Cellular stress stimulates nuclear localization signal (NLS) independent nuclear transport of MRJ

PubMed Central

Andrews, Joel F.; Sykora, Landon J.; Barik-Letostak, Tiasha; Menezes, Mitchell E.; Mitra, Aparna; Barik, Sailen; Shevde, Lalita A.; Samant, Rajeev S.

2012-01-01

HSP40 family member MRJ (DNAJB6) has been in the spot light for its relevance to Huntington’s, Parkinson’s diseases, limb-girdle muscular dystrophy, placental development, neural stem cells, cell cycle and malignancies such as breast cancer and melanoma. This gene has two spliced variants coding for 2 distinct proteins with significant homology. However, MRJ(L) (large variant) is predominantly localized to the nucleus whereas MRJ(S) (small variant) is predominantly cytoplasmic. Interestingly MRJ(S) translocates to the nucleus in response to heat shock. The classical heat shock proteins respond to crises (stress) by increasing the number of molecules, usually by transcriptional up-regulation. Our studies imply that a quick increase in the molar concentration of MRJ in the nuclear compartment is a novel method by which MRJ responds to stress. We found that MRJ(S) shows NLS (nuclear localization signal) independent nuclear localization in response to heat shock and hypoxia. The specificity of this response is realized due to lack of such response by MRJ(S) when challenged by other stressors, such as some cytokines or UV light. Deletion analysis has allowed us to narrow down on a 20 amino acid stretch at the C-terminal region of MRJ(S) as a potential stress sensing region. Functional studies indicated that constitutive nuclear localization of MRJ(S) promoted attributes of malignancy such as proliferation and invasiveness overall indicating distinct phenotypic characteristics of nuclear MRJ(S). PMID:22504047

Heat shock proteins HSP70 and MRJ cooperatively regulate cell adhesion and migration through urokinase receptor.

PubMed

Lin, Yuli; Peng, Nana; Zhuang, Hongqin; Zhang, Di; Wang, Yao; Hua, Zi-Chun

2014-08-30

The urokinase-type plasminogen activator receptor (uPAR) is an important regulator of ECM proteolysis, cell-ECM interactions and cell signaling. uPAR and heat shock proteins HSP70 and MRJ (DNAJB6) have been implicated in tumor growth and metastasis. We have reported recently that MRJ (DNAJB6, a heat shock protein) can interact with uPAR and enhance cell adhesion. Here, we identified another heat shock protein HSP70 as a novel uPAR-interacting protein. We performed co-immunoprecipitation in human embryonic kidney (HEK) 293 and colon cancer HCT116 cells as well as immunofluorence assays in HEK293 cells stably transfected with uPAR to investigate the association of suPAR with HSP70/MRJ. To understand the biological functions of the triple complex of suPAR/HSP70/MRJ, we determined whether HSP70 and/or MRJ regulated uPAR-mediated cell invasion, migration, adhesion to vitronectin and MAPK pathway in two pair of human tumor cells (uPAR negative HEK293 cells vs HEK293 cells stably transfected with uPAR and HCT116 cells stably transfected with antisense-uPAR vs HCT116 mock cells transfected with vector only) using transwell assay, wound healing assay, quantitative RT-PCR analyzing mmp2 and mmp9 transcription levels, cell adhesion assay and Western blotting assay. HSP70 and MRJ formed a triple complex with uPAR and over-expression of MRJ enhanced the interaction between HSP70 and uPAR, while knockdown of MRJ decreased soluble uPAR in HCT116 cells (P < 0.05) and reduced the formation of the triple complex, suggesting that MRJ may act as an uPAR-specific adaptor protein to link uPAR to HSP70. Further experiments showed that knockdown of HSP70 and/or MRJ by siRNA inhibited uPAR-mediated cell adhesion to vitronectin as well as suppressed cell invasion and migration. Knockdown of HSP70 and/or MRJ inhibited expression of invasion related genes mmp2 and mmp9. Finally, HSP70 and/or MRJ up-regulated phosphorylation levels of ERK1/2 and FAK suggesting MAPK pathway was involved

