Role In Pinning Research Articles

Invited commentary

Cellular senescence is an important contributor to the development of atherosclerosis. The mechanisms by which senescence promotes atherosclerosis, however, remain poorly understood. This important study by Lv et al demonstrates the causal association between reduced expression of peptidyl-prolyl cis/trans isomerase (Pin 1), increased vascular smooth muscle cell (VSMC) senescence, increased cellular senescence molecules p21 and p53, and reduced cell cycle-related cyclin-dependent kinases based on gain- and loss-of-function studies performed in vitro. In subsequent experiments, inhibition of Pin 1 was found to exacerbate experimental atherosclerosis. Thus, the authors postulate that Pin 1, likely acting upstream of the cellular senescence cascade, limits atherosclerosis by limiting VSMC senescence. An unexpected finding was that manipulation of the Pin 1 gene in vitro altered the expression of messenger RNA for p21, p53, p65, Gadd45, and cyclin-dependent kinases. These modulations are not attributable to variation in Pin 1 isomerase activity per se, leaving open the question of exactly which Pin 1-mediated actions suppress VSMC senescence. Senescent VSMCs express high levels of proatherogenic secretory molecules, which promote cell migration, extracellular matrix degradation, and the formation and activity of the inflammasome.1Gardner S.E. Humphry M. Bennett M.R. Clarke M.C. Senescent vascular smooth muscle cells drive inflammation through an interleukin-1alpha-dependent senescence-associated secretory phenotype.Arterioscl Thromb Vasc Biol. 2015; 35: 1963-1974Crossref PubMed Scopus (164) Google Scholar Further experiments should investigate how Pin 1 affects the VSMC senescence-associated secretory phenotype. In addition to senescent VSMCs, senescent foam cells are potent promoters of atherogenesis.2Childs B.G. Baker D.J. Wijshake T. Conover C.A. Campisi J. van Deursen J.M. Senescent intimal foam cells are deleterious at all stages of atherosclerosis.Science. 2016; 354: 472-477Crossref PubMed Scopus (605) Google Scholar This raises possibility that senescent foam cells may contribute to Pin 1 inhibition-mediated atherosclerosis. Thus, further experiments should be performed using VSMC- or myeloid cell-specific Pin 1-deficient mice to clarify the relative contributions of VSMC- and macrophage-derived Pin 1 to atherogenesis. The potential influence of Pin 1 on autophagy should also be investigated, given the causal association between defective autophagy and atherosclerosis.3Grootaert M.O. da Costa Martins P.A. Bitsch N. Pintelon I. De Meyer G.R. Martinet W. et al.Defective autophagy in vascular smooth muscle cells accelerates senescence and promotes neointima formation and atherogenesis.Autophagy. 2015; 11: 2014-2032Crossref PubMed Scopus (178) Google Scholar Several polymorphisms in the gene encoding for Pin 1 are associated with a reduced risk for various cancers.4Xu H.R. Xu Z.F. Sun Y.L. Han J.J. Li Z.J. The -842G/C polymorphisms of PIN1 contributes to cancer risk: a meta-analysis of 10 case-control studies.PLoS One. 2013; 8: e71516Crossref PubMed Scopus (3) Google Scholar These or other known Pin 1 variants should be investigated to shed more light on the heritable susceptibility for atherosclerosis. Also, do hyperlipidemia and diabetes, two major atherosclerotic risk factors, influence Pin 1 expression? In a previous study,5Paneni F. Costantino S. Castello L. Battista R. Capretti G. Chiandotto S. et al.Targeting prolyl-isomerase Pin1 prevents mitochondrial oxidative stress and vascular dysfunction: insights in patients with diabetes.Eur Heart J. 2015; 36: 817-828Crossref PubMed Scopus (71) Google Scholar circulating monocytes harvested from diabetic patients demonstrate increased Pin 1 expression, and hyperglycemia has been found to upregulate expression in human endothelial cells in vitro. This study adds to the growing body of knowledge regarding the role of Pin 1 function in the regulation of atherosclerosis. Systemic augmentation of Pin 1 will isomerize phosphorylated serine/threonine-proline motif-containing proteins throughout the body, limiting clinical applicability due to undesirable off-target effects. And to date, no Pin 1 agonists or activators have been developed for clinical applications. Overcoming these obstacles will be necessary for the successful clinical translation of Pin 1-mediated therapeutic interventions in the treatment of atherosclerotic diseases. Downregulation of Pin1 in human atherosclerosis and its association with vascular smooth muscle cell senescenceJournal of Vascular SurgeryVol. 68Issue 3PreviewPin1 is prevalently overexpressed in human cancers and implicated to regulate cell growth and apoptosis. Thus far, however, no role for Pin1 has been described in modulating vascular smooth muscle cell (VSMC) senescence. Full-Text PDF Open Archive

Hydrogen embrittlement I. Analysis of hydrogen-enhanced localized plasticity: Effect of hydrogen on the velocity of screw dislocations inα-Fe

We demonstrate a kinetic Monte Carlo simulation tool, based on published data using first-principles quantum mechanics, applied to answer the question: under which conditions of stress, temperature, and nominal hydrogen concentration does the presence of hydrogen in iron increase or decrease the screw dislocation velocity? Furthermore, we examine the conditions under which hydrogen-induced shear localization is likely to occur. Our simulations yield quantitative data on dislocation velocity and the ranges of hydrogen concentration within which a large gradient of velocity as a function of concentration is expected to be observed and thereby contribute to a self-perpetuating localization of plasticity---a phenomenon that has been linked to hydrogen-induced fracture and fatigue failure in ultrahigh strength steel. We predict the effect of hydrogen in generating debris made up of edge dipoles trailing in the wake of gliding screw dislocations and their role in pinning. We also simulate the competing effects of softening by enhanced kink-pair generation and hardening by solute pinning. Our simulations act as a bridge between first-principles quantum mechanics and discrete dislocation dynamics, and at the same time offer the prospect of a fully physics-based dislocation dynamics method.

