the Result of ACL Injury and Reconstruction.

PubMed

Noehren, Brian; Andersen, Anders; Hardy, Peter; Johnson, Darren L; Ireland, Mary Lloyd; Thompson, Katherine L; Damon, Bruce

2016-09-21

Individuals who have had an anterior cruciate ligament (ACL) tear and reconstruction continue to experience substantial knee extensor strength loss despite months of physical therapy. Identification of the alterations in muscle morphology and cellular composition are needed to understand potential mechanisms of muscle strength loss, initially as the result of the injury and subsequently from surgery and rehabilitation. We performed diffusion tensor imaging-magnetic resonance imaging and analyzed muscle biopsies from the vastus lateralis of both the affected and unaffected limbs before surgery and again from the reconstructed limb following the completion of rehabilitation. Immunohistochemistry was done to determine fiber type and size, Pax-7-positive (satellite) cells, and extracellular matrix (via wheat germ agglutinin straining). Using the diffusion tensor imaging data, the fiber tract length, pennation angle, and muscle volume were determined, yielding the physiological cross-sectional area (PCSA). Paired t tests were used to compare the effects of the injury between injured and uninjured limbs and the effects of surgery and rehabilitation within the injured limb. We found significant reductions before surgery in type-IIA muscle cross-sectional area (CSA; p = 0.03), extracellular matrix (p < 0.01), satellite cells per fiber (p < 0.01), pennation angle (p = 0.03), muscle volume (p = 0.02), and PCSA (p = 0.03) in the injured limb compared with the uninjured limb. Following surgery, these alterations in the injured limb persisted and the frequency of the IIA fiber type decreased significantly (p < 0.01) and that of the IIA/X hybrid fiber type increased significantly (p < 0.01). Significant and prolonged differences in muscle quality and morphology occurred after ACL injury and persisted despite reconstruction and extensive physical therapy. These results suggest the need to develop more effective early interventions following an ACL tear to prevent deleterious alterations within the quadriceps. Copyright © 2016 by The Journal of Bone and Joint Surgery, Incorporated.

Intraoperative validation of CT-based lymph nodal levels, sublevels IIa and IIb: Is it of clinical relevance in selective radiation therapy?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Levendag, Peter; Gregoire, Vincent; Hamoir, Marc

2005-07-01

Purpose: The objectives of this study are to discuss the intraoperative validation of CT-based boundaries of lymph nodal levels in the neck, and in particular the clinical relevance of the delineation of sublevels IIa and IIb in case of selective radiation therapy (RT). Methods and Materials: To validate the radiologically defined level contours, clips were positioned intraoperatively at the level boundaries defined by surgical anatomy. In 10 consecutive patients, clips were placed, at the time of a neck dissection being performed, at the most cranial border of the neck. Anterior-posterior and lateral X-ray films were obtained intraoperatively. Next, in 3more » patients, neck levels were contoured on preoperative contrast-enhanced CT scans according to the international consensus guidelines. From each of these 3 patients, an intraoperative CT scan was also obtained, with clips placed at the surgical-anatomy-based level boundaries. The preoperative (CT-based) and intraoperative (surgery-defined) CT scans were matched. Results: Clips placed at the most cranial part of the neck lined up at the caudal part of the transverse process of the cervical vertebra C-I. The posterior border of surgical level IIa (spinal accessory nerve [SAN]) did not match with the posterior border of CT-based level IIa (internal jugular vein [IJV]). Other surgical boundaries and CT-based contours were in good agreement. Conclusions: The cranial border of the neck, i.e., the cranial border of level IIa/IIb, corresponds to the caudal edge of the lateral process of C-I. Except for the posterior border between level IIa and level IIb, a perfect match was observed between the other surgical-clip-identified levels II-V boundaries (surgical-anatomy) and the CT-based delineation contours. It is argued that (1) because of the parotid gland overlapping part of level II, and (2) the frequent infestation of occult metastatic cells in the lymph channels around the IJV, the division of level II into radiologic sublevels IIa and IIb may not be relevant. Sparing of, for example, the ipsilateral parotid gland in selective RT can even be a treacherous undertaking with respect to regional tumor control. In contrast, the surgeon's reasoning for preserving the surgical sublevel IIb is that the morbidity associated with dissection of the supraspinal accessory nerve compartment of level II is reduced, whereas there is evidence from the surgical literature that no extra risk for regional tumor control is observed. Therefore, in selective neck dissections, the division into surgical sublevels IIa/IIb makes sense.« less

30 CFR 57.22204 - Main fan operation and inspection (I-A, II-A, III, and V-A mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Main fan operation and inspection (I-A, II-A, III, and V-A mines). 57.22204 Section 57.22204 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... Main fan operation and inspection (I-A, II-A, III, and V-A mines). Main fans shall be— (a) Provided...

30 CFR 57.22207 - Booster fans (I-A, II-A, III, and V-A mines).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Booster fans (I-A, II-A, III, and V-A mines... NONMETAL MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22207 Booster fans (I-A, II-A, III, and V-A mines). (a) Booster fans shall be approved by MSHA under the applicable...

30 CFR 57.22207 - Booster fans (I-A, II-A, III, and V-A mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Booster fans (I-A, II-A, III, and V-A mines... NONMETAL MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22207 Booster fans (I-A, II-A, III, and V-A mines). (a) Booster fans shall be approved by MSHA under the applicable...

30 CFR 57.22207 - Booster fans (I-A, II-A, III, and V-A mines).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Booster fans (I-A, II-A, III, and V-A mines... NONMETAL MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22207 Booster fans (I-A, II-A, III, and V-A mines). (a) Booster fans shall be approved by MSHA under the applicable...

30 CFR 57.22207 - Booster fans (I-A, II-A, III, and V-A mines).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Booster fans (I-A, II-A, III, and V-A mines... NONMETAL MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22207 Booster fans (I-A, II-A, III, and V-A mines). (a) Booster fans shall be approved by MSHA under the applicable...

30 CFR 57.22204 - Main fan operation and inspection (I-A, II-A, III, and V-A mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Main fan operation and inspection (I-A, II-A, III, and V-A mines). 57.22204 Section 57.22204 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... Main fan operation and inspection (I-A, II-A, III, and V-A mines). Main fans shall be— (a) Provided...

30 CFR 57.22221 - Overcast and undercast construction (I-A, II-A, III, and V-A mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Overcast and undercast construction (I-A, II-A, III, and V-A mines). 57.22221 Section 57.22221 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... Overcast and undercast construction (I-A, II-A, III, and V-A mines). Overcasts and undercasts shall be— (a...

30 CFR 57.22228 - Preshift examination (I-A, I-C, II-A, III, and V-A mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Preshift examination (I-A, I-C, II-A, III, and V-A mines). 57.22228 Section 57.22228 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... Preshift examination (I-A, I-C, II-A, III, and V-A mines). (a) Preshift examinations shall be conducted...

30 CFR 57.22221 - Overcast and undercast construction (I-A, II-A, III, and V-A mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Overcast and undercast construction (I-A, II-A, III, and V-A mines). 57.22221 Section 57.22221 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... Overcast and undercast construction (I-A, II-A, III, and V-A mines). Overcasts and undercasts shall be— (a...

30 CFR 57.22214 - Changes in ventilation (I-A, II-A, III, and V-A mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Changes in ventilation (I-A, II-A, III, and V-A mines). 57.22214 Section 57.22214 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF... ventilation (I-A, II-A, III, and V-A mines). (a) Changes in ventilation which affect the main air current or...

30 CFR 57.22208 - Auxiliary fans (I-A, II-A, III, and V-A mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Auxiliary fans (I-A, II-A, III, and V-A mines). 57.22208 Section 57.22208 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF... fans (I-A, II-A, III, and V-A mines). (a) Auxiliary fans, except fans used in shops and other areas...

30 CFR 57.22228 - Preshift examination (I-A, I-C, II-A, III, and V-A mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Preshift examination (I-A, I-C, II-A, III, and V-A mines). 57.22228 Section 57.22228 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... Preshift examination (I-A, I-C, II-A, III, and V-A mines). (a) Preshift examinations shall be conducted...

30 CFR 57.22214 - Changes in ventilation (I-A, II-A, III, and V-A mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Changes in ventilation (I-A, II-A, III, and V-A mines). 57.22214 Section 57.22214 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF... ventilation (I-A, II-A, III, and V-A mines). (a) Changes in ventilation which affect the main air current or...

30 CFR 57.22220 - Air passing unsealed areas (I-A, II-A, III, and V-A mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Air passing unsealed areas (I-A, II-A, III, and V-A mines). 57.22220 Section 57.22220 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... passing unsealed areas (I-A, II-A, III, and V-A mines). Air that has passed by or through unsealed...

30 CFR 57.22220 - Air passing unsealed areas (I-A, II-A, III, and V-A mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Air passing unsealed areas (I-A, II-A, III, and V-A mines). 57.22220 Section 57.22220 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... passing unsealed areas (I-A, II-A, III, and V-A mines). Air that has passed by or through unsealed...

30 CFR 57.22103 - Open flames (I-A, II-A, III, and V-A mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Open flames (I-A, II-A, III, and V-A mines). 57.22103 Section 57.22103 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... Open flames (I-A, II-A, III, and V-A mines). Open flames shall not be permitted underground except for...

Arachidonic acid can function as a signaling modulator by activating the TRPM5 cation channel in taste receptor cells.

PubMed

Oike, Hideaki; Wakamori, Minoru; Mori, Yasuo; Nakanishi, Hiroki; Taguchi, Ryo; Misaka, Takumi; Matsumoto, Ichiro; Abe, Keiko

2006-09-01

Vertebrate sensory cells such as vomeronasal neurons and Drosophila photoreceptor cells use TRP channels to respond to exogenous stimuli. In mammalian taste cells, bitter and sweet substances as well as some amino acids are received by G protein-coupled receptors (T2Rs or T1Rs). As a result of activation of G protein and phospholipase Cbeta2, the TRPM5 channel is activated. Intracellular Ca(2+) is known to be a TRPM5 activator, but the participation of lipid activators remains unreported. To clarify the effect of arachidonic acid on TRPM5 in taste cells, we investigated the expression profile of a series of enzymes involved in controlling the intracellular free arachidonic acid level, with the result that in a subset of taste bud cells, monoglyceride lipase (MGL) and cyclooxygenase-2 (COX-2) are expressed as well as the previously reported group IIA phospholipase A(2) (PLA(2)-IIA). Double-labeling analysis revealed that MGL, COX-2 and PLA(2)-IIA are co-expressed in some cells that express TRPM5. We then investigated whether arachidonic acid activates TRPM5 via a heterologous expression system in HEK293 cells, and found that its activation occurred at 10 microM arachidonic acid. These results strongly suggest the possibility that arachidonic acid acts as a modulator of TRPM5 in taste signaling pathways.

30 CFR 57.22212 - Air flow (I-C, II-A, and V-A mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Air flow (I-C, II-A, and V-A mines). 57.22212 Section 57.22212 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22212 Air flow (I-C, II-A, and V-A mines...

Pelvic Arterial Anatomy Relevant to Prostatic Artery Embolisation and Proposal for Angiographic Classification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Assis, André Moreira de, E-mail: andre.maa@gmail.com; Moreira, Airton Mota, E-mail: motamoreira@gmail.com; Paula Rodrigues, Vanessa Cristina de, E-mail: vanessapaular@yahoo.com.br

PurposeTo describe and categorize the angiographic findings regarding prostatic vascularization, propose an anatomic classification, and discuss its implications for the PAE procedure.MethodsAngiographic findings from 143 PAE procedures were reviewed retrospectively, and the origin of the inferior vesical artery (IVA) was classified into five subtypes as follows: type I: IVA originating from the anterior division of the internal iliac artery (IIA), from a common trunk with the superior vesical artery (SVA); type II: IVA originating from the anterior division of the IIA, inferior to the SVA origin; type III: IVA originating from the obturator artery; type IV: IVA originating from themore » internal pudendal artery; and type V: less common origins of the IVA. Incidences were calculated by percentage.ResultsTwo hundred eighty-six pelvic sides (n = 286) were analyzed, and 267 (93.3 %) were classified into I–IV types. Among them, the most common origin was type IV (n = 89, 31.1 %), followed by type I (n = 82, 28.7 %), type III (n = 54, 18.9 %), and type II (n = 42, 14.7 %). Type V anatomy was seen in 16 cases (5.6 %). Double vascularization, defined as two independent prostatic branches in one pelvic side, was seen in 23 cases (8.0 %).ConclusionsDespite the large number of possible anatomical variations of male pelvis, four main patterns corresponded to almost 95 % of the cases. Evaluation of anatomy in a systematic fashion, following a standard classification, will make PAE a faster, safer, and more effective procedure.« less

Diffusion Modeling of Cooling Rates of Relict Olivine in Semarkona Chondrules

NASA Astrophysics Data System (ADS)

Hewins, R. H.; Ganguly, J.; Mariani, E.

2009-03-01

Diffusive exchange profiles between relict olivine and melt-grown olivine in Semarkona Type IIA chondrules were oriented by EBSD to correct D. Results for Fe-Mg (D from Dohmen) and Cr (Ito and Ganguly) are concordant at 300°-400°C/hr.

77 FR 42954 - Airworthiness Directives; Boeing Vertol (Type Certificate Currently Held by Columbia Helicopters...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-23

...)) and Kawasaki Heavy Industries, Limited Helicopters (Kawasaki) AGENCY: Federal Aviation Administration... Columbia Helicopters, Inc.) and Kawasaki Heavy Industries, Limited Helicopters: Amendment 39-17124; Docket... Heavy Industries, Limited Model KV107-II and KV107-IIA helicopters with an upper collective pitch...

[Odontoid bending stiffness after anterior fixation with a single lag screw: biomechanical study].

PubMed

Buchvald, P; Čapek, L; Barsa, P

2015-01-01

PURPOSE OF THE STUDY The aim of the experiment was to compare the bending stiffness of an intact odontoid process with bending stiffness after its simulated type II fracture was fixed with a single lag screw. The experiment was done with a desire to answer the question of whether a single osteosynthetic screw is sufficient for good fixation of a type II odontoid fracture. MATERIAL AND METHODS The C2 vertebrae of six cadavers were used. With simultaneous measurement of odontoid bending stiffness, the occurrence of a fracture (type IIA, Grauer's modification of the Anderson- D'Alonzo classification) was simulated using action exerted by a tearing machine in the direction perpendicular to the odontoid axis. Each odontoid fracture was subsequently treated by direct osteosynthesis with a single lag screw inserted in the axial direction by a standard surgical procedure in order to provide conditions similar to those achieved by routine surgical management. The treated odontoid process was subsequently subjected to the same tearing machine loading as applied to it at the start of the experiment. The bending stiffness measured was then compared with that found before the fracture occurred. The results were statistically evaluated by the t-test for paired samples at the level of significance α = 0.05. RESULTS The average value of bending stiffness for odontoid processes of intact vertebrae at the moment of fracture occurrence was 318.3 N/mm. After single axial lag screw fixation of the fracture, the average bending stiffness for the odontoid processes treated was 331.3 N/mm. DISCUSSION Higher values of bending stiffness after screw fixation were found in all specimens and, in comparison with the values recorded before simulated fractures, the increase was statistically significant. CONCLUSIONS The results of our measurements suggest that the single lag screw fixation of a type IIA odontoid fracture will provide better stability for the fracture fragment-C2 body complex on antero-posterior perpendicular loading than can be found in intact C2 vertebrae. Key words: odontoid fracture, odontoid fixation, bending stiffness, lag screw.

Surgical Management of Ipsilateral Fracture of the Femur and Tibia in Adults (the Floating Knee): Postoperative Clinical, Radiological, and Functional Outcomes

PubMed Central

2011-01-01

Background This study evaluated the outcomes of surgical management of ipsilateral femoral and tibial fractures in adults. Methods Fifteen patients (13 men, 2 women; mean age, 34.8 years; range, 18 to 65 years) were enrolled in this study. The fractures types were classified according to the classification by Fraser et al. as follows: type I (5), type IIa (3), IIb (4), IIc (3). Femur fractures were treated using locked intramedullary nails, plate-screws, or dynamic condylar screws, and tibia fractures were treated with an external fixator (in open fractures), or plate-screws, and locked intramedullary nailing. The mean follow-up duration was 2.2 years (range, 1.3 to 4 years). Results The extent of bony union according to the Karlstrom criteria was as follows: excellent, 8; good, 4; acceptable, 2; poor, 1. Conclusions The associated injuries and type of fracture (open, intra-articular, comminution) are prognostic factors in a floating knee. The best management of the associated injuries for good final outcome involves intramedullary nailing of both the fractures and postoperative rehabilitation. PMID:21629474

Molecular cloning, expression and characterization of albolamin: a type P-IIa snake venom metalloproteinase from green pit viper (Cryptelytrops albolabris).

PubMed

Jangprasert, Panchalee; Rojnuckarin, Ponlapat

2014-03-01

Snake venom metalloproteinases (SVMPs) can damage vessel wall, degrade clotting factors, inhibit integrins and block platelet functions. Studying them not only gives us deeper insights in pathogenesis of snakebites, but also potentially yields novel therapeutic agents. Here, we discovered a clone of an RGD-containing SVMP from the green pit viper (Cryptelytrops albolabris) venom gland cDNA library. Sequence analysis revealed that it belonged to the P-IIa subclass of SVMP comprising signal peptide, prodomain, metalloproteinase and disintegrin. Compared with other P-II SVMPs, it contained 2 additional conserved cysteines that were predicted to prevent the release of disintegrin from the metalloproteinase domain in the mature protein. The N-terminal histidine-tagged construct of metalloproteinase and disintegrin domains of albolamin was inserted into the pPICZαA vector and expressed in Pichia pastoris. The recombinant protein molecular weight was approximately 35 kDa on Western blot probed with anti-polyhistidine antibody. The recombinant albolamin could digest human type IV collagen starting within 15 min after incubation. In addition, it dose-dependently inhibited collagen-induced platelet aggregation with the IC50 of 1.8 μM. However, there was no effect on ADP-induced platelet aggregation. Therefore, the inhibition mechanism is probably through blocking collagen receptor(s). Albolamin activities probably contributed to pathology of green pit viper bites. Its disintegrin domain deserves further studies for the potential to be a useful agent affecting platelet functions. Copyright © 2013 Elsevier Ltd. All rights reserved.

Occurrence and activity of a type II CRISPR-Cas system in Lactobacillus gasseri.

PubMed

Sanozky-Dawes, Rosemary; Selle, Kurt; O'Flaherty, Sarah; Klaenhammer, Todd; Barrangou, Rodolphe

2015-09-01

Bacteria encode clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated genes (cas), which collectively form an RNA-guided adaptive immune system against invasive genetic elements. In silico surveys have revealed that lactic acid bacteria harbour a prolific and diverse set of CRISPR-Cas systems. Thus, the natural evolutionary role of CRISPR-Cas systems may be investigated in these ecologically, industrially, scientifically and medically important microbes. In this study, 17 Lactobacillus gasseri strains were investigated and 6 harboured a type II-A CRISPR-Cas system, with considerable diversity in array size and spacer content. Several of the spacers showed similarity to phage and plasmid sequences, which are typical targets of CRISPR-Cas immune systems. Aligning the protospacers facilitated inference of the protospacer adjacent motif sequence, determined to be 5'-NTAA-3' flanking the 3' end of the protospacer. The system in L. gasseri JV-V03 and NCK 1342 interfered with transforming plasmids containing sequences matching the most recently acquired CRISPR spacers in each strain. We report the distribution and function of a native type II-A CRISPR-Cas system in the commensal species L. gasseri. Collectively, these results open avenues for applications for bacteriophage protection and genome modification in L. gasseri, and contribute to the fundamental understanding of CRISPR-Cas systems in bacteria.

30 CFR 57.22205 - Doors on main fans (I-A, II-A, III, and V-A mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Doors on main fans (I-A, II-A, III, and V-A mines). 57.22205 Section 57.22205 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF... main fans (I-A, II-A, III, and V-A mines). In mines ventilated by multiple main fans, each main fan...

Ion chemistry of NOO+

DTIC Science & Technology

2006-03-21

IP (eV) Production of NO’ ions was found in the reactions of NOOW with NO, C 6F 6 , CS 2 , CF 3 I, C 3F 6 , OCS, Xe, 03, N20, w/ ZPE " w/o ZPE w/ ZPE w/o... ZPE and CO. It was the predominant reaction channel for all spe- cies with IP-> 10.28 eV, except for C 2H 6 , where no NO+ was MRCISD/AVQZ.//CASPT2...either 0 atom transfer or simple dis- obtain the ZPE value. fl~l,.,n41I A-,)n. 9ffý , 4Ar Irl 1AA 𔃻 +ýda+hi,, .,IIa. , AID~ Ii,-.,,a , - -- l hf+ .^. k0

Secretory phospholipase A2 in dromedary tears: a host defense against staphylococci and other gram-positive bacteria.

PubMed

Ben Bacha, Abir; Abid, Islem

2013-03-01

The best known physiologic function of secreted phospholipase A2 (sPLA2) group IIA (sPLA2-IIA) is defense against bacterial infection through hydrolytic degradation of bacterial membrane phospholipids. In fact, sPLA2-IIA effectively kills Gram-positive bacteria and to a lesser extent Gram-negative bacteria and is considered a major component of the eye's innate immune defense system. The antibacterial properties of sPLA2 have been demonstrated in rabbit and human tears. In this report, we have analyzed the bactericidal activity of dromedary tears and the subsequently purified sPLA2 on several Gram-positive bacteria. Our results showed that the sPLA2 displays a potent bactericidal activity against all the tested bacteria particularly against the Staphylococcus strains when tested in the ionic environment of tears. There is a synergic action of the sPLA2 with lysozyme when added to the bacteria culture prior to sPLA2. Interestingly, lysozyme purified from dromedary tears showed a significant bactericidal activity against Listeria monocytogene and Staphylococcus epidermidis, whereas the one purified from human tears displayed no activity against these two strains. We have also demonstrated that Ca(2+) is crucial for the activity of dromedary tear sPLA2 and to a less extent Mg(2+) ions. Given the presence of sPLA2 in tears and intestinal secretions, this enzyme may play a substantial role in innate mucosal and systemic bactericidal defenses against Gram-positive bacteria.

A promising anti-cancer and anti-oxidant agents based on the pyrrole and fused pyrrole: synthesis, docking studies and biological evaluation.

PubMed

Fatahala, Samar Said; Shalaby, Emad Ahmed; Kassab, Shaymaa Emam; Mohamed, Mossad Said

2015-01-01

A series of N-aryl derivatives of pyrrole and its related derivatives of fused form (namely; tetrahydroindole and dihydroindenopyrroles) were prepared in fair to good yields. The newly synthesized compounds were confirmed using IR, (1)H NMR, Mass spectral and elemental analysis. Tetrahydrobenzo[b] pyrroles Ia-d, 1,4-dihydroindeno[1,2-b]pyrroles IIa,b and pyrroles IIIa-c,e were evaluated for anticancer activity, coinciding with the antioxidant activity; using Di-Phenyl Picryl Hydrazyl (DPPH) tests. The cytotoxicity of the tested compounds (at a concentration of 100 and 200 μg /mL) was performed against HepG-2 and EACC cell lines. Compounds Ib, d and IIa showed promising antioxidant activity beside their anticancer activity. Docking studies were employed to justify the promising anticancer activity of Ib,d and IIa. Protein kinase (PKase)-PDB entry 1FCQ was chosen as target enzyme for this purpose using the MOLSOFT ICM 3.4-8C program. The docking results of the tested compounds went aligned with the respective anticancer assay results.

Magnetic properties of point defects in proton irradiated diamond

NASA Astrophysics Data System (ADS)

Makgato, T. N.; Sideras-Haddad, E.; Ramos, M. A.; García-Hernández, M.; Climent-Font, A.; Zucchiatti, A.; Muñoz-Martin, A.; Shrivastava, S.; Erasmus, R.

2016-09-01

We investigate the magnetic properties of ultra-pure type-IIa diamond following irradiation with proton beams of ≈1-2 MeV energy. SQUID magnetometry indicate the formation of Curie type paramagnetism according to the Curie law. Raman and Photoluminescence spectroscopy measurements show that the primary structural features created by proton irradiation are the centers: GR1, ND1, TR12 and 3H. The Stopping and Range of Ions in Matter (SRIM) Monte Carlo simulations together with SQUID observations show a strong correlation between vacancy production, proton fluence and the paramagnetic factor. At an average surface vacancy spacing of ≈1-1.6 nm and bulk (peak) vacancy spacing of ≈0.3-0.5 nm Curie paramagnetism is induced by formation of ND1 centres with an effective magnetic moment μeff~(0.1-0.2)μB. No evidence of long range magnetic ordering is observed in the temperature range 4.2-300 K.

PD-1 immunoreceptor inhibits B cell receptor-mediated signaling by recruiting src homology 2-domain-containing tyrosine phosphatase 2 to phosphotyrosine

PubMed Central

Okazaki, Taku; Maeda, Akito; Nishimura, Hiroyuki; Kurosaki, Tomohiro; Honjo, Tasuku

2001-01-01

PD-1 is an immunoreceptor that belongs to the immunoglobulin (Ig) superfamily and contains two tyrosine residues in the cytoplasmic region. Studies on PD-1-deficient mice have shown that PD-1 plays critical roles in establishment and/or maintenance of peripheral tolerance, but the mode of action is totally unknown. To study the molecular mechanism for negative regulation of lymphocytes through the PD-1 receptor, we generated chimeric molecules composed of the IgG Fc receptor type IIB (FcγRIIB) extracellular region and the PD-1 cytoplasmic region and expressed them in a B lymphoma cell line, IIA1.6. Coligation of the cytoplasmic region of PD-1 with the B cell receptor (BCR) in IIA1.6 transformants inhibited BCR-mediated growth retardation, Ca2+ mobilization, and tyrosine phosphorylation of effector molecules, including Igβ, Syk, phospholipase C-γ2 (PLCγ2), and ERK1/2, whereas phosphorylation of Lyn and Dok was not affected. Mutagenesis studies indicated that these inhibitory effects do not require the N-terminal tyrosine in the immunoreceptor tyrosine-based inhibitory motif-like sequence, but do require the other tyrosine residue in the C-terminal tail. This tyrosine was phosphorylated and recruited src homology 2-domain-containing tyrosine phosphatase 2 (SHP-2) on coligation of PD-1 with BCR. These results show that PD-1 can inhibit BCR signaling by recruiting SHP-2 to its phosphotyrosine and dephosphorylating key signal transducers of BCR signaling. PMID:11698646

Identification of the group IIa WRKY subfamily and the functional analysis of GhWRKY17 in upland cotton (Gossypium hirsutum L.).

PubMed

Gu, Lijiao; Li, Libei; Wei, Hengling; Wang, Hantao; Su, Junji; Guo, Yaning; Yu, Shuxun

2018-01-01

WRKY transcription factors play important roles in plant defense, stress response, leaf senescence, and plant growth and development. Previous studies have revealed the important roles of the group IIa GhWRKY genes in cotton. To comprehensively analyze the group IIa GhWRKY genes in upland cotton, we identified 15 candidate group IIa GhWRKY genes in the Gossypium hirsutum genome. The phylogenetic tree, intron-exon structure, motif prediction and Ka/Ks analyses indicated that most group IIa GhWRKY genes shared high similarity and conservation and underwent purifying selection during evolution. In addition, we detected the expression patterns of several group IIa GhWRKY genes in individual tissues as well as during leaf senescence using public RNA sequencing data and real-time quantitative PCR. To better understand the functions of group IIa GhWRKYs in cotton, GhWRKY17 (KF669857) was isolated from upland cotton, and its sequence alignment, promoter cis-acting elements and subcellular localization were characterized. Moreover, the over-expression of GhWRKY17 in Arabidopsis up-regulated the senescence-associated genes AtWRKY53, AtSAG12 and AtSAG13, enhancing the plant's susceptibility to leaf senescence. These findings lay the foundation for further analysis and study of the functions of WRKY genes in cotton.