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

Andrews, Joel F.; Sykora, Landon J.; Barik Letostak, Tiasha

HSP40 family member MRJ (DNAJB6) has been in the spot light for its relevance to Huntington's, Parkinson's diseases, limb-girdle muscular dystrophy, placental development, neural stem cells, cell cycle and malignancies such as breast cancer and melanoma. This gene has two spliced variants coding for 2 distinct proteins with significant homology. However, MRJ(L) (large variant) is predominantly localized to the nucleus whereas MRJ(S) (small variant) is predominantly cytoplasmic. Interestingly MRJ(S) translocates to the nucleus in response to heat shock. The classical heat shock proteins respond to crises (stress) by increasing the number of molecules, usually by transcriptional up-regulation. Our studies implymore » that a quick increase in the molar concentration of MRJ in the nuclear compartment is a novel method by which MRJ responds to stress. We found that MRJ(S) shows NLS (nuclear localization signal) independent nuclear localization in response to heat shock and hypoxia. The specificity of this response is realized due to lack of such response by MRJ(S) when challenged by other stressors, such as some cytokines or UV light. Deletion analysis has allowed us to narrow down on a 20 amino acid stretch at the C-terminal region of MRJ(S) as a potential stress sensing region. Functional studies indicated that constitutive nuclear localization of MRJ(S) promoted attributes of malignancy such as proliferation and invasiveness overall indicating distinct phenotypic characteristics of nuclear MRJ(S).« less

The Rio de Janeiro Municipality's Services Portfolio and Health Actions in Primary Care in Brazil.

PubMed

Salazar, Bianca Alves; Campos, Mônica Rodrigues; Luiza, Vera Lucia

2017-03-01

This study aimed to identify the provision of actions and procedures by family health teams (FHSt), based on Rio de Janeiro Municipality's (MRJ) Health Services Portfolio (HSP) and the main factors associated with this provision, in the different population strata. Data from the National Program for Improving Access and Quality of Primary Healthcare were used and implemented at the national level into 17,202 FHSts from June to September 2012. Outcome variables were "FHSt belonging to MRJ" and "FHSt providing all nine CS-MRJ procedures". Uni-, bi- and multivariate analysis were performed. A better performance of the MRJ in relation to other major urban centers (EP6#) (p<5%) was noted in 10 of the 14 health actions analyzed. The electronic medical record showed a level of deployment in MRJ's FHSts of 96%, contrasting with 34% in the EP6# and 14% in Brazil. Both the MRJ and EP6# evidenced low supply of mental health services (about 56%). While the supply of low-complexity procedures was a major problem in large cities, the supply of health actions in the different health care lines was a larger problem in small municipalities. Overall, the MRJ showed better performance when compared to the average of large municipalities. The health service portfolio appeared to be an important management tool.

Radiographic features of cardiogenic pulmonary edema in dogs with mitral regurgitation: 61 cases (1998-2007).

PubMed

Diana, Alessia; Guglielmini, Carlo; Pivetta, Mauro; Sanacore, Antonina; Di Tommaso, Morena; Lord, Peter F; Cipone, Mario

2009-11-01

To evaluate radiographic distribution of pulmonary edema (PE) in dogs with mitral regurgitation (MR) and investigate the association between location of radiographic findings and direction of the mitral regurgitant jet (MRJ). Retrospective case series. 61 dogs with cardiogenic PE and MR resulting from mitral valve disease (MVD; 51 dogs), dilated cardiomyopathy (9), and hypertrophic cardiomyopathy (1). Thoracic radiographs of dogs with Doppler echocardiographic evidence of MR were reviewed for location (diffuse, perihilar, or focal) of PE. Also, direction (central or eccentric) of the MRJ, as evaluated by Doppler color flow mapping (DCFM), and distribution (symmetric or asymmetric) of radiographic findings were evaluated. Diffuse, perihilar, and focal increases in pulmonary opacity were observed in 11 (18.0%), 7 (11.5%), and 43 (70.5%) of 61 dogs, respectively. Radiographic evidence of asymmetric PE in a single lung lobe or 2 ipsilateral lobes was found in 21 dogs, with involvement of only the right caudal lung lobe in 17 dogs. Doppler color flow mapping of the MRJ was available for 46 dogs. Of 31 dogs with a central MRJ, 28 had radiographic findings indicative of symmetric PE. Of 15 dogs with eccentric MRJ, 11 had radiographic evidence of asymmetric PE, and all of these dogs had MVD. In dogs with cardiogenic PE, a symmetric radiographic distribution of increased pulmonary opacity was predominantly associated with a central MRJ, whereas an asymmetric radiographic distribution was usually associated with eccentric MRJ, especially in dogs with MVD.

