Negative-Mass Instability in Nonlinear Plasma Waves

The negative-mass instability (NMI), previously found in ion traps, appears as a distinct regime of the sideband instability in nonlinear plasma waves with trapped particles. As the bounce frequency of these particles decreases with the bounce action, bunching can occur if the action distribution is inverted in trapping islands. In contrast to existing theories that also infer instabilities from the anharmonicity of bounce oscillations, spatial periodicity of the islands turns out to be unimportant, and the particle distribution can be unstable even if it is at at the resonance. An analytical model is proposed which describes both single traps and periodic nonlinear waves and concisely generalizes the conventional description of the sideband instability in plasma waves. The theoretical results are supported by particle-in-cell simulations carried out for a regime accentuating the NMI effect

High ultra-processed food consumption is associated with elevated psychological distress as an indicator of depression in adults from the Melbourne Collaborative Cohort Study

Background: Few studies have tested longitudinal associations between ultra-processed food consumption and depressive outcomes. As such, further investigation and replication are necessary. The aim of this study is to examine associations of ultra-processed food intake with elevated psychological distress as an indicator of depression after 15 years. Method: Data from the Melbourne Collaborative Cohort Study (MCCS) were analysed (n = 23,299). We applied the NOVA food classification system to a food frequency questionnaire (FFQ) to determine ultra-processed food intake at baseline. We categorised energy-adjusted ultra-processed food consumption into quartiles by using the distribution of the dataset. Psychological distress was measured by the ten-item Kessler Psychological Distress Scale (K10). We fitted unadjusted and adjusted logistic regression models to assess the association of ultra-processed food consumption (exposure) with elevated psychological distress (outcome and defined as K10 ≥ 20). We fitted additional logistic regression models to determine whether these associations were modified by sex, age and body mass index. Results: After adjusting for sociodemographic characteristics and lifestyle and health-related behaviours, participants with the highest relative intake of ultra-processed food were at increased odds of elevated psychological distress compared to participants with the lowest intake (aOR: 1.23; 95%CI: 1.10, 1.38, p for trend = 0.001). We found no evidence for an interaction of sex, age and body mass index with ultra-processed food intake. Conclusion: Higher ultra-processed food intake at baseline was associated with subsequent elevated psychological distress as an indicator of depression at follow-up. Further prospective and intervention studies are necessary to identify possible underlying pathways, specify the precise attributes of ultra-processed food that confer harm, and optimise nutrition-related and public health strategies for common mental disorders

X-ray and UV spectroscopy of Galactic diffuse hot gas along the LMC X--3 sight line

We present Suzaku spectra of X-ray emission in the fields just off the LMC X-3 sight line. OVII, OVIII, and NeIX emission lines are clearly detected, suggesting the presence of an optically thin thermal plasma with an average temperature of 2.4E6. This temperature is significantly higher than that inferred from existing X-ray absorption line data obtained with Chandra grating observations of LMC X-3, strongly suggesting that the gas is not isothermal. We then jointly analyze these data to characterize the spatial and temperature distributions of the gas. Assuming a vertical exponential Galactic disk model, we estimate the gas temperature and density at the Galactic plane and their scale heights as 3.6(2.9, 4.7)E6 K and 1.4(0.3, 3.4)E-3 cm^{-3} and 1.4(0.2, 5.2) kpc and $2.8(1.0, 6.4)$ kpc, respectively. This characterization can account for all the \ovi line absorption, as observed in a FUSE spectrum of LMC X-3, but only predicts less than one tenth of the OVI line emission intensity typically detected at high Galactic latitudes. The bulk of the OVI emission most likely arises at interfaces between cool and hot gases.Comment: 10 pages, 7 figures, 3 tables, accepted for publication in ApJ, 200

Cumulative regulatory potential of clustered methyl-arginine protein modifications

Systematic analysis of human arginine methylation events bifurcates its signaling mechanism, functioning either in isolation akin to canonical PTM regulation or clustered within disordered protein sequence. Hundreds of proteins contain methyl-arginine clusters and are more prone to mutation and more tightly expression-regulated than dispersed methylation targets. Arginine clusters in the highly methylated RNA binding protein SYNCRIP were experimentally shown to function in concert providing a tunable protein interaction interface. Quantitative immuno-precipitation assays defined two distinct cumulative regulatory mechanisms operating across 18 proximal arginine-glycine motifs in SYNCRIP. Functional binding to the methyl-transferase PRMT1 was promoted by continual arginine stretches while interaction with the methyl-binding protein SMN1 was arginine content dependent irrespective of linear position within the unstructured region. This study highlights how highly repetitive di-amino acid motifs in otherwise low structural complexity regions can provide regulatory potential, and with SYNCRIP as an extreme example how PTMs leverage these disordered sequences to drive cellular functions