Mesenteric lymphangitis and sepsis due to RTX toxin-producing Actinobacillus spp in 2 foals with hypothyroidism-dysmaturity syndrome.

PubMed

Löhr, C V; Polster, U; Kuhnert, P; Karger, A; Rurangirwa, F R; Teifke, J P

2012-07-01

Actinobacillus suis-like organisms (ASLOs) have been isolated from the genital, respiratory, and digestive tracts of healthy adult horses, horses with respiratory disease, and septic foals. Two foals with congenital hypothyroidism-dysmaturity syndrome from separate farms developed ASLO infection. At necropsy, both had contracted carpal flexor tendons, thyroid hyperplasia, and thrombotic and necrotizing mesenteric lymphangitis and lymphadenitis; one foal also had mandibular prognathism. Numerous ASLOs were isolated from tissues from both foals, including intestine. Biochemical testing and mass spectrometric analysis of the two Actinobacillus isolates did not allow unequivocal identification. Comparative genetic analysis was done on these and similar isolates, including phylogeny based on 16S rRNA, rpoB and recN genes, as well as RTX (repeat in toxin) toxin typing of apxIA-apxIVA and aqxA genes. One isolate was identified as Actinobacillus suis sensu stricto, based on the presence of apxIA and apxIIA but not aqxA, whereas the other isolate had aqxA but neither apxIA nor apxIIA, consistent with A equuli ssp haemolyticus. Based on genotypic analysis of the isolates included for comparison, 3 of 3 equine ASLOs and 2 of 5 A equuli isolates were reclassified as A equuli subsp haemolyticus, emphasizing the importance of toxin genotyping in accurate classification of actinobacilli.

Using the Fe/Mn Ratio of FeO-Rich Olivine In WILD 2, Chondrite Matrix, and Type IIA Chondrules to Disentangle Their Histories

NASA Technical Reports Server (NTRS)

Frank, David R.; Le, L.; Zolensky, M. E.

2012-01-01

The Stardust Mission returned a large abundance of impactors from Comet 81P/Wild2 in the 5-30 m range. The preliminary examination of just a limited number of these particles showed that the collection captured abundant crystalline grains with a diverse mineralogy [1,2]. Many of these grains resemble those found in chondrite matrix and even contain fragments of chondrules and CAIs [1-3]. In particular, the olivine found in Wild 2 exhibits a wide compositional range (Fa0-97) with minor element abundances similar to the matrix olivine found in many carbonaceous chondrites (CCs) and unequilibrated ordinary chondrites (UOCs). Despite the wide distribution of Fa content, the olivine found in the matrices of CCs, UOCs, and Wild 2 can be roughly lumped into two types based solely on fayalite content. In fact, in some cases, a distinct bi-modal distribution is observed.

30 CFR 57.22205 - Doors on main fans (I-A, II-A, III, and V-A mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Doors on main fans (I-A, II-A, III, and V-A... main fans (I-A, II-A, III, and V-A mines). In mines ventilated by multiple main fans, each main fan... reversal through the fan. The doors shall be located so that they are not in direct line with explosive...

30 CFR 57.22222 - Ventilation materials (I-A, I-B, I-C, II-A, III, V-A, and V-B mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Ventilation materials (I-A, I-B, I-C, II-A, III, V-A, and V-B mines). 57.22222 Section 57.22222 Mineral Resources MINE SAFETY AND HEALTH....22222 Ventilation materials (I-A, I-B, I-C, II-A, III, V-A, and V-B mines). Brattice cloth and...

30 CFR 57.22222 - Ventilation materials (I-A, I-B, I-C, II-A, III, V-A, and V-B mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Ventilation materials (I-A, I-B, I-C, II-A, III, V-A, and V-B mines). 57.22222 Section 57.22222 Mineral Resources MINE SAFETY AND HEALTH....22222 Ventilation materials (I-A, I-B, I-C, II-A, III, V-A, and V-B mines). Brattice cloth and...

Rapid actions of aldosterone revisited: Receptors in the limelight.

PubMed

Wehling, Martin

2018-02-01

Steroid hormones like aldosterone have been conclusively shown to elicit both late genomic and rapid, nongenomically initiated responses. Aldosterone was among the first for which rapid, clinically relevant effects were even shown in humans. Yet, after over 30 years of research, the nature of receptors involved in rapid actions of aldosterone is still unclear. Such effects may be assigned to the classical, intracellular steroid receptors, in this case mineralocorticoid receptors (MR, class IIa action Mannheim classification). They typically disappear in knockout models and are blocked by MR-antagonists such as spironolactone, as shown for several cellular and physiological, e.g. renal or cardiovascular effects. In contrast, there is also consistent evidence suggesting type IIb effects involving structurally different receptors ("membrane receptors") being insensitive to classic antagonists and persistent in knockout models; IIb effects have lately even been confirmed by atomic force detection of surface receptors which bind aldosterone but not spironolactone. Type IIa and b may coexist in the same cell with IIa often augmenting early IIb effects. So far cloning of IIb receptors was unsuccessful; therefore results on G-protein coupled estrogen receptor 1 (GPER1) being potentially involved in rapid aldosterone action raised considerable interest. Surprisingly, GPER1 does not bind aldosterone. Though under these circumstances GPER1 should not yet be considered as IIb-receptor, it might be an intermediary signaling enhancer of mineralocorticoid action as shown for epithelial growth factor receptors reconciling those results. We still seem to be left without IIb-receptors whose identification would however be highly desirable and essential for clinical translation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Detection and genetic characterization of Canine parvovirus and Canine coronavirus strains circulating in district of Tirana in Albania.

PubMed

Cavalli, Alessandra; Desario, Costantina; Kusi, Ilir; Mari, Viviana; Lorusso, Eleonora; Cirone, Francesco; Kumbe, Ilirjan; Colaianni, Maria Loredana; Buonavoglia, Domenico; Decaro, Nicola

2014-07-01

An epidemiological survey for Canine parvovirus 2 (CPV-2) and Canine coronavirus (CCoV) was conducted in Albania. A total of 57 fecal samples were collected from diarrheic dogs in the District of Tirana during 2011-2013. The molecular assays detected 53 and 31 CPV- and CCoV-positive specimens, respectively, with mixed CPV-CCoV infections diagnosed in 28 dogs. The most frequently detected CPV type was 2a, whereas IIa was the predominant CCoV subtype. A better comprehension of the CPV-CCoV epidemiology in eastern European countries will help to assess the most appropriate vaccination strategies to prevent disease due to infections with these widespread agents of acute gastroenteritis in the dog.

Intrauterine growth-restricted sheep fetuses exhibit smaller hindlimb muscle fibers and lower proportions of insulin-sensitive Type I fibers near term.

PubMed

Yates, Dustin T; Cadaret, Caitlin N; Beede, Kristin A; Riley, Hannah E; Macko, Antoni R; Anderson, Miranda J; Camacho, Leticia E; Limesand, Sean W

2016-06-01

Intrauterine growth restriction (IUGR) reduces muscle mass and insulin sensitivity in offspring. Insulin sensitivity varies among muscle fiber types, with Type I fibers being most sensitive. Differences in fiber-type ratios are associated with insulin resistance in adults, and thus we hypothesized that near-term IUGR sheep fetuses exhibit reduced size and proportions of Type I fibers. Placental insufficiency-induced IUGR fetuses were ∼54% smaller (P < 0.05) than controls and exhibited hypoxemia and hypoglycemia, which contributed to 6.9-fold greater (P < 0.05) plasma norepinephrine and ∼53% lower (P < 0.05) plasma insulin concentrations. IUGR semitendinosus muscles contained less (P < 0.05) myosin heavy chain-I protein (MyHC-I) and proportionally fewer (P < 0.05) Type I and Type I/IIa fibers than controls, but MyHC-II protein concentrations, Type II fibers, and Type IIx fibers were not different. IUGR biceps femoris muscles exhibited similar albeit less dramatic differences in fiber type proportions. Type I and IIa fibers are more responsive to adrenergic and insulin regulation than Type IIx and may be more profoundly impaired by the high catecholamines and low insulin in our IUGR fetuses, leading to their proportional reduction. In both muscles, fibers of each type were uniformly smaller (P < 0.05) in IUGR fetuses than controls, which indicates that fiber hypertrophy is not dependent on type but rather on other factors such as myoblast differentiation or protein synthesis. Together, our findings show that IUGR fetal muscles develop smaller fibers and have proportionally fewer Type I fibers, which is indicative of developmental adaptations that may help explain the link between IUGR and adulthood insulin resistance. Copyright © 2016 the American Physiological Society.

Radiotherapy Treatment Planning for Testicular Seminoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wilder, Richard B., E-mail: richardbwilder@yahoo.com; Buyyounouski, Mark K.; Efstathiou, Jason A.

2012-07-15

Virtually all patients with Stage I testicular seminoma are cured regardless of postorchiectomy management. For patients treated with adjuvant radiotherapy, late toxicity is a major concern. However, toxicity may be limited by radiotherapy techniques that minimize radiation exposure of healthy normal tissues. This article is an evidence-based review that provides radiotherapy treatment planning recommendations for testicular seminoma. The minority of Stage I patients who choose adjuvant treatment over surveillance may be considered for (1) para-aortic irradiation to 20 Gy in 10 fractions, or (2) carboplatin chemotherapy consisting of area under the curve, AUC = 7 Multiplication-Sign 1-2 cycles. Two-dimensional radiotherapymore » based on bony anatomy is a simple and effective treatment for Stage IIA or IIB testicular seminoma. Centers with expertise in vascular and nodal anatomy may consider use of anteroposterior-posteroanterior fields based on three-dimensional conformal radiotherapy instead. For modified dog-leg fields delivering 20 Gy in 10 fractions, clinical studies support placement of the inferior border at the top of the acetabulum. Clinical and nodal mapping studies support placement of the superior border of all radiotherapy fields at the top of the T12 vertebral body. For Stage IIA and IIB patients, an anteroposterior-posteroanterior boost is then delivered to the adenopathy with a 2-cm margin to the block edge. The boost dose consists of 10 Gy in 5 fractions for Stage IIA and 16 Gy in 8 fractions for Stage IIB. Alternatively, bleomycin, etoposide, and cisplatin chemotherapy for 3 cycles or etoposide and cisplatin chemotherapy for 4 cycles may be delivered to Stage IIA or IIB patients (e.g., if they have a horseshoe kidney, inflammatory bowel disease, or a history of radiotherapy).« less

Inducer bacteria, unique signal peptides and low nutrient media stimulate in-vitro bacteriocin production by Lactobacillus spp. and Enterococcus spp. strains

USDA-ARS?s Scientific Manuscript database

Bacteriocins (BCN) provide promising potential to control bacterial infections in a variety of applications. We previously reported three Type IIa BCN produced by Lactobacillus salivarius B-30514 (OR-7), Enterococcus durans/faecium/hirae B-30745 (E 760) and Enterococcus faecium B-30746 (E 50-52). ...

30 CFR 57.22235 - Actions at 1.0 percent methane (I-C, II-A, II-B, and IV mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Actions at 1.0 percent methane (I-C, II-A, II-B... AND NONMETAL MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22235 Actions at 1.0 percent methane (I-C, II-A, II-B, and IV mines). (a) If methane reaches 1.0 percent in the...

30 CFR 57.22235 - Actions at 1.0 percent methane (I-C, II-A, II-B, and IV mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Actions at 1.0 percent methane (I-C, II-A, II-B, and IV mines). 57.22235 Section 57.22235 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... Actions at 1.0 percent methane (I-C, II-A, II-B, and IV mines). (a) If methane reaches 1.0 percent in the...

Embolization of the Internal Iliac Artery: Cost-Effectiveness of Two Different Techniques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pellerin, Olivier, E-mail: olivier.pellerin@egp.aphp.f; Caruba, Thibaud; Kandounakis, Yanis

2008-11-15

The purpose of this study was to compare the cost-effectiveness of coils versus the Amplatzer Vascular Plug (AVP) for occlusion of the internal iliac artery (IAA). Between 2002 and January 2006, 13 patients (mean age 73 {+-} 13 years) were referred for stent-grafting of abdominal aortic aneurysm (n = 6); type I distal endoleak (n = 3), isolated iliac aneurysm (n = 3), or rupture of a common iliac aneurysm (n = 1). In all patients, extension of the stent-graft was needed because the distal neck was absent. Two different techniques were used to occlude the IIA: AVP in sevenmore » patients (group A) and coil embolization in six patients (group C). Immediate results and direct material costs were assessed retrospectively. Immediate success was achieved in all patients, and simultaneous stent-grafting was successfully performed in two of six patients in group C versus five of seven patients in group A. In all group A patients, a single AVP was sufficient to achieve occlusion of the IIA, accounting for a mean cost of 485 Euro , whereas in group C patients, an average of 7 {+-} 3 coils were used, accounting for a mean cost of 1,745 Euro . Mean average cost savings using the AVP was 1,239 Euro . When IIA occlusion is needed, the AVP allows a single-step procedure at significant cost savings.« less

Massless spectra and gauge couplings at one-loop on non-factorisable toroidal orientifolds

NASA Astrophysics Data System (ADS)

Berasaluce-González, Mikel; Honecker, Gabriele; Seifert, Alexander

2018-01-01

So-called 'non-factorisable' toroidal orbifolds can be rewritten in a factorised form as a product of three two-tori by imposing an additional shift symmetry. This finding of Blaszczyk et al. [1] provides a new avenue to Conformal Field Theory methods, by which the vector-like massless matter spectrum - and thereby the type of gauge group enhancement on orientifold invariant fractional D6-branes - and the one-loop corrections to the gauge couplings in Type IIA orientifold theories can be computed in addition to the well-established chiral matter spectrum derived from topological intersection numbers among three-cycles. We demonstrate this framework for the Z4 × ΩR orientifolds on the A3 ×A1 ×B2-type torus. As observed before for factorisable backgrounds, also here the one-loop correction can drive the gauge groups to stronger coupling as demonstrated by means of a four-generation Pati-Salam example.

A newly discovered Bordetella species carries a transcriptionally active CRISPR-Cas with a small Cas9 endonuclease

USDA-ARS?s Scientific Manuscript database

The Cas9 endonuclease of the Type II-a clustered regularly interspersed short palindromic repeats (CRISPR), of Streptococcus pyogenes (SpCas9) has been adapted as a widely used tool for genome editing and genome engineering. Herein, we describe a gene encoding a novel Cas9 ortholog (BpsuCas9) and th...

40 CFR 75.64 - Quarterly reports.

Code of Federal Regulations, 2010 CFR

2010-07-01

... facility system ID; (C) State facility ID; (D) Source category/type; (E) Primary SIC code; (F) State postal... information required by § 75.53 and hardcopy test data and results required by § 75.59; (viii) Records of flow... § 75.59(a)(7)(ii)(A) through (T) and under § 75.59(a)(7)(iii)(A) through (M) shall be reported for flow...

Spines vs. microspines: an overview of the sculpture exine in selected basal and derived Asteraceae with focus on Asteroideae.

PubMed

Tellería, María C

2017-11-01

This study presents a detailed examination of the echinate and microechinate sculpturing in relation to the size of pollen grains in 31 selected species of Asteraceae belonging to the subfamilies Barnadesioideae, Mutisioideae, Carduoideae and Asteroideae. The aims were to recognize sculpturing patterns, under LM and SEM, within large and small pollen of both basal and derived species and to explore the features that could have taxonomic value to apply in palynological disciplines. The detailed examination of the exine surface showed both the relevance and limits of sculptural patterns for taxonomy. Under LM, the microechinate sculpture gave little taxonomic information, whereas in the echinate sculpture, three exine types and two subtypes were recognized. Type I included microechinate exine, which is commonly present in large pollen grains of the basal lineages. Types II (subtypes IIa and IIb) and III included echinate and smaller pollen grains. In these types, spines were always regularly arranged and, were characterized by the length, shape, tip, perforations and distribution. Type IIa included more or less conical spines usually with a distended base, less than 4 µm in length, present in species of different tribes like Astereae, Eupatorieae, Helenieae, Gnaphalieae, Senecioideae and Heliantheae to a lesser extent. Type IIb includes slender spines with narrower bases, longer than 4 µm, present in species of Coreopsideae, Heliantheae, Tageteae and Eupatorieae to a lesser extent. Type III included spines with swollen base, blunt tip and perforations over their entire surface. This type was present in only one of the basal species-Carduus thoermeri-and in one species of the derived tribe Helenieae, Gaillardia megapotamica. Probably, this is due to evolutionary convergence.

Effect of controlled exercise on middle gluteal muscle fibre composition in Thoroughbred foals.

PubMed

Eto, D; Yamano, S; Kasashima, Y; Sugiura, T; Nasu, T; Tokuriki, M; Miyata, H

2003-11-01

Most racehorses are trained regularly from about age 18 months; therefore, little information is available on the effect of training in Thoroughbred foals. Well-controlled exercise could improve muscle potential ability for endurance running. Thoroughbred foals at age 2 months were separated into control and training (treadmill exercise) groups and samples obtained from the middle gluteal muscle at 2 and 12 months post partum. Muscle fibre compositions were determined by histochemical and electrophoretical techniques and succinic dehydrogenase (SDH) activity was analysed in each fibre type. All fibre types were hypertrophied with growth and type I and IIA fibres were significantly larger in the training than the control group at age 12 months. A significant increase of SDH activity was found in type IIX muscle fibres in the training group. Training in young Thoroughbred horses can facilitate muscle fibre hypertrophy and increase the oxidative capacity of type IIX fibres, which could potentially enhance stamina at high speeds. To apply this result to practical training, further studies are needed to determine more effective and safe intensities of controlled exercise.

Nerve-sparing radical hysterectomy for stage IA2-IIB cervical cancer: 5-year survival of 501 consecutive cases.

PubMed

Papp, Z; Csapó, Zs; Hupuczi, P; Mayer, A

2006-01-01

The purpose of this study was to assess the 5-year survival and morbidity in cases with radical hysterectomy and pelvic lymphadenectomy with pre- and postoperative irradiation performed to treat Stage IA2-IIB cervical cancer. During a 10(1/2)-year period between July 1990 and December 2000, 501 consecutive radical hysterectomies with bilateral pelvic lymphadenectomy were performed by the same gynecological surgeon in Stage IA2, IB, IIA and IIB cervical cancer. The patients were treated by pre- and postoperative irradiation as well. Apart from recurrence, perioperative complications were minimal with no long-term morbidity. The absolute 5-year survival rates for the patients in Stage IA2, IB1, IB2, IIA and IIB were 94.4%, 90.7%, 84.1%, 71.1%, and 55.4%, respectively. The respective 5-year survival rates for patients without or with lymph node metastasis were 94.5% and 33.3% in Stage IB2, 81.7% and 48.7% in Stage IIA and 70.2% and 36.5% in Stage IIB, respectively. Nerve-sparing radical hysterectomy with pelvic lymph node dissection and pre- and postoperative irradiation remains the treatment of choice for most patients with early-stage and even Stage IIB cervical cancer. The radicalism and extent of lymph node dissection and parametrial resection should be individualized and tailored to tumor- and patient-related risk factors.

Identification of the group IIa WRKY subfamily and the functional analysis of GhWRKY17 in upland cotton (Gossypium hirsutum L.)

PubMed Central

Gu, Lijiao; Li, Libei; Wei, Hengling; Wang, Hantao; Su, Junji; Guo, Yaning

2018-01-01

WRKY transcription factors play important roles in plant defense, stress response, leaf senescence, and plant growth and development. Previous studies have revealed the important roles of the group IIa GhWRKY genes in cotton. To comprehensively analyze the group IIa GhWRKY genes in upland cotton, we identified 15 candidate group IIa GhWRKY genes in the Gossypium hirsutum genome. The phylogenetic tree, intron-exon structure, motif prediction and Ka/Ks analyses indicated that most group IIa GhWRKY genes shared high similarity and conservation and underwent purifying selection during evolution. In addition, we detected the expression patterns of several group IIa GhWRKY genes in individual tissues as well as during leaf senescence using public RNA sequencing data and real-time quantitative PCR. To better understand the functions of group IIa GhWRKYs in cotton, GhWRKY17 (KF669857) was isolated from upland cotton, and its sequence alignment, promoter cis-acting elements and subcellular localization were characterized. Moreover, the over-expression of GhWRKY17 in Arabidopsis up-regulated the senescence-associated genes AtWRKY53, AtSAG12 and AtSAG13, enhancing the plant’s susceptibility to leaf senescence. These findings lay the foundation for further analysis and study of the functions of WRKY genes in cotton. PMID:29370286

SCOUT Nozzle Data Book

NASA Technical Reports Server (NTRS)

Shieds, S.

1976-01-01

Available analyses and material property information are summarized relevant to the design of four rocket motor nozzles currently incorporated in the four solid propellant rocket stages of the NASA SCOUT launch vehicle. The nozzles discussed include those for the following motors: (1) first stage - Algol IIIA; (2) second stage - Castor IIA; (3) third stage - Antares IIA; and (4) fourth stage - Altair IIIA. Separate sections for each nozzle provide complete data packages. Information on the Antares IIB motor which had limited usage as an alternate motor for the third stage is included.

30 CFR 57.22232 - Actions at 0.5 percent methane (I-B, II-A, II-B, IV, V-B, and VI mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Actions at 0.5 percent methane (I-B, II-A, II-B...-UNDERGROUND METAL AND NONMETAL MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22232 Actions at 0.5 percent methane (I-B, II-A, II-B, IV, V-B, and VI mines). If methane reaches 0.5...

30 CFR 57.22232 - Actions at 0.5 percent methane (I-B, II-A, II-B, IV, V-B, and VI mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Actions at 0.5 percent methane (I-B, II-A, II-B, IV, V-B, and VI mines). 57.22232 Section 57.22232 Mineral Resources MINE SAFETY AND HEALTH....22232 Actions at 0.5 percent methane (I-B, II-A, II-B, IV, V-B, and VI mines). If methane reaches 0.5...

Interactive Image Analysis System Design,

DTIC Science & Technology

1982-12-01

This report describes a design for an interactive image analysis system (IIAS), which implements terrain data extraction techniques. The design... analysis system. Additionally, the system is fully capable of supporting many generic types of image analysis and data processing, and is modularly...employs commercially available, state of the art minicomputers and image display devices with proven software to achieve a cost effective, reliable image

The calibration of photographic and spectroscopic films. Part 1: Film batch variations of reciprocity failure in IIaO film. Part 2: Thermal and aging effects in relationship to reciprocity failure. P art 3: Shifting of reciprocity failure points as a function of thermal and aging effects

NASA Technical Reports Server (NTRS)

Peters, Kevin A.; Atkinson, Pamela F.; Hammond, Ernest C., Jr

1987-01-01

Reciprocity failure was examined for IIaO spectroscopic film. Three separate experiments were performed in order to study film batch variations, thermal and aging effects in relationship to reciprocity failure, and shifting of reciprocity failure points as a function of thermal and aging effects. The failure was examined over ranges of time between 5 and 60 seconds. The variation to illuminance was obtained by using thirty neutral density filters. A standard sensitometer device imprinted the wedge pattern on the film as exposure time was subjected to variation. Results indicate that film batch differences, temperature, and aging play an important role in reciprocity failure of IIaO spectroscopic film. A shifting of the failure points was also observed in various batches of film.

Chemoenzymatic Synthesis of Heparin Oligosaccharides with both Anti-factor Xa and Anti-factor IIa Activities*

PubMed Central

Xu, Yongmei; Pempe, Elizabeth H.; Liu, Jian

2012-01-01

Heparan sulfate (HS) and heparin are highly sulfated polysaccharides. Heparin is a commonly used anticoagulant drug that inhibits the activities of factors Xa and IIa (also known as thrombin) to prevent blood clot formation. Here, we report the synthesis of a series of size-defined oligosaccharides to probe the minimum size requirement for an oligosaccharide with anti-IIa activity. The synthesis was completed by a chemoenzymatic approach involving glycosyltransferases, HS sulfotransferases, and C5-epimerase. We demonstrate the ability to synthesize highly purified N-sulfo-oligosaccharides having up to 21 saccharide residues. The results from anti-Xa and anti-IIa activity measurements revealed that an oligosaccharide longer than 19 saccharide residues is necessary to display anti-IIa activity. The oligosaccharides also exhibit low binding toward platelet factor 4, raising the possibility of preparing a synthetic heparin with a reduced effect of heparin-induced thrombocytopenia. The results from this study demonstrate the ability to synthesize large HS oligosaccharides and provide a unique tool to probe the structure and function relationships of HS that require the use of large HS fragments. PMID:22773834

30 CFR 57.22227 - Approved testing devices (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Approved testing devices (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). 57.22227 Section 57.22227 Mineral Resources MINE SAFETY AND... Ventilation § 57.22227 Approved testing devices (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). (a...

30 CFR 57.22201 - Mechanical ventilation (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Mechanical ventilation (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). 57.22201 Section 57.22201 Mineral Resources MINE SAFETY AND HEALTH....22201 Mechanical ventilation (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). All mines shall...

30 CFR 57.22501 - Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). 57.22501 Section 57.22501 Mineral Resources MINE SAFETY AND... Illumination § 57.22501 Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines...

30 CFR 57.22501 - Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). 57.22501 Section 57.22501 Mineral Resources MINE SAFETY AND... Illumination § 57.22501 Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines...

30 CFR 57.22201 - Mechanical ventilation (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Mechanical ventilation (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). 57.22201 Section 57.22201 Mineral Resources MINE SAFETY AND HEALTH....22201 Mechanical ventilation (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). All mines shall...

Partial Diversity Generates Effector Immunity Specificity of the Bac41-Like Bacteriocins of Enterococcus faecalis Clinical Strains.

PubMed

Kurushima, Jun; Ike, Yasuyoshi; Tomita, Haruyoshi

2016-09-01

Bacteriocin 41 (Bac41) is the plasmid-encoded bacteriocin produced by the opportunistic pathogen Enterococcus faecalis Its genetic determinant consists of bacL1 (effector), bacL2 (regulator), bacA (effector), and bacI (immunity). The secreted effectors BacL1 and BacA coordinate to induce the lytic cell death of E. faecalis Meanwhile, the immunity factor BacI provides self-resistance to the Bac41 producer, E. faecalis, against the action of BacL1 and BacA. In this study, we demonstrated that more than half of the 327 clinical strains of E. faecalis screened had functional Bac41 genes. Analysis of the genetic structure of the Bac41 genes in the DNA sequences of the E. faecalis strains revealed that the Bac41-like genes consist of a relatively conserved region and a variable region located downstream from bacA Based on similarities in the variable region, the Bac41-like genes could be classified into type I, type IIa, and type IIb. Interestingly, the distinct Bac41 types had specific immunity factors for self-resistance, BacI1 or BacI2, and did not show cross-immunity to the other type of effector. We also demonstrated experimentally that the specificity of the immunity was determined by the combination of the C-terminal region of BacA and the presence of the unique BacI1 or BacI2 factor. These observations suggested that Bac41-like bacteriocin genes are extensively disseminated among E. faecalis strains in the clinical environment and can be grouped into at least three types. It was also indicated that the partial diversity results in specificity of self-resistance which may offer these strains a competitive advantage. Bacteriocins are antibacterial effectors produced by bacteria. In general, a bacteriocin-coding gene is accompanied by a cognate immunity gene that confers self-resistance on the bacteriocin-producing bacterium itself. We demonstrated that one of the bacteriocins, Bac41, is disseminated among E. faecalis clinical strains and the Bac41 subtypes with partial diversity. The Bac41-like bacteriocins were found to be classified into type I, type IIa, and type IIb by variation of the cognate immunity factors. The antibacterial activity of the respective effectors was specifically inhibited by the immunity factor from the same type of Bac41 but not the other types. This specificity of effector-immunity pairs suggests that bacteriocin genes might have evolved to change the immunity specificity to acquire an advantage in interbacterial competition. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

30 CFR 57.22501 - Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Personal electric lamps (I-A, I-B, I-C, II-A... Illumination § 57.22501 Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). Electric lamps used for personal illumination shall be approved by MSHA under the requirements of 30 CFR...