A carbon, nitrogen, and sulfur elemental and isotopic study in dated sediment cores from the Louisiana Shelf

USGS Publications Warehouse

Rosenbauer, R.J.; Swarzenski, P.W.; Kendall, C.; Orem, W.H.; Hostettler, F.D.; Rollog, M.E.

2009-01-01

Three sediment cores were collected off the Mississippi River delta on the Louisiana Shelf at sites that are variably influenced by recurring, summer-time water-column hypoxia and fluvial loadings. The cores, with established chronology, were analyzed for their respective carbon, nitrogen, and sulfur elemental and isotopic composition to examine variable organic matter inputs, and to assess the sediment record for possible evidence of hypoxic events. Sediment from site MRJ03-3, which is located close to the Mississippi Canyon and generally not influenced by summer-time hypoxia, is typical of marine sediment in that it contains mostly marine algae and fine-grained material from the erosion of terrestrial C4 plants. Sediment from site MRJ03-2, located closer to the mouth of the Mississippi River and at the periphery of the hypoxic zone (annual recurrence of summer-time hypoxia >50%), is similar in composition to core MRJ03-3, but exhibits more isotopic and elemental variability down-core, suggesting that this site is more directly influenced by river discharge. Site MRJ03-5 is located in an area of recurring hypoxia (annual recurrence >75%), and is isotopically and elementally distinct from the other two cores. The carbon and nitrogen isotopic composition of this core prior to 1960 is similar to average particulate organic matter from the lower Mississippi River, and approaches the composition of C3 plants. This site likely receives a greater input of local terrestrial organic matter to the sediment. After 1960 and to the present, a gradual shift to higher values of ??13C and ??15N and lower C:N ratios suggests that algal input to these shelf sediments increased as a result of increased productivity and hypoxia. The values of C:S and ??34S reflect site-specific processes that may be influenced by the higher likelihood of recurring seasonal hypoxia. In particular, the temporal variations in the C:S and ??34S down-core are likely caused by changes in the rate of

Program 6 Technical Interchange Meeting Proceedings

DTIC Science & Technology

1992-10-01

Buteau PRC (703)556-1355 Gary R. Dolson PRC (703) 5561859 David J. Gray Sterling (315)336-0500 Noreen S. Heyda Harris (407)984-6384 Jay Jesse GTE (719)570...Reed Sterling John Sautter Sterling (315)336-0500 Kevin Sculley PRC (402)291-5533 Stefan Shrier MRJ (703)934-9249 Peter Soliz Orion (505)262-2260...4730 Howard A. Melching GTE (719)570-8898 Noreen S. Heyda Harris (407)984-6384 Jonathan H. Reed Harris (407)984-6008 Stefan Shrier MRJ (703) 934-9249

Characterization of maximally random jammed sphere packings. III. Transport and electromagnetic properties via correlation functions

NASA Astrophysics Data System (ADS)

Klatt, Michael A.; Torquato, Salvatore

2018-01-01

In the first two papers of this series, we characterized the structure of maximally random jammed (MRJ) sphere packings across length scales by computing a variety of different correlation functions, spectral functions, hole probabilities, and local density fluctuations. From the remarkable structural features of the MRJ packings, especially its disordered hyperuniformity, exceptional physical properties can be expected. Here we employ these structural descriptors to estimate effective transport and electromagnetic properties via rigorous bounds, exact expansions, and accurate analytical approximation formulas. These property formulas include interfacial bounds as well as universal scaling laws for the mean survival time and the fluid permeability. We also estimate the principal relaxation time associated with Brownian motion among perfectly absorbing traps. For the propagation of electromagnetic waves in the long-wavelength limit, we show that a dispersion of dielectric MRJ spheres within a matrix of another dielectric material forms, to a very good approximation, a dissipationless disordered and isotropic two-phase medium for any phase dielectric contrast ratio. We compare the effective properties of the MRJ sphere packings to those of overlapping spheres, equilibrium hard-sphere packings, and lattices of hard spheres. Moreover, we generalize results to micro- and macroscopically anisotropic packings of spheroids with tensorial effective properties. The analytic bounds predict the qualitative trend in the physical properties associated with these structures, which provides guidance to more time-consuming simulations and experiments. They especially provide impetus for experiments to design materials with unique bulk properties resulting from hyperuniformity, including structural-color and color-sensing applications.