The Milky Way's Kiloparsec Scale Wind: A Hybrid Cosmic-Ray and Thermally Driven Outflow

We apply a wind model, driven by combined cosmic-ray and thermal-gas pressure, to the Milky Way, and show that the observed Galactic diffuse soft X-ray emission can be better explained by a wind than by previous static gas models. We find that cosmic-ray pressure is essential to driving the observed wind. Having thus defined a "best-fit" model for a Galactic wind, we explore variations in the base parameters and show how the wind's properties vary with changes in gas pressure, cosmic-ray pressure and density. We demonstrate the importance of cosmic rays in launching winds, and the effect cosmic rays have on wind dynamics. In addition, this model adds support to the hypothesis of Breitschwerdt and collaborators that such a wind may help explain the relatively small gradient observed in gamma-ray emission as a function of galactocentric radius.Comment: 14 pages, 11 figures; Accepted to Ap

ADAMTS1 alters blood vessel morphology and TSP1 levels in LNCaP and LNCaP-19 prostate tumors

<p>Abstract</p> <p>Background</p> <p>Decreased expression of the angiogenesis inhibitor ADAMTS1 (ADAM metallopeptidase with thrombospondin type 1 motif, 1) has previously been reported during prostate cancer progression. The aim of this study was to investigate the function of ADAMTS1 in prostate tumors.</p> <p>Methods</p> <p>ADAMTS1 was downregulated by shRNA technology in the human prostate cancer cell line LNCaP (androgen-dependent), originally expressing ADAMTS1, and was upregulated by transfection in its subline LNCaP-19 (androgen-independent), expressing low levels of ADAMTS1. Cells were implanted subcutaneously in nude mice and tumor growth, microvessel density (MVD), blood vessel morphology, pericyte coverage and thrombospondin 1 (TSP1) were studied in the tumor xenografts.</p> <p>Results</p> <p>Modified expression of ADAMTS1 resulted in altered blood vessel morphology in the tumors. Low expression levels of ADAMTS1 were associated with small diameter blood vessels both in LNCaP and LNCaP-19 tumors, while high levels of ADAMTS1 were associated with larger vessels. In addition, TSP1 levels in the tumor xenografts were inversely related to ADAMTS1 expression. MVD and pericyte coverage were not affected. Moreover, upregulation of ADAMTS1 inhibited tumor growth of LNCaP-19, as evidenced by delayed tumor establishment. In contrast, downregulation of ADAMTS1 in LNCaP resulted in reduced tumor growth rate.</p> <p>Conclusions</p> <p>The present study demonstrates that ADAMTS1 is an important regulatory factor of angiogenesis and tumor growth in prostate tumors, where modified ADAMTS1 expression resulted in markedly changed blood vessel morphology, possibly related to altered TSP1 levels.</p

A characteristic lengthscale causes anomalous size effects and boundary programmability in mechanical metamaterials

The architecture of mechanical metamaterialsis designed to harness geometry, non-linearity and topology to obtain advanced functionalities such as shape morphing, programmability and one-way propagation. While a purely geometric framework successfully captures the physics of small systems under idealized conditions, large systems or heterogeneous driving conditions remain essentially unexplored. Here we uncover strong anomalies in the mechanics of a broad class of metamaterials, such as auxetics, shape-changers or topological insulators: a non-monotonic variation of their stiffness with system size, and the ability of textured boundaries to completely alter their properties. These striking features stem from the competition between rotation-based deformations---relevant for small systems---and ordinary elasticity, and are controlled by a characteristic length scale which is entirely tunable by the architectural details. Our study provides new vistas for designing, controlling and programming the mechanics of metamaterials in the thermodynamic limit.Comment: Main text has 4 pages, 4 figures + Methods and Supplementary Informatio