30 CFR 57.22501 - Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Personal electric lamps (I-A, I-B, I-C, II-A... Illumination § 57.22501 Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). Electric lamps used for personal illumination shall be approved by MSHA under the requirements of 30 CFR...

30 CFR 57.22501 - Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Personal electric lamps (I-A, I-B, I-C, II-A... Illumination § 57.22501 Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). Electric lamps used for personal illumination shall be approved by MSHA under the requirements of 30 CFR...

Mechanistic Insights into the Binding of Class IIa HDAC Inhibitors toward Spinocerebellar Ataxia Type-2: A 3D-QSAR and Pharmacophore Modeling Approach

PubMed Central

Sinha, Siddharth; Goyal, Sukriti; Somvanshi, Pallavi; Grover, Abhinav

2017-01-01

Spinocerebellar ataxia (SCA-2) type-2 is a rare neurological disorder among the nine polyglutamine disorders, mainly caused by polyQ (CAG) trinucleotide repeats expansion within gene coding ataxin-2 protein. The expanded trinucleotide repeats within the ataxin-2 protein sequesters transcriptional cofactors i.e., CREB-binding protein (CBP), Ataxin-2 binding protein 1 (A2BP1) leading to a state of hypo-acetylation and transcriptional repression. Histone de-acetylases inhibitors (HDACi) have been reported to restore transcriptional balance through inhibition of class IIa HDAC's, that leads to an increased acetylation and transcription as demonstrated through in-vivo studies on mouse models of Huntington's. In this study, 61 di-aryl cyclo-propanehydroxamic acid derivatives were used for developing three dimensional (3D) QSAR and pharmacophore models. These models were then employed for screening and selection of anti-ataxia compounds. The chosen QSAR model was observed to be statistically robust with correlation coefficient (r2) value of 0.6774, cross-validated correlation coefficient (q2) of 0.6157 and co-relation coefficient for external test set (pred_r2) of 0.7570. A high F-test value of 77.7093 signified the robustness of the model. Two potential drug leads ZINC 00608101 (SEI) and ZINC 00329110 (ACI) were selected after a coalesce procedure of pharmacophore based screening using the pharmacophore model ADDRR.20 and structural analysis using molecular docking and dynamics simulations. The pharmacophore and the 3D-QSAR model generated were further validated for their screening and prediction ability using the enrichment factor (EF), goodness of hit (GH), and receiver operating characteristics (ROC) curve analysis. The compounds SEI and ACI exhibited a docking score of −10.097 and −9.182 kcal/mol, respectively. An evaluation of binding conformation of ligand-bound protein complexes was performed with MD simulations for a time period of 30 ns along with free energy binding calculations using the g_mmpbsa technique. Prediction of inhibitory activities of the two lead compounds SEI (7.53) and ACI (6.84) using the 3D-QSAR model reaffirmed their inhibitory characteristics as potential anti-ataxia compounds. PMID:28119557

Mechanistic Insights into the Binding of Class IIa HDAC Inhibitors toward Spinocerebellar Ataxia Type-2: A 3D-QSAR and Pharmacophore Modeling Approach.

PubMed

Sinha, Siddharth; Goyal, Sukriti; Somvanshi, Pallavi; Grover, Abhinav

2016-01-01

Spinocerebellar ataxia (SCA-2) type-2 is a rare neurological disorder among the nine polyglutamine disorders, mainly caused by polyQ (CAG) trinucleotide repeats expansion within gene coding ataxin-2 protein. The expanded trinucleotide repeats within the ataxin-2 protein sequesters transcriptional cofactors i.e., CREB-binding protein (CBP), Ataxin-2 binding protein 1 (A2BP1) leading to a state of hypo-acetylation and transcriptional repression. Histone de-acetylases inhibitors (HDACi) have been reported to restore transcriptional balance through inhibition of class IIa HDAC's, that leads to an increased acetylation and transcription as demonstrated through in-vivo studies on mouse models of Huntington's. In this study, 61 di-aryl cyclo-propanehydroxamic acid derivatives were used for developing three dimensional (3D) QSAR and pharmacophore models. These models were then employed for screening and selection of anti-ataxia compounds. The chosen QSAR model was observed to be statistically robust with correlation coefficient ( r 2 ) value of 0.6774, cross-validated correlation coefficient ( q 2 ) of 0.6157 and co-relation coefficient for external test set ( pred _ r 2 ) of 0.7570. A high F -test value of 77.7093 signified the robustness of the model. Two potential drug leads ZINC 00608101 (SEI) and ZINC 00329110 (ACI) were selected after a coalesce procedure of pharmacophore based screening using the pharmacophore model ADDRR.20 and structural analysis using molecular docking and dynamics simulations. The pharmacophore and the 3D-QSAR model generated were further validated for their screening and prediction ability using the enrichment factor (EF), goodness of hit (GH), and receiver operating characteristics (ROC) curve analysis. The compounds SEI and ACI exhibited a docking score of -10.097 and -9.182 kcal/mol, respectively. An evaluation of binding conformation of ligand-bound protein complexes was performed with MD simulations for a time period of 30 ns along with free energy binding calculations using the g_mmpbsa technique. Prediction of inhibitory activities of the two lead compounds SEI (7.53) and ACI (6.84) using the 3D-QSAR model reaffirmed their inhibitory characteristics as potential anti-ataxia compounds.

Skeletal muscle myostatin mRNA expression is fiber-type specific and increases during hindlimb unloading

NASA Technical Reports Server (NTRS)

Carlson, C. J.; Booth, F. W.; Gordon, S. E.

1999-01-01

Transgenic mice lacking a functional myostatin (MSTN) gene demonstrate greater skeletal muscle mass resulting from muscle fiber hypertrophy and hyperplasia (McPherron, A. C., A. M. Lawler, and S. -J. Lee. Nature 387: 83-90, 1997). Therefore, we hypothesized that, in normal mice, MSTN may act as a negative regulator of muscle mass. Specifically, we hypothesized that the predominately slow (type I) soleus muscle, which demonstrates greater atrophy than the fast (type II) gastrocnemius-plantaris complex (Gast/PLT), would show more elevation in MSTN mRNA abundance during hindlimb unloading (HU). Surprisingly, MSTN mRNA was not detectable in weight-bearing or HU soleus muscle, which atrophied 42% by the 7th day of HU in female ICR mice. In contrast, MSTN mRNA was present in weight-bearing Gast/PLT muscle and was significantly elevated (67%) at 1 day but not at 3 or 7 days of HU. However, the Gast/PLT muscle had only atrophied 17% by the 7th day of HU. Because the soleus is composed only of type I and IIa fibers, whereas the Gast/PLT expresses type IId/x and IIb in addition to type I and IIa, it was necessary to perform a more careful analysis of the relationship between MSTN mRNA levels and myosin heavy-chain (MHC) isoform expression (as a marker of fiber type). A significant correlation (r = 0.725, P < 0. 0005) was noted between the percentage of MHC isoform IIb expression and MSTN mRNA abundance in several muscles of the mouse hindlimb. These results indicate that MSTN expression is not strongly associated with muscle atrophy induced by HU; however, it is strongly associated with MHC isoform IIb expression in normal muscle.

Universal consistent truncation for 6d/7d gauge/gravity duals

NASA Astrophysics Data System (ADS)

Passias, Achilleas; Rota, Andrea; Tomasiello, Alessandro

2015-10-01

Recently, AdS7 solutions of IIA supergravity have been classified; there are infinitely many of them, whose expression is known analytically, and with internal space of S 3 topology. Their field theory duals are six-dimensional (1,0) SCFT's. In this paper we show that for each of these AdS7 solutions there exists a consistent truncation from massive IIA supergravity to minimal gauged supergravity in seven dimensions. This theory has an SU(2) gauge group, and a single scalar, whose value is related to a certain distortion of the internal S 3. This explains the universality observed in recent work on AdS5 and AdS4 solutions dual to compactifications of the (1, 0) SCFT6's. Thanks to previous work on the minimal gauged supergravity, the truncation also implies the existence of holographic RG-flows connecting those solutions to the AdS7 vacuum, as well as new classes of IIA AdS3 solutions.

Overexpression of the Mitochondrial T3 Receptor p43 Induces a Shift in Skeletal Muscle Fiber Types

PubMed Central

Casas, François; Pessemesse, Laurence; Grandemange, Stéphanie; Seyer, Pascal; Gueguen, Naïg; Baris, Olivier; Lepourry, Laurence; Cabello, Gérard; Wrutniak-Cabello, Chantal

2008-01-01

In previous studies, we have characterized a new hormonal pathway involving a mitochondrial T3 receptor (p43) acting as a mitochondrial transcription factor and consequently stimulating mitochondrial activity and mitochondrial biogenesis. We have established the involvement of this T3 pathway in the regulation of in vitro myoblast differentiation.We have generated mice overexpressing p43 under control of the human α-skeletal actin promoter. In agreement with the previous characterization of this promoter, northern-blot and western-blot experiments confirmed that after birth p43 was specifically overexpressed in skeletal muscle. As expected from in vitro studies, in 2-month old mice, p43 overexpression increased mitochondrial genes expression and mitochondrial biogenesis as attested by the increase of mitochondrial mass and mt-DNA copy number. In addition, transgenic mice had a body temperature 0.8°C higher than control ones and displayed lower plasma triiodothyronine levels. Skeletal muscles of transgenic mice were redder than wild-type animals suggesting an increased oxidative metabolism. In line with this observation, in gastrocnemius, we recorded a strong increase in cytochrome oxidase activity and in mitochondrial respiration. Moreover, we observed that p43 drives the formation of oxidative fibers: in soleus muscle, where MyHC IIa fibers were partly replaced by type I fibers; in gastrocnemius muscle, we found an increase in MyHC IIa and IIx expression associated with a reduction in the number of glycolytic fibers type IIb. In addition, we found that PGC-1α and PPARδ, two major regulators of muscle phenotype were up regulated in p43 transgenic mice suggesting that these proteins could be downstream targets of mitochondrial activity. These data indicate that the direct mitochondrial T3 pathway is deeply involved in the acquisition of contractile and metabolic features of muscle fibers in particular by regulating PGC-1α and PPARδ. PMID:18575627

Autosomal-Recessive Mutations in SLC34A1 Encoding Sodium-Phosphate Cotransporter 2A Cause Idiopathic Infantile Hypercalcemia

PubMed Central

Schlingmann, Karl P.; Ruminska, Justyna; Kaufmann, Martin; Dursun, Ismail; Patti, Monica; Kranz, Birgitta; Pronicka, Ewa; Ciara, Elzbieta; Akcay, Teoman; Bulus, Derya; Cornelissen, Elisabeth A.M.; Gawlik, Aneta; Sikora, Przemysław; Patzer, Ludwig; Galiano, Matthias; Boyadzhiev, Veselin; Dumic, Miroslav; Vivante, Asaf; Kleta, Robert; Dekel, Benjamin; Levtchenko, Elena; Bindels, René J.; Rust, Stephan; Forster, Ian C.; Hernando, Nati; Jones, Glenville; Wagner, Carsten A.

2016-01-01

Idiopathic infantile hypercalcemia (IIH) is characterized by severe hypercalcemia with failure to thrive, vomiting, dehydration, and nephrocalcinosis. Recently, mutations in the vitamin D catabolizing enzyme 25-hydroxyvitamin D3-24-hydroxylase (CYP24A1) were described that lead to increased sensitivity to vitamin D due to accumulation of the active metabolite 1,25-(OH)2D3. In a subgroup of patients who presented in early infancy with renal phosphate wasting and symptomatic hypercalcemia, mutations in CYP24A1 were excluded. Four patients from families with parental consanguinity were subjected to homozygosity mapping that identified a second IIH gene locus on chromosome 5q35 with a maximum logarithm of odds (LOD) score of 6.79. The sequence analysis of the most promising candidate gene, SLC34A1 encoding renal sodium-phosphate cotransporter 2A (NaPi-IIa), revealed autosomal-recessive mutations in the four index cases and in 12 patients with sporadic IIH. Functional studies of mutant NaPi-IIa in Xenopus oocytes and opossum kidney (OK) cells demonstrated disturbed trafficking to the plasma membrane and loss of phosphate transport activity. Analysis of calcium and phosphate metabolism in Slc34a1-knockout mice highlighted the effect of phosphate depletion and fibroblast growth factor-23 suppression on the development of the IIH phenotype. The human and mice data together demonstrate that primary renal phosphate wasting caused by defective NaPi-IIa function induces inappropriate production of 1,25-(OH)2D3 with subsequent symptomatic hypercalcemia. Clinical and laboratory findings persist despite cessation of vitamin D prophylaxis but rapidly respond to phosphate supplementation. Therefore, early differentiation between SLC34A1 (NaPi-IIa) and CYP24A1 (24-hydroxylase) defects appears critical for targeted therapy in patients with IIH. PMID:26047794

Clinical outcomes of stage I and IIA non-small cell lung cancer patients treated with stereotactic body radiotherapy using a real-time tumor-tracking radiotherapy system.

PubMed

Katoh, Norio; Soda, Itaru; Tamamura, Hiroyasu; Takahashi, Shotaro; Uchinami, Yusuke; Ishiyama, Hiromichi; Ota, Kiyotaka; Inoue, Tetsuya; Onimaru, Rikiya; Shibuya, Keiko; Hayakawa, Kazushige; Shirato, Hiroki

2017-01-05

To investigate the clinical outcomes of stage I and IIA non-small cell lung cancer (NSCLC) patients treated with stereotactic body radiotherapy (SBRT) using a real-time tumor-tracking radiotherapy (RTRT) system. Patterns-of-care in SBRT using RTRT for histologically proven, peripherally located, stage I and IIA NSCLC was retrospectively investigated in four institutions by an identical clinical report format. Patterns-of-outcomes was also investigated in the same manner. From September 2000 to April 2012, 283 patients with 286 tumors were identified. The median age was 78 years (52-90) and the maximum tumor diameters were 9 to 65 mm with a median of 24 mm. The calculated biologically effective dose (10) at the isocenter using the linear-quadratic model was from 66 Gy to 126 Gy with a median of 106 Gy. With a median follow-up period of 28 months (range 0-127), the overall survival rate for the entire group, for stage IA, and for stage IB + IIA was 75%, 79%, and 65% at 2 years, and 64%, 70%, and 50% at 3 years, respectively. In the multivariate analysis, the favorable predictive factor was female for overall survival. There were no differences between the clinical outcomes at the four institutions. Grade 2, 3, 4, and 5 radiation pneumonitis was experienced by 29 (10.2%), 9 (3.2%), 0, and 0 patients. The subgroup analyses revealed that compared to margins from gross tumor volume (GTV) to planning target volume (PTV) ≥ 10 mm, margins < 10 mm did not worsen the overall survival and local control rates, while reducing the risk of radiation pneumonitis. This multi-institutional retrospective study showed that the results were consistent with the recent patterns-of-care and patterns-of-outcome analysis of SBRT. A prospective study will be required to evaluate SBRT using a RTRT system with margins from GTV to PTV < 10mm.

The role of social isolation in ethanol effects on the preweanling rat

PubMed Central

Kozlov, Andrey P.; Nizhnikov, Michael; Varlinskaya, Elena I.; Spear, Norman E.

2011-01-01

The present experiments investigated the effects of acute ethanol exposure on voluntary intake of 0.1% saccharin or water as well as behavioral and nociceptive reactivity in twelve–day-old (P12) rats exposed to differing levels of isolation. The effects of ethanol emerged only during short-term social isolation (STSI) with different patterns observed in males and females and in pups exposed to saccharin or water. The 0.5 g/kg ethanol dose selectively increased saccharin intake in females, decreased rearing activity in males and attenuated isolation-induced analgesia (IIA) in all water-exposed pups. Ingestion of saccharin decreased IIA, and the 0.5 g/kg ethanol dose further reduced IIA. The 1.0 g/kg ethanol dose, administered either intragastrically or intraparentionally, also decreased IIA in P12 females, but not in P9 pups. A significant correlation between voluntary saccharin intake and baseline nociceptive reactivity was revealed in saline injected animals, saccharin intake was inversely correlated with behavioral activation and latency of reaction to noxious heat after 0.5 g/kg ethanol in females. The 0.5 g/kg ethanol dose did not affect plasma corticosterone (CORT) measured 5 hours after maternal separation or 20 minutes after ethanol injection. Female pups CORT level was inversely correlated with magnitude of IIA that accompanied the first episode of STSI (pretest isolation) 1.5–2 hours before CORT measurement. The present findings suggest that the anxiolytic properties of ethanol are responsible for enhancement of saccharin intake during STSI. Furthermore, differential reactivity of P12 males and females to STSI plays an important role in ethanol effects observed at this age. PMID:22051944

Computer Simulation of Ejection Seat Performance and Preliminary Correlation with Empirical Data

DTIC Science & Technology

1980-04-01

L. . .. . 3 I r AFFDL-TR-79-31 50 TABLE OF CONTENTS SECTION PAGE I INTRODUCTION 1 1I SAFEST COMPUTER PROGRAM DESCRIPTION 8 III HITECH ...ZEARTH vs TIME 49E-I1A 53 34 ZEARTH vs XEARTH 49E-IIA 54 AFFDL-TR-79-3150 LIST OF TABLES TABLE PAGE 1 ACES II EVENT-TIME SEQUENCE 3 2 HITECH 49E-JlF...Initial Conditions 13 3 HITECH 49E-I1A Initial Conditions 14 4 HITECH Program Test Data Summary 15 5 SAFEST 49E-JIF Initial Conditions 20 6 SAFEST 49E-IIA

Pre-Training Muscle Characteristics of Subjects Who Are Obese Determine How Well Exercise Training Will Improve Their Insulin Responsiveness

PubMed Central

Stuart, Charles A.; Lee, Michelle L.; South, Mark A.; Howell, Mary E.A.; Cartwright, Brian M.; Ramsey, Michael W.; Stone, Michael H.

2016-01-01

Only half of pre-diabetic, subjects who are obese who underwent exercise training without weight loss increased their insulin responsiveness. We hypothesized that those who improved their insulin responsiveness might have pre-training characteristics favoring a positive response to exercise training. Thirty non-diabetic, subjects who are obese volunteered for eight weeks of either strength training or endurance training. During training, subjects increased their caloric intake to prevent weight loss. Insulin responsiveness by euglycemic clamps and muscle fiber composition and expression of muscle key biochemical pathways were quantified. Positive responders initially had 52% higher intermediate muscle fibers (fiber type IIa) with 27% lower slow twitch fibers (type I) and 23% lower expression of muscle insulin receptors. Whether after weight training or stationary bike training, positive responders' fiber type shifted away from type I and type IIa fibers to an increased proportion of type IIx fibers (fast twitch). Muscle insulin receptor expression and GLUT4 expression increased in all trained subjects, but these moderate changes did not consistently translate to improvement in whole body insulin responsiveness. Exercise training of previously sedentary subjects who are obese can result in muscle remodeling and increased expression of key elements of the insulin pathway, but in the absence of weight loss, insulin sensitivity improvement was modest and limited to about half of the participants. Our data suggest rather than responders being more fit, they may have been less fit, only catching up to the other half of subjects who are obese whose insulin responsiveness did not increase beyond their pre-training baseline. PMID:27379957

Myosin heavy chain composition of tiger (Panthera tigris) and cheetah (Acinonyx jubatus) hindlimb muscles.

PubMed

Hyatt, Jon-Philippe K; Roy, Roland R; Rugg, Stuart; Talmadge, Robert J

2010-01-01

Felids have a wide range of locomotor activity patterns and maximal running speeds, including the very fast cheetah (Acinonyx jubatas), the roaming tiger (Panthera tigris), and the relatively sedentary domestic cat (Felis catus). As previous studies have suggested a relationship between the amount and type of activity and the myosin heavy chain (MHC) isoform composition of a muscle, we assessed the MHC isoform composition of selected hindlimb muscles from these three felid species with differing activity regimens. Using gel electrophoresis, western blotting, histochemistry, and immunohistochemistry with MHC isoform-specific antibodies, we compared the MHC composition in the tibialis anterior, medial gastrocnemius (MG), plantaris (Plt), and soleus muscles of the tiger, cheetah, and domestic cat. The soleus muscle was absent in the cheetah. At least one slow (type I) and three fast (types IIa, IIx, and IIb) MHC isoforms were present in the muscles of each felid. The tiger had a high combined percentage of the characteristically slower isoforms (MHCs I and IIa) in the MG (62%) and the Plt (86%), whereas these percentages were relatively low in the MG (44%) and Plt (55%) of the cheetah. In general, the MHC isoform characteristics of the hindlimb muscles matched the daily activity patterns of these felids: the tiger has daily demands for covering long distances, whereas the cheetah has requirements for speed and power. (c) 2009 Wiley-Liss, Inc.

Growth hormone, IGF-I, and exercise effects on non-weight-bearing fast muscles of hypophysectomized rats

NASA Technical Reports Server (NTRS)

Grossman, E. J.; Grindeland, R. E.; Roy, R. R.; Talmadge, R. J.; Evans, J.; Edgerton, V. R.

1997-01-01

The effects of growth hormone (GH) or insulin-like growth factor I (IGF-I) with or without exercise (ladder climbing) in countering the effects of unweighting on fast muscles of hypophysectomized rats during 10 days of hindlimb suspension were determined. Compared with untreated suspended rats, muscle weights were 16-29% larger in GH-treated and 5-15% larger in IGF-I-treated suspended rats. Exercise alone had no effect on muscle weights. Compared with ambulatory control, the medial gastrocnemius weight in suspended, exercised rats was larger after GH treatment and maintained with IGF-I treatment. The combination of GH or IGF-I plus exercise in suspended rats resulted in an increase in size of each predominant fiber type, i.e., types I, I + IIa and IIa + IIx, in the medial gastrocnemius compared with untreated suspended rats. Normal ambulation or exercise during suspension increased the proportion of fibers expressing embryonic myosin heavy chain in hypophysectomized rats. The phenotype of the medial gastrocnemius was minimally affected by GH, IGF-I, and/or exercise. These results show that there is an IGF-I, as well as a GH, and exercise interactive effect in maintaining medial gastrocnemius fiber size in suspended hypophysectomized rats.

SPIRE - combining SGI-110 with cisplatin and gemcitabine chemotherapy for solid malignancies including bladder cancer: study protocol for a phase Ib/randomised IIa open label clinical trial.

PubMed

Crabb, Simon; Danson, Sarah J; Catto, James W F; McDowell, Cathy; Lowder, James N; Caddy, Joshua; Dunkley, Denise; Rajaram, Jessica; Ellis, Deborah; Hill, Stephanie; Hathorn, David; Whitehead, Amy; Kalevras, Mihalis; Huddart, Robert; Griffiths, Gareth

2018-04-03

Urothelial bladder cancer (UBC) accounts for 10,000 new diagnoses and 5000 deaths annually in the UK (Cancer Research UK, http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/bladder-cancer , Cancer Research UK, Accessed 26 Mar 2018). Cisplatin-based chemotherapy is standard of care therapy for UBC for both palliative first-line treatment of advanced/metastatic disease and radical neoadjuvant treatment of localised muscle invasive bladder cancer. However, cisplatin resistance remains a critical cause of treatment failure and a barrier to therapeutic advance in UBC. Based on supportive pre-clinical data, we hypothesised that DNA methyltransferase inhibition would circumvent cisplatin resistance in UBC and potentially other cancers. The addition of SGI-110 (guadecitabine, a DNA methyltransferase inhibitor) to conventional doublet therapy of gemcitabine and cisplatin (GC) is being tested within the phase Ib/IIa SPIRE clinical trial. SPIRE incorporates an initial, modified rolling six-dose escalation phase Ib design of up to 36 patients with advanced solid tumours followed by a 20-patient open-label randomised controlled dose expansion phase IIa component as neoadjuvant treatment for UBC. Patients are being recruited from UK secondary care sites. The dose escalation phase will determine a recommended phase II dose (RP2D, primary endpoint) of SGI-110, by subcutaneous injection, on days 1-5 for combination with GC at conventional doses (cisplatin 70 mg/m 2 , IV infusion, day 8; gemcitabine 1000 mg/m 2 , IV infusion, days 8 and 15) in every 21-day cycle. In the dose expansion phase, patients will be randomised 1:1 to GC with or without SGI-110 at the proposed RP2D. Secondary endpoints will include toxicity profiles, SGI-110 pharmacokinetics and pharmacodynamic biomarkers, and pathological complete response rates in the dose expansion phase. Analyses will not be powered for formal statistical comparisons and descriptive statistics will be used to describe rates of toxicity, efficacy and translational endpoints by treatment arm. SPIRE will provide evidence for whether SGI-110 in combination with GC chemotherapy is safe and biologically effective prior to future phase II/III trials as a neoadjuvant therapy for UBC and potentially in other cancers treated with GC. EudraCT Number: 2015-004062-29 (entered Dec 7, 2015) ISRCTN registry number: 16332228 (registered on Feb 3, 2016).

Ion-beam-assisted etching of diamond

NASA Technical Reports Server (NTRS)

Efremow, N. N.; Geis, M. W.; Flanders, D. C.; Lincoln, G. A.; Economou, N. P.

1985-01-01

The high thermal conductivity, low RF loss, and inertness of diamond make it useful in traveling wave tubes operating in excess of 500 GHz. Such use requires the controlled etching of type IIA diamond to produce grating like structures tens of micrometers deep. Previous work on reactive ion etching with O2 gave etching rates on the order of 20 nm/min and poor etch selectivity between the masking material (Ni or Cr) and the diamond. An alternative approach which uses a Xe(+) beam and a reactive gas flux of NO2 in an ion-beam-assisted etching system is reported. An etching rate of 200 nm/min was obtained with an etching rate ratio of 20 between the diamond and an aluminum mask.

Structural analyses of von Willebrand factor C domains of collagen 2A and CCN3 reveal an alternative mode of binding to bone morphogenetic protein-2.

PubMed

Xu, Emma-Ruoqi; Blythe, Emily E; Fischer, Gerhard; Hyvönen, Marko

2017-07-28

Bone morphogenetic proteins (BMPs) are secreted growth factors that promote differentiation processes in embryogenesis and tissue development. Regulation of BMP signaling involves binding to a variety of extracellular proteins, among which are many von Willebrand factor C (vWC) domain-containing proteins. Although the crystal structure of the complex of crossveinless-2 (CV-2) vWC1 and BMP-2 previously revealed one mode of the vWC/BMP-binding mechanism, other vWC domains may bind to BMP differently. Here, using X-ray crystallography, we present for the first time structures of the vWC domains of two proteins thought to interact with BMP-2: collagen IIA and matricellular protein CCN3. We found that these two vWC domains share a similar N-terminal fold that differs greatly from that in CV-2 vWC, which comprises its BMP-2-binding site. We analyzed the ability of these vWC domains to directly bind to BMP-2 and detected an interaction only between the collagen IIa vWC and BMP-2. Guided by the collagen IIa vWC domain crystal structure and conservation of surface residues among orthologous domains, we mapped the BMP-binding epitope on the subdomain 1 of the vWC domain. This binding site is different from that previously observed in the complex between CV-2 vWC and BMP-2, revealing an alternative mode of interaction between vWC domains and BMPs. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Disabling Cas9 by an anti-CRISPR DNA mimic.