Electrorheology leads to healthier and tastier chocolate

PubMed Central

Tao, Rongjia; Tang, Hong; Tawhid-Al-Islam, Kazi; Du, Enpeng; Kim, Jeongyoo

2016-01-01

Chocolate is one of the most popular food types and flavors in the world. Unfortunately, at present, chocolate products contain too much fat, leading to obesity. Although this issue was called into attention decades ago, no actual solution was found. To bypass this critical outstanding problem, two manufacturers introduced some low-calorie fats to substitute for cocoa butter. Somehow, their products are not allowed in most countries. Here we show that this issue is deeply related to the basic science of soft matter, especially to the viscosity of liquid suspension and maximally random jammed (MRJ) density. When the concentration of cocoa solid is high, close to the MRJ density, removing a small amount of fat will jam the chocolate flow. Applying unconventional electrorheology to liquid chocolate with applied field in the flow direction, we aggregate the cocoa particles into prolate spheroids in micrometers. This microstructure change breaks the rotational symmetry, reduces liquid chocolate’s viscosity along the flow direction, and increases its MRJ density significantly. Hence the fat level in chocolate can be effectively reduced. We are expecting a new class of healthier and tastier chocolate soon. PMID:27325758

Electrorheology leads to healthier and tastier chocolate.

PubMed

Tao, Rongjia; Tang, Hong; Tawhid-Al-Islam, Kazi; Du, Enpeng; Kim, Jeongyoo

2016-07-05

Chocolate is one of the most popular food types and flavors in the world. Unfortunately, at present, chocolate products contain too much fat, leading to obesity. Although this issue was called into attention decades ago, no actual solution was found. To bypass this critical outstanding problem, two manufacturers introduced some low-calorie fats to substitute for cocoa butter. Somehow, their products are not allowed in most countries. Here we show that this issue is deeply related to the basic science of soft matter, especially to the viscosity of liquid suspension and maximally random jammed (MRJ) density. When the concentration of cocoa solid is high, close to the MRJ density, removing a small amount of fat will jam the chocolate flow. Applying unconventional electrorheology to liquid chocolate with applied field in the flow direction, we aggregate the cocoa particles into prolate spheroids in micrometers. This microstructure change breaks the rotational symmetry, reduces liquid chocolate's viscosity along the flow direction, and increases its MRJ density significantly. Hence the fat level in chocolate can be effectively reduced. We are expecting a new class of healthier and tastier chocolate soon.

Characterization of major allergens of royal jelly Apis mellifera.

PubMed

Rosmilah, M; Shahnaz, M; Patel, G; Lock, J; Rahman, D; Masita, A; Noormalin, A

2008-12-01

Royal jelly is widely consumed in the community and has perceived benefits ranging from promoting growth in children and improvement of general health status to enhancement of longevity for the elderly. However, royal jelly consumption has been linked to contact dermatitis, acute asthma, anaphylaxis and death. High prevalence of positive skin tests to royal jelly have been reported among atopic populations in countries with a high rate of royal jelly consumption. The present study is aimed to identify the major allergens of royal jelly. Royal jelly extract was separated by sodium dodecyl polyacrylamide gel electrophoresis (SDS-PAGE) and 2-dimensional electrophoresis (2-D). Immunoblotting of the SDS-PAGE and 2-D profiles were performed to identify the allergenic spots. Spots were then excised from the 2-D gel, digested with trypsin and analyzed by mass spectrometry. The SDS-PAGE of royal jelly extract revealed 18 bands between 10 to 167 kD. Western blot of the fractionated proteins detected 15 IgE-binding bands between 14 to 127 kD with seven major allergens of 32, 40, 42, 49, 55, 60 and 67 kD using serum from 53 subjects with royal jelly allergy. The 2-D gel fractionated the royal jelly proteins to more than 50 different protein spots. Out of these, 30 spots demonstrated specific IgE affinity to the sera tested. Eight spots of the major royal jelly allergens were selected for mass-spectrometry analysis. Digested tryptic peptides of the spots were compared to the amino acid sequence search in protein databases which identified the fragments of royal jelly homologus to major royal jelly protein 1 (MRJ1) and major royal jelly protein 2 (MRJ2). In conclusion, the major allergens of royal jelly are MRJ1 and MRJ2 in our patients' population.

