Early postnatal exposure to lithium in vitro induces changes in AMPAR mEPSCs and vesicular recycling at hippocampal glutamatergic synapses

Lithium is an effective mood stabilizer but its use is associated with many side effects. Electrophysiological recordings of miniature excitatory postsynaptic currents (mEPSCs) mediated by glutamate receptor AMPA-subtype (AMPARs) in hippocampal pyramidal neurons revealed that CLi (therapeutic concentration of 1 mM lithium, from days in vitro 4-10) decreased the mean amplitude and mean rectification index (RI) of AMPAR mEPSCs. Lowered mean RI indicate that contribution of Ca2+-permeable AMPARs in synaptic events is higher in CLi neurons (supported by experiments sensitive to Ca2+-permeable AMPAR modulation). Co-inhibiting PKA, GSK-3 beta and glutamate reuptake was necessary to bring about changes in AMPAR mEPSCs similar to that seen in CLi neurons. FM1-43 experiments revealed that recycling pool size was affected in CLi cultures. Results from minimum loading, chlorpromazine treatment and hyperosmotic treatment experiments indicate that endocytosis in CLi is affected while not much difference is seen in modes of exocytosis. CLi cultures did not show the high KCl associated presynaptic potentiation observed in control cultures. This study, by calling attention to long-term lithium-exposure-induced synaptic changes, might have implications in understanding the side effects such as CNS complications occurring in perinatally exposed babies and cognitive dulling seen in patients on lithium treatment.

BLOC-2 targets recycling endosomal tubules to melanosomes for cargo delivery

Hermansky-Pudlak syndrome (HPS) is a group of disorders characterized by the malformation of lysosome-related organelles, such as pigment cell melanosomes. Three of nine characterized HPS subtypes result from mutations in subunits of BLOC-2, a protein complex with no known molecular function. In this paper, we exploit melanocytes from mouse HPS models to place BLOC-2 within a cargo transport pathway from recycling endosomal domains to maturing melanosomes. In BLOC-2-deficient melanocytes, the melanosomal protein TYRP1 was largely depleted from pigment granules and underwent accelerated recycling from endosomes to the plasma membrane and to the Golgi. By live-cell imaging, recycling endosomal tubules of wild-type melanocytes made frequent and prolonged contacts with maturing melanosomes; in contrast, tubules from BLOC-2-deficient cells were shorter in length and made fewer, more transient contacts with melanosomes. These results support a model in which BLOC-2 functions to direct recycling endosomal tubular transport intermediates to maturing melanosomes and thereby promote cargo delivery and optimal pigmentation.

Smaller is Plastic: Polymorphic Structures and Mechanism of Deformation in Nanoscale hcp Metals

Using first-principles calculations, we establish the existence of highly-stable polymorphs of hcp metals (Ti, Mg, Be, La and Y) with nanoscale structural periodicity. They arise from heterogeneous deformation of the hcp structure occurring in response to large shear stresses localized at the basal planes separated by a few nanometers. Through Landau theoretical analysis, we show that their stability derives from nonlinear coupling between strains at different length scales. Such multiscale hyperelasticity and long-period structures constitute a new mechanism of size-dependent plasticity and its enhancement in nanoscale hcp metals.

STX13 regulates cargo delivery from recycling endosomes during melanosome biogenesis

Melanosomes are a class of lysosome-related organelles produced by melanocytes. Biogenesis of melanosomes requires the transport of melanin-synthesizing enzymes from tubular recycling endosomes to maturing melanosomes. The SNARE proteins involved in these transport or fusion steps have been poorly studied. We found that depletion of syntaxin 13 (STX13, also known as STX12), a recycling endosomal Qa-SNARE, inhibits pigment granule maturation in melanocytes by rerouting the melanosomal proteins such as TYR and TYRP1 to lysosomes. Furthermore, live-cell imaging and electron microscopy studies showed that STX13 co-distributed with melanosomal cargo in the tubular-vesicular endosomes that are closely associated with the maturing melanosomes. STX family proteins contain an N-terminal regulatory domain, and deletion of this domain in STX13 increases both the SNARE activity in vivo and melanosome cargo transport and pigmentation, suggesting that STX13 acts as a fusion SNARE in melanosomal trafficking pathways. In addition, STX13-dependent cargo transport requires the melanosomal R-SNARE VAMP7, and its silencing blocks the melanosome maturation, reflecting a defect in endosome-melanosome fusion. Moreover, we show mutual dependency between STX13 and VAMP7 in regulating their localization for efficient cargo delivery to melanosomes.