PubMed

Shin, Jiyung; Jiang, Fuguo; Liu, Jun-Jie; Bray, Nicolas L; Rauch, Benjamin J; Baik, Seung Hyun; Nogales, Eva; Bondy-Denomy, Joseph; Corn, Jacob E; Doudna, Jennifer A

2017-07-01

CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 gene editing technology is derived from a microbial adaptive immune system, where bacteriophages are often the intended target. Natural inhibitors of CRISPR-Cas9 enable phages to evade immunity and show promise in controlling Cas9-mediated gene editing in human cells. However, the mechanism of CRISPR-Cas9 inhibition is not known, and the potential applications for Cas9 inhibitor proteins in mammalian cells have not been fully established. We show that the anti-CRISPR protein AcrIIA4 binds only to assembled Cas9-single-guide RNA (sgRNA) complexes and not to Cas9 protein alone. A 3.9 Å resolution cryo-electron microscopy structure of the Cas9-sgRNA-AcrIIA4 complex revealed that the surface of AcrIIA4 is highly acidic and binds with a 1:1 stoichiometry to a region of Cas9 that normally engages the DNA protospacer adjacent motif. Consistent with this binding mode, order-of-addition experiments showed that AcrIIA4 interferes with DNA recognition but has no effect on preformed Cas9-sgRNA-DNA complexes. Timed delivery of AcrIIA4 into human cells as either protein or expression plasmid allows on-target Cas9-mediated gene editing while reducing off-target edits. These results provide a mechanistic understanding of AcrIIA4 function and demonstrate that inhibitors can modulate the extent and outcomes of Cas9-mediated gene editing.

Stadium IB - IIA cervical cancer patient’s survival rate after receiving definitive radiation and radical operation therapy followed by adjuvant radiation therapy along with analysis of factors affecting the patient’s survival rate

NASA Astrophysics Data System (ADS)

Ruslim, S. K.; Purwoto, G.; Widyahening, I. S.; Ramli, I.

2017-08-01

To evaluate the characteristics and overall survival rates of early stage cervical cancer (FIGO IB-IIA) patients who receive definitive radiation therapy and those who are prescribed adjuvant postoperative radiation and to conduct a factors analysis of the variables that affect the overall survival rates in both groups of therapy. The medical records of 85 patients with cervical cancer FIGO stages IB-IIA who were treated at the Department of Radiotherapy of Cipto Mangunkusumo Hospital were reviewed and analyzed to determine their overall survival and the factors that affected it between a definitive radiation group and an adjuvant postoperative radiation group. There were 25 patients in the definitive radiation and 60 patients in the adjuvant radiation group. The overall survival rates in the adjuvant radiation group at years one, two, and three were 96.7%, 95%, and 93.3%, respectively. Negative lymph node metastasis had an average association with overall survival (p < 0.2). In the definitive radiation group, overall survival at years one, two, and three were 96%, 92%, and 92%, respectively. A hemoglobin (Hb) level >12 g/dl was a factor with an average association with the overall survival (p < 0.2). The differences between both groups of therapy were not statistically significant (92% vs. 93.3%; p = 0.138). This study did not show any statistically significant overall survival for cervical cancer FIGO stage IB-IIA patients who received definitive radiation or adjuvant postoperative radiation. Negative lymph node metastasis had an effect on the overall survival rate in the adjuvant postoperative radiation group, while a preradiation Hb level >12 g/dl tended to affect the overall survival in the definitive radiation group patients.

[Types of dislipidemia in children with metabolic syndrome].

PubMed

Hromnats'ka, N M

2014-01-01

To study dyslipidemia types in children with metabolic syndrome. From 1520 children of total population 155 children aged from 9 to 18 years were selected, who formed 2 groups: 1 group--85 children with metabolic syndrome, 2 group--54 children with normal body mass. Anthropometry, blood pressure measurement, estimation of total cholesterol, low density cholesterol, very low density cholesterol, high density cholesterol, tryglicerides in blood were done. The total cholesterol level was 1,1 times higher (p = 0.001), low density cholesterol 1,4 times higher (p = 0.001), very low density cholesterol 1,1 times higher (p= 0.015), tryglicerides 1,1 times higher (p = 0.020) in children with metabolic syndrome than in children of control group. In children with metabolic syndrome sensitively more often IIa, IV dislipidemia types and isolated hypercholesterolemia and less often IIb, III dislipidemia types and high density cholesterol isolated decrease were diagnosed. So children with metabolic syndrome were characterized by atherogenic types of dislipidemias which determine early atherosclerosis development. Children with metabolic syndrome must be examined on the lipid metabolism violation with the aim of its prevention and correction.

Class IIa Bacteriocins: Diversity and New Developments

PubMed Central

Cui, Yanhua; Zhang, Chao; Wang, Yunfeng; Shi, John; Zhang, Lanwei; Ding, Zhongqing; Qu, Xiaojun; Cui, Hongyu

2012-01-01

Class IIa bacteriocins are heat-stable, unmodified peptides with a conserved amino acids sequence YGNGV on their N-terminal domains, and have received much attention due to their generally recognized as safe (GRAS) status, their high biological activity, and their excellent heat stability. They are promising and attractive agents that could function as biopreservatives in the food industry. This review summarizes the new developments in the area of class IIa bacteriocins and aims to provide uptodate information that can be used in designing future research. PMID:23222636

Electrical Conductivity Of Diamond Up To 1,200 Degrees C

NASA Technical Reports Server (NTRS)

Vandersande, Jan W.; Zoltan, Leslie D.

1993-01-01

Report discusses measurements of electrical conductivities of two synthetic diamond films, three synthetic diamondlike films, and two natural type IIa diamonds at temperatures from ambient to 1,200 degrees C. Measurements performed to compare electrical conductivities of state-of-the-art diamond films with those of natural insulating diamond, particularly at temperatures above 700 degrees C.

Dual role for myosin II in GLUT4-mediated glucose uptake in 3T3-L1 adipocytes.

PubMed

Fulcher, F Kent; Smith, Bethany T; Russ, Misty; Patel, Yashomati M

2008-10-15

Insulin-stimulated glucose uptake requires the activation of several signaling pathways to mediate the translocation and fusion of GLUT4 vesicles to the plasma membrane. Our previous studies demonstrated that GLUT4-mediated glucose uptake is a myosin II-dependent process in adipocytes. The experiments described in this report are the first to show a dual role for the myosin IIA isoform specifically in regulating insulin-stimulated glucose uptake in adipocytes. We demonstrate that inhibition of MLCK but not RhoK results in impaired insulin-stimulated glucose uptake. Furthermore, our studies show that insulin specifically stimulates the phosphorylation of the RLC associated with the myosin IIA isoform via MLCK. In time course experiments, we determined that GLUT4 translocates to the plasma membrane prior to myosin IIA recruitment. We further show that recruitment of myosin IIA to the plasma membrane requires that myosin IIA be activated via phosphorylation of the RLC by MLCK. Our findings also reveal that myosin II is required for proper GLUT4-vesicle fusion at the plasma membrane. We show that once at the plasma membrane, myosin II is involved in regulating the intrinsic activity of GLUT4 after insulin stimulation. Collectively, our results are the first to reveal that myosin IIA plays a critical role in mediating insulin-stimulated glucose uptake in 3T3-LI adipocytes, via both GLUT4 vesicle fusion at the plasma membrane and GLUT4 activity.

Dual role for myosin II in GLUT4-mediated glucose uptake in 3T3-L1 adipocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fulcher, F. Kent; Smith, Bethany T.; Russ, Misty

2008-10-15

Insulin-stimulated glucose uptake requires the activation of several signaling pathways to mediate the translocation and fusion of GLUT4 vesicles to the plasma membrane. Our previous studies demonstrated that GLUT4-mediated glucose uptake is a myosin II-dependent process in adipocytes. The experiments described in this report are the first to show a dual role for the myosin IIA isoform specifically in regulating insulin-stimulated glucose uptake in adipocytes. We demonstrate that inhibition of MLCK but not RhoK results in impaired insulin-stimulated glucose uptake. Furthermore, our studies show that insulin specifically stimulates the phosphorylation of the RLC associated with the myosin IIA isoform viamore » MLCK. In time course experiments, we determined that GLUT4 translocates to the plasma membrane prior to myosin IIA recruitment. We further show that recruitment of myosin IIA to the plasma membrane requires that myosin IIA be activated via phosphorylation of the RLC by MLCK. Our findings also reveal that myosin II is required for proper GLUT4-vesicle fusion at the plasma membrane. We show that once at the plasma membrane, myosin II is involved in regulating the intrinsic activity of GLUT4 after insulin stimulation. Collectively, our results are the first to reveal that myosin IIA plays a critical role in mediating insulin-stimulated glucose uptake in 3T3-LI adipocytes, via both GLUT4 vesicle fusion at the plasma membrane and GLUT4 activity.« less

Structural and Functional Analysis of the Human HDAC4 Catalytic Domain Reveals a Regulatory Structural Zinc-binding Domain*S⃞

PubMed Central

Bottomley, Matthew J.; Lo Surdo, Paola; Di Giovine, Paolo; Cirillo, Agostino; Scarpelli, Rita; Ferrigno, Federica; Jones, Philip; Neddermann, Petra; De Francesco, Raffaele; Steinkühler, Christian; Gallinari, Paola; Carfí, Andrea

2008-01-01

Histone deacetylases (HDACs) regulate chromatin status and gene expression, and their inhibition is of significant therapeutic interest. To date, no biological substrate for class IIa HDACs has been identified, and only low activity on acetylated lysines has been demonstrated. Here, we describe inhibitor-bound and inhibitor-free structures of the histone deacetylase-4 catalytic domain (HDAC4cd) and of an HDAC4cd active site mutant with enhanced enzymatic activity toward acetylated lysines. The structures presented, coupled with activity data, provide the molecular basis for the intrinsically low enzymatic activity of class IIa HDACs toward acetylated lysines and reveal active site features that may guide the design of class-specific inhibitors. In addition, these structures reveal a conformationally flexible structural zinc-binding domain conserved in all class IIa enzymes. Importantly, either the mutation of residues coordinating the structural zinc ion or the binding of a class IIa selective inhibitor prevented the association of HDAC4 with the N-CoR·HDAC3 repressor complex. Together, these data suggest a key role of the structural zinc-binding domain in the regulation of class IIa HDAC functions. PMID:18614528

Structural and functional analysis of the human HDAC4 catalytic domain reveals a regulatory structural zinc-binding domain.

PubMed

Bottomley, Matthew J; Lo Surdo, Paola; Di Giovine, Paolo; Cirillo, Agostino; Scarpelli, Rita; Ferrigno, Federica; Jones, Philip; Neddermann, Petra; De Francesco, Raffaele; Steinkühler, Christian; Gallinari, Paola; Carfí, Andrea

2008-09-26

Histone deacetylases (HDACs) regulate chromatin status and gene expression, and their inhibition is of significant therapeutic interest. To date, no biological substrate for class IIa HDACs has been identified, and only low activity on acetylated lysines has been demonstrated. Here, we describe inhibitor-bound and inhibitor-free structures of the histone deacetylase-4 catalytic domain (HDAC4cd) and of an HDAC4cd active site mutant with enhanced enzymatic activity toward acetylated lysines. The structures presented, coupled with activity data, provide the molecular basis for the intrinsically low enzymatic activity of class IIa HDACs toward acetylated lysines and reveal active site features that may guide the design of class-specific inhibitors. In addition, these structures reveal a conformationally flexible structural zinc-binding domain conserved in all class IIa enzymes. Importantly, either the mutation of residues coordinating the structural zinc ion or the binding of a class IIa selective inhibitor prevented the association of HDAC4 with the N-CoR.HDAC3 repressor complex. Together, these data suggest a key role of the structural zinc-binding domain in the regulation of class IIa HDAC functions.

Exploring hydrophobic subdomain IIA of the protein bovine serum albumin in the native, intermediate, unfolded, and refolded states by a small fluorescence molecular reporter.

PubMed

Paul, Bijan Kumar; Samanta, Anuva; Guchhait, Nikhil

2010-05-13

A simple intramolecular charge transfer (ICT) compound, 5-(4-dimethylamino-phenyl)-penta-2,4-dienoic acid methyl ester (DPDAME), has been documented to be a potential molecular reporter for probing microheterogeneous environments of a model transport protein bovine serum albumin (BSA) using spectroscopic techniques. Meteoric modifications to the emission profile of DPDAME upon addition of BSA come out to be a result of its binding to hydrophobic subdomain IIA. The highly polarity-sensitive ICT emission of DPDAME is found to be a proficient extrinsic molecular reporter for efficient mapping of native, intermediate, unfolded, and refolded states of the protein. Experimental data coupled with a reinforcing support from theoretical simulation using CHARMM22 software confirm the binding site of the probe to be the subdomain IIA of BSA, while FRET study reveals a remarkably close approach of our extrinsic molecular reporter to Trp-212 (in domain IIA): the distance between DPDAME and Trp-212 is 1.437 nm. The caliber of DPDAME as an external fluorescence marker also extends to the depiction of protein-surfactant (BSA-SDS) interaction to commendable fruition. Additionally, the protective action of small amounts of SDS on urea-denatured protein is documented by polarity-sensitive ICT emission of the probe. The present study also reflects the enhancement of the stability of BSA with respect to chemically induced denaturation by urea as a result of binding to the probe DPDAME.

The E3 ligase Ubr3 regulates Usher syndrome and MYH9 disorder proteins in the auditory organs of Drosophila and mammals.

PubMed

Li, Tongchao; Giagtzoglou, Nikolaos; Eberl, Daniel F; Jaiswal, Sonal Nagarkar; Cai, Tiantian; Godt, Dorothea; Groves, Andrew K; Bellen, Hugo J

2016-06-22

Myosins play essential roles in the development and function of auditory organs and multiple myosin genes are associated with hereditary forms of deafness. Using a forward genetic screen in Drosophila, we identified an E3 ligase, Ubr3, as an essential gene for auditory organ development. Ubr3 negatively regulates the mono-ubiquitination of non-muscle Myosin II, a protein associated with hearing loss in humans. The mono-ubiquitination of Myosin II promotes its physical interaction with Myosin VIIa, a protein responsible for Usher syndrome type IB. We show that ubr3 mutants phenocopy pathogenic variants of Myosin II and that Ubr3 interacts genetically and physically with three Usher syndrome proteins. The interactions between Myosin VIIa and Myosin IIa are conserved in the mammalian cochlea and in human retinal pigment epithelium cells. Our work reveals a novel mechanism that regulates protein complexes affected in two forms of syndromic deafness and suggests a molecular function for Myosin IIa in auditory organs.

Mechanism of phosphoryl transfer and protein-protein interaction in the PTS system-an NMR study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rajagopal, P.; Klevit, R.E.

1994-12-01

HPr and Enzyme IIA{sup Glc} are two of the components of the bacterial PTS (phosphoenolpyruvate: sugar phosphotranferase system) and are involved in the phosphorylation and concomitant translocation of sugars across the membrane. These PTS protein complexes also regulate sugar transport. HPr, phosphorylated at a histidine N1 site by Enzyme I and phosphoenol pyruvate, transfers the phosphoryl group to a histidine N3 position in Enzyme IIA{sup Glc}. HPrs from Gram-positive bacteria undergo regulatory phosphorylation at Ser{sup 46}, whereby phosphorylation of the histidine residue is inhibited. Conversely, histidine phosphorylation inhibits phosphorylation at Ser{sup 46}. HPrs from Gram-negative bacteria possess a serine residuemore » at position 46, but do not undergo regulatory phosphorylation. HPr forms an open-faced sandwich structure with a four-strand S-sheet and 2 to 3 helices lying on top of the sheet. The active-site histidine and Ser{sup 46} occur in conformationally flexible regions. P-His-HPr from the Gram-positive bacterium Bacillus subtilus has been investigated by both homonuclear and heteronuclear two-dimensional and three-dimensional NMR experiments using an in-situ enzymatic regeneration system to maintain a constant level of P-His-HPr. The results show that localized conformational changes occur in the vicinity of the active-site histidine and also near Ser{sup 46}. HPr-Enzyme IIA{sup Glc} complexes from both Bacillus subtilis and Gram-negative Escherichia coli were also studied by a variety of {sup 15}N-edited two-dimensional NMR experiments, which were performed on uniformly {sup 15}N-labeled HPr complexed to unlabeled Enzyme IIA{sup Glc}. The complex is in fast exchange with a molecular weight of about 27 kDa. The focus of our work is to assess the changes undergone by HPr (the smaller of the two components), and so all the experiments were performed with excess Enzyme IIA present in the system.« less

Microthymoma in elderly-onset myasthenia gravis detected preoperatively.

PubMed

Hino, Haruaki; Nishimura, Takashi; Seki, Atsuko; Nitadori, Jun-Ichi; Arai, Tomio; Nakajima, Jun

2016-10-01

A 77-year-old woman with a 3-month history of muscle weakness was diagnosed with elderly-onset generalized myasthenia gravis (Myasthenia Gravis Foundation of America classification IIa) based on a high serum acetylcholine receptor antibody level (25.4 nmol·L -1 ) and neurological findings. Computed tomography detected a small nodule (diameter 15 mm) in the anterior mediastinum, which was suspected to be a thymoma. An extended thymectomy was performed. The pathological examination revealed a 6-mm-diameter thymoma, termed a microthymoma, accompanied with a unilocular thymic cyst without capsule formation (type B2 according to the World Health Organization classification). Some fat tissue was also found within the tumor. © The Author(s) 2016.

A comparison of rat myosin from fast and slow skeletal muscle and the effect of disuse

NASA Technical Reports Server (NTRS)

Unsworth, B. R.; Witzmann, F. A.; Fitts, R. H.

1981-01-01

Certain enzymatic and structural features of myosin, purified from rat skeletal muscles representative of the fast twitch glycolytic (type IIb), the fast twitch oxidative (type IIa), and the slow twitch oxidative (type I) fiber, were determined and the results were compared with the measured contractile properties. Good correlation was found between the shortening velocities and Ca(2+)-activated ATPase activity for each fiber type. Short term hind limb immobilization caused prolongation of contraction time and one-half relaxation time in the fast twitch muscles and a reduction of these contractile properties in slow twitch soleus. Furthermore, the increased maximum shortening velocity in the immobilized soleus could be correlated with increased Ca(2+)-ATPase, but no change was observed in the enzymatic activity of the fast twitch muscles. No alteration in light chain distribution with disuse was observed in any of the fiber types. The myosin from slow twitch soleus could be distinguished from fast twitch myosins on the basis of the pattern of peptides generated by proteolysis of the heavy chains. Six weeks of hind limb immobilization resulted in both an increased ATPase activity and an altered heavy chain primary structure in the slow twitch soleus muscle.

Myosin heavy chain expression in rodent skeletal muscle: effects of exposure to zero gravity

NASA Technical Reports Server (NTRS)

Haddad, F.; Herrick, R. E.; Adams, G. R.; Baldwin, K. M.

1993-01-01

This study ascertained the effects of 9 days of zero gravity on the relative (percentage of total) and calculated absolute (mg/muscle) content of isomyosin expressed in both antigravity and locomotor skeletal muscle of ground control (CON) and flight-exposed (FL) rats. Results showed that although there were no differences in body weight between FL and CON animals, a significant reduction in muscle mass occurred in the vastus intermedius (VI) (P < 0.05) but not in the vastus lateralis (VL) or the tibialis anterior. Both total muscle protein and myofibril protein content were not different between the muscle regions examined in the FL and CON groups. In the VI, there were trends for reductions in the relative content of type I and IIa myosin heavy chains (MHCs) that were offset by increases in the relative content of both type IIb and possibly type IIx MHC protein (P > 0.05). mRNA levels were consistent with this pattern (P < 0.05). The same pattern held true for the red region of the VL as examined at both the protein and mRNA level (P < 0.05). When the atrophy process was examined, there were net reductions in the absolute content of both type I and IIa MHCs that were offset by calculated increases in type IIb MHC in both VI and red VL. Collectively, these findings suggest that there are both absolute and relative changes occurring in MHC expression in the "red" regions of antigravity skeletal muscle during exposure to zero gravity that could affect muscle function.

Effect of recovery mode following hind-limb suspension on soleus muscle composition in the rat

NASA Technical Reports Server (NTRS)

McNulty, A. L.; Otto, A. J.; Kasper, C. E.; Thomas, D. P.

1992-01-01

The purpose of this study was to compare the effects of two different recovery modes from hind-limb suspension-induced hypodynamia on whole body and muscle (soleus) growth as well as soleus composition and size changes of different fiber types within this same muscle. Following 28 days of tail-suspension, rats were returned to their cages and sedentarily recovered (HS), or were exercised by running on a treadmill 5 days/wk, at progressively increasing workloads (HR) for one month. Sedentary and running control groups of animals (CS, CR) were also evaluated for comparative purposes. The exercise program, which was identical for CR and HR groups, had no effect on body wt., soleus wt., soleus muscle composition or fiber size in CR rats. Atrophied soleus muscle and reduced soleus wt./body wt. ratio (both 60% of control) had returned to control values by day 7 of recovery in both suspended groups despite the fact that whole body wt. gain was significantly reduced (p less than 0.05) in HR as compared to HS rats. Atrophied soleus Type I fiber mean cross-sectional area in both HR and HS groups demonstrated similar and significant (p less than 0.01) increases during recovery. Increases in Type IIa and IIc fiber area during this same period were significant only in the HR group. While the percentage area of muscle composed of Type I fibers increased in both hypodynamic groups during recovery, the reduction in area percentage of muscle made up of Type IIa fibers was again only significant in the HR group.(ABSTRACT TRUNCATED AT 250 WORDS).

Constant Fiber Number During Skeletal Muscle Atrophy and Modified Arachidonate Metabolism During Hypertrophy

NASA Technical Reports Server (NTRS)

Templeton, G.

1985-01-01

A previously documented shift from Type I to IIA predominance of the soleus muscle during rat suspension was further investigated to determine if this shift was by selective reduction of a single fiber type, simultaneous reduction and formation of fibers with different fiber types, or a transformation of fiber type by individual fibers. By partial acid digestion and dissection, average total soleus fiber number was found to be 3022 + or - 80 (SE) and 3008 + or - 64 before and after four-week suspension (n=12). Another area of current research was based on previous studies which indicate that prostaglandins are biosynthesized by skeletal muscle and evoke protein synthesis and degradation.

Spacer capture and integration by a type I-F Cas1-Cas2-3 CRISPR adaptation complex.

PubMed

Fagerlund, Robert D; Wilkinson, Max E; Klykov, Oleg; Barendregt, Arjan; Pearce, F Grant; Kieper, Sebastian N; Maxwell, Howard W R; Capolupo, Angela; Heck, Albert J R; Krause, Kurt L; Bostina, Mihnea; Scheltema, Richard A; Staals, Raymond H J; Fineran, Peter C

2017-06-27

CRISPR-Cas adaptive immune systems capture DNA fragments from invading bacteriophages and plasmids and integrate them as spacers into bacterial CRISPR arrays. In type I-E and II-A CRISPR-Cas systems, this adaptation process is driven by Cas1-Cas2 complexes. Type I-F systems, however, contain a unique fusion of Cas2, with the type I effector helicase and nuclease for invader destruction, Cas3. By using biochemical, structural, and biophysical methods, we present a structural model of the 400-kDa Cas1 4 -Cas2-3 2 complex from Pectobacterium atrosepticum with bound protospacer substrate DNA. Two Cas1 dimers assemble on a Cas2 domain dimeric core, which is flanked by two Cas3 domains forming a groove where the protospacer binds to Cas1-Cas2. We developed a sensitive in vitro assay and demonstrated that Cas1-Cas2-3 catalyzed spacer integration into CRISPR arrays. The integrase domain of Cas1 was necessary, whereas integration was independent of the helicase or nuclease activities of Cas3. Integration required at least partially duplex protospacers with free 3'-OH groups, and leader-proximal integration was stimulated by integration host factor. In a coupled capture and integration assay, Cas1-Cas2-3 processed and integrated protospacers independent of Cas3 activity. These results provide insight into the structure of protospacer-bound type I Cas1-Cas2-3 adaptation complexes and their integration mechanism.

Protective effect of tanshinone IIA against cardiac hypertrophy in spontaneously hypertensive rats through inhibiting the Cys-C/Wnt signaling pathway

PubMed Central

Feng, Jun; Chen, Hua-Wen; Pi, Li-Juan; Wang, Jin; Zhan, Da-Qian

2017-01-01

The study aimed to investigate the protective effect of tanshinone IIA against cardiac hypertrophy in spontaneously hypertensive rats (SHRs) through the Cys-C/Wnt signaling pathway. Thirty SHRs were randomly divided into cardiac hypertrophy, low- and high-dose tanshinone IIA groups. Ten Wistar-Kyoto rats were selected as control group. The systolic blood pressure (SBP), heart weight (HW), left ventricular weight (LVW) and body weight (BW) of all rats were recorded. HE staining and qRT-PCR were applied to observe the morphology of myocardial tissue and mRNA expressions of COL1A1 and COL3A1. ELISA and Western blotting were used to measure the serum asymmetric dimethylarginine (ADMA), nitric oxide (NO) and cardiac troponin I (cTnI) levels, and the expressions of the Cys-C/Wnt signaling pathway-related proteins, eNOS and Nox4. Compared with the cardiac hypertrophy group, the SBP, HW/BW, LVW/BW, swelling degree of myocardial cells, COL1A1 and COL3A1 mRNA expressions, serum cTnI and ADMA levels, and the Cys-C/Wnt signaling pathway-related proteins and Nox4 expressions in the low- and high-dose tanshinone IIA groups were decreased, but the endothelial NO synthase (eNOS), phosphorylated eNOS (Ser1177) and NO expressions were increased. No significant difference was found between the low- and high-dose tanshinone IIA groups. Our study indicated a protective effect of tanshinone IIA against cardiac hypertrophy in SHRs through inhibiting the Cys-C/Wnt signaling pathway. PMID:28053285

Production and immunogenicity of Actinobacillus pleuropneumoniae ApxIIA protein in transgenic rice callus.

PubMed

Kim, Mi-Young; Kim, Tae-Geum; Yang, Moon-Sik

2017-04-01

Actinobacillus pleuropneumoniae is a major etiological agent that is responsible for swine pleuropneumonia, a highly contagious respiratory infection that causes severe economic losses in the swine production industry. ApxIIA is one of the virulence factors in A. pleuropneumoniae and has been considered as a candidate for developing a vaccine against the bacterial infection. A gene encoding an ApxIIA fragment (amino acids 439-801) was modified based on a plant-optimized codon and constructed into a plant expression vector under the control of a promoter and the 3' UTR of the rice amylase 3D gene. The plant expression vector was introduced into rice embryogenic callus (Oryza sativa L. cv. Dongjin) via particle bombardment-mediated transformation. The integration and transcription of the ApxIIA 439-801 gene were confirmed by using genomic DNA PCR amplification and Northern blot analysis, respectively. The synthesis of ApxIIA 439-801 antigen protein in transgenic rice callus was confirmed by western blot analysis. The concentration of antigen protein in lyophilized samples of transgenic rice callus was 250 μg/g. Immunizing mice with protein extracts from transgenic plants intranasally elicited secretory IgA. These results demonstrate the feasibility of using a transgenic plant to elicit immune responses against A. pleuropneumoniae. Copyright © 2017 Elsevier Inc. All rights reserved.