Statistical analysis of earthquakes after the 1999 MW 7.7 Chi-Chi, Taiwan, earthquake based on a modified Reasenberg-Jones model

NASA Astrophysics Data System (ADS)

Chen, Yuh-Ing; Huang, Chi-Shen; Liu, Jann-Yenq

2015-12-01

We investigated the temporal-spatial hazard of the earthquakes after the 1999 September 21 MW = 7.7 Chi-Chi shock in a continental region of Taiwan. The Reasenberg-Jones (RJ) model (Reasenberg and Jones, 1989, 1994) that combines the frequency-magnitude distribution (Gutenberg and Richter, 1944) and time-decaying occurrence rate (Utsu et al., 1995) is conventionally employed for assessing the earthquake hazard after a large shock. However, it is found that the b values in the frequency-magnitude distribution of the earthquakes in the study region dramatically decreased from background values after the Chi-Chi shock, and then gradually increased up. The observation of a time-dependent frequency-magnitude distribution motivated us to propose a modified RJ model (MRJ) to assess the earthquake hazard. To see how the models perform on assessing short-term earthquake hazard, the RJ and MRJ models were separately used to sequentially forecast earthquakes in the study region. To depict the potential rupture area for future earthquakes, we further constructed relative hazard (RH) maps based on the two models. The Receiver Operating Characteristics (ROC) curves (Swets, 1988) finally demonstrated that the RH map based on the MRJ model was, in general, superior to the one based on the original RJ model for exploring the spatial hazard of earthquakes in a short time after the Chi-Chi shock.

Markers for Routine Assessment of Fatigue and Recovery in Male and Female Team Sport Athletes during High-Intensity Interval Training.

PubMed

Wiewelhove, Thimo; Raeder, Christian; Meyer, Tim; Kellmann, Michael; Pfeiffer, Mark; Ferrauti, Alexander

2015-01-01

Our study aimed to investigate changes of different markers for routine assessment of fatigue and recovery in response to high-intensity interval training (HIIT). 22 well-trained male and female team sport athletes (age, 23.0 ± 2.7 years; V̇O2 max, 57.6 ± 8.6 mL · min · kg(-1)) participated in a six-day running-based HIIT-microcycle with a total of eleven HIIT sessions. Repeated sprint ability (RSA; criterion measure of fatigue and recovery), countermovement jump (CMJ) height, jump efficiency in a multiple rebound jump test (MRJ), 20-m sprint performance, muscle contractile properties, serum concentrations of creatinkinase (CK), c-reactive protein (CRP) and urea as well as perceived muscle soreness (DOMS) were measured pre and post the training program as well as after 72 h of recovery. Following the microcycle significant changes (p < 0.05) in RSA as well as in CMJ and MRJ performance could be observed, showing a decline (%Δ ± 90% confidence limits, ES = effect size; RSA: -3.8 ± 1.0, ES = -1.51; CMJ: 8.4 ± 2.9, ES = -1.35; MRJ: 17.4 ± 4.5, ES = -1.60) and a return to baseline level (RSA: 2.8 ± 2.6, ES = 0.53; CMJ: 4.1 ± 2.9, ES = 0.68; MRJ: 6.5 ± 4.5, ES = 0.63) after 72 h of recovery. Athletes also demonstrated significant changes (p < 0.05) in muscle contractile properties, CK, and DOMS following the training program and after the recovery period. In contrast, CRP and urea remained unchanged throughout the study. Further analysis revealed that the accuracy of markers for assessment of fatigue and recovery in comparison to RSA derived from a contingency table was insufficient. Multiple regression analysis also showed no correlations between changes in RSA and any of the markers. Mean changes in measures of neuromuscular function, CK and DOMS are related to HIIT induced fatigue and subsequent recovery. However, low accuracy of a single or combined use of these markers requires the verification of their applicability on an individual basis.