General framework for acoustic emission during plastic deformation

Despite the long history, so far there is no general theoretical framework for calculating the acoustic emission spectrum accompanying any plastic deformation. We set up a discrete wave equation with plastic strain rate as a source term and include the Rayleigh-dissipation function to represent dissipation accompanying acoustic emission. We devise a method of bridging the widely separated time scales of plastic deformation and elastic degrees of freedom. While this equation is applicable to any type of plastic deformation, it should be supplemented by evolution equations for the dislocation microstructure for calculating the plastic strain rate. The efficacy of the framework is illustrated by considering three distinct cases of plastic deformation. The first one is the acoustic emission during a typical continuous yield exhibiting a smooth stress-strain curve. We first construct an appropriate set of evolution equations for two types of dislocation densities and then show that the shape of the model stress-strain curve and accompanying acoustic emission spectrum match very well with experimental results. The second and the third are the more complex cases of the Portevin-Le Chatelier bands and the Luders band. These two cases are dealt with in the context of the Ananthakrishna model since the model predicts the three types of the Portevin-Le Chatelier bands and also Luders-like bands. Our results show that for the type-C bands where the serration amplitude is large, the acoustic emission spectrum consists of well-separated bursts of acoustic emission. At higher strain rates of hopping type-B bands, the burst-type acoustic emission spectrum tends to overlap, forming a nearly continuous background with some sharp acoustic emission bursts. The latter can be identified with the nucleation of new bands. The acoustic emission spectrum associated with the continuously propagating type-A band is continuous. These predictions are consistent with experimental results. More importantly, our study shows that the low-amplitude continuous acoustic emission spectrum seen in both the type-B and type-A band regimes is directly correlated to small-amplitude serrations induced by propagating bands. The acoustic emission spectrum of the Luders-like band matches with recent experiments as well. In all of these cases, acoustic emission signals are burstlike, reflecting the intermittent character of dislocation-mediated plastic flow.

Rab9A is required for delivery of cargo from recycling endosomes to melanosomes

Melanosomes are a type of lysosome-related organelle that is commonly defective in Hermansky-Pudlak syndrome. Biogenesis of melanosomes is regulated by BLOC-1, -2, -3, or AP-1, -3 complexes, which mediate cargo transport from recycling endosomes to melanosomes. Although several Rab GTPases have been shown to regulate these trafficking steps, the precise role of Rab9A remains unknown. Here, we found that a cohort of Rab9A associates with the melanosomes and its knockdown in melanocytes results in hypopigmented melanosomes due to mistargeting of melanosomal proteins to lysosomes. In addition, the Rab9A-depletion phenotype resembles Rab38/ 32-inactivated or BLOC-3-deficient melanocytes, suggesting that Rab9A works in line with BLOC-3 and Rab38/ 32 during melanosome cargo transport. Furthermore, silencing of Rab9A, Rab38/ 32 or its effector VARP, or BLOC-3-deficiency in melanocytes decreased the length of STX13-positive recycling endosomal tubules and targeted the SNARE to lysosomes. This result indicates a defect in directing recycling endosomal tubules to melanosomes. Thus, Rab9A and its co-regulatory GTPases control STX13-mediated cargo delivery to maturing melanosomes.

Botulinum neurotoxin type-A enters a non-recycling pool of synaptic vesicles

Neuronal communication relies on synaptic vesicles undergoing regulated exocytosis and recycling for multiple rounds of fusion. Whether all synaptic vesicles have identical protein content has been challenged, suggesting that their recycling ability may differ greatly. Botulinum neurotoxin type-A (BoNT/A) is a highly potent neurotoxin that is internalized in synaptic vesicles at motor nerve terminals and induces flaccid paralysis. Recently, BoNT/A was also shown to undergo retrograde transport, suggesting it might enter a specific pool of synaptic vesicles with a retrograde trafficking fate. Using high-resolution microscopy techniques including electron microscopy and single molecule imaging, we found that the BoNT/A binding domain is internalized within a subset of vesicles that only partially co-localize with cholera toxin B-subunit and have markedly reduced VAMP2 immunoreactivity. Synaptic vesicles loaded with pHrodo-BoNT/A-Hc exhibited a significantly reduced ability to fuse with the plasma membrane in mouse hippocampal nerve terminals when compared with pHrodo-dextran-containing synaptic vesicles and pHrodo-labeled anti-GFP nanobodies bound to VAMP2-pHluorin or vGlut-pHluorin. Similar results were also obtained at the amphibian neuromuscular junction. These results reveal that BoNT/A is internalized in a subpopulation of synaptic vesicles that are not destined to recycle, highlighting the existence of significant molecular and functional heterogeneity between synaptic vesicles.

On the critical thickness for non-localized to localized plastic flow transition in metallic glasses: A molecular dynamics study

Molecular dynamics simulations were employed to investigate the specimen thickness-dependent tensile behavior of a series of Cu(x)Z(100-x) (x = 20, 40, 50, 64 and 80 at%) metallic glass (MG) films, with a particular focus on the critical thickness, tc, below which non-localized plastic flow takes place. The simulation results reveal that while the transition occurs in all the alloys examined, t(c) is sensitive to the composition. We rationalize t(c) by postulating that the strain energy stored in the sample at the onset of plastic deformation has to be sufficient for the formation of shear bands. The composition-dependence of t(c) was found to correlate with the average activation energy of the atomic level plastic deformation events. (C) 2015 Elsevier Ltd. All rights reserved.