[The inhibitive effect produced by local perfusion of tanshinone IIA nanoparticle on neointimal hyperplasia of rabbit carotid artery following intimal denudation].

PubMed

Liang, Ling; Chen, Yucheng; Xiong, Subin; Zeng, Zhi; Sun, Mingliang; Zhang, Haihong

2007-08-01

Tanshinone IIA nanoparticles were constructed and perfused in rabbit's right carotid after intimal denudation with ballon. Localization and retention at different time points of the coumarin-labeled drug nanoparticles were evaluated under laser confocal microscope. Nanoparticles were seen in the three layers of the cross-section artery. At 7 days, they were mainly deposited in the medial layer, while the deposition was generally observed in the adventitia and media at 14 days and 28 days. In the Tanshinone IIA nanoparticle study, a significant reduction of the neo-intimal hyperplasia was noted by comparing the intimal area and the intima-media ratio in the three groups. And the PLGA nanoparticles appeared to be fully biocompatible. As a result, the local administration of the nanoparticles with incorporated Tanshinone IIA showed not only the preventive effects, but aslo the high absorption and good biocompatability in the whole arterial wall.

Skeletal Muscle Fatigability and Myosin Heavy Chain Fiber Type in Resistance Trained Men.

PubMed

Bagley, James R; McLeland, Kathryn A; Arevalo, Jose A; Brown, Lee E; Coburn, Jared W; Galpin, Andrew J

2017-03-01

Bagley, JR, McLeland, KA, Arevalo, JA, Brown, LE, Coburn, JW, and Galpin, AJ. Skeletal muscle fatigability and myosin heavy chain fiber type in resistance trained men. J Strength Cond Res 31(3): 602-607, 2017-Forty years ago, Thorstensson and Karlsson in 1976 described the link between muscle fatigability and fiber type, finding that more fast-twitch fibers were associated with a quicker onset of quadriceps fatigue. This provided the foundation for the Classic Thorstensson Test of fatigability and subsequent noninvasive fiber type prediction equation. This equation was developed with data from recreationally active (REC) men but has been implemented in participants with heterogeneous physical activity/exercise backgrounds. The accuracy of this approach in resistance trained (RET) men has not been established. Moreover, muscle fiber typing techniques have evolved considerably since this seminal work. Therefore, we reexamined this relationship using RET men and a more sensitive fiber typing method (single fiber myosin heavy chain [MHC] isoform classification). Fifteen RET men (age = 24.8 ± 1.3 years) performed maximal knee extensions (via isokinetic dynamometry) to determine peak torque (PT) and quadriceps fatigue percentage (FP) after 30 and 50 repetitions. Vastus lateralis (VL) single fiber MHC type was determined and fibers were grouped as %Fast (expressing MHC IIa, IIa/IIX, or IIx; no MHC I containing fibers). Resistance trained men exhibited 46% greater PT (RET = 207 ± 28 N·m vs. REC = 130 ± 8 N·m) and 28% more %Fast (RET = 61 ± 4% vs. REC = 44 ± 4%) than REC men. Additionally, RET men had a relatively homogeneous FP (64 ± 1%) ranging from 53 to 72%. No relationship was found between FP and MHC fiber type (R = 0.01, p > 0.05). The Classic Thorstensson Test may not accurately estimate VL fiber type composition in RET men, highlighting the (a) unique phenotypical/functional adaptations induced by chronic RET and (b) the need for more sensitive cellular/molecular analyses in RET muscle.

Family Caregiver Palliative Care Intervention in Supporting Caregivers of Patients With Stage II-IV Gastrointestinal, Gynecologic, Urologic and Lung Cancers

ClinicalTrials.gov

2018-02-12

Healthy Subject; Localized Transitional Cell Cancer of the Renal Pelvis and Ureter; Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Psychosocial Effects of Cancer and Its Treatment; Recurrent Bladder Cancer; Recurrent Cervical Cancer; Recurrent Colon Cancer; Recurrent Gastric Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Renal Cell Cancer; Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter; Recurrent Urethral Cancer; Recurrent Uterine Sarcoma; Regional Transitional Cell Cancer of the Renal Pelvis and Ureter; Stage II Bladder Cancer; Stage II Renal Cell Cancer; Stage II Urethral Cancer; Stage IIA Cervical Cancer; Stage IIA Colon Cancer; Stage IIA Gastric Cancer; Stage IIA Ovarian Epithelial Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIA Pancreatic Cancer; Stage IIA Rectal Cancer; Stage IIA Uterine Sarcoma; Stage IIB Cervical Cancer; Stage IIB Colon Cancer; Stage IIB Gastric Cancer; Stage IIB Ovarian Epithelial Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIB Pancreatic Cancer; Stage IIB Rectal Cancer; Stage IIB Uterine Sarcoma; Stage IIC Colon Cancer; Stage IIC Ovarian Epithelial Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage IIC Rectal Cancer; Stage III Bladder Cancer; Stage III Pancreatic Cancer; Stage III Renal Cell Cancer; Stage III Urethral Cancer; Stage IIIA Cervical Cancer; Stage IIIA Colon Cancer; Stage IIIA Gastric Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Rectal Cancer; Stage IIIA Uterine Sarcoma; Stage IIIB Cervical Cancer; Stage IIIB Colon Cancer; Stage IIIB Gastric Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Rectal Cancer; Stage IIIB Uterine Sarcoma; Stage IIIC Colon Cancer; Stage IIIC Gastric Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Rectal Cancer; Stage IIIC Uterine Sarcoma; Stage IV Bladder Cancer; Stage IV Gastric Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Pancreatic Cancer; Stage IV Renal Cell Cancer; Stage IV Urethral Cancer; Stage IVA Cervical Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVA Uterine Sarcoma; Stage IVB Cervical Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer; Stage IVB Uterine Sarcoma; Ureter Cancer; Stage IIA Lung Carcinoma; Stage IIB Lung Carcinoma; Stage IIIA Lung Carcinoma; Stage IIIB Lung Carcinoma

SMARTDIAB: a communication and information technology approach for the intelligent monitoring, management and follow-up of type 1 diabetes patients.

PubMed

Mougiakakou, Stavroula G; Bartsocas, Christos S; Bozas, Evangelos; Chaniotakis, Nikos; Iliopoulou, Dimitra; Kouris, Ioannis; Pavlopoulos, Sotiris; Prountzou, Aikaterini; Skevofilakas, Marios; Tsoukalis, Alexandre; Varotsis, Kostas; Vazeou, Andrianni; Zarkogianni, Konstantia; Nikita, Konstantina S

2010-05-01

SMARTDIAB is a platform designed to support the monitoring, management, and treatment of patients with type 1 diabetes mellitus (T1DM), by combining state-of-the-art approaches in the fields of database (DB) technologies, communications, simulation algorithms, and data mining. SMARTDIAB consists mainly of two units: 1) the patient unit (PU); and 2) the patient management unit (PMU), which communicate with each other for data exchange. The PMU can be accessed by the PU through the internet using devices, such as PCs/laptops with direct internet access or mobile phones via a Wi-Fi/General Packet Radio Service access network. The PU consists of an insulin pump for subcutaneous insulin infusion to the patient and a continuous glucose measurement system. The aforementioned devices running a user-friendly application gather patient's related information and transmit it to the PMU. The PMU consists of a diabetes data management system (DDMS), a decision support system (DSS) that provides risk assessment for long-term diabetes complications, and an insulin infusion advisory system (IIAS), which reside on a Web server. The DDMS can be accessed from both medical personnel and patients, with appropriate security access rights and front-end interfaces. The DDMS, apart from being used for data storage/retrieval, provides also advanced tools for the intelligent processing of the patient's data, supporting the physician in decision making, regarding the patient's treatment. The IIAS is used to close the loop between the insulin pump and the continuous glucose monitoring system, by providing the pump with the appropriate insulin infusion rate in order to keep the patient's glucose levels within predefined limits. The pilot version of the SMARTDIAB has already been implemented, while the platform's evaluation in clinical environment is being in progress.

Genetic Polymorphisms of Hemostatic Factors and Thrombotic Risk in Non BCR-ABL Myeloproliferative Neoplasms: A Pilot Study

PubMed Central

Dambrauskienė, R; Gerbutavičius, R; Ugenskienė, R; Jankauskaitė, R; Savukaitytė, A; Šimoliūnienė, R; Rudžianskienė, M; Gerbutavičienė, R; Juozaitytė, E

2017-01-01

Abstract The most important complications of Philadelphianegagive (non BCR-ABL) myeloproliferative neoplasms (MPNs) are vascular events. Our aim was to evaluate the effects of single nucleotide polymorphisms (SNPs), platelet glycoproteins (GPs) (Ia/IIa, Ibα, IIb/IIIa and VI), von Willebrand factor (vWF), coagulation factor VII (FVII), β-fibrinogen, and the risk of thrombosis in patients with non BCR-ABL MPNs at the Lithuanian University of Health Sciences. Kaunas, Lithuania. Genotyping was done for 108 patients. The TT genotype of the GP Ia/IIa c.807C>T polymorphism was more frequently found in the group of MPN patients with arterial thrombosis compared to MPN patients who were thrombosis-free [26.5 vs. 11.5%, p = 0.049; odds ratio (OR) 2.68; 95% confidence interval (95% CI) 1.01-7.38]. The CT genotype of the β-fibrinogen c.-148C>T polymorphism occurred more frequently in MPN patients with arterial, and total thrombosis compared to the wild or homozygous genotype (57.7 vs. 40.0 vs. 12.5%; p = 0.027), (64.7 vs. 44.4 vs. 25%; p = 0.032), respectively. The carrier state for the c.-323P10 variant of FVII SNP (summation of P10/10 and P0/10) was more frequent in MPN patients with thrombosis compared to the wild-type genotype carriers (71.4 vs. 43.4%; p = 0.049; OR 3.26; 95% CI 1.01-11.31). The coexistence of heterozygous β-fibrinogen c.-148C>T and FVII c.-323P0/10 SNP, increased the risk of arterial thrombosis (21.1 vs. 3.7%, p = 0.008; OR 6.93; 95% CI 1.38-34.80). The TT genotype of GP Ia/IIa c.807C>T, the CT genotype of β-fibrinogen c.-148C>T and FVII c.-323P0/10 SNP could be associated with risk of thrombosis in MPN patients. PMID:28924539

Hormone replacement therapy improves contractile function and myonuclear organization of single muscle fibres from postmenopausal monozygotic female twin pairs.

PubMed

Qaisar, Rizwan; Renaud, Guillaume; Hedstrom, Yvette; Pöllänen, Eija; Ronkainen, Paula; Kaprio, Jaakko; Alen, Markku; Sipilä, Sarianna; Artemenko, Konstantin; Bergquist, Jonas; Kovanen, Vuokko; Larsson, Lars

2013-05-01

Ageing is associated with a decline in muscle mass and strength leading to increased physical dependency in old age. Postmenopausal women experience a greater decline than men of similar age in parallel with the decrease in female sex steroid hormone production. We recruited six monozygous female twin pairs (55-59 years old) where only one twin pair was on hormone replacement therapy (HRT use = 7.8 ± 4.3 years) to investigate the association of HRT with the cytoplasmic volume supported by individual myonuclei (myonuclear domain (MND) size,) together with specific force at the single fibre level. HRT use was associated with a significantly smaller (∼27%; P < 0.05) mean MND size in muscle fibres expressing the type I but not the IIa myosin heavy chain (MyHC) isoform. In comparison to non-users, higher specific force was recorded in HRT users both in muscle fibres expressing type I (∼27%; P < 0.05) and type IIa (∼23%; P < 0.05) MyHC isoforms. These differences were fibre-type dependent, i.e. the higher specific force in fast-twitch muscle fibres was primarily caused by higher force per cross-bridge while slow-twitch fibres relied on both a higher number and force per cross-bridge. HRT use had no effect on fibre cross-sectional area (CSA), velocity of unloaded shortening (V0) and relative proportion of MyHC isoforms. In conclusion, HRT appears to have significant positive effects on both regulation of muscle contraction and myonuclei organization in postmenopausal women.

Non-perturbative String Theory from Water Waves

DOE Office of Scientific and Technical Information (OSTI.GOV)

Iyer, Ramakrishnan; Johnson, Clifford V.; /Southern California U.

2012-06-14

We use a combination of a 't Hooft limit and numerical methods to find non-perturbative solutions of exactly solvable string theories, showing that perturbative solutions in different asymptotic regimes are connected by smooth interpolating functions. Our earlier perturbative work showed that a large class of minimal string theories arise as special limits of a Painleve IV hierarchy of string equations that can be derived by a similarity reduction of the dispersive water wave hierarchy of differential equations. The hierarchy of string equations contains new perturbative solutions, some of which were conjectured to be the type IIA and IIB string theoriesmore » coupled to (4, 4k ? 2) superconformal minimal models of type (A, D). Our present paper shows that these new theories have smooth non-perturbative extensions. We also find evidence for putative new string theories that were not apparent in the perturbative analysis.« less

Rhenium-osmium concentration and isotope systematics in group IIAB iron meteorites

USGS Publications Warehouse

Morgan, J.W.; Horan, M.F.; Walker, R.J.; Grossman, J.N.

1995-01-01

Rhenium and osmium abundances, and osmium isotopic compositions were measured by negative thermal ionization mass spectrometry in thirty samples, including replicates, of five IIA and eight IIB iron meteorites. Log plots of Os vs. Re abundances for IIA and IIB irons describe straight lines that approximately converge on Lombard, which has the lowest Re and Os abundances and highest 187Re/188Os measured in a IIA iron to date. The linear IIA trend may be exactly reproduced by fractional crystallization, but is not well fitted using variable partition coefficients. The IIB iron trend, however, cannot be entirely explained by simple fractional crystallization. One explanation is that small amounts of Re and Os were added to the asteroid core during the final stages of crystallization. Another possibility is that diffusional enrichment of Os may have occurred in samples most depleted in Re and Os. -from Authors

Developing Anticancer Copper(II) Pro-drugs Based on the Nature of Cancer Cells and the Human Serum Albumin Carrier IIA Subdomain.

PubMed

Gou, Yi; Qi, Jinxu; Ajayi, Joshua-Paul; Zhang, Yao; Zhou, Zuping; Wu, Xiaoyang; Yang, Feng; Liang, Hong

2015-10-05

To synergistically enhance the selectivity and efficiency of anticancer copper drugs, we proposed and built a model to develop anticancer copper pro-drugs based on the nature of human serum albumin (HSA) IIA subdomain and cancer cells. Three copper(II) compounds of a 2-hydroxy-1-naphthaldehyde benzoyl hydrazone Schiff-base ligand in the presence pyridine, imidazole, or indazole ligands were synthesized (C1-C3). The structures of three HSA complexes revealed that the Cu compounds bind to the hydrophobic cavity in the HSA IIA subdomain. Among them, the pyridine and imidazole ligands of C1 and C2 are replaced by Lys199, and His242 directly coordinates with Cu(II). The indazole and Br ligands of C3 are replaced by Lys199 and His242, respectively. Compared with the Cu(II) compounds alone, the HSA complexes enhance cytotoxicity in MCF-7 cells approximately 3-5-fold, but do not raise cytotoxicity levels in normal cells in vitro through selectively accumulating in cancer cells to some extent. We find that the HSA complex has a stronger capacity for cell cycle arrest in the G2/M phase of MCF-7 by targeting cyclin-dependent kinase 1 (CDK1) and down-regulating the expression of CDK1 and cyclin B1. Moreover, the HSA complex promotes MCF-7 cell apoptosis possibly through the intrinsic reactive oxygen species (ROS) mediated mitochondrial pathway, accompanied by the regulation of Bcl-2 family proteins.

Lion (Panthera leo) and caracal (Caracal caracal) type IIx single muscle fibre force and power exceed that of trained humans.

PubMed

Kohn, Tertius A; Noakes, Timothy D

2013-03-15

This study investigated for the first time maximum force production, shortening velocity (Vmax) and power output in permeabilised single muscle fibres at 12°C from lion, Panthera leo (Linnaeus 1758), and caracal, Caracal caracal (Schreber 1776), and compared the values with those from human cyclists. Additionally, the use and validation of previously frozen tissue for contractile experiments is reported. Only type IIx muscle fibres were identified in the caracal sample, whereas type IIx and only two type I fibres were found in the lion sample. Only pure type I and IIa, and hybrid type IIax fibres were identified in the human samples - there were no pure type IIx fibres. Nevertheless, compared with all the human fibre types, the lion and caracal fibres were smaller (P<0.01) in cross-sectional area (human: 6194±230 μm(2), lion: 3008±151 μm(2), caracal: 2583±221 μm(2)). On average, the felid type IIx fibres produced significantly greater force (191-211 kN m(-2)) and ~3 times more power (29.0-30.3 kN m(-2) fibre lengths s(-1)) than the human IIax fibres (100-150 kN m(-2), 4-11 kN m(-2) fibre lengths s(-1)). Vmax values of the lion type IIx fibres were also higher than those of human type IIax fibres. The findings suggest that the same fibre type may differ substantially between species and potential explanations are discussed.

Group IIA secretory phospholipase A2 (GIIA) mediates apoptotic death during NMDA receptor activation in rat primary cortical neurons.

PubMed

Chiricozzi, Elena; Fernandez-Fernandez, Seila; Nardicchi, Vincenza; Almeida, Angeles; Bolaños, Juan Pedro; Goracci, Gianfrancesco

2010-03-01

Phospholipases A(2) (PLA(2)) participate in neuronal death signalling pathways because of their ability to release lipid mediators, although the contribution of each isoform and mechanism of neurotoxicity are still elusive. Using a novel fluorogenic method to assess changes in a PLA(2) activity by flow cytometry, here we show that the group IIA secretory phospholipase A(2) isoform (GIIA) was specifically activated in cortical neurons following stimulation of N-methyl-d-aspartate glutamate receptor subtype (NMDAR). For activation, GIIA required Ca(2+) and reactive oxygen/nitrogen species, and inhibition of its activity fully prevented NMDAR-mediated neuronal apoptotic death. Superoxide, nitric oxide or peroxynitrite donors stimulated GIIA activity, which mediated neuronal death. Intriguingly, we also found that GIIA activity induced mitochondrial superoxide production after NMDAR stimulation. These results reveal a novel role for GIIA in excitotoxicity both as target and producer of superoxide in a positive-loop of activation that may contribute to the propagation of neurodegeneration.

Genetic differentiation of methicillin-resistant Staphylococcus aureus strains from Korea and Japan.

PubMed

Soo Ko, Kwan; Peck, Kyong Ran; Sup Oh, Won; Lee, Nam Yong; Hiramatsu, Keiichi; Song, Jae-Hoon

2005-01-01

In this study, we evaluated genetic differentiation between methicillin-resistant Staphylococcus aureus (MRSA) strains from Korea and Japan. Seventy-five MRSA strains, including 25 h VISA strains, were analyzed by molecular typing methods, including multilocus sequence typing (MLST), SCC mec typing, and spa typing. The most prevalent genotype of MRSA strains, in both Korea and Japan, was ST 5-MRSA-II with the DMGMK spa motif, characteristic of the New York/Japan MRSA clone. In spite of these common features in MRSA strains from Korea and Japan, we also observed some genotypic divergence in MRSA from the two countries. Several spa types might be differentiated from a prevalent prototype (TJMBMDMGMK) that is shared by the two countries, revealing a unique geographic distribution. SCC mec type II lacking pUB110, designated type IIA, was found more frequently in Korea than in Japan. The rate of gentamicin resistance was also dramatically different between the two countries: 87.2% (Korea) vs. 28.6% (Japan). These preliminary findings suggested that MRSA strains from Korea and Japan might have originated from a common ancestor, but then clearly differentiated according to locality. A further comprehensive study should be performed to document the hypotheses from this study.

30 CFR 57.22212 - Air flow (I-C, II-A, and V-A mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22212 Air flow (I-C, II-A, and V-A mines). Air flow across each working face shall be sufficient to carry away any accumulation of methane, smoke...

Peptide-bacteria interactions using engineered surface-immobilized peptides from class IIa bacteriocins.

PubMed

Etayash, Hashem; Norman, Lana; Thundat, Thomas; Kaur, Kamaljit

2013-03-26

Specificity of the class IIa bacteriocin Leucocin A (LeuA), an antimicrobial peptide active against Gram-positive bacteria, including Listeria monocytogenes , is known to be dictated by the C-terminal amphipathic helical region, including the extended hairpin-like structure. However, its specificity when attached to a substrate has not been investigated. Exploiting properties of LeuA, we have synthesized two LeuA derivatives, which span the amphipathic helical region of the wild-type LeuA, consisting of 14- (14AA LeuA, CWGEAFSAGVHRLA) and 24-amino acid residues (24AA LeuA, CSVNWGEAFSAGVHRLANGGNGFW). The peptides were purified to >95% purity, as shown by analytical RP-HPLC and mass spectrometry. By including an N-terminal cysteine group, the tailored peptide fragments were readily immobilized at the gold interfaces. The resulting thickness and molecular orientation, determined by ellipsometry and grazing angle infrared spectroscopy, respectively, indicated that the peptides were covalently immobilized in a random helical orientation. The bacterial specificity of the anchored peptide fragments was tested against Gram-positive and Gram-negative bacteria. Our results showed that the adsorbed 14AA LeuA exhibited no specificity toward the bacterial strains, whereas the surface-immobilized 24AA LeuA displayed significant binding toward Gram-positive bacteria with various binding affinities from one strain to another. The 14AA LeuA did not show binding as this fragment is most likely too short in length for recognition by the membrane-bound receptor on the target bacterial cell membrane. These results support the potential use of class IIa bacteriocins as molecular recognition elements in biosensing platforms.

Effects of arachidonic acid supplementation on training adaptations in resistance-trained males

PubMed Central

Roberts, Michael D; Iosia, Mike; Kerksick, Chad M; Taylor, Lem W; Campbell, Bill; Wilborn, Colin D; Harvey, Travis; Cooke, Matthew; Rasmussen, Chris; Greenwood, Mike; Wilson, Ronald; Jitomir, Jean; Willoughby, Darryn; Kreider, Richard B

2007-01-01

Background To determine the impact of AA supplementation during resistance training on body composition, training adaptations, and markers of muscle hypertrophy in resistance-trained males. Methods In a randomized and double blind manner, 31 resistance-trained male subjects (22.1 ± 5.0 years, 180 ± 0.1 cm, 86.1 ± 13.0 kg, 18.1 ± 6.4% body fat) ingested either a placebo (PLA: 1 g·day-1 corn oil, n = 16) or AA (AA: 1 g·day-1 AA, n = 15) while participating in a standardized 4 day·week-1 resistance training regimen. Fasting blood samples, body composition, bench press one-repetition maximum (1RM), leg press 1RM and Wingate anaerobic capacity sprint tests were completed after 0, 25, and 50 days of supplementation. Percutaneous muscle biopsies were taken from the vastus lateralis on days 0 and 50. Results Wingate relative peak power was significantly greater after 50 days of supplementation while the inflammatory cytokine IL-6 was significantly lower after 25 days of supplementation in the AA group. PGE2 levels tended to be greater in the AA group. However, no statistically significant differences were observed between groups in body composition, strength, anabolic and catabolic hormones, or markers of muscle hypertrophy (i.e. total protein content or MHC type I, IIa, and IIx protein content) and other intramuscular markers (i.e. FP and EP3 receptor density or MHC type I, IIa, and IIx mRNA expression). Conclusion AA supplementation during resistance-training may enhance anaerobic capacity and lessen the inflammatory response to training. However, AA supplementation did not promote statistically greater gains in strength, muscle mass, or influence markers of muscle hypertrophy. PMID:18045476

Muscle cell and motor protein function in patients with a IIa myosin missense mutation (Glu-706 to Lys).

PubMed

Li, M; Lionikas, A; Yu, F; Tajsharghi, H; Oldfors, A; Larsson, L

2006-11-01

The pathogenic events leading to the progressive muscle weakness in patients with a E706K mutation in the head of the myosin heavy chain (MyHC) IIa were analyzed at the muscle cell and motor protein levels. Contractile properties were measured in single muscle fiber segments using the skinned fiber preparation and a single muscle fiber in vitro motility assay. A dramatic impairment in the function of the IIa MyHC isoform was observed at the motor protein level. At the single muscle fiber level, on the other hand, a general decrease was observed in the number of preparations where the specific criteria for acceptance were fulfilled irrespective of MyHC isoform expression. Our results provide evidence that the pathogenesis of the MyHC IIa E706K myopathy involves defective function of the mutated myosin as well as alterations in the structural integrity of all muscle cells irrespective of MyHC isoform expression.

Design of Training Systems, Phase II-A Report. An Educational Technology Assessment Model (ETAM)

DTIC Science & Technology

1975-07-01

34format" for the perceptual tasks. This is applicable to auditory as well as visual tasks. Student Participation in Learning Route. When a student enters...skill formats Skill training 05.05 Vehicle properties Instructional functions: Type of stimulus presented to student visual auditory ...Subtask 05.05. For example, a trainer to identify and interpret auditory signals would not be represented in the above list. Trainers in the vehicle

Myofiber metabolic type determination by mass spectrometry imaging.

PubMed

Centeno, Delphine; Vénien, Annie; Pujos-Guillot, Estelle; Astruc, Thierry; Chambon, Christophe; Théron, Laëtitia

2017-08-01

Matrix assisted laser desorption/ionization (MALDI) mass spectrometry imaging is a powerful tool that opens new research opportunities in the field of biology. In this work, predictive model was developed to discriminate metabolic myofiber types using the MALDI spectral data. Rat skeletal muscles are constituted of type I and type IIA fiber, which have an oxidative metabolism for glycogen degradation, and type IIX and type IIB fiber which have a glycolytic metabolism, present in different proportions according to the muscle function and physiological state. So far, myofiber type is determined by histological methods that are time consuming. Thanks to the predictive model, we were able to predict not only the metabolic fiber type but also their location, on the same muscle section that was used for MALDI imaging. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Selective class IIa histone deacetylase inhibition via a nonchelating zinc-binding group.

PubMed

Lobera, Mercedes; Madauss, Kevin P; Pohlhaus, Denise T; Wright, Quentin G; Trocha, Mark; Schmidt, Darby R; Baloglu, Erkan; Trump, Ryan P; Head, Martha S; Hofmann, Glenn A; Murray-Thompson, Monique; Schwartz, Benjamin; Chakravorty, Subhas; Wu, Zining; Mander, Palwinder K; Kruidenier, Laurens; Reid, Robert A; Burkhart, William; Turunen, Brandon J; Rong, James X; Wagner, Craig; Moyer, Mary B; Wells, Carrow; Hong, Xuan; Moore, John T; Williams, Jon D; Soler, Dulce; Ghosh, Shomir; Nolan, Michael A

2013-05-01

In contrast to studies on class I histone deacetylase (HDAC) inhibitors, the elucidation of the molecular mechanisms and therapeutic potential of class IIa HDACs (HDAC4, HDAC5, HDAC7 and HDAC9) is impaired by the lack of potent and selective chemical probes. Here we report the discovery of inhibitors that fill this void with an unprecedented metal-binding group, trifluoromethyloxadiazole (TFMO), which circumvents the selectivity and pharmacologic liabilities of hydroxamates. We confirm direct metal binding of the TFMO through crystallographic approaches and use chemoproteomics to demonstrate the superior selectivity of the TFMO series relative to a hydroxamate-substituted analog. We further apply these tool compounds to reveal gene regulation dependent on the catalytic active site of class IIa HDACs. The discovery of these inhibitors challenges the design process for targeting metalloenzymes through a chelating metal-binding group and suggests therapeutic potential for class IIa HDAC enzyme blockers distinct in mechanism and application compared to current HDAC inhibitors.