Markers for Routine Assessment of Fatigue and Recovery in Male and Female Team Sport Athletes during High-Intensity Interval Training

PubMed Central

Wiewelhove, Thimo; Raeder, Christian; Meyer, Tim; Kellmann, Michael; Pfeiffer, Mark; Ferrauti, Alexander

2015-01-01

Aim Our study aimed to investigate changes of different markers for routine assessment of fatigue and recovery in response to high-intensity interval training (HIIT). Methods 22 well-trained male and female team sport athletes (age, 23.0 ± 2.7 years; V̇O2max, 57.6 ± 8.6 mL·min·kg−1) participated in a six-day running-based HIIT-microcycle with a total of eleven HIIT sessions. Repeated sprint ability (RSA; criterion measure of fatigue and recovery), countermovement jump (CMJ) height, jump efficiency in a multiple rebound jump test (MRJ), 20-m sprint performance, muscle contractile properties, serum concentrations of creatinkinase (CK), c-reactive protein (CRP) and urea as well as perceived muscle soreness (DOMS) were measured pre and post the training program as well as after 72 h of recovery. Results Following the microcycle significant changes (p < 0.05) in RSA as well as in CMJ and MRJ performance could be observed, showing a decline (%Δ ± 90% confidence limits, ES = effect size; RSA: -3.8 ± 1.0, ES = -1.51; CMJ: 8.4 ± 2.9, ES = -1.35; MRJ: 17.4 ± 4.5, ES = -1.60) and a return to baseline level (RSA: 2.8 ± 2.6, ES = 0.53; CMJ: 4.1 ± 2.9, ES = 0.68; MRJ: 6.5 ± 4.5, ES = 0.63) after 72 h of recovery. Athletes also demonstrated significant changes (p < 0.05) in muscle contractile properties, CK, and DOMS following the training program and after the recovery period. In contrast, CRP and urea remained unchanged throughout the study. Further analysis revealed that the accuracy of markers for assessment of fatigue and recovery in comparison to RSA derived from a contingency table was insufficient. Multiple regression analysis also showed no correlations between changes in RSA and any of the markers. Conclusions Mean changes in measures of neuromuscular function, CK and DOMS are related to HIIT induced fatigue and subsequent recovery. However, low accuracy of a single or combined use of these markers requires the verification of their applicability on an

Hyperuniformity, quasi-long-range correlations, and void-space constraints in maximally random jammed particle packings. II. Anisotropy in particle shape.

PubMed

Zachary, Chase E; Jiao, Yang; Torquato, Salvatore

2011-05-01

We extend the results from the first part of this series of two papers by examining hyperuniformity in heterogeneous media composed of impenetrable anisotropic inclusions. Specifically, we consider maximally random jammed (MRJ) packings of hard ellipses and superdisks and show that these systems both possess vanishing infinite-wavelength local-volume-fraction fluctuations and quasi-long-range pair correlations scaling as r(-(d+1)) in d Euclidean dimensions. Our results suggest a strong generalization of a conjecture by Torquato and Stillinger [Phys. Rev. E 68, 041113 (2003)], namely, that all strictly jammed saturated packings of hard particles, including those with size and shape distributions, are hyperuniform with signature quasi-long-range correlations. We show that our arguments concerning the constrained distribution of the void space in MRJ packings directly extend to hard-ellipse and superdisk packings, thereby providing a direct structural explanation for the appearance of hyperuniformity and quasi-long-range correlations in these systems. Additionally, we examine general heterogeneous media with anisotropic inclusions and show unexpectedly that one can decorate a periodic point pattern to obtain a hard-particle system that is not hyperuniform with respect to local-volume-fraction fluctuations. This apparent discrepancy can also be rationalized by appealing to the irregular distribution of the void space arising from the anisotropic shapes of the particles. Our work suggests the intriguing possibility that the MRJ states of hard particles share certain universal features independent of the local properties of the packings, including the packing fraction and average contact number per particle.