Loss of the canonical spindle orientation function in the Pins/LGN homolog AGS3.

In many cell types, mitotic spindle orientation relies on the canonical "LGN complex" composed of Pins/LGN, Mud/NuMA, and Gαi subunits. Membrane localization of this complex recruits motor force generators that pull on astral microtubules to orient the spindle. Drosophila Pins shares highly conserved functional domains with its two vertebrate homologs LGN and AGS3. Whereas the role of Pins and LGN in oriented divisions is extensively documented, involvement of AGS3 remains controversial. Here, we show that AGS3 is not required for planar divisions of neural progenitors in the mouse neocortex. AGS3 is not recruited to the cell cortex and does not rescue LGN loss of function. Despite conserved interactions with NuMA and Gαiin vitro, comparison of LGN and AGS3 functional domains in vivo reveals unexpected differences in the ability of these interactions to mediate spindle orientation functions. Finally, we find that Drosophila Pins is unable to substitute for LGN loss of function in vertebrates, highlighting that species-specific modulations of the interactions between components of the Pins/LGN complex are crucial in vivo for spindle orientation.

Magnetoelastic relaxations in EuTiO3

The multiferroic properties of EuTiO3 are greatly enhanced when a sample is strained, signifying that coupling between strain and structural, magnetic or ferroelectric order parameters is extremely important. Here resonant ultrasound spectroscopy has been used to investigate strain coupling effects, as well as possible additional phase transitions, through their influence on elastic and anelastic relaxations that occur as a function of temperature between 2 and 300 K and with applied magnetic field up to 14 T. Antiferromagnetic ordering is accompanied by acoustic loss and softening, and a weak magnetoelastic effect is also associated with the change in magnetization direction below . Changes in loss due to the influence of magnetic field suggest the existence of magnetic defects which couple with strain and may play a role in pinning of ferroelastic twin walls.

Temperature Dependence of the Zero-Field In-Plane Critical Current Density of YBa<sub>2</sub>Cu<sub>3</sub>O<sub>7-d</sub> High-<i>T</i><sub>c</sub> Superconductors

The nature of the temperature dependence of the zero-field critical current density, Jc0(T), in the CuO2 planes has been investigated for c-axis oriented YBa2Cu3O7-d (Y123) thin films over a range of hole content, p. The hole concentration was varied by changing the oxygen deficiency, d, in the CuO1-d chains by annealing the films under different oxygen partial pressures and temperatures. The Jc0(T) values were extracted from the magnetic hysteresis (M-H) loops obtained at different temperatures. From the analysis of the Jc0(T) data for different sample compositions, we have extracted valuable information regarding the nature of the underlying magnetic flux pinning mechanisms in Y123 superconductors. We have found that the oxygen defects play only a secondary role in pinning of the vortices, the superfluid density, on the other hand plays a significant role. The exponent, n, governing the Jc0(T) behavior for a given sample composition showed a systematic behavior as hole contents are changed. Keywords: Y123 superconductors; Critical current density; Flux pinning.© 2012 JSR Publications. ISSN: 2070-0237 (Print); 2070-0245 (Online). All rights reserved.doi: http://dx.doi.org/10.3329/jsr.v4i2.9653 J. Sci. Res. 4 (2), 287-296 (2012)

A reappraisal of person recognition and identification

In the last years an increasing number of cases (Gainotti et al., 2008, this issue) have been reported in whom difficulty to recognise and identify familiar people occurs in everyday multimodal settings, differently from unimodal face-specific impairments (i.e., prosopagnosia). A reappraisal of current person processing models is presented in order to account for such deficits as well as for the common slips of recognition occurring in healthy subjects. The model we propose is based upon three main modifications of current models, namely: (1) the role of PINs as stores of multimodal perceptual knowledge; (2) the richness of perceptual nuances characterizing PINs of most familiar people; (3) the PINs' addressing of Exemplar Semantics by a provisional Gestalt guessing and an analytical check, to be negotiated whenever a conflict arises. A single case report of Capgras delusion is presented as a crossmodal person processing disorder in everyday settings for whom the proposed model allows a cognitive interpretation.

Localization and the effective mass of a vortex

In the problem of a vortex escaping from a metastable potential, we derive the localizationcriterion of a vortex at finite dissipation and temperature by analysing both the crossovertemperature formula and the escape rate formula. In the absence of a pinning potential inthe stable direction, this criterion shows that a vortex will be localized in a metastablepotential when the Magnus force is strong enough. Using the concept of this localizationcriterion, the effective mass of a vortex can be defined and interpreted. Moreover, the roleof pinning and dissipation in the process of vortex escape can also be discussed.

Full coverage, partial coverage, and the role of pins

The indications, advantages, and disadvantages of various types of restorations and retainers have been discussed. The proper use of pins makes it possible to use conservative partial coverage in many teeth. For badly broken down teeth, the proper use of full coverage is the only successful method of treatment.