Dissociation of I II in chemical oxygen-iodine lasers: experiment, modeling, and pre-dissociation by electrical discharge

NASA Astrophysics Data System (ADS)

Katz, A.; Waichman, K.; Dahan, Z.; Rybalkin, V.; Barmashenko, B. D.; Rosenwaks, S.

2007-06-01

The dissociation of I II molecules at the optical axis of a supersonic chemical oxygen-iodine laser (COIL) was studied via detailed measurements and three dimensional computational fluid dynamics calculations. Comparing the measurements and the calculations enabled critical examination of previously proposed dissociation mechanisms and suggestion of a mechanism consistent with the experimental and theoretical results obtained in a supersonic COIL for the gain, temperature and I II dissociation fraction at the optical axis. The suggested mechanism combines the recent scheme of Azyazov and Heaven (AIAA J. 44, 1593 (2006)), where I II(A' 3Π 2u), I II(A 3Π 1u) and O II(a1Δ g, v) are significant dissociation intermediates, with the "standard" chain branching mechanism of Heidner et al. (J. Phys. Chem. 87, 2348 (1983)), involving I(2P 1/2) and I II(X1Σ + g, v). In addition, we examined a new method for enhancement of the gain and power in a COIL by applying DC corona/glow discharge in the transonic section of the secondary flow in the supersonic nozzle, dissociating I II prior to its mixing with O II(1Δ). The loss of O II(1Δ) consumed for dissociation was thus reduced and the consequent dissociation rate downstream of the discharge increased, resulting in up to 80% power enhancement. The implication of this method for COILs operating beyond the specific conditions reported here is assessed.

A Prospective Study of Level IIB Nodal Metastasis (Supraretrospinal) in Clinically N0 Oral Squamous Cell Carcinoma in Indian Population.

PubMed

Chheda, Yogen P; Pillai, Sundaram K; Parikh, Devendra G; Dipayan, Nandy; Shah, Shakuntala V; Alaknanda, Gupta

2017-06-01

Oral cavity carcinoma is the most common cancer in Indian population. Metastatic nodal disease is the most important prognostic factor for oral cancers. In head and neck cancers with clinically N0 neck, standard selective neck dissection is performed by protecting the spinal accessory nerve to remove level IIA & IIB lymph nodes. The purpose of this study was to analyze the significance of level IIB dissection in patients of oral cavity cancer who underwent primary surgery with functional neck dissection. Two hundred ten patients with clinically N0 neck underwent neck dissection, where level IIB lymph nodes were dissected, labelled and processed separately. Among 210 patients of clinically N0 neck, 168 patients were pathologically N0 (80 %). Out of remaining 42 (20 %), 36 (17.14 %) were pN1 and 6 (2.86 %) were pN2. Among those with pN1 (36), level IB was involved in 24 patients (66.67 %) and level IIA was involved in 12 patients (33.33 %). Only 2 patients had involvement of level IIB lymph nodes. Among 6 patients of pN2 disease, 4 patients had simultaneous involvement of level IB and level IIA lymph nodes. Remaining 2 patients had isolated involvement of level III lymph nodes. Thus only 2 patients (< 1 %) out of 210 clinically N0 oral squamous cell carcinoma showed level IIB lymph node involvement. Thus we conclude that a frozen section of level 2a is advisable to decide the need for level 2b node dissection in clinically N0 neck as the sensitivity of clinical evaluation is extremely low.

Unifying Type-II Strings by Exceptional Groups

NASA Astrophysics Data System (ADS)

Arvanitakis, Alex S.; Blair, Chris D. A.

2018-05-01

We construct the exceptional sigma model: a two-dimensional sigma model coupled to a supergravity background in a manifestly (formally) ED (D )-covariant manner. This formulation of the background is provided by exceptional field theory (EFT), which unites the metric and form fields of supergravity in ED (D ) multiplets before compactification. The realization of the symmetries of EFT on the world sheet uniquely fixes the Weyl-invariant Lagrangian and allows us to relate our action to the usual type-IIA fundamental string action and a form of the type-IIB (m , n ) action. This uniqueness "predicts" the correct form of the couplings to gauge fields in both Neveu-Schwarz and Ramond sectors, without invoking supersymmetry.

Inhibitor-induced structural change in the HCV IRES domain IIa RNA

PubMed Central

Paulsen, Ryan B.; Seth, Punit P.; Swayze, Eric E.; Griffey, Richard H.; Skalicky, Jack J.; Cheatham, Thomas E.; Davis, Darrell R.

2010-01-01

Translation of the hepatitis C virus (HCV) RNA is initiated from a highly structured internal ribosomal entry site (IRES) in the 5′ untranslated region (5′ UTR) of the RNA genome. An important structural feature of the native RNA is an approximately 90° helical bend localized to domain IIa that positions the apical loop of domain IIb of the IRES near the 40S ribosomal E-site to promote eIF2-GDP release, facilitating 80S ribosome assembly. We report here the NMR structure of a domain IIa construct in complex with a potent small-molecule inhibitor of HCV replication. Molecular dynamics refinement in explicit solvent and subsequent energetic analysis indicated that each inhibitor stereoisomer bound with comparable affinity and in an equivalent binding mode. The in silico analysis was substantiated by fluorescence-based assays showing that the relative binding free energies differed by only 0.7 kcal/mol. Binding of the inhibitor displaces key nucleotide residues within the bulge region, effecting a major conformational change that eliminates the bent RNA helical trajectory, providing a mechanism for the antiviral activity of this inhibitor class. PMID:20360559

Low cell pH depresses peak power in rat skeletal muscle fibres at both 30 degrees C and 15 degrees C: implications for muscle fatigue.

PubMed

Knuth, S T; Dave, H; Peters, J R; Fitts, R H

2006-09-15

Historically, an increase in intracellular H(+) (decrease in cell pH) was thought to contribute to muscle fatigue by direct inhibition of the cross-bridge leading to a reduction in velocity and force. More recently, due to the observation that the effects were less at temperatures closer to those observed in vivo, the importance of H(+) as a fatigue agent has been questioned. The purpose of this work was to re-evaluate the role of H(+) in muscle fatigue by studying the effect of low pH (6.2) on force, velocity and peak power in rat fast- and slow-twitch muscle fibres at 15 degrees C and 30 degrees C. Skinned fast type IIa and slow type I fibres were prepared from the gastrocnemius and soleus, respectively, mounted between a force transducer and position motor, and studied at 15 degrees C and 30 degrees C and pH 7.0 and 6.2, and fibre force (P(0)), unloaded shortening velocity (V(0)), force-velocity, and force-power relationships determined. Consistent with previous observations, low pH depressed the P(0) of both fast and slow fibres, less at 30 degrees C (4-12%) than at 15 degrees C (30%). However, the low pH-induced depressions in slow type I fibre V(0) and peak power were both significantly greater at 30 degrees C (25% versus 9% for V(0) and 34% versus 17% for peak power). For the fast type IIa fibre type, the inhibitory effect of low pH on V(0) was unaltered by temperature, while for peak power the inhibition was reduced at 30 degrees C (37% versus 18%). The curvature of the force-velocity relationship was temperature sensitive, and showed a higher a/P(0) ratio (less curvature) at 30 degrees C. Importantly, at 30 degrees C low pH significantly depressed the ratio of the slow type I fibre, leading to less force and velocity at peak power. These data demonstrate that the direct effect of low pH on peak power in both slow- and fast-twitch fibres at near-in vivo temperatures (30 degrees C) is greater than would be predicted based on changes in P(0), and that the fatigue-inducing effects of low pH on cross-bridge function are still substantial and important at temperatures approaching those observed in vivo.

Spontaneous closure of intracranial dural arteriovenous fistulas: a report of 3 cases.

PubMed

Clarençon, Frédéric; Biondi, Alessandra; Sourour, Nader-Antoine; Di Maria, Federico; Iosif, Christina; Nouet, Aurélien; Navarro, Soledad; Le Jean, Lise; Chiras, Jacques

2013-07-01

Spontaneous closures of dural arteriovenous fistulas (dAVFs) are rare. We present spontaneous occlusion of dAVFs in 3 cases (one type IIa dAVF, one type IIb and one type III). Patients were 3 males with a mean age of 55 years (range 45-61). For two patients, the dAVF was revealed by hemorrhage. No head trauma was recorded at the interrogatory. Mean delay for spontaneous closure was 4 months (3-5 months). Review of the literature about this rare occurrence is presented and the factors that may lead to spontaneous occlusion of dAVFs are discussed. Copyright © 2012 Elsevier B.V. All rights reserved.

Modulation of skeletal muscle fiber type by mitogen-activated protein kinase signaling.

PubMed

Shi, Hao; Scheffler, Jason M; Pleitner, Jonathan M; Zeng, Caiyun; Park, Sungkwon; Hannon, Kevin M; Grant, Alan L; Gerrard, David E

2008-08-01

Skeletal muscle is composed of diverse fiber types, yet the underlying molecular mechanisms responsible for this diversification remain unclear. Herein, we report that the extracellular signal-regulated kinase (ERK) 1/2 pathway, but not p38 or c-Jun NH(2)-terminal kinase (JNK), is preferentially activated in fast-twitch muscles. Pharmacological blocking of ERK1/2 pathway increased slow-twitch fiber type-specific reporter activity and repressed those associated with the fast-twitch fiber phenotype in vitro. Overexpression of a constitutively active ERK2 had an opposite effect. Inhibition of ERK signaling in cultured myotubes increased slow-twitch fiber-specific protein accumulation while repressing those characteristic of fast-twitch fibers. Overexpression of MAP kinase phosphatase-1 (MKP1) in mouse and rat muscle fibers containing almost exclusively type IIb or IIx fast myosin heavy chain (MyHC) isoforms induced de novo synthesis of the slower, more oxidative type IIa and I MyHCs in a time-dependent manner. Conversion to the slower phenotype was confirmed by up-regulation of slow reporter gene activity and down-regulation of fast reporter activities in response to forced MKP1 expression in vivo. In addition, activation of ERK2 signaling induced up-regulation of fast-twitch fiber program in soleus. These data suggest that the MAPK signaling, most likely the ERK1/2 pathway, is necessary to preserve the fast-twitch fiber phenotype with a concomitant repression of slow-twitch fiber program.

Lymphovascular Invasion Increases the Risk of Nodal and Distant Recurrence in Node-Negative Stage I-IIA Non-Small-Cell Lung Cancer.

PubMed

Sung, Soo Yoon; Kwak, Yoo-Kang; Lee, Sea-Won; Jo, In Young; Park, Jae Kil; Kim, Kyung Soo; Lee, Kyo Young; Kim, Yeon-Sil

2018-05-30

Despite complete surgical resection, 30-40% of patients with stage I-IIA non-small-cell lung cancer (NSCLC) have recurrences. We aimed to elucidate the effect of lymphovascular invasion (LVI) on the prognosis and patterns of recurrence in patients with pathologically confirmed T1-2N0 NSCLC. We evaluated 381 patients who underwent complete resection and were diagnosed with pathologic T1-2N0 NSCLC between March 2000 and January 2012. Local recurrence, nodal recurrence, and distant metastasis were defined and analyzed. LVI was present in 72 patients (18.9%). The 5-year disease-free survival (DFS) for all patients was 69.9%. Patients with LVI showed a significant decrease in 5-year DFS (47.3 vs. 74.4%, p < 0.001). LVI was a significant prognostic predictor in multivariate analysis (p = 0.003). The patients with LVI showed a significantly increased 5-year cumulative incidence of nodal recurrence (22.5 vs. 8.7%, p < 0.001) and distant metastasis (30.4 vs. 14.9%, p = 0.004). However, no difference was shown between the two groups in the 5-year cumulative incidence of local recurrence (p = 0.416). LVI is a negative prognostic factor in patients with stage I-IIA NSCLC. The presence of LVI significantly increases the risk of nodal and distant recurrence. © 2018 S. Karger AG, Basel.

The E3 ligase Ubr3 regulates Usher syndrome and MYH9 disorder proteins in the auditory organs of Drosophila and mammals

PubMed Central

Li, Tongchao; Giagtzoglou, Nikolaos; Eberl, Daniel F; Jaiswal, Sonal Nagarkar; Cai, Tiantian; Godt, Dorothea; Groves, Andrew K; Bellen, Hugo J

2016-01-01

Myosins play essential roles in the development and function of auditory organs and multiple myosin genes are associated with hereditary forms of deafness. Using a forward genetic screen in Drosophila, we identified an E3 ligase, Ubr3, as an essential gene for auditory organ development. Ubr3 negatively regulates the mono-ubiquitination of non-muscle Myosin II, a protein associated with hearing loss in humans. The mono-ubiquitination of Myosin II promotes its physical interaction with Myosin VIIa, a protein responsible for Usher syndrome type IB. We show that ubr3 mutants phenocopy pathogenic variants of Myosin II and that Ubr3 interacts genetically and physically with three Usher syndrome proteins. The interactions between Myosin VIIa and Myosin IIa are conserved in the mammalian cochlea and in human retinal pigment epithelium cells. Our work reveals a novel mechanism that regulates protein complexes affected in two forms of syndromic deafness and suggests a molecular function for Myosin IIa in auditory organs. DOI: http://dx.doi.org/10.7554/eLife.15258.001 PMID:27331610

Effect of 23-day muscle disuse on sarcoplasmic reticulum Ca2+ properties and contractility in human type I and type II skeletal muscle fibers.

PubMed

Lamboley, C R; Wyckelsma, V L; Perry, B D; McKenna, M J; Lamb, G D

2016-08-01

Inactivity negatively impacts on skeletal muscle function mainly through muscle atrophy. However, recent evidence suggests that the quality of individual muscle fibers is also altered. This study examined the effects of 23 days of unilateral lower limb suspension (ULLS) on specific force and sarcoplasmic reticulum (SR) Ca(2+) content in individual skinned muscle fibers. Muscle biopsies of the vastus lateralis were taken from six young healthy adults prior to and following ULLS. After disuse, the endogenous SR Ca(2+) content was ∼8% lower in type I fibers and maximal SR Ca(2+) capacity was lower in both type I and type II fibers (-11 and -5%, respectively). The specific force, measured in single skinned fibers from three subjects, decreased significantly after ULLS in type II fibers (-23%) but not in type I fibers (-9%). Western blot analyses showed no significant change in the amounts of myosin heavy chain (MHC) I and MHC IIa following the disuse, whereas the amounts of sarco(endo)plasmic reticulum Ca(2+)-ATPase 1 (SERCA1) and calsequestrin increased by ∼120 and ∼20%, respectively, and the amount of troponin I decreased by ∼21%. These findings suggest that the decline in force and power occurring with muscle disuse is likely to be exacerbated in part by reductions in maximum specific force in type II fibers, and in the amount of releasable SR Ca(2+) in both fiber types, the latter not being attributable to a reduced calsequestrin level. Furthermore, the ∼3-wk disuse in human elicits change in SR properties, in particular a more than twofold upregulation in SERCA1 density, before any fiber-type shift. Copyright © 2016 the American Physiological Society.

K-theoretic aspects of string theory dualities

NASA Astrophysics Data System (ADS)

Mendez-Diez, Stefan Milo

String theory is a a physical field theory in which point particles are replaced by 1-manifolds propagating in time, called strings. The 2-manifold representing the time evolution of a string is called the string worldsheet. Strings can be either closed (meaning their worldsheets are closed surfaces) or open (meaning their worldsheets have boundary). A D-brane is a submanifold of the spacetime manifold on which string endpoints are constrained to lie. There are five different string theories that have supersymmetry, and they are all related by various dualities. This dissertation will review how D-branes are classified by K-theory. We will then explore the K-theoretic aspects of a hypothesized duality between the type I theory compactified on a 4-torus and the type IIA theory compactified on a K3 surface, by looking at a certain blow down of the singular limit of K3. This dissertation concludes by classifying D-branes on the type II orientifold Tn/Z2 when the Z2 action is multiplication by -1 and the H-flux is trivial. We find that classifying D-branes on the singular limit of K3, T4/Z2 by equivariant K-theory agrees with the classification of D-branes on a smooth K3 surface by ordinary K-theory.

Effects of dietary starch types on growth performance, meat quality and myofibre type of finishing pigs.

PubMed

Li, Y J; Li, J L; Zhang, L; Gao, F; Zhou, G H

2017-09-01

To investigate the effects of dietary starch types on growth performance and meat quality of finishing pigs, ninety barrows (68.0±2.0kg) were randomly allotted to three experimental diets with five replicates of six pigs, containing pure waxy maize starch (WMS), nonwaxy maize starch (NMS) and pea starch (PS) (amylose/amylopectin were 0.07, 0.19 and 0.28 respectively). Compared with WMS diet, PS diet increased the average daily gain, loin eye area, pH 45 value, NMR transverse relaxation (T 2 ) 2 peak area ratio and sarcoplasmic protein solubility, decreased the feed to gain ratio, back fat, drip loss, cooking loss and T 23 peak area ratio (P<0.05). Moreover, PS diet increased the myosin heavy-chain (MyHC)-I and IIa levels, decreased the MyHC-IIb level, decreased the miR23a level and increased its target gene level, increased the miR499 level and decreased its target gene level (P<0.05). Diet with high amylose content might be beneficial to the growth performance and meat quality of finishing pigs. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Animal Reproduction and Breeding.] Student Materials. V.A. III. [II-A-1 through II-A-8].

ERIC Educational Resources Information Center

Texas A and M Univ., College Station. Vocational Instructional Services.

Part of a series of eight student learning modules in vocational agriculture, this booklet deals with animal reproduction and breeding. The topics covered are genetics, animal reproduction, breeding methods, artificial insemination, pregnancy diagnosis, and parturition care. Each section ends with a glossary and a quiz. (PLB)

Geothermal Potential of Ascension Island, South Atlantic.

DTIC Science & Technology

1982-11-05

7AD-A141 763 GEOTHERMAL POTENTIAL OF ASCENSION ISLAND SOUTH ATLANTIC 1/1. (U) UTAH UNIV RESEARCH IN T SALT LAKE CITY EARTH U LfIS SCIENCE LAB D L...STANDARDS 1%A A ~ 7- ESMC-TR-83-02 Geothermal Potential Of Ascension Island, South Atlantic Dennis L. Nielson Bruce S. Sibbett University Of Utah...Security Classification) Geothermal Potential of Ascension Island, South Atlantic 12 PERSONAL AUTHOR(S) Dennis L. Neilson and Bruce S. Sibbett IIa TYPE

Effects of Nitric Oxide Synthase Inhibition on Fiber-Type Composition, Mitochondrial Biogenesis, and SIRT1 Expression in Rat Skeletal Muscle

PubMed Central

Suwa, Masataka; Nakano, Hiroshi; Radak, Zsolt; Kumagai, Shuzo

2015-01-01

It was hypothesized that nitric oxide synthases (NOS) regulated SIRT1 expression and lead to a corresponding changes of contractile and metabolic properties in skeletal muscle. The purpose of the present study was to investigate the influence of long-term inhibition of nitric oxide synthases (NOS) on the fiber-type composition, metabolic regulators such as and silent information regulator of transcription 1 (SIRT1) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), and components of mitochondrial biogenesis in the soleus and plantaris muscles of rats. Rats were assigned to two groups: control and NOS inhibitor (Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME), ingested for 8 weeks in drinking water)-treated groups. The percentage of Type I fibers in the L-NAME group was significantly lower than that in the control group, and the percentage of Type IIA fibers was concomitantly higher in soleus muscle. In plantaris muscle, muscle fiber composition was not altered by L-NAME treatment. L-NAME treatment decreased the cytochrome C protein expression and activity of mitochondrial oxidative enzymes in the plantaris muscle but not in soleus muscle. NOS inhibition reduced the SIRT1 protein expression level in both the soleus and plantaris muscles, whereas it did not affect the PGC-1α protein expression. L-NAME treatment also reduced the glucose transporter 4 protein expression in both muscles. These results suggest that NOS plays a role in maintaining SIRT1 protein expression, muscle fiber composition and components of mitochondrial biogenesis in skeletal muscle. Key points NOS inhibition by L-NAME treatment decreased the SIRT1 protein expression in skeletal muscle. NOS inhibition induced the Type I to Type IIA fiber type transformation in soleus muscle. NOS inhibition reduced the components of mitochondrial biogenesis and glucose metabolism in skeletal muscle. PMID:26336341

Nutlin-3 plus tanshinone IIA exhibits synergetic anti-leukemia effect with imatinib by reactivating p53 and inhibiting the AKT/mTOR pathway in Ph+ ALL.

PubMed

Guo, Yong; Li, Yi; Xiang, Bing; Huang, Xiao-Ou; Ma, Hong-Bing; Wang, Fang-Fang; Gong, Yu-Ping

2017-12-06

Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is triggered by BCR/ABL kinase. Recent efforts focused on the development of more potent tyrosine kinase inhibitors (TKIs) that also inhibit mutant tyrosine kinases such as nilotinib and dasatinib. Although major advances in the treatment of this aggressive disease with potent inhibitors of the BCR/ABL kinases, patients in remission frequently relapse due to drug resistance possibly mediated, at least in part, by compensatory activation of growth-signaling pathways and protective feedback signaling of leukemia cells in response to TKI treatment. Continuous activation of AKT/mTOR signaling and inactivation of p53 pathway were two mechanisms of TKI resistance. Here, we reported that nutlin-3 plus tanshinone IIA significantly potentiated the cytotoxic and apoptotic induction effects of imatinib by down-regulation of the AKT/mTOR pathway and reactivating the p53 pathway deeply in Ph+ ALL cell line. In primary samples from Ph+ ALL patients, nutlin-3 plus tanshinone IIA also exhibited synergetic cytotoxic effects with imatinib. Of note, three samples from Ph+ ALL patients harboring T315I mutation also showed sensitivity to the combined treatment of imatinib, nutlin-3 plus tanshinone IIA. In Ph+ ALL mouse models, imatinib combined with nutlin-3 plus tanshinone IIA also exhibited synergetic effects on reduction in leukemia burden. These results demonstrated that nutlin-3 plus tanshinone IIA combined TKI might be a promising treatment strategy for Ph+ ALL patients. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Emission from Crystals Irradiated with a Beam of Runaway Electrons

NASA Astrophysics Data System (ADS)

Buranchenko, A. G.; Tarasenko, V. F.; Beloplotov, D. V.; Baksht, E. Kh.

2018-01-01

An investigation of the spectral and amplitude-temporal characteristics of emission from different crystals, promising in terms of their application as detectors of runaway electrons, is performed. This emission is excited by subnanosecond electron beams generated in a gas diode. It is found out that at the electron energies of tens-hundreds of kiloelectronvolts, the main contribution into the emission from CsI, ZnS, type IIa artificial and natural diamonds, sapphire, CaF2, ZrO2, Ga2O3, CaCO3, CdS, and ZnSe crystals comes from the cathodoluminescence; the radiation pulse duration depends on the crystal used and sufficiently exceeds the Cherenkov radiation pulse duration. It is demonstrated that the latter radiation exhibits low intensity and can be detected in the short-wave region of the spectrum in the cases where a monochromator and a high-sensitivity photomultiplier tube (PMT) are used.

Investigating mycobacterial topoisomerase I mechanism from the analysis of metal and DNA substrate interactions at the active site.

PubMed

Cao, Nan; Tan, Kemin; Annamalai, Thirunavukkarasu; Joachimiak, Andrzej; Tse-Dinh, Yuk-Ching

2018-06-14

We have obtained new crystal structures of Mycobacterium tuberculosis topoisomerase I, including structures with ssDNA substrate bound to the active site, with and without Mg2+ ion present. Significant enzyme conformational changes upon DNA binding place the catalytic tyrosine in a pre-transition state position for cleavage of a specific phosphodiester linkage. Meanwhile, the enzyme/DNA complex with bound Mg2+ ion may represent the post-transition state for religation in the enzyme's multiple-step DNA relaxation catalytic cycle. The first observation of Mg2+ ion coordinated with the TOPRIM residues and DNA phosphate in a type IA topoisomerase active site allows assignment of likely catalytic role for the metal and draws a comparison to the proposed mechanism for type IIA topoisomerases. The critical function of a strictly conserved glutamic acid in the DNA cleavage step was assessed through site-directed mutagenesis. The functions assigned to the observed Mg2+ ion can account for the metal requirement for DNA rejoining but not DNA cleavage by type IA topoisomerases. This work provides new structural insights into a more stringent requirement for DNA rejoining versus cleavage in the catalytic cycle of this essential enzyme, and further establishes the potential for selective interference of DNA rejoining by this validated TB drug target.

Cryptosporidium species and Cryptosporidium parvum subtypes in dairy calves and goat kids reared under traditional farming systems in Turkey.

PubMed

Taylan-Ozkan, Aysegul; Yasa-Duru, Sibel; Usluca, Selma; Lysen, Colleen; Ye, Jianbin; Roellig, Dawn M; Feng, Yaoyu; Xiao, Lihua

2016-11-01

Molecular characterizations of Cryptosporidium spp. in ruminants reared under traditional animal management systems are scarce and studies conducted thus far have revealed largely an absence of the pathogenic and zoonotic species Cryptosporidium parvum in pre-weaned animals. In this study, we examined Cryptosporidium species and subtype distribution in free-range pre-weaned dairy calves and goat kids with diarrhea. Cryptosporidium-positive specimens from pre-weaned calves on 10 farms and goat kids on 4 farms in Ankara, Balikesir, Corum, Kirikkale, and Kirsehir Provinces, Turkey were genotyped by PCR-restriction length polymorphism analysis of the small subunit rRNA gene, which identified C. parvum in 27 calves and 9 goat kids and Cryptosporidium ryanae in 1 calf. Among the C. parvum isolates successfully subtyped by DNA sequence analysis of the 60 kDa glycoprotein gene, three subtypes were detected in calves, including IIaA13G2R1 (20/23), IIdA18G1 (2/23), and IIdA20G1b (1/23), and four subtypes were detected in goat kids, including IIaA13G2R1 (3/8), IIaA15G1R1 (2/8), IIdA22G1 (2/8), and IIdA18G1 (1/8). Data of the study suggest that dairy calves reared in a traditional cow-calf system in Turkey are mainly infected with a C. parvum subtype rarely seen elsewhere, whereas goat kids are infected with diverse subtypes. As all five C. parvum subtypes found in this study are known human pathogens, pre-weaned farm animals could play a potential role in the transmission of human cryptosporidiosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Resolution and some properties of enzymes involved in enantioselective transformation of 1,3-dichloro-2-propanol to (R)-3-chloro-1,2-propanediol by Corynebacterium sp. strain N-1074.