The Perfect Glass Paradigm: Disordered Hyperuniform Glasses Down to Absolute Zero

NASA Astrophysics Data System (ADS)

Zhang, G.; Stillinger, F. H.; Torquato, S.

2016-11-01

Rapid cooling of liquids below a certain temperature range can result in a transition to glassy states. The traditional understanding of glasses includes their thermodynamic metastability with respect to crystals. However, here we present specific examples of interactions that eliminate the possibilities of crystalline and quasicrystalline phases, while creating mechanically stable amorphous glasses down to absolute zero temperature. We show that this can be accomplished by introducing a new ideal state of matter called a “perfect glass”. A perfect glass represents a soft-interaction analog of the maximally random jammed (MRJ) packings of hard particles. These latter states can be regarded as the epitome of a glass since they are out of equilibrium, maximally disordered, hyperuniform, mechanically rigid with infinite bulk and shear moduli, and can never crystallize due to configuration-space trapping. Our model perfect glass utilizes two-, three-, and four-body soft interactions while simultaneously retaining the salient attributes of the MRJ state. These models constitute a theoretical proof of concept for perfect glasses and broaden our fundamental understanding of glass physics. A novel feature of equilibrium systems of identical particles interacting with the perfect-glass potential at positive temperature is that they have a non-relativistic speed of sound that is infinite.

Non-pathogenic protein aggregates in skeletal muscle in MLF1 transgenic mice.

PubMed

Li, Zhi-Fang; Wu, Xiaohua; Jiang, Yun; Liu, Jianxiang; Wu, Chun; Inagaki, Masaki; Izawa, Ichiro; Mizisin, Andrew P; Engvall, Eva; Shelton, G Diane

2008-01-15

Protein aggregate formation in muscle is thought to be pathogenic and associated with clinical weakness. Over-expression of either wild type or a mutant form of myeloid leukemia factor 1 (MLF1) in transgenic mouse skeletal muscle and in cultured cells resulted in aggregate formation. Aggregates were detected in MLF1 transgenic mice at 6 weeks of age, and increased in size with age. However, histological examination of skeletal muscles of MLF1 transgenic mice revealed no pathological changes other than the aggregates, and RotaRod testing did not detect functional deficits. MLF1 has recently been identified as a protein that could neutralize the toxicity of intracellular protein aggregates in a Drosophila model of Huntington's disease (HD). We also demonstrate that MLF1 interacts with MRJ, a heat shock protein, which can independently neutralize the toxicity of intracellular protein aggregates in the Drosophila HD model. Our data suggest that over-expression of MLF1 has no significant impact on skeletal muscle function in mice; that progressive formation of protein aggregates in muscle are not necessarily pathogenic; and that MLF1 and MRJ may function together to ameliorate the toxic effects of polyglutamine or mutant proteins in myodegenerative diseases such as inclusion body myositis and oculopharyngeal muscular dystrophy, as well as neurodegenerative disease.

The Perfect Glass Paradigm: Disordered Hyperuniform Glasses Down to Absolute Zero.

PubMed

Zhang, G; Stillinger, F H; Torquato, S

2016-11-28

Rapid cooling of liquids below a certain temperature range can result in a transition to glassy states. The traditional understanding of glasses includes their thermodynamic metastability with respect to crystals. However, here we present specific examples of interactions that eliminate the possibilities of crystalline and quasicrystalline phases, while creating mechanically stable amorphous glasses down to absolute zero temperature. We show that this can be accomplished by introducing a new ideal state of matter called a "perfect glass". A perfect glass represents a soft-interaction analog of the maximally random jammed (MRJ) packings of hard particles. These latter states can be regarded as the epitome of a glass since they are out of equilibrium, maximally disordered, hyperuniform, mechanically rigid with infinite bulk and shear moduli, and can never crystallize due to configuration-space trapping. Our model perfect glass utilizes two-, three-, and four-body soft interactions while simultaneously retaining the salient attributes of the MRJ state. These models constitute a theoretical proof of concept for perfect glasses and broaden our fundamental understanding of glass physics. A novel feature of equilibrium systems of identical particles interacting with the perfect-glass potential at positive temperature is that they have a non-relativistic speed of sound that is infinite.