Conversion of plastic waste into CNTs using Ni/Mo/MgO catalystAn optimization approach by mixture experiment

A combustion technique is used to study the synthesis of carbon nano tubes from waste plastic as a precursor and Ni/Mo/MgO as a catalyst. The catalytic activity of three components Ni, Mo, MgO is measured in terms of amount of carbon product obtained. Different proportions of metal ions are optimized using mixture experiment in Design expert software. D-optimal design technique is adopted due to nonsimplex region and presence of constraints in the mixture experiment. The activity of the components is observed to be interdependent and the component Ni is found to be more effective. The catalyst containing Ni0.8Mo0.1MgO0.1 yields more carbon product. The structure of catalyst and CNTs are studied by using SEM, XRD, and Raman spectroscopy. SEM analysis shows the formation of longer CNTs with average diameter of 40-50 nm.

The thermo-visco-plastic instability analysis of saturated soil

A theoretical analysis of instability of saturated soil is presented considering the simple shearing of a heat conducting thermo-visco-plastic material. It is shown that the instability is mainly the consequence of thermal softening which overcomes the strain hardening and the other type of instability is controlled by strain softening. The effects of other factors such as permeability to the instability are discussed in this paper.

Detection and Characterization of Long-Pulse Low-Velocity Impact Damage in Plastic Bonded Explosives

Damage not only degrades the mechanical properties of explosives, but also influences the shock sensitivity, combustion and even detonation behavior of explosives. The study of impact damage is crucial in the vulnerability evaluation of explosives. A long-pulse low-velocity gas gun with a gas buffer was developed and used to induce impact damage in a hot pressed plastic bonded explosive. Various methods were used to detect and characterize the impact damage of the explosive. The microstructure was examined by use of polarized light microscopy. Fractal analysis of the micrographs was conducted by use of box counting method. The correlation between the fractal dimensions and microstructures was analyzed. Ultrasonic testing was conducted using a pulse through-transmission method to obtain the ultrasonic velocity and ultrasonic attenuation. Spectra analyses were carried out for recorded ultrasonic signals using fast Fourier transform. The correlations between the impact damage and ultrasonic parameters including ultrasonic velocities and attenuation coefficients were also analyzed. To quantitatively assess the impact induced explosive crystal fractures, particle size distribution analyses of explosive crystals were conducted by using a thorough etching technique, in which the explosives samples were soaked in a solution for enough time that the binder was totally removed. Impact induces a large extent of explosive crystal fractures and a large number of microcracks. The ultrasonic velocity decreases and attenuation coefficients increase with the presence of impact damage. Both ultrasonic parameters and fractal dimension can be used to quantitatively assess the impact damage of plastic bonded explosives.

Scaling relationships in conical indentation of elastic perfectly plastic solids

Using dimensional analysis and finite element calculations we derive several scaling relationships for conical indentation into elastic-perfectly plastic solids. These scaling relationships provide new insights into the shape of indentation curves and form the basis for understanding indentation measurements, including nano- and micro-indentation techniques. They are also helpful as a guide to numerical and finite element calculations of conical indentation problems. Finally, the scaling relationships are used to reveal the general relationships between hardness, contact area, initial unloading slope, and mechanical properties of solids.

Saturated duration for dynamic structural plastic response and fundamental periods of elastic vibration

The relationship is determined between saturated duration of rectangular pressure pulses applied to rigid, perfectly plastic structures and their fundamental periods of elastic vibration. It is shown that the ratio between the saturated duration and the fundamental period of elastic vibration of a structure is dependent upon two factors: the first one is the slenderness or thinness ratio of the structure; and the second one is the square root of ratio between the Young's elastic modulus and the yield stress of the structural material. Dimensional analysis shows that the aforementioned ratio is one of the basic similarity parameters for elastic-plastic modeling under dynamic loading.

Generalization of Response Number for Dynamic Plastic Response of Shells Subjected to impulsive Loading

A dimensionless number, termed as response number in Zhao [Archive of Applied Mechanics 68 (1998) 524], has been suggested for the dynamic plastic response of beams and plates made up of rigidly perfect plastic materials subjected to dynamic loading. Many theoretical and experimental results can be reformulated into new concise forms with the response number. The concept of a new dimensionless number, response number, termed as Rn(n), is generalized in Zhao [Forschung im Ingenieurwesen 65 (1999) 107] to study the elastic, plastic, dynamic elastic as well as dynamic plastic buckling problems of columns, plates as well as shells. The response number Rn(n) is generalized to the dynamic behaviour of shells of various shapes in the present paper.

Application of response number for dynamic plastic response of plates subjected to impulsive loading

A dimensionless number, termed response number, is applied to the dynamic plastic response of plates subjected to dynamic loading. Many theoretical and experimental results presented by different researchers are reformulated into new concise forms with the response number. The advantage of the new forms is twofold: (1) they are more physically meaningful, and (2) they are independent of the choice of units, thus, they have wider range of applications.