PubMed Central

Nakamura, T; Nagasawa, T; Yu, F; Watanabe, I; Yamada, H

1992-01-01

During the course of the transformation of 1,3-dichloro-2-propanol (DCP) into (R)-3-chloro-1,2-propanediol [(R)-MCP] with the cell extract of Corynebacterium sp. strain N-1074, epichlorohydrin (ECH) was transiently formed. The cell extract was fractionated into two DCP-dechlorinating activities (fractions Ia and Ib) and two ECH-hydrolyzing activities (fractions IIa and IIb) by TSKgel DEAE-5PW column chromatography. Fractions Ia and Ib catalyzed the interconversion of DCP to ECH, and fractions IIa and IIb catalyzed the transformation of ECH into MCP. Fractions Ia and IIa showed only low enantioselectivity for each reaction, whereas fractions Ib and IIb exhibited considerable enantioselectivity, yielding R-rich ECH and MCP, respectively. Enzymes Ia and Ib were isolated from fractions Ia and Ib, respectively. Enzyme Ia had a molecular mass of about 108 kDa and consisted of four subunits identical in molecular mass (about 28 kDa). Enzyme Ib was a protein of 115 kDa, composed of two different polypeptides (about 35 and 32 kDa). The specific activity of enzyme Ib for DCP was about 30-fold higher than that of enzyme Ia. Both enzymes catalyzed the transformation of several halohydrins into the corresponding epoxides with liberation of halides and its reverse reaction. Their substrate specificities and immunological properties differed from each other. Enzyme Ia seemed to be halohydrin hydrogen-halide-lyase which was already purified from Escherichia coli carrying a gene from Corynebacterium sp. strain N-1074. Images PMID:1447132

30 CFR 57.22603 - Blasting from the surface (II-A mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... MINES Safety Standards for Methane in Metal and Nonmetal Mines Explosives § 57.22603 Blasting from the surface (II-A mines). (a) All development, production, and bench rounds shall be initiated from the... least one atmospheric monitoring sensor. (b) If the monitoring system indicates that methane in the mine...

30 CFR 57.22603 - Blasting from the surface (II-A mines).

Code of Federal Regulations, 2014 CFR

2014-07-01

... MINES Safety Standards for Methane in Metal and Nonmetal Mines Explosives § 57.22603 Blasting from the surface (II-A mines). (a) All development, production, and bench rounds shall be initiated from the... least one atmospheric monitoring sensor. (b) If the monitoring system indicates that methane in the mine...

30 CFR 57.22603 - Blasting from the surface (II-A mines).

Code of Federal Regulations, 2013 CFR

2013-07-01

... MINES Safety Standards for Methane in Metal and Nonmetal Mines Explosives § 57.22603 Blasting from the surface (II-A mines). (a) All development, production, and bench rounds shall be initiated from the... least one atmospheric monitoring sensor. (b) If the monitoring system indicates that methane in the mine...

30 CFR 57.22603 - Blasting from the surface (II-A mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... MINES Safety Standards for Methane in Metal and Nonmetal Mines Explosives § 57.22603 Blasting from the surface (II-A mines). (a) All development, production, and bench rounds shall be initiated from the... least one atmospheric monitoring sensor. (b) If the monitoring system indicates that methane in the mine...

30 CFR 57.22603 - Blasting from the surface (II-A mines).

Code of Federal Regulations, 2012 CFR

2012-07-01

... MINES Safety Standards for Methane in Metal and Nonmetal Mines Explosives § 57.22603 Blasting from the surface (II-A mines). (a) All development, production, and bench rounds shall be initiated from the... least one atmospheric monitoring sensor. (b) If the monitoring system indicates that methane in the mine...

Rigid Calabi-Yau threefolds, Picard Eisenstein series and instantons

NASA Astrophysics Data System (ADS)

Bao, L.; Kleinschmidt, A.; Nilsson, B. E. W.; Persson, D.; Pioline, B.

2013-12-01

Type IIA string theory compactified on a rigid Calabi-Yau threefold gives rise to a classical moduli space that carries an isometric action of U(2, 1). Various quantum corrections break this continuous isometry to a discrete subgroup. Focussing on the case where the intermediate Jacobian of the Calabi-Yau admits complex multiplication by the ring of quadratic imaginary integers d, we argue that the remaining quantum duality group is an arithmetic Picard modular group PU(2, 1; d). Based on this proposal we construct an Eisenstein series invariant under this duality group and study its non-Abelian Fourier expansion. This allows the prediction of non-perturbative effects, notably the contribution of D2- and NS5-brane instantons. The present work extends our previous analysis in 0909.4299 which was restricted to the special case of the Gaussian integers 1 = Bbb Z[i].

Triapine With Chemotherapy and Radiation Therapy in Treating Patients With IB2-IVA Cervical or Vulvar Cancer

ClinicalTrials.gov

2018-04-25

Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Stage IB Vulvar Cancer AJCC v7; Stage IB2 Cervical Cancer AJCC v6 and v7; Stage II Vulvar Cancer AJCC v7; Stage IIA1 Cervical Cancer AJCC v7; Stage IIA2 Cervical Cancer AJCC v7; Stage IIB Cervical Cancer AJCC v6 and v7; Stage IIIA Cervical Cancer AJCC v6 and v7; Stage IIIA Vulvar Cancer AJCC v7; Stage IIIB Cervical Cancer AJCC v6 and v7; Stage IIIB Vulvar Cancer AJCC v7; Stage IIIC Vulvar Cancer AJCC v7; Stage IVA Cervical Cancer AJCC v6 and v7; Stage IVA Vulvar Cancer AJCC v7; Vulvar Adenocarcinoma; Vulvar Squamous Cell Carcinoma

Single-Center Experience and 1-Year Follow-up Results of 'Sandwich Technique' in the Management of Common Iliac Artery Aneurysms During EVAR

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ricci, Carmelo; Ceccherini, Claudio, E-mail: claudiocec@hotmail.it; Cini, Marco

Purpose: Abdominal aortic aneurysm (AAA) accompanied by common iliac artery (CIA) aneurysms requires a more demanding procedure owing to the difficulties in obtaining an adequate distal landing zone for the stent-graft limb(s), a potential site of endoleak. The 'sandwich technique' is a procedure to increase EVAR feasibility in the setting of adverse or challenging CIA anatomy. Its main advantages include no restrictions in terms of CIA diameter or length or internal iliac artery (IIA) diameter, no need to wait for a specific stent-graft. Our purpose is to describe our single-center experience and one year follow-up results of this new procedure.more » Materials and Methods: From April 2009 to June 2010, the sandwich technique was performed in our institution in 7 patients treated for AAA and unilateral CIA aneurysms (n. 5) or bilateral CIA aneurysms (n. 2). Inclusion criteria were the presence of unilateral or bilateral CIA aneurysm (independently from its diameter), IIA artery measuring up to 9 mm in its maximum diameter, not dilatation of IIA and EIA. Results: The mean follow-up length was 15 months (range: 14-20 months). All stent-implanted iliac branches remained patent on 1 year follow-up and IIA flow was preserved. None of the patients had symptoms of pelvic ischemia. CT scan follow-up showed aneurysm shrinkage in five patients, without any sign of endoleaks in all cases. Conclusions: In selected cases, the 'sandwich technique' showed good outcomes confirming to be a safe and easy to perform way to overcome anatomical constraints and expanding the limits of EVAR.« less

Skeletal muscle fiber size and fiber type distribution in human cancer: Effects of weight loss and relationship to physical function.

PubMed

Toth, Michael J; Callahan, Damien M; Miller, Mark S; Tourville, Timothy W; Hackett, Sarah B; Couch, Marion E; Dittus, Kim

2016-12-01

Cancer patients frequently experience weight loss, with negative consequences for functionality and prognosis. The extent to which muscle atrophy contributes to weight loss, however, is not clear, as few studies have directly measured muscle fiber morphology in cancer patients. Whole body and regional tissue composition were measured, along with the cross-sectional area (CSA) and fiber type of mechanically-isolated, single muscle fibers, in 19 cancer patients (8 with a history of weight loss, 11 weight-stable) and 15 non-diseased controls. Whole body fat mass was reduced in cancer patients with a history of weight loss, but no differences in whole body or leg fat-free mass were apparent. In contrast, reductions (∼20%) in single muscle fiber CSA were found in both slow-twitch, myosin heavy chain (MHC) I and fast-twitch, MHC IIA fibers in both weight-stable patients and those with a history of weight loss. Fiber type distribution showed a shift towards a fast-twitch phenotype compared to controls, which may preserve muscle function in cancer patients despite atrophy, as positive relationships were found between the fractions of hybrid MHC IIAX and I/IIA fibers and 6-min walk performance. Our results suggest that, although not apparent from whole body or regional measurements, cancer is associated with reduced skeletal muscle fiber size independent of weight loss history and a shift towards fast-twitch fibers, phenotypes that resemble adaptations to muscle disuse. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer

ClinicalTrials.gov

2018-06-08

Ductal Breast Carcinoma; Invasive Breast Carcinoma; Lobular Breast Carcinoma; Medullary Breast Carcinoma; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Tubular Breast Carcinoma

Experimental infection with Cryptosporidium parvum IIaA21G1R1 subtype in immunosuppressed mice

USDA-ARS?s Scientific Manuscript database

Cryptosporidium parvum subtype IIaA21G1R1 oocysts were used to infect dexamethasone immunosuppressed N: NIH Swiss mice. Histology showed developmental stages in the duodenum, proximal and distal jejunum, ileum, cecum and colon, with the small intestine remaining infected until day 35 post infection....

47 CFR 64.1190 - Preferred carrier freezes.

Code of Federal Regulations, 2010 CFR

2010-10-01

... or social security number) and the information required in §§ 64.1190(d)(3)(ii)(A) through (D... subscriber's date of birth or social security number) and the information required in § 64.1190(d)(3)(ii)(A... or the carrier's marketing agent; must not have any financial incentive to confirm preferred carrier...

Characterization of Class IIa Bacteriocin Resistance in Enterococcus faecium.

PubMed

Geldart, Kathryn; Kaznessis, Yiannis N

2017-04-01

Vancomycin-resistant enterococci, particularly resistant Enterococcus faecium , pose an escalating threat in nosocomial environments because of their innate resistance to many antibiotics, including vancomycin, a treatment of last resort. Many class IIa bacteriocins strongly target these enterococci and may offer a potential alternative for the management of this pathogen. However, E. faecium 's resistance to these peptides remains relatively uncharacterized. Here, we explored the development of resistance of E. faecium to a cocktail of three class IIa bacteriocins: enterocin A, enterocin P, and hiracin JM79. We started by quantifying the frequency of resistance to these peptides in four clinical isolates of E. faecium We then investigated the levels of resistance of E. faecium 6E6 mutants as well as their fitness in different carbon sources. In order to elucidate the mechanism of resistance of E. faecium to class IIa bacteriocins, we completed whole-genome sequencing of resistant mutants and performed reverse transcription-quantitative PCR (qRT-PCR) of a suspected target mannose phosphotransferase (ManPTS). We then verified this ManPTS's role in bacteriocin susceptibility by showing that expression of the ManPTS in Lactococcus lactis results in susceptibility to the peptide cocktail. Based on the evidence found from these studies, we conclude that, in accord with other studies in E. faecalis and Listeria monocytogenes , resistance to class IIa bacteriocins in E. faecium 6E6 is likely caused by the disruption of a particular ManPTS, which we believe we have identified. Copyright © 2017 American Society for Microbiology.

Characterization of Class IIa Bacteriocin Resistance in Enterococcus faecium

PubMed Central

Geldart, Kathryn

2017-01-01

ABSTRACT Vancomycin-resistant enterococci, particularly resistant Enterococcus faecium, pose an escalating threat in nosocomial environments because of their innate resistance to many antibiotics, including vancomycin, a treatment of last resort. Many class IIa bacteriocins strongly target these enterococci and may offer a potential alternative for the management of this pathogen. However, E. faecium's resistance to these peptides remains relatively uncharacterized. Here, we explored the development of resistance of E. faecium to a cocktail of three class IIa bacteriocins: enterocin A, enterocin P, and hiracin JM79. We started by quantifying the frequency of resistance to these peptides in four clinical isolates of E. faecium. We then investigated the levels of resistance of E. faecium 6E6 mutants as well as their fitness in different carbon sources. In order to elucidate the mechanism of resistance of E. faecium to class IIa bacteriocins, we completed whole-genome sequencing of resistant mutants and performed reverse transcription-quantitative PCR (qRT-PCR) of a suspected target mannose phosphotransferase (ManPTS). We then verified this ManPTS's role in bacteriocin susceptibility by showing that expression of the ManPTS in Lactococcus lactis results in susceptibility to the peptide cocktail. Based on the evidence found from these studies, we conclude that, in accord with other studies in E. faecalis and Listeria monocytogenes, resistance to class IIa bacteriocins in E. faecium 6E6 is likely caused by the disruption of a particular ManPTS, which we believe we have identified. PMID:28115354

Identification and prevalence of RND family multidrug efflux pump oqxAB genes in Enterococci isolates from swine manure in China.

PubMed

Yuan, Li; Zhai, Ya-Jun; Wu, Hua; Sun, Hua-Run; He, Zhi-Pei; Wang, Ya-Bin; Pan, Yu-Shan; Kuang, Nan-Nan; Hu, Gong-Zheng

2018-06-01

The resistance/nodulation/cell division (RND) family multidrug efflux pump, OqxAB, has been identified as one of the leading mechanisms of plasmid-mediated quinolone resistance and has become increasingly prevalent among Enterobacteriaceae in recent years. However, oqxAB genes have not yet been reported in Enterococcus isolates. The aim of the present study was to identify the oqxAB genes and investigate their prevalence among Enterococcus from swine manure in China. The oqxAB genes were screened in 87 Enterococcus isolates by PCR. The transferability of the oqxAB genes in Enterococcus was determined by conjugation experiments. The genetic environment of oqxAB genes was investigated by cloning experiments, PCR mapping and sequencing. A high prevalence (86.2 %) of olaquindox resistance was observed in Enterococcus and 98.9 % isolates exhibited multidrug-resistance phenotypes. The occurrence of oqxA and oqxB in Enterococcus was also high (79.3 and 65.5 %, respectively). Sequence analysis of the cloned fragment indicated that the oqxAB cassette was linked to an incomplete Tn5 transposon containing aph(3')-IIa and flanked by IS26 [IS26-oqxAB-IS26-aph(3')-IIa]. The oqxAB-aph(3')-IIa-positive transconjugant or transformant showed resistance or reduced susceptibility to enrofloxacin, ciprofloxacin, olaquindox, mequindox, florfenicol, neomycin and kanamycin. This is the first time that the oqxAB genes have been identified in Enterococcus faecalis from swine manure. The genetic linkage of oqxAB-aph(3')-IIa in Enterococcus has not been described before. The high prevalence of oqxAB genes in Enterococcus suggests that it may constitute a reservoir for oqxAB genes and pose a potential threat to public health.

PGC-1α is important for maintaining the balance of muscle mass and myofiber types in unloaded muscle atrophy

NASA Astrophysics Data System (ADS)

Chen, Xiaoping; He, Jian; Wang, Fei; Zhang, Peng; Liu, Hongju; Li, Wenjiong

2016-07-01

PGC-1α, a transcriptional co-activator, has been shown mainly to determine the development of oxidative myofibers in skeletal muscle. However, whether PGC-1α functions to regulate the unloaded muscle atrophy and composition of myofiber types keeps unclear. MCK-PGC-1α overexpression transgenic mice (TG) and its wild type littermates (WT) were subjected to hindlimb unloading (HU) and induced unloaded muscle atrophy. After 14 days of HU, the mass of gastrocnemius, soleus, and plantaris muscles in WT mice decreased 17.9%, 28.2%, and 14.8%, respectively (P<0.01), compared with ground weight-bearing control muscles. PGC-1α transgenic mice showed a 14.0% (P<0.05), 20.4% (P<0.01), 11.8% decrease in gastrocnemius, soleus, and plantaris muscles mass after HU. To further confirm the effect of PGC-1α over-expression on the muscle mass loss under HU, change rate of muscle-body weight ratio was calculated, and the results indicated that the reduction of change rate of muscle-body weight ratio in PGC-1α transgenic gastrocnemius and soleus was significantly less than in WT mice (P<0.01). Moreover, in TG mice compared to WT mice there were significantly less reduction rate of slow-twitch myofiber MHC-I and MHC-IIa (MHC-I, -3.0±0.2% vs -14.9±4.2%, p<0.01, MHC-IIa, -3.5±2.7% vs -6.2±3.7%, p<0.01 ), while there was significantly less induction rate of fast-twitch myofiber MHC-IIb (MHC-IIb, +0.6±0.6% vs +3.7±2.9%, p<0.01 ). The real-time PCR and Western blot analysis confirmed that PGC-1α overexpression mice markedly rescued the muscle atrophy and myofiber switching from oxidative to glycolytic associated with a decrease in pSmad3 level after 14 days of HU. Importantly, overexpression of PGC-1α in C2C12 myoblasts protected PGC-1α-transfected myotubes from atrophy in vitro and the effect could be partially blocked by inducing pSmad3 with constitutively activated Smad3(C.A. smad3) transfection. Therefore, this study demonstrated a novel role and mechanism for PGC-1α in maintaining the balance of muscle mass and myofiber type MHCs in unloaded muscle atrophy via suppressing Smad3 activation. This report may prompt a hopeful therapeutic strategy for maintaining muscle mass and fiber type composition in disused muscle atrophies such as space weightlessness- or immobilization-induced muscle atrophy. Acknowledgments This work was supported by the Natural Sciences Foundation of China (31171144, 81272177 and 31171148), the State Key Laboratory Grant of Space Medicine Fundamentals and Application (SMFA13A01), and the National Key Laboratory Grant of Human Factors Engineering (SYFD140051801).

Ubiquitous production of branched glycerol dialkyl glycerol tetraethers (brGDGTs) in global marine environments: a new source indicator for brGDGTs

NASA Astrophysics Data System (ADS)

Xiao, Wenjie; Wang, Yinghui; Zhou, Shangzhe; Hu, Limin; Yang, Huan; Xu, Yunping

2016-10-01

Presumed source specificity of branched glycerol dialkyl glycerol tetraethers (brGDGTs) from bacteria thriving in soil/peat and isoprenoid GDGTs (iGDGTs) from aquatic organisms led to the development of several biomarker proxies for biogeochemical cycle and paleoenvironmental reconstructions. However, recent studies reveal that brGDGTs are also produced in aquatic environments besides soils and peat. Here we examined three cores from the Bohai Sea, and found distinct difference in brGDGT compositions varying with the distance from the Yellow River mouth. We thus propose an abundance ratio of hexamethylated to pentamethylated brGDGT (IIIa / IIa) to evaluate brGDGT sources. The compilation of globally distributed 1354 marine sediments and 589 soils shows that the IIIa / IIa ratio is generally < 0.59 in soils and 0.59-0.92 and > 0.92 in marine sediments with and without significant terrestrial inputs, respectively. Such disparity confirms the existence of two sources for brGDGTs, a terrestrial origin with lower IIIa / IIa and a marine origin with higher IIIa / IIa, which is likely attributed to a generally higher pH and the production of brGDGTs in cold deep water in marine waters. The application of the IIIa / IIa ratio to the East Siberian Arctic Shelf proves it to be a sensitive source indicator for brGDGTs, which is helpful for accurate estimation of organic carbon source and paleoclimates in marine settings.

Pre-Training Muscle Characteristics of Subjects Who Are Obese Determine How Well Exercise Training Will Improve Their Insulin Responsiveness.

PubMed

Stuart, Charles A; Lee, Michelle L; South, Mark A; Howell, Mary E A; Cartwright, Brian M; Ramsey, Michael W; Stone, Michael H

2017-03-01

Stuart, CA, Lee, ML, South, MA, Howell, MEA, Cartwright, BM, Ramsey, MW, and Stone, MH. Pre-training muscle characteristics of subjects who are obese determine how well exercise training will improve their insulin responsiveness. J Strength Cond Res 31(3): 798-808, 2017-Only half of prediabetic subjects who are obese who underwent exercise training without weight loss increased their insulin responsiveness. We hypothesized that those who improved their insulin responsiveness might have pretraining characteristics favoring a positive response to exercise training. Thirty nondiabetic subjects who were obese volunteered for 8 weeks of either strength training or endurance training. During training, subjects increased their caloric intake to prevent weight loss. Insulin responsiveness by euglycemic clamps and muscle fiber composition, and expression of muscle key biochemical pathways were quantified. Positive responders initially had 52% higher intermediate muscle fibers (fiber type IIa) with 27% lower slow-twitch fibers (type I) and 23% lower expression of muscle insulin receptors. Whether after weight training or stationary bike training, positive responders' fiber type shifted away from type I and type IIa fibers to an increased proportion of type IIx fibers (fast twitch). Muscle insulin receptor expression and glucose transporter type 4 (GLUT4) expression increased in all trained subjects, but these moderate changes did not consistently translate to improvement in whole-body insulin responsiveness. Exercise training of previously sedentary subjects who are obese can result in muscle remodeling and increased expression of key elements of the insulin pathway, but in the absence of weight loss, insulin sensitivity improvement was modest and limited to about half of the participants. Our data suggest rather than responders being more fit, they may have been less fit, only catching up to the other half of subjects who are obese whose insulin responsiveness did not increase beyond their pretraining baseline.

Pharmacokinetics of Caffeic Acid, Ferulic Acid, Formononetin, Cryptotanshinone, and Tanshinone IIA after Oral Administration of Naoxintong Capsule in Rat by HPLC-MS/MS.

PubMed

Li, Jin; Bai, Yang; Bai, Yun; Zhu, Ruichao; Liu, Wei; Cao, Jun; An, Mingrui; Tan, Zhijing; Chang, Yan-Xu

2017-01-01

Naoxintong capsule (NXTC) was a famous patent medicine of Traditional Chinese Medicine (TCM) to treat cerebrovascular diseases in China. An LC-MS/MS method was developed for simultaneous determination of 11 major ingredients (paeoniflorin, ecdysterone, amygdalin, mulberroside A, caffeic acid, ferulic acid, salvianolic acid B, astragaloside IV, formononetin, cryptotanshinone, and tanshinone IIA) in NXTC in rat plasma. All analytes were separated on an Eclipse plus C 18 column using a gradient mobile phase system of acetonitrile-0.1% formic acid aqueous solution. The lower limits of quantification of 11 ingredients were between 0.075 and 10 ng mL -1 . The precision was less than 15% and the accuracies were between 85% and 115%. The results showed that caffeic acid, ferulic acid, formononetin, cryptotanshinone, and tanshinone IIA could be detected after oral administration of NXTC. The validated method was successfully applied to pharmacokinetic study of the caffeic acid, ferulic acid, formononetin, cryptotanshinone, and tanshinone IIA in rats after oral administration of NXTC at single and triple dose.

Explosive and pyrotechnic aging demonstration

NASA Technical Reports Server (NTRS)

Rouch, L. L., Jr.; Maycock, J. N.

1976-01-01

The survivability was experimentally verified of fine selected explosive and pyrotechnic propellant materials when subjected to sterilization, and prolonged exposure to space environments. This verification included thermal characterization, sterilization heat cycling, sublimation measurements, isothermal decomposition measurements, and accelerated aging at a preselected elevated temperature. Temperatures chosen for sublimation and isothermal decomposition measurements were those in which the decomposition processess occurring would be the same as those taking place in real-time aging. The elevated temperature selected (84 C) for accelerated aging was based upon the parameters calculated from the kinetic data obtained in the isothermal measurement tests and was such that one month of accelerated aging in the laboratory approximated one year of real-time aging at 66 C. Results indicate that HNS-IIA, pure PbN6, KDNBF, and Zr/KC10 are capable of withstanding sterilization. The accelerated aging tests indicated that unsterilized HNS-IIA and Zr/KC104 can withstand the 10 year, elevated temperature exposure, pure PbN6 and KDNBF exhibit small weight losses (less than 2 percent) and B/KC104 exhibits significant changes in its thermal characteristics. Accelerated aging tests after sterilization indicated that only HNS-IIA exhibited high stability.

Histone deacetylase inhibitors: Isoform selectivity improves survival in a hemorrhagic shock model.

PubMed

Chang, Panpan; Weykamp, Michael; Dennahy, Isabel S; Williams, Aaron M; Bhatti, Umar F; Liu, Baoling; Nikolian, Vahagn C; Li, Yongqing; Alam, Hasan B

2018-05-01

Hemorrhage is a leading preventable cause of death. Nonselective histone deacetylase inhibitors (HDACIs), such as valproic acid (VPA), have been shown to improve outcomes in hemorrhagic shock (HS). The HDACs can be divided into four functional classes (I, IIa/IIb, III, and IV). Classes I, IIa/IIb, and III have previously been implicated in the pathophysiology of HS. This study aimed to determine which HDAC class, or classes, are responsible for the survival benefit observed with nonselective HDACIs. Survival study: Sprague-Dawley rats were subjected to lethal HS (50% hemorrhage) and randomized to the following groups (n = 8): (1) no treatment, (2) normal saline vehicle, (3) cyclodextrin vehicle, (4) MS275 (class I HDACI), (5) VPA (class I/IIa HDACI), (6) MC1568 (class IIa HDACI), (7) ACY1083 (class IIb HDACI), and (8) EX527 (class III HDACI). Survival was monitored for 24 hours. Mechanistic study: Sprague-Dawley rats were subjected to sublethal HS (40% hemorrhage) and randomized to the same groups (n = 3), excluding EX527, based on results of the survival study. Tissues were harvested at 3 hours posttreatment, and expression of phosphorylated-AKT, β-catenin, acetylated histones H3 and H4, and acetylated α-tubulin were analyzed in myocardial tissue. Survival rate was 12.5% in the untreated group, and did not improve with vehicle or MS275 treatment. EX527 improved survival to 50%, although this did not achieve statistical significance (p = 0.082). However, treatment with VPA, MC1568, and ACY1083 improved survival rates to 87.5%, 75%, and 75%, respectively (p < 0.05). The VPA-induced acetylation of both histones H3 and H4, while MC1568 and ACY1083 increased acetylation of histone H4. ACY1083 also induced acetylation of α-tubulin. All treatment groups, except MS275, increased phosphorylated-AKT, and β-catenin. Inhibition of HDAC classes IIa or IIb, but not class I, activates prosurvival pathways, which may be responsible for the improved outcomes in rodent models of HS.

30 CFR 57.22206 - Main ventilation failure (I-A, II-A, III, and V-A mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... AND NONMETAL MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22206..., tests for methane shall be conducted in affected active workings until normal air flow has resumed. (b... less than 1.0 percent methane. Persons other than examiners shall not reenter a Subcategory II-A mine...

Survivorship Care Planning in Patients With Colorectal or Non-Small Cell Lung Cancer

ClinicalTrials.gov

2013-12-16

Stage I Colon Cancer; Stage I Rectal Cancer; Stage IA Non-small Cell Lung Cancer; Stage IB Non-small Cell Lung Cancer; Stage IIA Colon Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIA Rectal Cancer; Stage IIB Colon Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIB Rectal Cancer; Stage IIC Colon Cancer; Stage IIC Rectal Cancer; Stage IIIA Colon Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer

Anesthetic cardioprotection in clinical practice from proof-of-concept to clinical applications.