The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) family

The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) enzymes are secreted, multi-domain matrix-associated zinc metalloendopeptidases that have diverse roles in tissue morphogenesis and patho-physiological remodeling, in inflammation and in vascular biology. The human family includes 19 members that can be sub-grouped on the basis of their known substrates, namely the aggrecanases or proteoglycanases (ADAMTS1, 4, 5, 8, 9, 15 and 20), the procollagen N-propeptidases (ADAMTS2, 3 and 14), the cartilage oligomeric matrix protein-cleaving enzymes (ADAMTS7 and 12), the von-Willebrand Factor proteinase (ADAMTS13) and a group of orphan enzymes (ADAMTS6, 10, 16, 17, 18 and 19). Control of the structure and function of the extracellular matrix (ECM) is a central theme of the biology of the ADAMTS, as exemplified by the actions of the procollagen-N-propeptidases in collagen fibril assembly and of the aggrecanases in the cleavage or modification of ECM proteoglycans. Defects in certain family members give rise to inherited genetic disorders, while the aberrant expression or function of others is associated with arthritis, cancer and cardiovascular disease. In particular, ADAMTS4 and 5 have emerged as therapeutic targets in arthritis. Multiple ADAMTSs from different sub-groupings exert either positive or negative effects on tumorigenesis and metastasis, with both metalloproteinase-dependent and -independent actions known to occur. The basic ADAMTS structure comprises a metalloproteinase catalytic domain and a carboxy-terminal ancillary domain, the latter determining substrate specificity and the localization of the protease and its interaction partners; ancillary domains probably also have independent biological functions. Focusing primarily on the aggrecanases and proteoglycanases, this review provides a perspective on the evolution of the ADAMTS family, their links with developmental and disease mechanisms, and key questions for the future

Identification of Giardia lamblia DHHC Proteins and the Role of Protein S-palmitoylation in the Encystation Process

Protein S-palmitoylation, a hydrophobic post-translational modification, is performed by protein acyltransferases that have a common DHHC Cys-rich domain (DHHC proteins), and provides a regulatory switch for protein membrane association. In this work, we analyzed the presence of DHHC proteins in the protozoa parasite Giardia lamblia and the function of the reversible S-palmitoylation of proteins during parasite differentiation into cyst. Two specific events were observed: encysting cells displayed a larger amount of palmitoylated proteins, and parasites treated with palmitoylation inhibitors produced a reduced number of mature cysts. With bioinformatics tools, we found nine DHHC proteins, potential protein acyltransferases, in the Giardia proteome. These proteins displayed a conserved structure when compared to different organisms and are distributed in different monophyletic clades. Although all Giardia DHHC proteins were found to be present in trophozoites and encysting cells, these proteins showed a different intracellular localization in trophozoites and seemed to be differently involved in the encystation process when they were overexpressed. dhhc transgenic parasites showed a different pattern of cyst wall protein expression and yielded different amounts of mature cysts when they were induced to encyst. Our findings disclosed some important issues regarding the role of DHHC proteins and palmitoylation during Giardia encystation.Fil: Merino, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Zamponi, Nahuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Vranych, Cecilia Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Touz, Maria Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Ropolo, Andrea Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentin

Acyl-Protein Thioesterase 2 Catalizes the Deacylation of Peripheral Membrane-Associated GAP-43

An acylation/deacylation cycle is necessary to maintain the steady-state subcellular distribution and biological activity of S-acylated peripheral proteins. Despite the progress that has been made in identifying and characterizing palmitoyltransferases (PATs), much less is known about the thioesterases involved in protein deacylation. In this work, we investigated the deacylation of growth-associated protein-43 (GAP-43), a dually acylated protein at cysteine residues 3 and 4. Using fluorescent fusion constructs, we measured in vivo the rate of deacylation of GAP-43 and its single acylated mutants in Chinese hamster ovary (CHO)-K1 and human HeLa cells. Biochemical and live cell imaging experiments demonstrated that single acylated mutants were completely deacylated with similar kinetic in both cell types. By RT-PCR we observed that acyl-protein thioesterase 1 (APT-1), the only bona fide thioesterase shown to mediate deacylation in vivo, is expressed in HeLa cells, but not in CHO-K1 cells. However, APT-1 overexpression neither increased the deacylation rate of single acylated GAP-43 nor affected the steady-state subcellular distribution of dually acylated GAP-43 both in CHO-K1 and HeLa cells, indicating that GAP-43 deacylation is not mediated by APT-1. Accordingly, we performed a bioinformatic search to identify putative candidates with acyl-protein thioesterase activity. Among several candidates, we found that APT-2 is expressed both in CHO-K1 and HeLa cells and its overexpression increased the deacylation rate of single acylated GAP-43 and affected the steady-state localization of diacylated GAP-43 and H-Ras. Thus, the results demonstrate that APT-2 is the protein thioesterase involved in the acylation/deacylation cycle operating in GAP-43 subcellular distribution