The Perfect Glass Paradigm: Disordered Hyperuniform Glasses Down to Absolute Zero

PubMed Central

Zhang, G.; Stillinger, F. H.; Torquato, S.

2016-01-01

Rapid cooling of liquids below a certain temperature range can result in a transition to glassy states. The traditional understanding of glasses includes their thermodynamic metastability with respect to crystals. However, here we present specific examples of interactions that eliminate the possibilities of crystalline and quasicrystalline phases, while creating mechanically stable amorphous glasses down to absolute zero temperature. We show that this can be accomplished by introducing a new ideal state of matter called a “perfect glass”. A perfect glass represents a soft-interaction analog of the maximally random jammed (MRJ) packings of hard particles. These latter states can be regarded as the epitome of a glass since they are out of equilibrium, maximally disordered, hyperuniform, mechanically rigid with infinite bulk and shear moduli, and can never crystallize due to configuration-space trapping. Our model perfect glass utilizes two-, three-, and four-body soft interactions while simultaneously retaining the salient attributes of the MRJ state. These models constitute a theoretical proof of concept for perfect glasses and broaden our fundamental understanding of glass physics. A novel feature of equilibrium systems of identical particles interacting with the perfect-glass potential at positive temperature is that they have a non-relativistic speed of sound that is infinite. PMID:27892452

Neuromuscular Fatigue and Physiological Responses After Five Dynamic Squat Exercise Protocols.

PubMed

Raeder, Christian; Wiewelhove, Thimo; Westphal-Martinez, Marc P; Fernandez-Fernandez, Jaime; de Paula Simola, Rauno A; Kellmann, Michael; Meyer, Tim; Pfeiffer, Mark; Ferrauti, Alexander

2016-04-01

This aimed to analyze neuromuscular, physiological and perceptual responses to a single bout of 5 different dynamic squat exercise protocols. In a randomized and counterbalanced order, 15 male resistance-trained athletes (mean ± SD; age: 23.1 ± 1.9 years, body mass: 77.4 ± 8.0 kg) completed traditional multiple sets (MS: 4 × 6, 85% 1 repetition maximum [RM]), drop sets (DS: 1 × 6, 85% 1RM + 3 drop sets), eccentric overload (EO: 4 × 6, 70% 1RM concentric, 100% 1RM eccentric), flywheel YoYo squat (FW: 4 × 6, all-out), and a plyometric jump protocol (PJ: 4 × 15, all-out). Blood lactate (La), ratings of perceived exertion (RPE), counter movement jump height (CMJ), multiple rebound jump (MRJ) performance, maximal voluntary isometric contraction force, serum creatine kinase (CK) and delayed onset muscle soreness were measured. Immediately post exercise, La was significantly (p < 0.001) higher in FW (mean ± 95% confidence limit; 12.2 ± 0.9 mmol·L) and lower in PJ (3.0 ± 0.8 mmol·L) compared with MS (7.7 ± 1.5 mmol·L), DS (8.5 ± 0.6 mmol·L), and EO (8.2 ± 1.6 mmol·L), accompanied by similar RPE responses. Neuromuscular performance (CMJ, MRJ) significantly remained decreased (p < 0.001) from 0.5 to 48 hours post exercise in all protocols. There was a significant time × protocol interaction (p ≤ 0.05) in MRJ with a significant lower performance in DS, EO, and FW compared with PJ (0.5 hours post exercise), and in EO compared with all other protocols (24 hours post exercise). A significant main time effect with peak values 24 hours post exercise was observed in CK serum concentrations (p < 0.001), but there was no time × protocol interaction. In conclusion, (a) metabolic and perceptual demands were higher in FW and EO compared with MS, DS and PJ, (b) neuromuscular fatigue was consistent up to 48 hours post exercise in all protocols, and (c) EO induced the greatest neuromuscular fatigue.