PubMed

Zaugg, Michael; Lucchinetti, Eliana; Behmanesh, Saeid; Clanachan, Alexander S

2014-01-01

In 2007, the American Heart Association (AHA) recommended (class IIa, level of evidence B) in their guidelines on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery volatile anesthetics as first choice for general anesthesia in hemodynamically stable patients at risk for myocardial ischemia. This recommendation was based on results from patients undergoing coronary artery bypass grafting (CABG) surgery and thus subject to criticism. However, since a "good anesthetic" often resembles a piece of art in the complex perioperative environment, and is difficult to highly standardize, it seems unlikely that large-scale randomized control trials in noncardiac surgical patients will be performed in the near future to tackle this question. There is growing evidence that ether-derived volatile anesthetics and opioids provide cardioprotection in patients undergoing CABG surgery. Since 2011, the American College of Cardiology Foundation/AHA have recommended a "volatile-based anesthesia" for these procedures (class IIa, level of evidence A). It is very likely that volatile anesthetics and opioids also protect hearts of noncardiac surgical patients. However, age, diabetes and myocardial remodeling diminish the cardioprotective benefits of anesthetics. In patients at risk for perioperative cardiovascular complications, it is essential to abandon the use of "anti-conditioning" drugs (sulfonylureas and COX-2 inhibitors) and probably glitazones. There is significant interference in cardioprotection between sevoflurane and propofol, which should not be used concomitantly during anesthesia if possible. Any type of ischemic "conditioning" appears to exhibit markedly reduced protection or completely loses protection in the presence of volatile anesthetics and/or opioids.

Spinal arterial anatomy and risk factors for lower extremity weakness following endovascular thoracoabdominal aortic aneurysm repair with branched stent-grafts.

PubMed

Chang, Catherine K; Chuter, Timothy A M; Reilly, Linda M; Ota, Maile K; Furtado, Andre; Bucci, Monica; Wintermark, Max; Hiramoto, Jade S

2008-06-01

To evaluate spinal arterial anatomy and identify risk factors for lower extremity weakness (LEW) following endovascular thoracoabdominal aortic aneurysm (TAAA) repair. A retrospective review was conducted of 37 patients (27 men; mean age 74.8+/-7.1 years, range 58-86) undergoing endovascular TAAA repair with branched stent-grafts at a single academic institution from July 2005 to December 2007. Data were collected on preoperative comorbidities, duration of operation, blood loss, type of anesthesia, extent of aortic coverage, blood pressure, cerebrospinal fluid (CSF) pressure and drainage, and postoperative development of LEW. Pre- and postoperative contrast-enhanced computed tomographic angiograms (CTA) in a 26-patient subset were analyzed to evaluate the number of patent intercostal and lumbar arteries before and after repair. All patients were neurologically intact at the end of the operation. Seven (19%) patients developed LEW postoperatively: 6 perioperatively and 1 after discharge. LEW was associated with postoperative hypotension, internal iliac artery (IIA) occlusion, and fewer patent segmental arteries on preoperative CTA. Lowest mean systolic blood pressure was <90 mmHg in all 6 (100%) patients who developed LEW in hospital compared to 12 (44%) of the 27 patients who did not develop LEW (p = 0.02). Complete resolution of LEW (n = 4) followed prompt measures to raise blood pressure and lower CSF pressure. Persistent LEW (n = 3) was associated with sustained hypotension from sepsis, postoperative bleeding, and hemodialysis, respectively. Two (29%) of 7 patients with LEW either lost prograde flow to an IIA during repair or had bilaterally occluded IIAs preoperatively compared to 2 (7%) of 30 patients without LEW (p = 0.16). Comparison of pre- and postoperative CTAs showed no reduction in the mean number of patent segmental arteries in patients with or without LEW. Endovascular TAAA repair inevitably occludes direct inflow to lumbar and intercostal arteries. The distal segments of these arteries to the spine, however, are seen to remain patent through collaterals. Measures to preserve collateral pathways and increase perfusion pressure may help prevent or treat LEW.

Specific Molecular Signatures for Type II Crustins in Penaeid Shrimp Uncovered by the Identification of Crustin-Like Antimicrobial Peptides in Litopenaeus vannamei

PubMed Central

Barreto, Cairé; Coelho, Jaqueline da Rosa; Yuan, Jianbo; Xiang, Jianhai; Perazzolo, Luciane Maria

2018-01-01

Crustins form a large family of antimicrobial peptides (AMPs) in crustaceans composed of four sub-groups (Types I-IV). Type II crustins (Type IIa or “Crustins” and Type IIb or “Crustin-like”) possess a typical hydrophobic N-terminal region and are by far the most representative sub-group found in penaeid shrimp. To gain insight into the molecular diversity of Type II crustins in penaeids, we identified and characterized a Type IIb crustin in Litopenaeus vannamei (Crustin-like Lv) and compared Type II crustins at both molecular and transcriptional levels. Although L. vannamei Type II crustins (Crustin Lv and Crustin-like Lv) are encoded by separate genes, they showed a similar tissue distribution (hemocytes and gills) and transcriptional response to the shrimp pathogens Vibrio harveyi and White spot syndrome virus (WSSV). As Crustin Lv, Crustin-like Lv transcripts were found to be present early in development, suggesting a maternal contribution to shrimp progeny. Altogether, our in silico and transcriptional data allowed to conclude that (1) each sub-type displays a specific amino acid signature at the C-terminal end holding both the cysteine-rich region and the whey acidic protein (WAP) domain, and that (2) shrimp Type II crustins evolved from a common ancestral gene that conserved a similar pattern of transcriptional regulation. PMID:29337853

Conversion of 2,3-butanediol to butadiene

DOEpatents

Lilga, Michael A.; Frye, Jr, John G.; Lee, Suh-Jane; Albrecht, Karl O.

2016-09-06

A composition comprising 2,3-butanediol is dehydrated to methyl vinyl carbinol and/or 1,3-butadiene by exposure to a catalyst comprising (a) M.sub.xO.sub.y wherein M is a rare earth metal, a group IIIA metal, Zr, or a combination thereof, and x and y are based upon an oxidation state of M, or (b) M.sup.3.sub.a(PO.sub.4).sub.b where M.sup.3 is a group IA, a group IIA metal, a group IIIA metal, or a combination thereof, and a and b are based upon the oxidation state of M.sup.3. Embodiments of the catalyst comprising M.sub.xO.sub.y may further include M.sup.2, wherein M.sup.2 is a rare earth metal, a group IIA metal, Zr, Al, or a combination thereof. In some embodiments, 2,3-butanediol is dehydrated to methyl vinyl carbinol and/or 1,3-butadiene by a catalyst comprising M.sub.xO.sub.y, and the methyl vinyl carbinol is subsequently dehydrated to 1,3-butadiene by exposure to a solid acid catalyst.

26 CFR 1.141-5 - Private loan financing test.

Code of Federal Regulations, 2011 CFR

2011-04-01

... paragraph (c)(2)(ii)(A) of this section if— (A) The prepayment is made for— (1) Maintenance, repair, or an extended warranty with respect to personal property (for example, automobiles or electronic equipment); or (2) Updates or maintenance or support services with respect to computer software; and (B) The same...

26 CFR 1.141-5 - Private loan financing test.

Code of Federal Regulations, 2014 CFR

2014-04-01

... paragraph (c)(2)(ii)(A) of this section if— (A) The prepayment is made for— (1) Maintenance, repair, or an extended warranty with respect to personal property (for example, automobiles or electronic equipment); or (2) Updates or maintenance or support services with respect to computer software; and (B) The same...

26 CFR 1.141-5 - Private loan financing test.

Code of Federal Regulations, 2013 CFR

2013-04-01

... paragraph (c)(2)(ii)(A) of this section if— (A) The prepayment is made for— (1) Maintenance, repair, or an extended warranty with respect to personal property (for example, automobiles or electronic equipment); or (2) Updates or maintenance or support services with respect to computer software; and (B) The same...

26 CFR 1.141-5 - Private loan financing test.

Code of Federal Regulations, 2012 CFR

2012-04-01

... paragraph (c)(2)(ii)(A) of this section if— (A) The prepayment is made for— (1) Maintenance, repair, or an extended warranty with respect to personal property (for example, automobiles or electronic equipment); or (2) Updates or maintenance or support services with respect to computer software; and (B) The same...

Aerobic exercise training induces skeletal muscle hypertrophy and age-dependent adaptations in myofiber function in young and older men

PubMed Central

Konopka, Adam R.; Undem, Miranda K.; Hinkley, James M.; Minchev, Kiril; Kaminsky, Leonard A.; Trappe, Todd A.; Trappe, Scott

2012-01-01

To examine potential age-specific adaptations in skeletal muscle size and myofiber contractile physiology in response to aerobic exercise, seven young (YM; 20 ± 1 yr) and six older men (OM; 74 ± 3 yr) performed 12 wk of cycle ergometer training. Muscle biopsies were obtained from the vastus lateralis to determine size and contractile properties of isolated slow [myosin heavy chain (MHC) I] and fast (MHC IIa) myofibers, MHC composition, and muscle protein concentration. Aerobic capacity was higher (P < 0.05) after training in both YM (16 ± 2%) and OM (13 ± 3%). Quadriceps muscle volume, determined via MRI, was 5 ± 1 and 6 ± 1% greater (P < 0.05) after training for YM and OM, respectively, which was associated with an increase in MHC I myofiber cross-sectional area (CSA), independent of age. MHC I peak power was higher (P < 0.05) after training for both YM and OM, while MHC IIa peak power was increased (P < 0.05) with training in OM only. MHC I and MHC IIa myofiber peak and normalized (peak force/CSA) force were preserved with training in OM, while MHC I peak force/CSA and MHC IIa peak force were lower (P < 0.05) after training in YM. The age-dependent adaptations in myofiber function were not due to changes in protein content, as total muscle protein and myofibrillar protein concentration were unchanged (P > 0.05) with training. Training reduced (P < 0.05) the proportion of MHC IIx isoform, independent of age, whereas no other changes in MHC composition were observed. These data suggest relative improvements in muscle size and aerobic capacity are similar between YM and OM, while adaptations in myofiber contractile function showed a general improvement in OM. Training-related increases in MHC I and MHC IIa peak power reveal that skeletal muscle of OM is responsive to aerobic exercise training and further support the use of aerobic exercise for improving cardiovascular and skeletal muscle health in older individuals. PMID:22984247

Enterocin T, a novel class IIa bacteriocin produced by Enterococcus sp. 812.

PubMed

Chen, Yi-Sheng; Yu, Chi-Rong; Ji, Si-Hua; Liou, Min-Shiuan; Leong, Kun-Hon; Pan, Shwu-Fen; Wu, Hui-Chung; Lin, Yu-Hsuan; Yu, Bi; Yanagida, Fujitoshi

2013-09-01

Enterococcus sp. 812, isolated from fresh broccoli, was previously found to produce a bacteriocin active against a number of Gram-positive bacteria, including Listeria monocytogenes. Bacteriocin activity decreased slightly after autoclaving (121 °C for 15 min), but was inactivated by protease K. Mass spectrometry analysis revealed the bacteriocin mass to be approximately 4,521.34 Da. N-terminal amino acid sequencing yielded a partial sequence, NH2-ATYYGNGVYXDKKKXWVEWGQA, by Edman degradation, which contained the consensus class IIa bacteriocin motif YGNGV in the N-terminal region. The obtained partial sequence showed high homology with some enterococcal bacteriocins; however, no identical peptide or protein was found. This peptide was therefore considered to be a novel bacteriocin produced by Enterococcus sp. 812 and was termed enterocin T.

77 FR 68151 - Agency Information Collection Activities; Submission for OMB Review; Comment Request: Main Fan...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-15

... for OMB Review; Comment Request: Main Fan Operation and Inspection (I-A, II-A, III, and V-A Mines) ACTION: Notice. SUMMARY: The Department of Labor (DOL) is submitting the Mine Safety and Health... (I-A, II-A, III, and V-A Mines),'' to the Office of Management and Budget (OMB) for review and...

[Functional activity of the natural killers and macrophages in patients with breast tumors].

PubMed

Andrianov, I G; Voronov, S M; Dobkin, A N; Okulov, V B; Orlov, A B

1988-01-01

The activity of natural killers (NK) and macrophages of peripheral blood was studied in 37 female donors, 40 patients with benign and 43 with malignant tumors of the breast of various stages prior to treatment. Also the effect of Soviet-made recombinant interleukin-2 on NK activity was assessed. Natural killer activity (cytotoxic index) was 34.1 +/- 1.42 in healthy donors, 44.2 +/- 3.64 in cases of fibroadenomatosis, 43.1 +/- 5.6 in patients with stages I-IIa, 64.4 +/- 3.93--stage IIb, 45.8 +/- 6.32--stage III and 16.6 +/- 7.21% in cases of stage IV breast cancer, the scatter of values being greater in the tumor group. As many as 40% of patients with stages I-IIa and III cancer showed increased NK-activity values. An in vitro stimulating effect of NK activity of peripheral blood mononuclear cells by Soviet-made recombinant interleukin-2 was established.

The combined Mössbauer and XRF Spectrometer MIMOS IIA for In-Situ Geochemical and Mineralogical Analysis of Planetary Surfaces.

NASA Astrophysics Data System (ADS)

Klingelhoefer, Goestar; Morris, Richard; Blumers, Mathias; Girones-Lopez, Jordi; Bernhardt, Bodo; Henkel, Hartmut; D'Uston, Claude; Brueckner, Johannes; Rodionov, Daniel; Strueder, Lothar

The Miniaturised Mössbauer Spectrometers MIMOS II on board the two NASA Mars Exploration Rovers (MER) have now collected valuable scientific data for more than ten years [1-4]. This mission has demonstrated that Mössbauer spectroscopy is extremely valuable for the in situ exploration of extraterrestrial bodies and the study of Fe-bearing samples. A MIMOS instrument was also on the scientific payload of the Russian mission Phobos Grunt [5]. The instrument MIMOS IIA originally developed for the ESA ExoMars mission (now 2018) will use newly de-signed Si-Drift detectors with circular geometry (SDD) [6,7] allowing high resolution X-ray fluorescence spectroscopy simultaneously to Mössbauer measurements. The new design of the improved MIMOS II instrument is reduced in total mass (less than 400 g). The sensorhead of MIMOS IIA will be equipped with a ring of Silicon Drift Detectors (SDD) optimized for the backscatter geometry of the miniaturized Mössbauer spectrometer. The main goal of the new detector system design was to combine high energy resolution at high counting rates and large detector area while making maximum use of the area close to the collimator of the 57Co Mössbauer source. The active area per SDD segment is 2x45 mm2. The energy resolution at 5.9 keV is < 280 eV at room temperature and 131 eV FWHM at -40oC. This performance will increase the signal to noise ratio (SNR) and reduce the integration time of Mössbauer measurement by a factor of up to 10. In addition to the Mössbauer analysis simultaneous acquisition of the X-ray fluorescence spectrum will provide data on the sample's elemental composition [7]. Preliminary studies at room temperature and normal pressure show detection of X-rays down to ~1 keV. A new control- and readout electronics for MIMOS IIA allows spectra acquisition at highest possible countrates available at about 360 mm2 total detector area. A prototype of MIMOS IIA has been tested successfully during a field test at Mauna Kea, Hawaii, as part of the international NASA JSC lead In-Situ Resource Utilization field tests 2010 and 2012. Acknowledgment: Funded by german space agency DLR under contract 50 QX 0603 and 50QX0802. References: [1] Klingelhöfer et al., J. Geophys. Res. 108(E12) (2003) [2] Klingelhöfer et al., Science 306 (2004) 1740-1745. [3] Morris et al., Science 305 (2004) 833-836. [4] Morris et al., J. Geophys. Res. 111 (2006) [5] Rodionov et al., Solar System Research Vol. 44, No. 5 (2010) pp. 362-370 [6] P. Lechner et al., Nucl. Instr. and Meth. A 377 (1996) 346-351 [7] M. Blumers et al., Nucl. Instr. and Meth. A 624 (2010) 277-281

Structural and molecular study of the supraspinatus muscle of modern humans (Homo sapiens) and common chimpanzees (Pan troglodytes).

PubMed

Potau, J M; Casado, A; de Diego, M; Ciurana, N; Arias-Martorell, J; Bello-Hellegouarch, G; Barbosa, M; de Paz, F J; Pastor, J F; Pérez-Pérez, A

2018-04-21

To analyze the muscle architecture and the expression pattern of the myosin heavy chain (MyHC) isoforms in the supraspinatus of Pan troglodytes and Homo sapiens in order to identify differences related to their different types of locomotion. We have analyzed nine supraspinatus muscles of Pan troglodytes and ten of Homo sapiens. For each sample, we have recorded the muscle fascicle length (MFL), the pennation angle, and the physiological cross-sectional area (PCSA). In the same samples, by real-time quantitative polymerase chain reaction, we have assessed the percentages of expression of the MyHC-I, MyHC-IIa, and MyHC-IIx isoforms. The mean MFL of the supraspinatus was longer (p = 0.001) and the PCSA was lower (p < 0.001) in Homo sapiens than in Pan troglodytes. Although the percentage of expression of MyHC-IIa was lower in Homo sapiens than in Pan troglodytes (p = 0.035), the combination of MyHC-IIa and MyHC-IIx was expressed at a similar percentage in the two species. The longer MFL in the human supraspinatus is associated with a faster contractile velocity, which reflects the primary function of the upper limbs in Homo sapiens-the precise manipulation of objects-an adaptation to bipedal locomotion. In contrast, the larger PCSA in Pan troglodytes is related to the important role of the supraspinatus in stabilizing the glenohumeral joint during the support phase of knuckle-walking. These functional differences of the supraspinatus in the two species are not reflected in differences in the expression of the MyHC isoforms. © 2018 Wiley Periodicals, Inc.

Influence of complete spinal cord injury on skeletal muscle within 6 mo of injury.

PubMed

Castro, M J; Apple, D F; Staron, R S; Campos, G E; Dudley, G A

1999-01-01

This study examined the influence of spinal cord injury (SCI) on affected skeletal muscle. The right vastus lateralis muscle was biopsied in 12 patients as soon as they were clinically stable (average 6 wk after SCI), and 11 and 24 wk after injury. Samples were also taken from nine able-bodied controls at two time points 18 wk apart. Surface electrical stimulation (ES) was applied to the left quadriceps femoris muscle to assess fatigue at these same time intervals. Biopsies were analyzed for fiber type percent and cross-sectional area (CSA), fiber type-specific succinic dehydrogenase (SDH) and alpha-glycerophosphate dehydrogenase (GPDH) activities, and myosin heavy chain percent. Controls showed no change in any variable over time. Patients showed 27-56% atrophy (P = 0.000) of type I, IIa, and IIax+IIx fibers from 6 to 24 wk after injury, resulting in fiber CSA approximately one-third that of controls. Their fiber type specific SDH and GPDH activities increased (P

Use of plate fixation without coracoclavicular ligament augmentation for unstable distal clavicle fractures.

PubMed

Shin, Sang-Jin; Ko, Young-Won; Lee, Juyeob; Park, Min-Gyue

2016-06-01

The purpose of this study was to evaluate the clinical and radiologic outcomes of unstable distal clavicle fractures treated with anatomic plate fixation without coracoclavicular ligament augmentation and to compare the outcome of Neer type IIA with that of type IIB. Twenty-five patients with unstable distal clavicle fractures who underwent anatomic plate fixation without coracoclavicular ligament augmentation were enrolled prospectively, including 9 patients of Neer type IIA and 16 patients of Neer type IIB. Clinical outcomes were evaluated using Constant and University of California-Los Angeles (UCLA) scores. Coracoclavicular distance was measured on plain radiographs. Bone union was achieved in all patients. Satisfactory clinical and radiologic outcomes were obtained regardless of fracture type. After operation, the mean coracoclavicular distance on the injured side was increased by 10% compared with the uninjured side. However, between the patients who showed an increased coracoclavicular distance >10% (Constant score, 89.4 ± 3.7; UCLA score, 32.6 ± 3) and the patients with increased coracoclavicular distance <10% of the uninjured side (Constant score, 88.7 ± 3.6; UCLA score, 31.9 ± 3), there was no statistically significant difference in clinical outcomes of Constant score (P = .934) and UCLA score (P = .598). In unstable distal clavicle fractures, precontoured anatomic plate fixation without coracoclavicular ligament augmentation showed satisfactory clinical outcomes and high union rates even with a small lateral fragment. Patients who had increased coracoclavicular distance also demonstrated satisfactory shoulder functional outcomes regardless of the fracture type. Therefore, anatomic plate fixation without additional coracoclavicular ligament augmentation can be considered one of the treatment options for unstable distal clavicle fracture. Level IV; Case Series; Treatment Study. Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Human HDAC7 Harbors a Class IIa Histone Deacetylase-specific Zinc Binding Motif and Cryptic Deacetylase Activity*S⃞

PubMed Central

Schuetz, Anja; Min, Jinrong; Allali-Hassani, Abdellah; Schapira, Matthieu; Shuen, Michael; Loppnau, Peter; Mazitschek, Ralph; Kwiatkowski, Nick P.; Lewis, Timothy A.; Maglathin, Rebecca L.; McLean, Thomas H.; Bochkarev, Alexey; Plotnikov, Alexander N.; Vedadi, Masoud; Arrowsmith, Cheryl H.

2008-01-01

Histone deacetylases (HDACs) are protein deacetylases that play a role in repression of gene transcription and are emerging targets in cancer therapy. Here, we characterize the structure and enzymatic activity of the catalytic domain of human HDAC7 (cdHDAC7). Although HDAC7 normally exists as part of a multiprotein complex, we show that cdHDAC7 has a low level of deacetylase activity which can be inhibited by known HDAC inhibitors. The crystal structures of human cdHDAC7 and its complexes with two hydroxamate inhibitors are the first structures of the catalytic domain of class IIa HDACs and demonstrate significant differences with previously reported class I and class IIb-like HDAC structures. We show that cdHDAC7 has an additional class IIa HDAC-specific zinc binding motif adjacent to the active site which is likely to participate in substrate recognition and protein-protein interaction and may provide a site for modulation of activity. Furthermore, a different active site topology results in modified catalytic properties and in an enlarged active site pocket. Our studies provide mechanistic insights into class IIa HDACs and facilitate the design of specific modulators. PMID:18285338

Human HDAC7 harbors a class IIa histone deacetylase-specific zinc binding motif and cryptic deacetylase activity.

PubMed

Schuetz, Anja; Min, Jinrong; Allali-Hassani, Abdellah; Schapira, Matthieu; Shuen, Michael; Loppnau, Peter; Mazitschek, Ralph; Kwiatkowski, Nick P; Lewis, Timothy A; Maglathin, Rebecca L; McLean, Thomas H; Bochkarev, Alexey; Plotnikov, Alexander N; Vedadi, Masoud; Arrowsmith, Cheryl H

2008-04-25

Histone deacetylases (HDACs) are protein deacetylases that play a role in repression of gene transcription and are emerging targets in cancer therapy. Here, we characterize the structure and enzymatic activity of the catalytic domain of human HDAC7 (cdHDAC7). Although HDAC7 normally exists as part of a multiprotein complex, we show that cdHDAC7 has a low level of deacetylase activity which can be inhibited by known HDAC inhibitors. The crystal structures of human cdHDAC7 and its complexes with two hydroxamate inhibitors are the first structures of the catalytic domain of class IIa HDACs and demonstrate significant differences with previously reported class I and class IIb-like HDAC structures. We show that cdHDAC7 has an additional class IIa HDAC-specific zinc binding motif adjacent to the active site which is likely to participate in substrate recognition and protein-protein interaction and may provide a site for modulation of activity. Furthermore, a different active site topology results in modified catalytic properties and in an enlarged active site pocket. Our studies provide mechanistic insights into class IIa HDACs and facilitate the design of specific modulators.

Diet‐induced obesity alters skeletal muscle fiber types of male but not female mice

PubMed Central

DeNies, Maxwell S.; Johnson, Jordan; Maliphol, Amanda B.; Bruno, Michael; Kim, Annabelle; Rizvi, Abbas; Rustici, Kevyn; Medler, Scott

2014-01-01

Abstract Skeletal muscles are highly plastic tissues capable dramatic remodeling in response to use, disuse, disease, and other factors. Growing evidence suggests that adipose tissues exert significant effects on the basic fiber‐type composition of skeletal muscles. In the current study, we investigated the long‐term effects of a high‐fat diet and subsequent obesity on the muscle fiber types in C57 BLK/6J mice. Litters of mice were randomly assigned to either a high‐fat diet or a control group at the time of weaning, and were maintained on this diet for approximately 1 year. Single fibers were harvested from the soleus and plantaris muscles, and fiber types were determined using SDS‐PAGE. The high‐fat diet mice were significantly heavier than the control mice (39.17 ± 2.7 g vs. 56.87 ± 3.4 g; P < 0.0003), but muscle masses were not different. In male mice, the high‐fat diet was associated with a significantly lower proportion of slow, type I fibers in the soleus muscle (40.4 ± 3.5% vs. 29.33 ± 2.6%; P < 0.0165). Moreover, the proportion of type I fibers in the soleus of male mice was inversely proportional to the relative fatness of the male mice (P < 0.003; r2 = 0.65), but no association was observed in female mice. In male mice, the decline in type I fibers was correlated with an increase in type I/IIA hybrid fibers, suggesting that the type I fibers were transformed primarily into these hybrids. The reported trends indicate that type I fibers are most susceptible to the effects of obesity, and that these fiber‐type changes can be sex specific. PMID:24744883

A swamp of non-SUSY vacua

NASA Astrophysics Data System (ADS)

Danielsson, U. H.; Dibitetto, G.; Vargas, S. C.

2017-11-01

We consider known examples of non-supersymmetric AdS7 and AdS4 solutions arising from compactifications of massive type IIA supergravity and study their stability, taking into account the coupling between closed- and open-string sector excitations. Generically, open strings are found to develop modes with masses below the Breitenlohner-Freedman (BF) bound. We comment on the relation with the Weak Gravity Conjecture, and how this analysis may play an important role in examining the validity of non-supersymmetric constructions in string theory.

26 CFR 1.401(a)(4)-6 - Contributory defined benefit plans.

Code of Federal Regulations, 2011 CFR

2011-04-01

... to satisfy this paragraph (b)(2)(ii)(A) merely because it eliminates employee contributions for all... requirements—(1) In general. A contributory DB plan satisfies this paragraph (b)(2)(ii)(B) if it satisfies... employee's base benefit percentage as required under paragraph (b)(2)(iii)(B)(1) of this section, it may be...

26 CFR 1.401(a)(4)-6 - Contributory defined benefit plans.

Code of Federal Regulations, 2014 CFR

2014-04-01

... to satisfy this paragraph (b)(2)(ii)(A) merely because it eliminates employee contributions for all... requirements—(1) In general. A contributory DB plan satisfies this paragraph (b)(2)(ii)(B) if it satisfies... employee's base benefit percentage as required under paragraph (b)(2)(iii)(B)(1) of this section, it may be...

26 CFR 1.401(a)(4)-6 - Contributory defined benefit plans.

Code of Federal Regulations, 2012 CFR

2012-04-01

... to satisfy this paragraph (b)(2)(ii)(A) merely because it eliminates employee contributions for all... requirements—(1) In general. A contributory DB plan satisfies this paragraph (b)(2)(ii)(B) if it satisfies... employee's base benefit percentage as required under paragraph (b)(2)(iii)(B)(1) of this section, it may be...

26 CFR 1.401(a)(4)-6 - Contributory defined benefit plans.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (b)(2)(ii)(A) merely because it eliminates employee contributions for all employees with plan year...) In general. A contributory DB plan satisfies this paragraph (b)(2)(ii)(B) if it satisfies either of... employee's base benefit percentage as required under paragraph (b)(2)(iii)(B)(1) of this section, it may be...

26 CFR 1.401(a)(4)-6 - Contributory defined benefit plans.

Code of Federal Regulations, 2013 CFR

2013-04-01

... to satisfy this paragraph (b)(2)(ii)(A) merely because it eliminates employee contributions for all... requirements—(1) In general. A contributory DB plan satisfies this paragraph (b)(2)(ii)(B) if it satisfies... employee's base benefit percentage as required under paragraph (b)(2)(iii)(B)(1) of this section, it may be...